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Sample records for deep brain stimulators

  1. Pathways of translation: deep brain stimulation.

    Science.gov (United States)

    Gionfriddo, Michael R; Greenberg, Alexandra J; Wahegaonkar, Abhijeet L; Lee, Kendall H

    2013-12-01

    Electrical stimulation of the brain has a 2000 year history. Deep brain stimulation (DBS), one form of neurostimulation, is a functional neurosurgical approach in which a high-frequency electrical current stimulates targeted brain structures for therapeutic benefit. It is an effective treatment for certain neuropathologic movement disorders and an emerging therapy for psychiatric conditions and epilepsy. Its translational journey did not follow the typical bench-to-bedside path, but rather reversed the process. The shift from ancient and medieval folkloric remedy to accepted medical practice began with independent discoveries about electricity during the 19th century and was fostered by technological advances of the 20th. In this paper, we review that journey and discuss how the quest to expand its applications and improve outcomes is taking DBS from the bedside back to the bench. © 2013 Wiley Periodicals, Inc.

  2. Deep brain stimulation as a functional scalpel.

    Science.gov (United States)

    Broggi, G; Franzini, A; Tringali, G; Ferroli, P; Marras, C; Romito, L; Maccagnano, E

    2006-01-01

    Since 1995, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan (INNCB,) 401 deep brain electrodes were implanted to treat several drug-resistant neurological syndromes (Fig. 1). More than 200 patients are still available for follow-up and therapeutical considerations. In this paper our experience is reviewed and pioneered fields are highlighted. The reported series of patients extends the use of deep brain stimulation beyond the field of Parkinson's disease to new fields such as cluster headache, disruptive behaviour, SUNCt, epilepsy and tardive dystonia. The low complication rate, the reversibility of the procedure and the available image guided surgery tools will further increase the therapeutic applications of DBS. New therapeutical applications are expected for this functional scalpel.

  3. Deep Brain Stimulation for Parkinson's Disease

    Science.gov (United States)

    ... about the BRAIN initiative, see www.nih.gov/science/brain . Show More Show Less Search Disorders SEARCH SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Deep ...

  4. Closing the loop of deep brain stimulation.

    Science.gov (United States)

    Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance

    2013-12-20

    High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment.

  5. Closing the loop of deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Romain eCARRON

    2013-12-01

    Full Text Available High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfils these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment.

  6. Closing the loop of deep brain stimulation

    Science.gov (United States)

    Carron, Romain; Chaillet, Antoine; Filipchuk, Anton; Pasillas-Lépine, William; Hammond, Constance

    2013-01-01

    High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment. PMID:24391555

  7. Deep brain stimulation for Tourette syndrome.

    Science.gov (United States)

    Kim, Won; Pouratian, Nader

    2014-01-01

    Gilles de la Tourette syndrome is a movement disorder characterized by repetitive stereotyped motor and phonic movements with varying degrees of psychiatric comorbidity. Deep brain stimulation (DBS) has emerged as a novel therapeutic intervention for patients with refractory Tourette syndrome. Since 1999, more than 100 patients have undergone DBS at various targets within the corticostriatothalamocortical network thought to be implicated in the underlying pathophysiology of Tourette syndrome. Future multicenter clinical trials and the use of a centralized online database to compare the results are necessary to determine the efficacy of DBS for Tourette syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Deep brain stimulation for cluster headache

    DEFF Research Database (Denmark)

    Grover, Patrick J; Pereira, Erlick A C; Green, Alexander L

    2009-01-01

    Cluster headache is a severely debilitating disorder that can remain unrelieved by current pharmacotherapy. Alongside ablative neurosurgical procedures, neuromodulatory treatments of deep brain stimulation (DBS) and occipital nerve simulation have emerged in the last few years as effective...... treatments for medically refractory cluster headaches. Pioneers in the field have sought to publish guidelines for neurosurgical treatment; however, only small case series with limited long-term follow-up have been published. Controversy remains over which surgical treatments are best and in which...... circumstances to intervene. Here we review current data on neurosurgical interventions for chronic cluster headache focusing upon DBS and occipital nerve stimulation, and discuss the indications for and putative mechanisms of DBS including translational insights from functional neuroimaging, diffusion weighted...

  9. Technological Advances in Deep Brain Stimulation.

    Science.gov (United States)

    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.

  10. Deep brain stimulation for phantom limb pain.

    Science.gov (United States)

    Bittar, Richard G; Otero, Sofia; Carter, Helen; Aziz, Tipu Z

    2005-05-01

    Phantom limb pain is an often severe and debilitating phenomenon that has been reported in up to 85% of amputees. Its pathophysiology is poorly understood. Peripheral and spinal mechanisms are thought to play a role in pain modulation in affected individuals; however central mechanisms are also likely to be of importance. The neuromatrix theory postulates a genetically determined representation of body image, which is modified by sensory input to create a neurosignature. Persistence of the neurosignature may be responsible for painless phantom limb sensations, whereas phantom limb pain may be due to abnormal reorganisation within the neuromatrix. This study assessed the clinical outcome of deep brain stimulation of the periventricular grey matter and somatosensory thalamus for the relief of chronic neuropathic pain associated with phantom limb in three patients. These patients were assessed preoperatively and at 3 month intervals postoperatively. Self-rated visual analogue scale pain scores assessed pain intensity, and the McGill Pain Questionnaire assessed the quality of the pain. Quality of life was assessed using the EUROQOL EQ-5D scale. Periventricular gray stimulation alone was optimal in two patients, whilst a combination of periventricular gray and thalamic stimulation produced the greatest degree of relief in one patient. At follow-up (mean 13.3 months) the intensity of pain was reduced by 62% (range 55-70%). In all three patients, the burning component of the pain was completely alleviated. Opiate intake was reduced in the two patients requiring morphine sulphate pre-operatively. Quality of life measures indicated a statistically significant improvement. This data supports the role for deep brain stimulation in patients with phantom limb pain. The medical literature relating to the epidemiology, pathogenesis, and treatment of this clinical entity is reviewed in detail.

  11. Deep Brain Electrical Stimulation in Epilepsy

    Science.gov (United States)

    Rocha, Luisa L.

    2008-11-01

    The deep brain electrical stimulation has been used for the treatment of neurological disorders such as Parkinson's disease, chronic pain, depression and epilepsy. Studies carried out in human brain indicate that the application of high frequency electrical stimulation (HFS) at 130 Hz in limbic structures of patients with intractable temporal lobe epilepsy abolished clinical seizures and significantly decreased the number of interictal spikes at focus. The anticonvulsant effects of HFS seem to be more effective in patients with less severe epilepsy, an effect associated with a high GABA tissue content and a low rate of cell loss. In addition, experiments using models of epilepsy indicate that HFS (pulses of 60 μs width at 130 Hz at subthreshold current intensity) of specific brain areas avoids the acquisition of generalized seizures and enhances the postictal seizure suppression. HFS is also able to modify the status epilepticus. It is concluded that the effects of HFS may be a good strategy to reduce or avoid the epileptic activity.

  12. A Microfabricated Transduction Coil for Inductive Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Jie (Jayne WU

    2006-07-01

    Full Text Available "Inductively Coupled Deep Brain Stimulator" describes a chip/system design to inductively couple arbitrary waveforms to electrodes embedded in the brain for deep brain stimulation or other neurostimulation. This approach moves the conventionally implanted signal generator outside the body and provides flexibility in adjusting waveforms to investigate optimum stimulation waveforms. An "inlaid electroplating" process with through-wafer plating is used to reduce microcoil resistance and integrate microstructures and electronics. Utilizing inductive link resonance specific to microcoils, waveforms are selectively transmitted to microcoils, which further produces biphasic waveforms that are suitable for deep brain stimulation.

  13. Origin and evolution of deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Vittorio Alessandro eSironi

    2011-08-01

    Full Text Available This paper briefly describes how the electrical stimulation, used since antiquity to modulate the nervous system, has been a fundamental tool of neurophysiologic investigation in the second half of the 18th century and was subsequently used by the early 20th century, even for therapeutic purposes. In mid-20th century the advent of stereotactic procedures has allowed the drift from lesional to stimulating technique of deep nuclei of the brain for therapeutic purposes. In this way, DBS was born, that, over the last two decades, has led to positive results for the treatment of medically refractory Parkinson's disease, essential tremor and dystonia. In recent years, the indications for therapeutic use of DBS have been extended to epilepsy, Tourette's syndrome, psychiatric diseases (depression, obsessive-compulsive disorder, some kinds of headache, eating disorders and the minimally conscious state. The potentials of the DBS for therapeutic use are fascinating, but there are still many unresolved technical and ethical problems, concerning the identification of the targets for each disease, the selection of the patients and the evaluation of the results.

  14. Bibliometric profile of deep brain stimulation.

    Science.gov (United States)

    Hu, Kejia; Moses, Ziev B; Xu, Wendong; Williams, Ziv

    2017-10-01

    We aimed to identify and analyze the characteristics of the 100 most highly-cited papers in the research field of deep brain stimulation (DBS). The Web of Science was searched for highly-cited papers related to DBS research. The number of citations, countries, institutions of origin, year of publication, and research area were noted and analyzed. The 100 most highly-cited articles had a mean of 304.15 citations. These accrued an average of 25.39 citations a year. The most represented target by far was the subthalamic nucleus (STN). These articles were published in 46 high-impact journals, with Brain (n = 10) topping the list. These articles came from 11 countries, with the USA contributing the most highly-cited articles (n = 29); however, it was the University of Toronto (n = 13) in Canada that was the institution with the most highly-cited studies. This study identified the 100 most highly-cited studies and highlighted a historical perspective on the progress in the field of DBS. These findings allow for the recognition of the most influential reports and provide useful information that can indicate areas requiring further investigation.

  15. Ethical issues in deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Maartje eSchermer

    2011-05-01

    Full Text Available Deep brain stimulation (DBS is currently used to treat neurological disorders like Parkinson’s disease (PD, essential tremor and dystonia, and is explored as an experimental treatment for psychiatric disorders like Major Depression (MD and Obsessive Compulsive Disorder (OCD. This mini review discusses ethical issues in DBS treatment and research, as they have been discussed in the medical and ethical literature.With regard to DBS treatment, the most important issues are balancing risks and benefits and ensuring respect for the autonomous wish of the patient. This implies special attention to patient selection, psycho-social impact of treatment, effects on personal identity, and treatment of children. Moreover, it implies a careful informed consent process in which unrealistic expectations of patients and their families are addressed and in which special attention is given to competence. In the context of research, the fundamental ethical challenge is to promote high-quality scientific research in the interest of future patients, while at the same time safeguarding the rights and interests of vulnerable research subjects. Several guidelines have been proposed to ensure this. One of the preconditions to further development of responsible and transparent research practices is the establishment of a comprehensive registry.

  16. Short circuit in deep brain stimulation.

    Science.gov (United States)

    Samura, Kazuhiro; Miyagi, Yasushi; Okamoto, Tsuyoshi; Hayami, Takehito; Kishimoto, Junji; Katano, Mitsuo; Kamikaseda, Kazufumi

    2012-11-01

    The authors undertook this study to investigate the incidence, cause, and clinical influence of short circuits in patients treated with deep brain stimulation (DBS). After the incidental identification of a short circuit during routine follow-up, the authors initiated a policy at their institution of routinely evaluating both therapeutic impedance and system impendence at every outpatient DBS follow-up visit, irrespective of the presence of symptoms suggesting possible system malfunction. This study represents a report of their findings after 1 year of this policy. Implanted DBS leads exhibiting short circuits were identified in 7 patients (8.9% of the patients seen for outpatient follow-up examinations during the 12-month study period). The mean duration from DBS lead implantation to the discovery of the short circuit was 64.7 months. The symptoms revealing short circuits included the wearing off of therapeutic effect, apraxia of eyelid opening, or dysarthria in 6 patients with Parkinson disease (PD), and dystonia deterioration in 1 patient with generalized dystonia. All DBS leads with short circuits had been anchored to the cranium using titanium miniplates. Altering electrode settings resulted in clinical improvement in the 2 PD cases in which patients had specific symptoms of short circuits (2.5%) but not in the other 4 cases. The patient with dystonia underwent repositioning and replacement of a lead because the previous lead was located too anteriorly, but did not experience symptom improvement. In contrast to the sudden loss of clinical efficacy of DBS caused by an open circuit, short circuits may arise due to a gradual decrease in impedance, causing the insidious development of neurological symptoms via limited or extended potential fields as well as shortened battery longevity. The incidence of short circuits in DBS may be higher than previously thought, especially in cases in which DBS leads are anchored with miniplates. The circuit impedance of DBS

  17. Brain Stimulation Therapies

    Science.gov (United States)

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

  18. Modeling and simulation of deep brain stimulation in Parkinson's disease

    NARCIS (Netherlands)

    Heida, Tjitske; Moroney, R.; Marani, Enrico; Usunoff, K.G.; Pereira, M.; Freire, M.

    2009-01-01

    Deep Brain Stimulation (DBS) is effective in the Parkinsonian state, while it seems to produce rather non-selective stimulation over an unknown volume of tissue. Despite a huge amount of anatomical and physiological data regarding the structure of the basal ganglia (BG) and their connections, the

  19. Uncovering the mechanism(s) of deep brain stimulation

    International Nuclear Information System (INIS)

    Li Gang; Yu Chao; Lin Ling; Lu, Stephen C-Y

    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

  20. Computational analysis of transcranial magnetic stimulation in the presence of deep brain stimulation probes

    Science.gov (United States)

    Syeda, F.; Holloway, K.; El-Gendy, A. A.; Hadimani, R. L.

    2017-05-01

    Transcranial Magnetic Stimulation is an emerging non-invasive treatment for depression, Parkinson's disease, and a variety of other neurological disorders. Many Parkinson's patients receive the treatment known as Deep Brain Stimulation, but often require additional therapy for speech and swallowing impairment. Transcranial Magnetic Stimulation has been explored as a possible treatment by stimulating the mouth motor area of the brain. We have calculated induced electric field, magnetic field, and temperature distributions in the brain using finite element analysis and anatomically realistic heterogeneous head models fitted with Deep Brain Stimulation leads. A Figure of 8 coil, current of 5000 A, and frequency of 2.5 kHz are used as simulation parameters. Results suggest that Deep Brain Stimulation leads cause surrounding tissues to experience slightly increased E-field (Δ Emax =30 V/m), but not exceeding the nominal values induced in brain tissue by Transcranial Magnetic Stimulation without leads (215 V/m). The maximum temperature in the brain tissues surrounding leads did not change significantly from the normal human body temperature of 37 °C. Therefore, we ascertain that Transcranial Magnetic Stimulation in the mouth motor area may stimulate brain tissue surrounding Deep Brain Stimulation leads, but will not cause tissue damage.

  1. Deep brain stimulation for dystonia: patient selection and outcomes

    NARCIS (Netherlands)

    Speelman, J. D.; Contarino, M. F.; Schuurman, P. R.; Tijssen, M. A. J.; de Bie, R. M. A.

    2010-01-01

    In a literature survey, 341 patients with primary and 109 with secondary dystonias treated with deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) were identified. In general, the outcomes for primary dystonias were more favourable compared to the secondary forms. For

  2. Deep brain stimulation for dystonia : Patient selection and outcomes

    NARCIS (Netherlands)

    Speelman, J. D.; Contarino, M. F.; Schuurman, P. R.; Tijssen, M. A. J.; de Bie, R. M. A.

    In a literature survey, 341 patients with primary and 109 with secondary dystonias treated with deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) were identified. In general, the outcomes for primary dystonias were more favourable compared to the secondary forms. For

  3. Deep brain stimulation, continuity over time, and the true self

    NARCIS (Netherlands)

    Nyholm, S.R.; O'Neill, E.R.H.

    2016-01-01

    One of the topics that often comes up in ethical discussions of deep brain stimulation (DBS), is the question of what impact DBS has, or might have, on the patient’s self. This is often understood as a question of whether DBS poses a “threat” to personal identity, which is typically understood as

  4. Adaptive deep brain stimulation in advanced Parkinson disease.

    Science.gov (United States)

    Little, Simon; Pogosyan, Alex; Neal, Spencer; Zavala, Baltazar; Zrinzo, Ludvic; Hariz, Marwan; Foltynie, Thomas; Limousin, Patricia; Ashkan, Keyoumars; FitzGerald, James; Green, Alexander L; Aziz, Tipu Z; Brown, Peter

    2013-09-01

    Brain-computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS. We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale. Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p random intermittent stimulation. BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Copyright © 2013 American Neurological Association.

  5. Closed loop deep brain stimulation: an evolving technology.

    Science.gov (United States)

    Hosain, Md Kamal; Kouzani, Abbas; Tye, Susannah

    2014-12-01

    Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.

  6. MRI-induced heating of deep brain stimulation leads

    International Nuclear Information System (INIS)

    Mohsin, Syed A; Sheikh, Noor M; Saeed, Usman

    2008-01-01

    The radiofrequency (RF) field used in magnetic resonance imaging is scattered by medical implants. The scattered field of a deep brain stimulation lead can be very intense near the electrodes stimulating the brain. The effect is more pronounced if the lead behaves as a resonant antenna. In this paper, we examine the resonant length effect. We also use the finite element method to compute the near field for (i) the lead immersed in inhomogeneous tissue (fat, muscle, and brain tissues) and (ii) the lead connected to an implantable pulse generator. Electric field, specific absorption rate and induced temperature rise distributions have been obtained in the brain tissue surrounding the electrodes. The worst-case scenario has been evaluated by neglecting the effect of blood perfusion. The computed values are in good agreement with in vitro measurements made in the laboratory.

  7. [Deep brain stimulation in movement disorders: evidence and therapy standards].

    Science.gov (United States)

    Parpaley, Yaroslav; Skodda, Sabine

    2017-07-01

    The deep brain stimulation (DBS) in movement disorders is well established and in many aspects evidence-based procedure. The treatment indications are very heterogeneous and very specific in their course and therapy. The deep brain stimulation plays very important, but usually not the central role in this conditions. The success in the application of DBS is essentially associated with the correct, appropriate and timely indication of the therapy in the course of these diseases. Thanks to the good standardization of the DBS procedure and sufficient published data, the recommendations for indication, diagnosis and operative procedures can be generated. The following article attempts to summarize the most important decision-making criteria and current therapy standards in this fairly comprehensive subject and to present them in close proximity to practice. Georg Thieme Verlag KG Stuttgart · New York.

  8. Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

    Science.gov (United States)

    Conen, Silke; Matthews, Julian C; Patel, Nikunj K; Anton-Rodriguez, José; Talbot, Peter S

    2018-04-01

    Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [ 15 O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.

  9. Systems for deep brain stimulation: review of technical features.

    Science.gov (United States)

    Amon, A; Alesch, F

    2017-09-01

    The use of deep brain stimulation (DBS) is an important treatment option for movement disorders and other medical conditions. Today, three major manufacturers provide implantable systems for DBS. Although the underlying principle is basically the same for all available systems, the differences in the technical features vary considerably. This article outlines aspects regarding the technical features of DBS systems. The differences between voltage and current sources are addressed and their effect on stimulation is shown. To maintain clinical benefit and minimize side effects the stimulation field has to be adapted to the requirements of the patient. Shaping of the stimulation field can be achieved by the electrode design and polarity configuration. Furthermore, the electric signal consisting of stimulation rate, stimulation amplitude and pulse width affect the stimulation field. Interleaving stimulation is an additional concept, which permits improved treatment outcomes. Therefore, the electrode design, the polarity, the electric signal, and the concept of interleaving stimulation are presented. The investigated systems can be also categorized as rechargeable and non-rechargeable, which is briefly discussed. Options for interconnecting different system components from various manufacturers are presented. The present paper summarizes the technical features and their combination possibilities, which can have a major impact on the therapeutic effect.

  10. Deep brain transcranial magnetic stimulation using variable "Halo coil" system

    Science.gov (United States)

    Meng, Y.; Hadimani, R. L.; Crowther, L. J.; Xu, Z.; Qu, J.; Jiles, D. C.

    2015-05-01

    Transcranial Magnetic Stimulation has the potential to treat various neurological disorders non-invasively and safely. The "Halo coil" configuration can stimulate deeper regions of the brain with lower surface to deep-brain field ratio compared to other coil configurations. The existing "Halo coil" configuration is fixed and is limited in varying the site of stimulation in the brain. We have developed a new system based on the current "Halo coil" design along with a graphical user interface system that enables the larger coil to rotate along the transverse plane. The new system can also enable vertical movement of larger coil. Thus, this adjustable "Halo coil" configuration can stimulate different regions of the brain by adjusting the position and orientation of the larger coil on the head. We have calculated magnetic and electric fields inside a MRI-derived heterogeneous head model for various positions and orientations of the coil. We have also investigated the mechanical and thermal stability of the adjustable "Halo coil" configuration for various positions and orientations of the coil to ensure safe operation of the system.

  11. Penfield's prediction: a mechanism for deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Richard W. Murrow

    2014-10-01

    Full Text Available (1Context: Despite its widespread use, the precise mechanism of action of Deep Brain Stimulation (DBS therapy remains unknown. The modern urgency to publish more and new data can obscure previously learned lessons by the giants who have preceded us and whose shoulders we now stand upon. Wilder Penfield extensively studied the effects of artificial electrical brain stimulation and his comments on the subject are still very relevant today. In particular, he noted two very different (and seemingly opposite effects of stimulation within the human brain. In some structures, artificial electrical stimulation has an effect which mimics ablation, while, in other structures, it produces a stimulatory effect on that tissue. (2Hypothesis:The hypothesis of this paper is fourfold. First, it proposes that some neural circuits are widely synchronized with other neural circuits, while some neural circuits are unsynchronized and operate independently. Second, it proposes that artificial high frequency electrical stimulation of a synchronized neural circuit results in an ablative effect, but artificial high frequency electrical stimulation of an unsynchronized neural circuit results in a stimulatory effect. Third, it suggests a part of the mechanism by which large scale physiologic synchronization of widely distributed independently processed information streams may occur. This may be the neural mechanism underlying Penfield’s centrencephalic system which he emphasized so many years ago. Fourth, it outlines the specific anatomic distribution of this physiologic synchronization, which Penfield has already clearly delineated as the distribution of his centrencephalic system. (3Evidence:This paper draws on a brief overview of previous theory regarding the mechanism of action of DBS and on historical, as well as widely known modern clinical data regarding the observed effects of stimulation delivered to various targets within the brain. Basic science in

  12. Avoiding Internal Capsule Stimulation With a New Eight-Channel Steering Deep Brain Stimulation Lead

    NARCIS (Netherlands)

    van Dijk, Kees J.; Verhagen, Rens; Bour, Lo J.; Heida, Ciska; Veltink, Peter H.

    2017-01-01

    Objective: Novel deep brain stimulation (DBS) lead designs are currently entering the market, which are hypothesized to provide a way to steer the stimulation field away from neural populations responsible for side effects and towards populations responsible for beneficial effects. The objective of

  13. Avoiding Internal Capsule Stimulation With a New Eight-Channel Steering Deep Brain Stimulation Lead

    NARCIS (Netherlands)

    van Dijk, Kees J.; Verhagen, Rens; Bour, Lo J.; Heida, Ciska; Veltink, Peter H.

    2017-01-01

    Novel deep brain stimulation (DBS) lead designs are currently entering the market, which are hypothesized to provide a way to steer the stimulation field away from neural populations responsible for side effects and towards populations responsible for beneficial effects. The objective of this study

  14. Moving the brain: Neuroimaging motivational changes of deep brain stimulation in obsessive-compulsive disorder

    NARCIS (Netherlands)

    Figee, M.

    2013-01-01

    Deep brain stimulation (DBS) is a neurosurgical technique that involves the implantation of electrodes in the brain. DBS enables electrical modulation of abnormal brain activity for treatment of neuropsychiatric disorders such as obsessive-compulsive disorder (OCD). Mrs. D. has been suffering from

  15. The safety of transcranial magnetic stimulation with deep brain stimulation instruments

    OpenAIRE

    Shimojima, Yoshio; Morita, Hiroshi; Nishikawa, Noriko; Kodaira, Minori; Hashimoto, Takao; Ikeda, Shu-ichi

    2010-01-01

    Objectives: Transcranial magnetic stimulation (TMS) has been employed in patients with an implanted deep brain Stimulation (DBS) device. We investigated the safety of TMS using Simulation models with an implanted DBS device. Methods: The DBS lead was inserted into plastic phantoms filled with dilute gelatin showing impedance similar to that of human brain. TMS was performed with three different types of magnetic coil. During TMS (I) electrode movement, (2) temperature change around the lead, ...

  16. The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease.

    Science.gov (United States)

    Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M; Tan, Huiling; Brown, Peter

    2017-04-01

    Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could

  17. Effect of sevoflurane on neuronal activity during deep brain stimulation surgery for epilepsy: A case report

    OpenAIRE

    Michaël J. Bos, MD; Linda Ackermans, MD, PhD; Frédéric L.W.V.J. Schaper, MD; Rob P.W. Rouhl, MD, PhD; Vivianne H.J.M. van Kranen-Mastenbroek, MD, PhD; Wolfgang F. Buhre, MD, PhD; Marcus L.F. Janssen, MD, PhD

    2018-01-01

    Deep brain stimulation of the anterior nucleus of the thalamus is an effective treatment for patients with refractory epilepsy who do not respond sufficiently to medical therapy. Optimal therapeutic effects of deep brain stimulation probably depend on accurate positioning of the stimulating electrodes. Microelectrode recordings show bursty firing neurons in the anterior nucleus of the thalamus region, which confirms the anatomical target determined by the surgeon. Deep brain stimulation elect...

  18. Closed-Loop Deep Brain Stimulation for Refractory Chronic Pain

    Directory of Open Access Journals (Sweden)

    Prasad Shirvalkar

    2018-03-01

    Full Text Available Pain is a subjective experience that alerts an individual to actual or potential tissue damage. Through mechanisms that are still unclear, normal physiological pain can lose its adaptive value and evolve into pathological chronic neuropathic pain. Chronic pain is a multifaceted experience that can be understood in terms of somatosensory, affective, and cognitive dimensions, each with associated symptoms and neural signals. While there have been many attempts to treat chronic pain, in this article we will argue that feedback-controlled ‘closed-loop’ deep brain stimulation (DBS offers an urgent and promising route for treatment. Contemporary DBS trials for chronic pain use “open-loop” approaches in which tonic stimulation is delivered with fixed parameters to a single brain region. The impact of key variables such as the target brain region and the stimulation waveform is unclear, and long-term efficacy has mixed results. We hypothesize that chronic pain is due to abnormal synchronization between brain networks encoding the somatosensory, affective and cognitive dimensions of pain, and that multisite, closed-loop DBS provides an intuitive mechanism for disrupting that synchrony. By (1 identifying biomarkers of the subjective pain experience and (2 integrating these signals into a state-space representation of pain, we can create a predictive model of each patient's pain experience. Then, by establishing how stimulation in different brain regions influences individual neural signals, we can design real-time, closed-loop therapies tailored to each patient. While chronic pain is a complex disorder that has eluded modern therapies, rich historical data and state-of-the-art technology can now be used to develop a promising treatment.

  19. Changes in brain glucose metabolism in subthalamic nucleus deep brain stimulation for advanced Parkinson's disease.

    Science.gov (United States)

    Volonté, M A; Garibotto, V; Spagnolo, F; Panzacchi, A; Picozzi, P; Franzin, A; Giovannini, E; Leocani, L; Cursi, M; Comi, G; Perani, D

    2012-07-01

    Despite its large clinical application, our understanding about the mechanisms of action of deep brain stimulation of the subthalamic nucleus is still limited. Aim of the present study was to explore cortical and subcortical metabolic modulations measured by Positron Emission Tomography associated with improved motor manifestations after deep brain stimulation in Parkinson disease, comparing the ON and OFF conditions. Investigations were performed in the stimulator off- and on-conditions in 14 parkinsonian patients and results were compared with a group of matched healthy controls. The results were also used to correlate metabolic changes with the clinical effectiveness of the procedure. The comparisons using Statistical parametric mapping revealed a brain metabolic pattern typical of advanced Parkinson disease. The direct comparison in ON vs OFF condition showed mainly an increased metabolism in subthalamic regions, corresponding to the deep brain stimulation site. A positive correlation exists between neurostimulation clinical effectiveness and metabolic differences in ON and OFF state, including the primary sensorimotor, premotor and parietal cortices, anterior cingulate cortex. Deep brain stimulation seems to operate modulating the neuronal network rather than merely exciting or inhibiting basal ganglia nuclei. Correlations with Parkinson Disease cardinal features suggest that the improvement of specific motor signs associated with deep brain stimulation might be explained by the functional modulation, not only in the target region, but also in surrounding and remote connecting areas, resulting in clinically beneficial effects. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Vocal Tremor: Novel Therapeutic Target for Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Vinod K. Ravikumar

    2016-10-01

    Full Text Available Tremulous voice is characteristically associated with essential tremor, and is referred to as essential vocal tremor (EVT. Current estimates suggest that up to 40% of individuals diagnosed with essential tremor also present with EVT, which is associated with an impaired quality of life. Traditional EVT treatments have demonstrated limited success in long-term management of symptoms. However, voice tremor has been noted to decrease in patients receiving deep brain stimulation (DBS with the targeting of thalamic nuclei. In this study, we describe our multidisciplinary procedure for awake, frameless DBS with optimal stimulation targets as well as acoustic analysis and laryngoscopic assessment to quantify tremor reduction. Finally, we investigate the most recent clinical evidence regarding the procedure.

  1. Thalamic Ventral Intermediate Nucleus Deep Brain Stimulation for Orthostatic Tremor

    Directory of Open Access Journals (Sweden)

    Alexander C. Lehn

    2017-07-01

    Full Text Available Background: Orthostatic tremor (OT was first described in 1977. It is characterized by rapid tremor of 13–18 Hz and can be recorded in the lower limbs and trunk muscles. OT remains difficult to treat, although some success has been reported with deep brain stimulation (DBS.Case Report: We report a 68-year-old male with OT who did not improve significantly after bilateral thalamic stimulation.Discussion: Although some patients were described who improved after DBS surgery, more information is needed about the effect of these treatment modalities on OT, ideally in the form of randomized trial data. 

  2. Deep-Brain Stimulation for Basal Ganglia Disorders.

    Science.gov (United States)

    Wichmann, Thomas; Delong, Mahlon R

    2011-07-01

    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.

  3. Tourette syndrome deep brain stimulation: a review and updated recommendations.

    Science.gov (United States)

    Schrock, Lauren E; Mink, Jonathan W; Woods, Douglas W; Porta, Mauro; Servello, Dominico; Visser-Vandewalle, Veerle; Silburn, Peter A; Foltynie, Thomas; Walker, Harrison C; Shahed-Jimenez, Joohi; Savica, Rodolfo; Klassen, Bryan T; Machado, Andre G; Foote, Kelly D; Zhang, Jian-Guo; Hu, Wei; Ackermans, Linda; Temel, Yasin; Mari, Zoltan; Changizi, Barbara K; Lozano, Andres; Auyeung, M; Kaido, Takanobu; Agid, Yves; Welter, Marie L; Khandhar, Suketu M; Mogilner, Alon Y; Pourfar, Michael H; Walter, Benjamin L; Juncos, Jorge L; Gross, Robert E; Kuhn, Jens; Leckman, James F; Neimat, Joseph A; Okun, Michael S

    2015-04-01

    Deep brain stimulation (DBS) may improve disabling tics in severely affected medication and behaviorally resistant Tourette syndrome (TS). Here we review all reported cases of TS DBS and provide updated recommendations for selection, assessment, and management of potential TS DBS cases based on the literature and implantation experience. Candidates should have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) diagnosis of TS with severe motor and vocal tics, which despite exhaustive medical and behavioral treatment trials result in significant impairment. Deep brain stimulation should be offered to patients only by experienced DBS centers after evaluation by a multidisciplinary team. Rigorous preoperative and postoperative outcome measures of tics and associated comorbidities should be used. Tics and comorbid neuropsychiatric conditions should be optimally treated per current expert standards, and tics should be the major cause of disability. Psychogenic tics, embellishment, and malingering should be recognized and addressed. We have removed the previously suggested 25-year-old age limit, with the specification that a multidisciplinary team approach for screening is employed. A local ethics committee or institutional review board should be consulted for consideration of cases involving persons younger than 18 years of age, as well as in cases with urgent indications. Tourette syndrome patients represent a unique and complex population, and studies reveal a higher risk for post-DBS complications. Successes and failures have been reported for multiple brain targets; however, the optimal surgical approach remains unknown. Tourette syndrome DBS, though still evolving, is a promising approach for a subset of medication refractory and severely affected patients. © 2014 International Parkinson and Movement Disorder Society.

  4. Selectively stimulating neural populations in the subthalamic region using a novel deep brain stimulation lead design

    NARCIS (Netherlands)

    van Dijk, Kees Joab; Verhagen, R.; Bour, L.J.; Heida, Tjitske

    2013-01-01

    Deep brain stimulation (DBS) of the Subthalamic Nucleus (STN) is widely used in advanced stages of Parkinson's disease(PD) and has proven to be an effective treatment of the various motor symptoms. The therapy involves implanting a lead consisting of multiple electrodes in the STN through which

  5. Stimulating the self: The influence of conceptual frameworks on reactions to deep brain stimulation

    NARCIS (Netherlands)

    Mecacci, G.; Haselager, W.F.G.

    2014-01-01

    Deep brain stimulation (DBS) is generally considered to have great practical potential. Yet along with its remarkable efficacy, which is currently being tested in application to many pathologies, come a certain number of complications. In particular, there seem to be several adverse psychological

  6. Stimulating at the right time: phase-specific deep brain stimulation.

    Science.gov (United States)

    Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

    2017-01-01

    SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  7. [Deep brain stimulation in parkinsonian patients with dopa intolerance].

    Science.gov (United States)

    García-Ruiz, Pedro J; Feliz-Feliz, Cici; Ayerbe Gracia, Joaquín; Matías Arbelo, José; Salvador, Carlos; Val Fernández, Javier Del; García-Caldentey, Juan

    2017-10-28

    Deep brain stimulation (DBS) is at present, a useful treatment for patients with advanced Parkinson's disease and motor complications. The crucial step toward consistent DBS outcomes remains careful patient selection; several conditions must be fulfilled including excellent levo dopa response. We report two cases of early onset Parkinson's disease with severe intolerance to levo dopa but excellent and sustained response to DBS. DBS can be a useful alternative for parkinsonian patients with severe intolerance to levo dopa, provided a positive acute response to levo dopa or apomorphine is obtained. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. State of the Art: Novel Applications for Deep Brain Stimulation.

    Science.gov (United States)

    Roy, Holly A; Green, Alexander L; Aziz, Tipu Z

    2018-02-01

    Deep brain stimulation (DBS) is a rapidly developing field of neurosurgery with potential therapeutic applications that are relevant to conditions traditionally viewed as beyond the limits of neurosurgery. Our objective, in this review, is to highlight some of the emerging applications of DBS within three distinct but overlapping spheres, namely trauma, neuropsychiatry, and autonomic physiology. An extensive literature review was carried out in MEDLINE, to identify relevant studies and review articles describing applications of DBS in the areas of trauma, neuropsychiatry and autonomic neuroscience. A wide range of applications of DBS in these spheres was identified, some having only been tested in one or two cases, others much better studied. We have identified various avenues for DBS to be applied for patient benefit in cases relevant to trauma, neuropsychiatry and autonomic neuroscience. Further developments in DBS technology and clinical trial design will enable these novel applications to be effectively and rigorously assessed and utilized most effectively. © 2017 International Neuromodulation Society.

  9. [Mental competence in the context of deep brain stimulation].

    Science.gov (United States)

    Berghmans, R L P; De Wert, G M W R

    2004-07-10

    In a case of Parkinson's disease, the patient was treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). STN-DBS affected the mental competence of the patient and ethical questions were raised about the decision as to the direction of further treatment. The patient was asked for his opinion on the therapeutic options during a phase of non-stimulation and chose to be stimulated and admitted to a psychiatric hospital because of mental incompetence rather than remaining unstimulated, mentally competent but bedridden. Developments in the neurosciences (including STN-DBS) raise a number of different fundamental (theoretical and philosophical) as well as practical questions. STN-DBS can have various unintended (behavioural) effects. In the case presented, more weight was rightly given to the mental competence of the unstimulated patient, although comments can be made with regard to his decision making, as his choice was made in a phase of serious distress. Attention is paid to the relevance of a so-called self-binding directive. STN-DBS is not morally neutral and the case involves a tragic dilemma: a conflict between irreconcilable duties for the physician. The further development and proliferation of STN-DBS requires caution and moral deliberation. It remains important to search for alternative treatment strategies with less undesirable side effects.

  10. Weight Gain following Pallidal Deep Brain Stimulation: A PET Study.

    Directory of Open Access Journals (Sweden)

    Paul Sauleau

    Full Text Available The mechanisms behind weight gain following deep brain stimulation (DBS surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN or the globus pallidus internus (GPi. Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET and weight gain following GPi-DBS in patients with Parkinson's disease (PD. Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040. There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6, left superior gyrus (BA 8, the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46, and the left and right somatosensory association cortices (BA 7. However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067. These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target.

  11. Differential impact of thalamic versus subthalamic deep brain stimulation on lexical processing.

    Science.gov (United States)

    Krugel, Lea K; Ehlen, Felicitas; Tiedt, Hannes O; Kühn, Andrea A; Klostermann, Fabian

    2014-10-01

    Roles of subcortical structures in language processing are vague, but, interestingly, basal ganglia and thalamic Deep Brain Stimulation can go along with reduced lexical capacities. To deepen the understanding of this impact, we assessed word processing as a function of thalamic versus subthalamic Deep Brain Stimulation. Ten essential tremor patients treated with thalamic and 14 Parkinson׳s disease patients with subthalamic Deep Brain Stimulation performed an acoustic Lexical Decision Task ON and OFF stimulation. Combined analysis of task performance and event-related potentials allowed the determination of processing speed, priming effects, and N400 as neurophysiological correlate of lexical stimulus processing. 12 age-matched healthy participants acted as control subjects. Thalamic Deep Brain Stimulation prolonged word decisions and reduced N400 potentials. No comparable ON-OFF effects were present in patients with subthalamic Deep Brain Stimulation. In the latter group of patients with Parkinson' disease, N400 amplitudes were, however, abnormally low, whether under active or inactive Deep Brain Stimulation. In conclusion, performance speed and N400 appear to be influenced by state functions, modulated by thalamic, but not subthalamic Deep Brain Stimulation, compatible with concepts of thalamo-cortical engagement in word processing. Clinically, these findings specify cognitive sequels of Deep Brain Stimulation in a target-specific way. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Optogenetically inspired deep brain stimulation: linking basic with clinical research.

    Science.gov (United States)

    Lüscher, Christian; Pollak, Pierre

    2016-01-01

    In the last decade, optogenetics has revolutionised the neurosciences. The technique, which allows for cell-type specific excitation and inhibition of neurons in the brain of freely moving rodents, has been used to tighten the links of causality between neural activity and behaviour. Optogenetics is also enabling an unprecedented characterisation of circuits and their dysfunction in a number of brain diseases, above all those conditions that are not caused by neurodegeneration. Notable progress has been made in addiction, depression and obsessive-compulsive disorders, as well as other anxiety disorders. By extension, the technique has also been used to propose blueprints for innovative rational treatment of these diseases. The goal is to design manipulations that disrupt pathological circuit function or restore normal activity. This can be achieved by targeting specific projections in order to apply specific stimulation protocols validated by ex-vivo analysis of the mechanisms underlying the dysfunction. In a number of cases, specific forms of pathological synaptic plasticity have been implicated. For example, addictive drugs via strong increase of dopamine trigger a myriad of alterations of glutamate and γ-aminobutyric acid transmission, also called drug-evoked synaptic plasticity. This opens the way to the design of optogenetic reversal protocols, which might restore normal transmission with the hope to abolish the pathological behaviour. Several proof of principle studies for this approach have recently been published. However, for many reasons, optogenetics will not be translatable to human applications in the near future. Here, we argue that an intermediate step is novel deep brain stimulation (DBS) protocols that emulate successful optogenetic approaches in animal models. We provide a roadmap for a translational path to rational, optogenetically inspired DBS protocols to refine existing approaches and expand to novel indications.

  13. Modulation of Human Time Processing by Subthalamic Deep Brain Stimulation

    Science.gov (United States)

    Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

    2011-01-01

    Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds. PMID:21931767

  14. Particle swarm optimization for programming deep brain stimulation arrays.

    Science.gov (United States)

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

    2017-02-01

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

  15. Particle Swarm Optimization for Programming Deep Brain Stimulation Arrays

    Science.gov (United States)

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

    2017-01-01

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

  16. Modulation of human time processing by subthalamic deep brain stimulation.

    Science.gov (United States)

    Wojtecki, Lars; Elben, Saskia; Timmermann, Lars; Reck, Christiane; Maarouf, Mohammad; Jörgens, Silke; Ploner, Markus; Südmeyer, Martin; Groiss, Stefan Jun; Sturm, Volker; Niedeggen, Michael; Schnitzler, Alfons

    2011-01-01

    Timing in the range of seconds referred to as interval timing is crucial for cognitive operations and conscious time processing. According to recent models of interval timing basal ganglia (BG) oscillatory loops are involved in time interval recognition. Parkinsońs disease (PD) is a typical disease of the basal ganglia that shows distortions in interval timing. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a powerful treatment of PD which modulates motor and cognitive functions depending on stimulation frequency by affecting subcortical-cortical oscillatory loops. Thus, for the understanding of BG-involvement in interval timing it is of interest whether STN-DBS can modulate timing in a frequency dependent manner by interference with oscillatory time recognition processes. We examined production and reproduction of 5 and 15 second intervals and millisecond timing in a double blind, randomised, within-subject repeated-measures design of 12 PD-patients applying no, 10-Hz- and ≥ 130-Hz-STN-DBS compared to healthy controls. We found under(re-)production of the 15-second interval and a significant enhancement of this under(re-)production by 10-Hz-stimulation compared to no stimulation, ≥ 130-Hz-STN-DBS and controls. Milliseconds timing was not affected. We provide first evidence for a frequency-specific modulatory effect of STN-DBS on interval timing. Our results corroborate the involvement of BG in general and of the STN in particular in the cognitive representation of time intervals in the range of multiple seconds.

  17. Computational modeling of pedunculopontine nucleus deep brain stimulation

    Science.gov (United States)

    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.

  18. Deep brain stimulation in addiction due to psychoactive substance use.

    Science.gov (United States)

    Kuhn, Jens; Bührle, Christian P; Lenartz, Doris; Sturm, Volker

    2013-01-01

    Addiction is one of the most challenging health problems. It is associated with enormous individual distress and tremendous socioeconomic consequences. Unfortunately, its underlying mechanisms are not fully understood, and pharmacological, psychological, or social interventions often fail to achieve long-lasting remission. Next to genetic, social, and contextual factors, a substance-induced dysfunction of the brain's reward system is considered a decisive factor for the establishment and maintenance of addiction. Due to its successful application and approval for several neurological disorders, deep brain stimulation (DBS) is known as a powerful tool for modulating dysregulated networks and has also been considered for substance addiction. Initial promising case reports of DBS in alcohol and heroin addiction in humans have recently been published. Likewise, results from animal studies mimicking different kinds of substance addiction point in a similar direction. The objective of this review is to provide an overview of the published results on DBS in addiction, and to discuss whether these preliminary results justify further research, given the novelty of this treatment approach. © 2013 Elsevier B.V. All rights reserved.

  19. Me, myself my brain implant : deep brain stimulation raises quistions of personal authenticity and alienation

    NARCIS (Netherlands)

    Kraemer, U.A.F.

    2013-01-01

    In this article, I explore select case studies of Parkinson patients treated with deep brain stimulation (DBS) in light of the notions of alienation and authenticity. While the literature on DBS has so far neglected the issues of authenticity and alienation, I argue that interpreting these cases in

  20. Deep brain stimulation affects conditioned and unconditioned anxiety in different brain areas

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    van Dijk, A.; Klanker, M.; van Oorschot, N.; Post, R.; Hamelink, R.; Feenstra, M. G. P.; Denys, D.

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of

  1. Complications of deep brain stimulation: a collective review.

    Science.gov (United States)

    Chan, Danny T M; Zhu, Xian Lun; Yeung, Jonas H M; Mok, Vincent C T; Wong, Edith; Lau, Clara; Wong, Rosanna; Lau, Christine; Poon, Wai S

    2009-10-01

    Since the first deep brain stimulation (DBS) performed for movement disorder more than a decade ago, DBS has become a standard operation for advanced Parkinson's disease. Its indications are expanding to areas of dystonia, psychiatric conditions and refractory epilepsy. Additionally, a new set of DBS-related complications have arisen. Many teams found a slow learning curve from this complication-prone operation. We would like to investigate complications arising from 100 DBS electrode insertions and its prevention. We performed an audit in all DBS patients for operation-related complications in our centre from 1997 to 2008. Complications were classified into operation-related, hardware-related and stimulation-related. Operation-related complications included intracranial haemorrhages and electrode malposition. Hardware-related complications included fracture of electrodes, electrode migration, infection and erosion. Stimulation-related complications included sensorimotor conditions, psychiatric conditions and life-threatening conditions. From 1997 to the end of 2008, 100 DBS electrodes were inserted in 55 patients for movement disorders, mostly for Parkinsons disease (50 patients). There was one symptomatic cerebral haemorrhage (1%) and two electrode malpositions (2%). Meticulous surgical planning, use of microdriver and a reliable electrode anchorage device would minimise this group of complications. There were two electrode fractures, one electrode migration and one pulse-generator infection which contributed to the hardware-related complication rate of 5%. There were no sensorimotor or life-threatening complications in our group. However, three patients suffered from reversible psychiatric symptoms after DBS. DBS is, on the one hand, an effective surgical treatment for movement disorders. On the other hand, it is a complication-prone operation. A dedicated "Movement Disorder Team" consisting of neurologists, neurophysiologists, functional neurosurgeons

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

    Science.gov (United States)

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

    2009-01-01

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

  3. Stereotactically Standard Areas: Applied Mathematics in the Service of Brain Targeting in Deep Brain Stimulation

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    Ioannis N. Mavridis

    2017-12-01

    Full Text Available The concept of stereotactically standard areas (SSAs within human brain nuclei belongs to the knowledge of the modern field of stereotactic brain microanatomy. These are areas resisting the individual variability of the nuclear location in stereotactic space. This paper summarizes the current knowledge regarding SSAs. A mathematical formula of SSAs was recently invented, allowing for their robust, reproducible, and accurate application to laboratory studies and clinical practice. Thus, SSAs open new doors for the application of stereotactic microanatomy to highly accurate brain targeting, which is mainly useful for minimally invasive neurosurgical procedures, such as deep brain stimulation.

  4. Stereotactically Standard Areas: Applied Mathematics in the Service of Brain Targeting in Deep Brain Stimulation.

    Science.gov (United States)

    Mavridis, Ioannis N

    2017-12-11

    The concept of stereotactically standard areas (SSAs) within human brain nuclei belongs to the knowledge of the modern field of stereotactic brain microanatomy. These are areas resisting the individual variability of the nuclear location in stereotactic space. This paper summarizes the current knowledge regarding SSAs. A mathematical formula of SSAs was recently invented, allowing for their robust, reproducible, and accurate application to laboratory studies and clinical practice. Thus, SSAs open new doors for the application of stereotactic microanatomy to highly accurate brain targeting, which is mainly useful for minimally invasive neurosurgical procedures, such as deep brain stimulation.

  5. Towards a Switched-Capacitor Based Stimulator for Efficient Deep-Brain Stimulation

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    Vidal, Jose; Ghovanloo, Maysam

    2013-01-01

    We have developed a novel 4-channel prototype stimulation circuit for implantable neurological stimulators (INS). This Switched-Capacitor based Stimulator (SCS) aims to utilize charge storage and charge injection techniques to take advantage of both the efficiency of conventional voltage-controlled stimulators (VCS) and the safety and controllability of current-controlled stimulators (CCS). The discrete SCS prototype offers fine control over stimulation parameters such as voltage, current, pulse width, frequency, and active electrode channel via a LabVIEW graphical user interface (GUI) when connected to a PC through USB. Furthermore, the prototype utilizes a floating current sensor to provide charge-balanced biphasic stimulation and ensure safety. The stimulator was analyzed using an electrode-electrolyte interface (EEI) model as well as with a pair of pacing electrodes in saline. The primary motivation of this research is to test the feasibility and functionality of a safe, effective, and power-efficient switched-capacitor based stimulator for use in Deep Brain Stimulation. PMID:21095987

  6. A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms.

    Science.gov (United States)

    Okun, Michael S; Foote, Kelly D; Wu, Samuel S; Ward, Herbert E; Bowers, Dawn; Rodriguez, Ramon L; Malaty, Irene A; Goodman, Wayne K; Gilbert, Donald M; Walker, Harrison C; Mink, Jonathan W; Merritt, Stacy; Morishita, Takashi; Sanchez, Justin C

    2013-01-01

    To collect the information necessary to design the methods and outcome variables for a larger trial of scheduled deep brain stimulation (DBS) for Tourette syndrome. We performed a small National Institutes of Health-sponsored clinical trials planning study of the safety and preliminary efficacy of implanted DBS in the bilateral centromedian thalamic region. The study used a cranially contained constant-current device and a scheduled, rather than the classic continuous, DBS paradigm. Baseline vs 6-month outcomes were collected and analyzed. In addition, we compared acute scheduled vs acute continuous vs off DBS. A university movement disorders center. Five patients with implanted DBS. A 50% improvement in the Yale Global Tic Severity Scale (YGTSS) total score. RESULTS Participating subjects had a mean age of 34.4 (range, 28-39) years and a mean disease duration of 28.8 years. No significant adverse events or hardware-related issues occurred. Baseline vs 6-month data revealed that reductions in the YGTSS total score did not achieve the prestudy criterion of a 50% improvement in the YGTSS total score on scheduled stimulation settings. However, statistically significant improvements were observed in the YGTSS total score (mean [SD] change, -17.8 [9.4]; P=.01), impairment score (-11.3 [5.0]; P=.007), and motor score (-2.8 [2.2]; P=.045); the Modified Rush Tic Rating Scale Score total score (-5.8 [2.9]; P=.01); and the phonic tic severity score (-2.2 [2.6]; P=.04). Continuous, off, and scheduled stimulation conditions were assessed blindly in an acute experiment at 6 months after implantation. The scores in all 3 conditions showed a trend for improvement. Trends for improvement also occurred with continuous and scheduled conditions performing better than the off condition. Tic suppression was commonly seen at ventral (deep) contacts, and programming settings resulting in tic suppression were commonly associated with a subjective feeling of calmness. This study provides

  7. Informed Consent Decision-Making in Deep Brain Stimulation.

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    Mandarelli, Gabriele; Moretti, Germana; Pasquini, Massimo; Nicolò, Giuseppe; Ferracuti, Stefano

    2018-05-11

    Deep brain stimulation (DBS) has proved useful for several movement disorders (Parkinson’s disease, essential tremor, dystonia), in which first and/or second line pharmacological treatments were inefficacious. Initial evidence of DBS efficacy exists for refractory obsessive-compulsive disorder, treatment-resistant major depressive disorder, and impulse control disorders. Ethical concerns have been raised about the use of an invasive surgical approach involving the central nervous system in patients with possible impairment in cognitive functioning and decision-making capacity. Most of the disorders in which DBS has been used might present with alterations in memory, attention, and executive functioning, which may have an impact on the mental capacity to give informed consent to neurosurgery. Depression, anxiety, and compulsivity are also common in DBS candidate disorders, and could also be associated with an impaired capacity to consent to treatment or clinical research. Despite these issues, there is limited empirical knowledge on the decision-making levels of these patients. The possible informed consent issues of DBS will be discussed by focusing on the specific treatable diseases.

  8. Informed Consent Decision-Making in Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Gabriele Mandarelli

    2018-05-01

    Full Text Available Deep brain stimulation (DBS has proved useful for several movement disorders (Parkinson’s disease, essential tremor, dystonia, in which first and/or second line pharmacological treatments were inefficacious. Initial evidence of DBS efficacy exists for refractory obsessive-compulsive disorder, treatment-resistant major depressive disorder, and impulse control disorders. Ethical concerns have been raised about the use of an invasive surgical approach involving the central nervous system in patients with possible impairment in cognitive functioning and decision-making capacity. Most of the disorders in which DBS has been used might present with alterations in memory, attention, and executive functioning, which may have an impact on the mental capacity to give informed consent to neurosurgery. Depression, anxiety, and compulsivity are also common in DBS candidate disorders, and could also be associated with an impaired capacity to consent to treatment or clinical research. Despite these issues, there is limited empirical knowledge on the decision-making levels of these patients. The possible informed consent issues of DBS will be discussed by focusing on the specific treatable diseases.

  9. Authenticity and autonomy in deep-brain stimulation.

    Science.gov (United States)

    Wardrope, Alistair

    2014-08-01

    Felicitas Kraemer draws on the experiences of patients undergoing deep-brain stimulation (DBS) to propose two distinct and potentially conflicting principles of respect: for an individual's autonomy (interpreted as mental competence), and for their authenticity. I argue instead that, according to commonly-invoked justifications of respect for autonomy, authenticity is itself in part constitutive of an analysis of autonomy worthy of respect; Kraemer's argument thus highlights the shortcomings of practical applications of respect for autonomy that emphasise competence while neglecting other important dimensions of autonomy such as authenticity, since it shows that competence alone cannot be interpreted as a reliable indicator of an individual's capacity for exercising autonomy. I draw from relational accounts to suggest how respect for a more expansive conception of autonomy might be interpreted for individuals undergoing DBS and in general. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Some technical nuances for deep brain stimulator implantation

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    Cole A. Giller, MD, PhD, MBA

    2015-03-01

    Full Text Available Protocols for deep brain stimulator (DBS implantation vary significantly among movement disorders centers despite the need to address similar operative problems. The general steps of this procedure are well accepted, but there are many seemingly minor, yet important nuances not extensively discussed in published descriptions. A classification and the details of the nuances adopted by a single institution may therefore be helpful in providing a basis for discussion and comparison. We describe operative nuances adopted at the Georgia Regents Medical Center (GRMC for DBS implantation that may not be universally employed. The problems of DBS implantation considered here include stereotactic planning, draping, creation and use of the burhole, physiological testing, anchoring of the electrode, financial considerations, and overall technique. Fourteen categories of operative nuances were identified and described in detail. These include the use of specific anatomical relationships for planning, the use of clear and watertight drapes, countersinking of the burhole, the use of gelfoam and tissue glue to seal the burhole, methods to review the entire microelectrode data simultaneously, blinded communication with the patient during macrostimulation, fluoroscopic marking, MRI compatible protection of the electrode tip, financial considerations effecting choice of operative materials, and restriction to a single operator. The majority of these have not been extensively described but may be in use at other centers. The many operative problems arising during DBS implantation can be addressed with specific technical nuances.

  11. Swallowing Quality of Life After Zona Incerta Deep Brain Stimulation.

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    Sundstedt, Stina; Nordh, Erik; Linder, Jan; Hedström, Johanna; Finizia, Caterina; Olofsson, Katarina

    2017-02-01

    The management of Parkinson's disease (PD) has been improved, but management of signs like swallowing problems is still challenging. Deep brain stimulation (DBS) alleviates the cardinal motor symptoms and improves quality of life, but its effect on swallowing is not fully explored. The purpose of this study was to examine self-reported swallowing-specific quality of life before and after caudal zona incerta DBS (cZI DBS) in comparison with a control group. Nine PD patients (2 women and 7 men) completed the self-report Swallowing Quality of Life questionnaire (SWAL-QOL) before and 12 months after cZI DBS surgery. The postoperative data were compared to 9 controls. Median ages were 53 years (range, 40-70 years) for patients and 54 years (range, 42-72 years) for controls. No significant differences were found between the pre- or postoperative scores. The SWAL-QOL total scores did not differ significantly between PD patients and controls. The PD patients reported significantly lower scores in the burden subscale and the symptom scale. Patients with PD selected for cZI DBS showed good self-reported swallowing-specific quality of life, in many aspects equal to controls. The cZI DBS did not negatively affect swallowing-specific quality of life in this study.

  12. Hemodynamic Perturbations in Deep Brain Stimulation Surgery: First Detailed Description

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    Tumul Chowdhury

    2017-08-01

    Full Text Available Background: Hemodynamic perturbations can be anticipated in deep brain stimulation (DBS surgery and may be attributed to multiple factors. Acute changes in hemodynamics may produce rare but severe complications such as intracranial bleeding, transient ischemic stroke and myocardium infarction. Therefore, this retrospective study attempts to determine the incidence of hemodynamic perturbances (rate and related risk factors in patients undergoing DBS surgery.Materials and Methods: After institutional approval, all patients undergoing DBS surgery for the past 10 years were recruited for this study. Demographic characteristics, procedural characteristics and intraoperative hemodynamic changes were noted. Event rate was calculated and the effect of all the variables on hemodynamic perturbations was analyzed by regression model.Results: Total hemodynamic adverse events during DBS surgery was 10.8 (0–42 and treated in 57% of cases.Conclusion: Among all the perioperative variables, the baseline blood pressure including systolic, diastolic, and mean arterial pressure was found to have highly significant effect on these intraoperative hemodynamic perturbations.

  13. Deep Brain Stimulation, Continuity over Time, and the True Self.

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    Nyholm, Sven; O'Neill, Elizabeth

    2016-10-01

    One of the topics that often comes up in ethical discussions of deep brain stimulation (DBS) is the question of what impact DBS has, or might have, on the patient's self. This is often understood as a question of whether DBS poses a threat to personal identity, which is typically understood as having to do with psychological and/or narrative continuity over time. In this article, we argue that the discussion of whether DBS is a threat to continuity over time is too narrow. There are other questions concerning DBS and the self that are overlooked in discussions exclusively focusing on psychological and/or narrative continuity. For example, it is also important to investigate whether DBS might sometimes have a positive (e.g., a rehabilitating) effect on the patient's self. To widen the discussion of DBS, so as to make it encompass a broader range of considerations that bear on DBS's impact on the self, we identify six features of the commonly used concept of a person's "true self." We apply these six features to the relation between DBS and the self. And we end with a brief discussion of the role DBS might play in treating otherwise treatment-refractory anorexia nervosa. This further highlights the importance of discussing both continuity over time and the notion of the true self.

  14. Uncommon Applications of Deep Brain Stimulation in Hyperkinetic Movement Disorders

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    Kara M. Smith

    2015-02-01

    Full Text Available Background: In addition to the established indications of tremor and dystonia, deep brain stimulation (DBS has been utilized less commonly for several hyperkinetic movement disorders, including medication-refractory myoclonus, ballism, chorea, and Gilles de la Tourette (GTS and tardive syndromes. Given the lack of adequate controlled trials, it is difficult to translate published reports into clinical use. We summarize the literature, draw conclusions regarding efficacy when possible, and highlight concerns and areas for future study.Methods: A Pubmed search was performed for English-language articles between January 1980 and June 2014. Studies were selected if they focused primarily on DBS to treat the conditions of focus. Results: We identified 49 cases of DBS for myoclonus-dystonia, 21 for Huntington's disease, 15 for choreacanthocytosis, 129 for GTS, and 73 for tardive syndromes. Bilateral globus pallidus interna (GPi DBS was the most frequently utilized procedure for all conditions except GTS, in which medial thalamic DBS was more common. While the majority of cases demonstrate some improvement, there are also reports of no improvement or even worsening of symptoms in each condition. The few studies including functional or quality of life outcomes suggest benefit. A limited number of studies included blinded on/off testing. There have been two double-blind controlled trials performed in GTS and a single prospective double-blind, uncontrolled trial in tardive syndromes. Patient characteristics, surgical target, stimulation parameters, and duration of follow-up varied among studies.Discussion: Despite these extensive limitations, the literature overall supports the efficacy of DBS in these conditions, in particular GTS and tardive syndromes. For other conditions, the preliminary evidence from small studies is promising and encourages further study.

  15. Deep-brain-stimulation does not impair deglutition in Parkinson's disease.

    Science.gov (United States)

    Lengerer, Sabrina; Kipping, Judy; Rommel, Natalie; Weiss, Daniel; Breit, Sorin; Gasser, Thomas; Plewnia, Christian; Krüger, Rejko; Wächter, Tobias

    2012-08-01

    A large proportion of patients with Parkinson's disease develop dysphagia during the course of the disease. Dysphagia in Parkinson's disease affects different phases of deglutition, has a strong impact on quality of life and may cause severe complications, i.e., aspirational pneumonia. So far, little is known on how deep-brain-stimulation of the subthalamic nucleus influences deglutition in PD. Videofluoroscopic swallowing studies on 18 patients with Parkinson's disease, which had been performed preoperatively, and postoperatively with deep-brain-stimulation-on and deep-brain-stimulation-off, were analyzed retrospectively. The patients were examined in each condition with three consistencies (viscous, fluid and solid). The 'New Zealand index for multidisciplinary evaluation of swallowing (NZIMES) Subscale One' for qualitative and 'Logemann-MBS-Parameters' for quantitative evaluation were assessed. Preoperatively, none of the patients presented with clinically relevant signs of dysphagia. While postoperatively, the mean daily levodopa equivalent dosage was reduced by 50% and deep-brain-stimulation led to a 50% improvement in motor symptoms measured by the UPDRS III, no clinically relevant influence of deep-brain-stimulation-on swallowing was observed using qualitative parameters (NZIMES). However quantitative parameters (Logemann scale) found significant changes of pharyngeal parameters with deep-brain-stimulation-on as compared to preoperative condition and deep-brain-stimulation-off mostly with fluid consistency. In Parkinson patients without dysphagia deep-brain-stimulation of the subthalamic nucleus modulates the pharyngeal deglutition phase but has no clinically relevant influence on deglutition. Further studies are needed to test if deep-brain-stimulation is a therapeutic option for patients with swallowing disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields.

    Science.gov (United States)

    Grossman, Nir; Bono, David; Dedic, Nina; Kodandaramaiah, Suhasa B; Rudenko, Andrii; Suk, Ho-Jun; Cassara, Antonino M; Neufeld, Esra; Kuster, Niels; Tsai, Li-Huei; Pascual-Leone, Alvaro; Boyden, Edward S

    2017-06-01

    We report a noninvasive strategy for electrically stimulating neurons at depth. By delivering to the brain multiple electric fields at frequencies too high to recruit neural firing, but which differ by a frequency within the dynamic range of neural firing, we can electrically stimulate neurons throughout a region where interference between the multiple fields results in a prominent electric field envelope modulated at the difference frequency. We validated this temporal interference (TI) concept via modeling and physics experiments, and verified that neurons in the living mouse brain could follow the electric field envelope. We demonstrate the utility of TI stimulation by stimulating neurons in the hippocampus of living mice without recruiting neurons of the overlying cortex. Finally, we show that by altering the currents delivered to a set of immobile electrodes, we can steerably evoke different motor patterns in living mice. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Connectivity derived thalamic segmentation in deep brain stimulation for tremor

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    Harith Akram

    Full Text Available The ventral intermediate nucleus (VIM of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS in the treatment of tremor in Parkinson's disease (PD and essential tremor (ET. It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT. The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female with ET underwent high angular resolution diffusion imaging (HARDI (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500 preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1, supplementary motor area (SMA, primary sensory area (S1 and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral

  18. Transcranial magnetic stimulation: Improved coil design for deep brain investigation

    Science.gov (United States)

    Crowther, L. J.; Marketos, P.; Williams, P. I.; Melikhov, Y.; Jiles, D. C.; Starzewski, J. H.

    2011-04-01

    This paper reports on a design for a coil for transcranial magnetic stimulation. The design shows potential for improving the penetration depth of the magnetic field, allowing stimulation of subcortical structures within the brain. The magnetic and induced electric fields in the human head have been calculated with finite element electromagnetic modeling software and compared with empirical measurements. Results show that the coil design used gives improved penetration depth, but also indicates the likelihood of stimulation of additional tissue resulting from the spatial distribution of the magnetic field.

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

    Science.gov (United States)

    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

  20. A Stepwise Approach: Decreasing Infection in Deep Brain Stimulation for Childhood Dystonic Cerebral Palsy.

    Science.gov (United States)

    Johans, Stephen J; Swong, Kevin N; Hofler, Ryan C; Anderson, Douglas E

    2017-09-01

    Dystonia is a movement disorder characterized by involuntary muscle contractions, which cause twisting movements or abnormal postures. Deep brain stimulation has been used to improve the quality of life for secondary dystonia caused by cerebral palsy. Despite being a viable treatment option for childhood dystonic cerebral palsy, deep brain stimulation is associated with a high rate of infection in children. The authors present a small series of patients with dystonic cerebral palsy who underwent a stepwise approach for bilateral globus pallidus interna deep brain stimulation placement in order to decrease the rate of infection. Four children with dystonic cerebral palsy who underwent a total of 13 surgical procedures (electrode and battery placement) were identified via a retrospective review. There were zero postoperative infections. Using a multistaged surgical plan for pediatric patients with dystonic cerebral palsy undergoing deep brain stimulation may help to reduce the risk of infection.

  1. Postoperative Displacement of Deep Brain Stimulation Electrodes Related to Lead-Anchoring Technique

    NARCIS (Netherlands)

    Contarino, M. Fiorella; Bot, Maarten; Speelman, Johannes D.; de Bie, Rob M. A.; Tijssen, Marina A.; Denys, Damiaan; Bour, Lo J.; Schuurman, P. Richard; van den Munckhof, Pepijn

    2013-01-01

    BACKGROUND: Displacement of deep brain stimulation (DBS) electrodes may occur after surgery, especially due to large subdural air collections, but other factors might contribute. OBJECTIVE: To investigate factors potentially contributing to postoperative electrode displacement, in particular,

  2. The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease

    NARCIS (Netherlands)

    Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M.; Tan, Huiling; Brown, Peter

    Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been

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

    Directory of Open Access Journals (Sweden)

    Cihun-Siyong Alex Gong

    2015-05-01

    Full Text Available 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.

  4. Avoiding Internal Capsule Stimulation With a New Eight-Channel Steering Deep Brain Stimulation Lead.

    Science.gov (United States)

    van Dijk, Kees J; Verhagen, Rens; Bour, Lo J; Heida, Ciska; Veltink, Peter H

    2017-10-15

    Novel deep brain stimulation (DBS) lead designs are currently entering the market, which are hypothesized to provide a way to steer the stimulation field away from neural populations responsible for side effects and towards populations responsible for beneficial effects. The objective of this study is to assess the performances of a new eight channel steering-DBS lead and compare this with a conventional cylindrical contact (CC) lead. The two leads were evaluated in a finite element electric field model combined with multicompartment neuron and axon models, representing the internal capsule (IC) fibers and subthalamic nucleus (STN) cells. We defined the optimal stimulation setting as the configuration that activated the highest percentage of STN cells, without activating any IC fibers. With this criterion, we compared monopolar stimulation using a single contact of the steering-DBS lead and CC lead, on three locations and four orientations of the lead. In addition, we performed a current steering test case by dividing the current over two contacts with the steering-DBS lead in its worst-case orientation. In most cases, the steering-DBS lead is able to stimulate a significantly higher percentage of STN cells compared to the CC lead using single contact stimulation or using a two contact current steering protocol when there is approximately a 1 mm displacement of the CC lead. The results also show that correct placement and orientation of the lead in the target remains an important aspect in achieving the optimal stimulation outcome. Currently, clinical trials are set up in Europe with a similar design as the steering-DBS lead. Our results illustrate the importance of the orientation of the new steering-DBS lead in avoiding side effects induced by stimulation of IC fibers. Therefore, in clinical trials sufficient attention should be paid to implanting the steering DBS-lead in the most effective orientation. © 2017 International Neuromodulation Society.

  5. Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

    Science.gov (United States)

    Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom

    2014-04-01

    Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

  6. The safety of transcranial magnetic stimulation with deep brain stimulation instruments.

    Science.gov (United States)

    Shimojima, Yoshio; Morita, Hiroshi; Nishikawa, Noriko; Kodaira, Minori; Hashimoto, Takao; Ikeda, Shu-Ichi

    2010-02-01

    Transcranial magnetic stimulation (TMS) has been employed in patients with an implanted deep brain stimulation (DBS) device. We investigated the safety of TMS using simulation models with an implanted DBS device. The DBS lead was inserted into plastic phantoms filled with dilute gelatin showing impedance similar to that of human brain. TMS was performed with three different types of magnetic coil. During TMS (1) electrode movement, (2) temperature change around the lead, and (3) TMS-induced current in various situations were observed. The amplitude and area of each evoked current were measured to calculate charge density of the evoked current. There was no movement or temperature increase during 0.2 Hz repetitive TMS with 100% stimulus intensity for 1 h. The size of evoked current linearly increased with TMS intensity. The maximum charge density exceeded the safety limit of 30 muC/cm(2)/phase during stimulation above the loops of the lead with intensity over 50% using a figure-eight coil. Strong TMS on the looped DBS leads should not be administered to avoid electrical tissue injury. Subcutaneous lead position should be paid enough attention for forthcoming situations during surgery. Copyright 2009 Elsevier Ltd. All rights reserved.

  7. Deep brain stimulation effects in dystonia: time course of electrophysiological changes in early treatment.

    Science.gov (United States)

    Ruge, Diane; Tisch, Stephen; Hariz, Marwan I; Zrinzo, Ludvic; Bhatia, Kailash P; Quinn, Niall P; Jahanshahi, Marjan; Limousin, Patricia; Rothwell, John C

    2011-08-15

    Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A) -ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia. Copyright © 2011 Movement Disorder Society.

  8. Connectivity derived thalamic segmentation in deep brain stimulation for tremor.

    Science.gov (United States)

    Akram, Harith; Dayal, Viswas; Mahlknecht, Philipp; Georgiev, Dejan; Hyam, Jonathan; Foltynie, Thomas; Limousin, Patricia; De Vita, Enrico; Jahanshahi, Marjan; Ashburner, John; Behrens, Tim; Hariz, Marwan; Zrinzo, Ludvic

    2018-01-01

    The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL

  9. Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson's disease.

    Science.gov (United States)

    Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir; Brown, Peter

    2016-05-01

    Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus-cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the

  10. Optogenetic stimulation of cholinergic projection neurons as an alternative for deep brain stimulation for Alzheimer's treatment

    Science.gov (United States)

    Mancuso, James; Chen, Yuanxin; Zhao, Zhen; Li, Xuping; Xue, Zhong; Wong, Stephen T. C.

    2013-03-01

    Deep brain stimulation (DBS) of the cholinergic nuclei has emerged as a powerful potential treatment for neurodegenerative disease and is currently in a clinical trial for Alzheimer's therapy. While effective in treatment for a number of conditions from depression to epilepsy, DBS remains somewhat unpredictable due to the heterogeneity of the projection neurons that are activated, including glutamatergic, GABAergic, and cholinergic neurons, leading to unacceptable side effects ranging from apathy to depression or even suicidal behavior. It would be highly advantageous to confine stimulation to specific populations of neurons, particularly in brain diseases involving complex network interactions such as Alzheimer's. Optogenetics, now firmly established as an effective approach to render genetically-defined populations of cells sensitive to light activation including mice expressing Channelrhodopsin-2 specifically in cholinergic neurons, provides just this opportunity. Here we characterize the light activation properties and cell density of cholinergic neurons in healthy mice and mouse models of Alzheimer's disease in order to evaluate the feasibility of using optogenetic modulation of cholinergic synaptic activity to slow or reverse neurodegeneration. This paper is one of the very first reports to suggest that, despite the anatomical depth of their cell bodies, cholinergic projection neurons provide a better target for systems level optogenetic modulation than cholinergic interneurons found in various brain regions including striatum and the cerebral cortex. Additionally, basal forebrain channelrhodopsin-expressing cholinergic neurons are shown to exhibit normal distribution at 60 days and normal light activation at 40 days, the latest timepoints observed. The data collected form the basis of ongoing computational modeling of light stimulation of entire populations of cholinergic neurons.

  11. The treatment of Parkinson's disease with deep brain stimulation: current issues.

    Science.gov (United States)

    Moldovan, Alexia-Sabine; Groiss, Stefan Jun; Elben, Saskia; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars

    2015-07-01

    Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients' mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

  12. The treatment of Parkinson′s disease with deep brain stimulation: current issues

    Directory of Open Access Journals (Sweden)

    Alexia-Sabine Moldovan

    2015-01-01

    Full Text Available Deep brain stimulation has become a well-established symptomatic treatment for Parkinson′s disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients′ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation.

  13. A randomized double-blind crossover trial comparing subthalamic and pallidal deep brain stimulation for dystonia

    DEFF Research Database (Denmark)

    Schjerling, Lisbeth; Hjermind, Lena E; Jespersen, Bo

    2013-01-01

    Object The authors' aim was to compare the subthalamic nucleus (STN) with the globus pallidus internus (GPi) as a stimulation target for deep brain stimulation (DBS) for medically refractory dystonia. Methods In a prospective double-blind crossover study, electrodes were bilaterally implanted in ...

  14. Improvement of both dystonia and tics with 60 Hz pallidal deep brain stimulation.

    Science.gov (United States)

    Hwynn, Nelson; Tagliati, Michele; Alterman, Ron L; Limotai, Natlada; Zeilman, Pamela; Malaty, Irene A; Foote, Kelly D; Morishita, Takashi; Okun, Michael S

    2012-09-01

    Deep brain stimulation has been utilized in both dystonia and in medication refractory Tourette syndrome. We present an interesting case of a patient with a mixture of disabling dystonia and Tourette syndrome whose coexistent dystonia and tics were successfully treated with 60 Hz-stimulation of the globus pallidus region.

  15. Deep Brain Stimulation for Essential Tremor: Aligning Thalamic and Posterior Subthalamic Targets in 1 Surgical Trajectory

    NARCIS (Netherlands)

    Bot, Maarten; van Rootselaar, Fleur; Contarino, Maria Fiorella; Odekerken, Vincent; Dijk, Joke; de Bie, Rob; Schuurman, Richard; van den Munckhof, Pepijn

    2017-01-01

    Ventral intermediate nucleus (VIM) deep brain stimulation (DBS) and posterior subthalamic area (PSA) DBS suppress tremor in essential tremor (ET) patients, but it is not clear which target is optimal. Aligning both targets in 1 surgical trajectory would facilitate exploring stimulation of either

  16. Emerging subspecialties in neurology: deep brain stimulation and electrical neuro-network modulation.

    Science.gov (United States)

    Hassan, Anhar; Okun, Michael S

    2013-01-29

    Deep brain stimulation (DBS) is a surgical therapy that involves the delivery of an electrical current to one or more brain targets. This technology has been rapidly expanding to address movement, neuropsychiatric, and other disorders. The evolution of DBS has created a niche for neurologists, both in the operating room and in the clinic. Since DBS is not always deep, not always brain, and not always simply stimulation, a more accurate term for this field may be electrical neuro-network modulation (ENM). Fellowships will likely in future years evolve their scope to include other technologies, and other nervous system regions beyond typical DBS therapy.

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

    Directory of Open Access Journals (Sweden)

    Monica Khetarpal

    2014-01-01

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

  18. Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex

    DEFF Research Database (Denmark)

    Gjedde, Albert; Geday, Jacob

    2009-01-01

    We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin......-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact...

  19. Deep brain stimulation and spinal cord stimulation for vegetative state and minimally conscious state.

    Science.gov (United States)

    Yamamoto, Takamitsu; Katayama, Yoichi; Obuchi, Toshiki; Kobayashi, Kazutaka; Oshima, Hideki; Fukaya, Chikashi

    2013-01-01

    On the basis of the findings of the electrophysiological evaluation of vegetative state (VS) and minimally conscious state (MCS), the effect of deep brain stimulation (DBS) was examined according to long-term follow-up results. The results of spinal cord stimulation (SCS) on MCS was also examined and compared with that of DBS. One hundred seven patients in VS and 21 patients in MCS were evaluated neurologically and electrophysiologically over 3 months after the onset of brain injury. Among the 107 VS patients, 21 were treated by DBS. Among the 21 MCS patients, 5 were treated by DBS and 10 by SCS. Eight of the 21 patients recovered from VS and were able to follow verbal instructions. These eight patients showed desynchronization on continuous electroencephalographic frequency analysis. The Vth wave of the auditory brainstem response and N20 of somatosensory evoked potential were recorded even with a prolonged latency, and pain-related P250 was recorded with an amplitude of more than 7 μV. In addition, DBS and SCS induced a marked functional recovery in MCS patients who satisfied the electrophysiological inclusion criteria. DBS for VS and MCS patients and SCS for MCS patients may be useful, when the candidates are selected on the basis of the electrophysiological inclusion criteria. Only 16 (14.9%) of the 107 VS patients and 15 (71.4%) of the 21 MCS patients satisfied the electrophysiological inclusion criteria. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Long-Term Efficacy of Constant Current Deep Brain Stimulation in Essential Tremor.

    Science.gov (United States)

    Rezaei Haddad, Ali; Samuel, Michael; Hulse, Natasha; Lin, Hsin-Ying; Ashkan, Keyoumars

    2017-07-01

    Ventralis intermedius deep brain stimulation is an established intervention for medication-refractory essential tremor. Newer constant current stimulation technology offers theoretical advantage over the traditional constant voltage systems in terms of delivering a more biologically stable therapy. There are no previous reports on the outcomes of constant current deep brain stimulation in the treatment of essential tremor. This study aimed to evaluate the long-term efficacy of ventralis intermedius constant current deep brain stimulation in patients diagnosed with essential tremor. Essential tremor patients implanted with constant current deep brain stimulation for a minimum of three years were evaluated. Clinical outcomes were assessed using the Fahn-Tolosa-Marin tremor rating scale at baseline and postoperatively at the time of evaluation. The quality of life in the patients was assessed using the Quality of Life in Essential Tremor questionnaire. Ten patients were evaluated with a median age at evaluation of 74 years (range 66-79) and a mean follow up time of 49.7 (range 36-78) months since starting stimulation. Constant current ventralis intermedius deep brain stimulation was well tolerated and effective in all patients with a mean score improvement from 50.7 ± 5.9 to 17.4 ± 5.7 (p = 0.0020) in the total Fahn-Tolosa-Marin rating scale score (65.6%). Furthermore, the total combined mean Quality of Life in Essential Tremor score was improved from 56.2 ± 4.9 to 16.8 ± 3.5 (p value = 0.0059) (70.1%). This report shows that long-term constant current ventralis intermedius deep brain stimulation is a safe and effective intervention for essential tremor patients. © 2017 International Neuromodulation Society.

  1. Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report

    Directory of Open Access Journals (Sweden)

    Stavrinou Lampis C

    2011-06-01

    Full Text Available Abstract Background The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. Case presentation We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. Conclusion The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

  2. Malignant neuroleptic syndrome following deep brain stimulation surgery: a case report.

    Science.gov (United States)

    Themistocleous, Marios S; Boviatsis, Efstathios J; Stavrinou, Lampis C; Stathis, Pantelis; Sakas, Damianos E

    2011-06-29

    The neuroleptic malignant syndrome is an uncommon but dangerous complication characterized by hyperthermia, autonomic dysfunction, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigor. It is most often caused by an adverse reaction to anti-psychotic drugs or abrupt discontinuation of neuroleptic or anti-parkinsonian agents. To the best of our knowledge, it has never been reported following the common practice of discontinuation of anti-parkinsonian drugs during the pre-operative preparation for deep brain stimulation surgery for Parkinson's disease. We present the first case of neuroleptic malignant syndrome associated with discontinuation of anti-parkinsonian medication prior to deep brain stimulation surgery in a 54-year-old Caucasian man. The characteristic neuroleptic malignant syndrome symptoms can be attributed to other, more common causes associated with deep brain stimulation treatment for Parkinson's disease, thus requiring a high index of clinical suspicion to timely establish the correct diagnosis. As more centers become eligible to perform deep brain stimulation, neurologists and neurosurgeons alike should be aware of this potentially fatal complication. Timely activation of the deep brain stimulation system may be important in accelerating the patient's recovery.

  3. Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia.

    Science.gov (United States)

    Ratnadurai-Giridharan, Shivakeshavan; Cheung, Chung C; Rubchinsky, Leonid L

    2017-11-01

    Conventional deep brain stimulation of basal ganglia uses high-frequency regular electrical pulses to treat Parkinsonian motor symptoms but has a series of limitations. Relatively new and not yet clinically tested, optogenetic stimulation is an effective experimental stimulation technique to affect pathological network dynamics. We compared the effects of electrical and optogenetic stimulation of the basal gangliaon the pathologicalParkinsonian rhythmic neural activity. We studied the network response to electrical stimulation and excitatory and inhibitory optogenetic stimulations. Different stimulations exhibit different interactions with pathological activity in the network. We studied these interactions for different network and stimulation parameter values. Optogenetic stimulation was found to be more efficient than electrical stimulation in suppressing pathological rhythmicity. Our findings indicate that optogenetic control of neural synchrony may be more efficacious than electrical control because of the different ways of how stimulations interact with network dynamics.

  4. Reoperation for suboptimal outcomes after deep brain stimulation surgery.

    Science.gov (United States)

    Ellis, Tina-Marie; Foote, Kelly D; Fernandez, Hubert H; Sudhyadhom, Atchar; Rodriguez, Ramon L; Zeilman, Pamela; Jacobson, Charles E; Okun, Michael S

    2008-10-01

    To examine a case series of reoperations for deep brain stimulation (DBS) leads in which clinical scenarios revealed suboptimal outcome from a previous operation. Suboptimally placed DBS leads are one potential reason for unsatisfactory results after surgery for Parkinson's disease (PD), essential tremor (ET), or dystonia. In a previous study of patients who experienced suboptimal results, 19 of 41 patients had misplaced leads. Similarly, another report commented that lead placement beyond a 2- to 3-mm window resulted in inadequate clinical benefit, and, in 1 patient, revision improved outcome. The goal of the current study was to perform an unblinded retrospective chart review of DBS patients with unsatisfactory outcomes who presented for reoperation. Patients who had DBS lead replacements after reoperation were assessed with the use of a retrospective review of an institutional review board-approved movement disorders database. Cases of reoperation for suboptimal clinical benefit were included, and cases of replacement of DBS leads caused by infection or hardware malfunction were excluded. Data points studied included age, disease duration, diagnosis, motor outcomes (the Unified Parkinson Disease Rating Scale III in PD, the Tremor Rating Scale in ET, and the Unified Dystonia Rating Scale in dystonia), quality of life (Parkinson's Disease Questionnaire-39 in PD), and the Clinician Global Impression scale. The data from before and after reoperation were examined to determine the estimated impact of repeat surgery. There were 11 patients with PD, 7 with ET, and 4 with dystonia. The average age of the PD group was 52 years, the disease duration was 10 years, and the average vector distance of the location of the active DBS contact was adjusted 5.5 mm. Six patients (54%) with PD had preoperative off medication on DBS Unified Parkinson Disease Rating Scale scores that could be compared with postoperative off medication on DBS scores. The average improvement across this

  5. Influence of deep brain stimulation on postural stability in patients with Parkinson disease

    OpenAIRE

    Zelenková, Jana

    2012-01-01

    Parkinson's disease is a neurodegenerative disease of the basal ganglia. Its main symptoms are rigidity, tremor, bradykinesia, hypokinesia and postural instability. One possible way how to infuence diseases is neurosurgical treatment - deep brain stimulation. The principle is the implantation of electrodes in the basal ganglia and modulation of activity of the basal ganglia circuits due to electrical stimulation. Stimulation affects the motor symptoms of Parkinson's disease. This thesis deals...

  6. Anaesthesia for a patient with Deep Brain Stimulator: Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Raj mala

    2014-07-01

    Full Text Available Deep brain stimulator (DBS devices are used for unilateral or bilateral stimulation of thalamus, subthalamus and globus pallidus to treat movement disorders. DBS can interfere with domestic and medical equipment such as electrocardiography (ECG, slow wave diathermy, electrocautery, peripheral nerve stimulators, pacemakers, external and implantable cardioverters and defibrillators. This case report describes a patient with such a device who presented for bilateral (B/L cataract surgery.

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

    Science.gov (United States)

    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.

  8. Twiddler's syndrome in a patient with a deep brain stimulation device for generalized dystonia

    DEFF Research Database (Denmark)

    Astradsson, Arnar; Schweder, Patrick M; Joint, Carole

    2011-01-01

    Deep brain stimulation (DBS) is the technique of neurostimulation of deep brain structures for the treatment of conditions such as essential tremor, dystonia, Parkinson's disease and chronic pain syndromes. The procedure uses implanted deep brain stimulation electrodes connected to extension leads...... and an implantable pulse generator (IPG). Hardware failure related to the DBS procedure is not infrequent, and includes electrode migration and disconnection. We describe a patient who received bilateral globus pallidus internus DBS for dystonia with initially good clinical response, but the device eventually failed....... Radiographs showed multiple twisting of the extension leads with disconnection from the brain electrodes and a diagnosis of Twiddler's syndrome was made. Twiddler's syndrome was first described in patients with cardiac pacemakers. Patients with mental disability, elderly and obese patients are at increased...

  9. Deep brain stimulation of the subthalamic nucleus enhances emotional processing in Parkinson disease.

    Science.gov (United States)

    Schneider, Frank; Habel, Ute; Volkmann, Jens; Regel, Sabine; Kornischka, Jürgen; Sturm, Volker; Freund, Hans-Joachim

    2003-03-01

    High-frequency electrical stimulation of the subthalamic nucleus is a new and highly effective therapy for complications of long-term levodopa therapy and motor symptoms in advanced Parkinson disease (PD). Clinical observations indicate additional influence on emotional behavior. Electrical stimulation of deep brain nuclei with pulse rates above 100 Hz provokes a reversible, lesioning-like effect. Here, the effect of deep brain stimulation of the subthalamic nucleus on emotional, cognitive, and motor performance in patients with PD (n = 12) was examined. The results were compared with the effects of a suprathreshold dose of levodopa intended to transiently restore striatal dopamine deficiency. Patients were tested during medication off/stimulation off (STIM OFF), medication off/stimulation on (STIM ON), and during the best motor state after taking levodopa without deep brain stimulation (MED). More positive self-reported mood and an enhanced mood induction effect as well as improvement in emotional memory during STIM ON were observed, while during STIM OFF, patients revealed reduced emotional performance. Comparable effects were revealed by STIM ON and MED. Cognitive performance was not affected by the different conditions and treatments. Deep brain stimulation of the subthalamic nucleus selectively enhanced affective processing and subjective well-being and seemed to be antidepressive. Levodopa and deep brain stimulation had similar effects on emotion. This finding may provide new clues about the neurobiologic bases of emotion and mood disorders, and it illustrates the important role of the basal ganglia and the dopaminergic system in emotional processing in addition to the well-known motor and cognitive functions.

  10. EKG-based detection of deep brain stimulation in fMRI studies.

    Science.gov (United States)

    Fiveland, Eric; Madhavan, Radhika; Prusik, Julia; Linton, Renee; Dimarzio, Marisa; Ashe, Jeffrey; Pilitsis, Julie; Hancu, Ileana

    2018-04-01

    To assess the impact of synchronization errors between the assumed functional MRI paradigm timing and the deep brain stimulation (DBS) on/off cycling using a custom electrocardiogram-based triggering system METHODS: A detector for measuring and predicting the on/off state of cycling deep brain stimulation was developed and tested in six patients in office visits. Three-electrode electrocardiogram measurements, amplified by a commercial bio-amplifier, were used as input for a custom electronics box (e-box). The e-box transformed the deep brain stimulation waveforms into transistor-transistor logic pulses, recorded their timing, and propagated it in time. The e-box was used to trigger task-based deep brain stimulation functional MRI scans in 5 additional subjects; the impact of timing accuracy on t-test values was investigated in a simulation study using the functional MRI data. Following locking to each patient's individual waveform, the e-box was shown to predict stimulation onset with an average absolute error of 112 ± 148 ms, 30 min after disconnecting from the patients. The subsecond accuracy of the e-box in predicting timing onset is more than adequate for our slow varying, 30-/30-s on/off stimulation paradigm. Conversely, the experimental deep brain stimulation onset prediction accuracy in the absence of the e-box, which could be off by as much as 4 to 6 s, could significantly decrease activation strength. Using this detector, stimulation can be accurately synchronized to functional MRI acquisitions, without adding any additional hardware in the MRI environment. Magn Reson Med 79:2432-2439, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  11. Chinese expert consensus on programming deep brain stimulation for patients with Parkinson's disease.

    Science.gov (United States)

    Chen, Shengdi; Gao, Guodong; Feng, Tao; Zhang, Jianguo

    2018-01-01

    Deep Brain Stimulation (DBS) therapy for the treatment of Parkinson's Disease (PD) is now a well-established option for some patients. Postoperative standardized programming processes can improve the level of postoperative management and programming, relieve symptoms and improve quality of life. In order to improve the quality of the programming, the experts on DBS and PD in neurology and neurosurgery in China reviewed the relevant literatures and combined their own experiences and developed this expert consensus on the programming of deep brain stimulation in patients with PD in China. This Chinese expert consensus on postoperative programming can standardize and improve postoperative management and programming of DBS for PD.

  12. [Abscess at the implant site following apical parodontitis. Hardware-related complications of deep brain stimulation].

    Science.gov (United States)

    Sixel-Döring, F; Trenkwalder, C; Kappus, C; Hellwig, D

    2006-08-01

    Deep brain stimulation of the subthalamic nucleus is an important treatment option for advanced stages of idiopathic Parkinson's disease, leading to significant improvement of motor symptoms in suited patients. Hardware-related complications such as technical malfunction, skin erosion, and infections however cause patient discomfort and additional expense. The patient presented here suffered a putrid infection of the impulse generator site following only local dental treatment of apical parodontitis. Therefore, prophylactic systemic antibiotic treatment is recommended for patients with implanted deep brain stimulation devices in case of operations, dental procedures, or infectious disease.

  13. OPTIMAL REPRESENTATION OF MER SIGNALS APPLIED TO THE IDENTIFICATION OF BRAIN STRUCTURES DURING DEEP BRAIN STIMULATION

    Directory of Open Access Journals (Sweden)

    Hernán Darío Vargas Cardona

    2015-07-01

    Full Text Available Identification of brain signals from microelectrode recordings (MER is a key procedure during deep brain stimulation (DBS applied in Parkinson’s disease patients. The main purpose of this research work is to identify with high accuracy a brain structure called subthalamic nucleus (STN, since it is the target structure where the DBS achieves the best therapeutic results. To do this, we present an approach for optimal representation of MER signals through method of frames. We obtain coefficients that minimize the Euclidean norm of order two. From optimal coefficients, we extract some features from signals combining the wavelet packet and cosine dictionaries. For a comparison frame with the state of the art, we also process the signals using the discrete wavelet transform (DWT with several mother functions. We validate the proposed methodology in a real data base. We employ simple supervised machine learning algorithms, as the K-Nearest Neighbors classifier (K-NN, a linear Bayesian classifier (LDC and a quadratic Bayesian classifier (QDC. Classification results obtained with the proposed method improves significantly the performance of the DWT. We achieve a positive identification of the STN superior to 97,6%. Identification outcomes achieved by the MOF are highly accurate, as we can potentially get a false positive rate of less than 2% during the DBS.

  14. European clinical guidelines for Tourette syndrome and other tic disorders. Part IV : deep brain stimulation

    NARCIS (Netherlands)

    Mueller-Vahl, Kirsten R.; Cath, Danielle C.; Cavanna, Andrea E.; Dehning, Sandra; Porta, Mauro; Robertson, Mary M.; Visser-Vandewalle, Veerle

    Ten years ago deep brain stimulation (DBS) has been introduced as an alternative and promising treatment option for patients suffering from severe Tourette syndrome (TS). It seemed timely to develop a European guideline on DBS by a working group of the European Society for the Study of Tourette

  15. Free-living energy expenditure reduced after deep brain stimulation surgery for Parkinson's disease

    DEFF Research Database (Denmark)

    Jørgensen, Hans Ulrik; Werdelin, Lene; Lokkegaard, Annemette

    2012-01-01

    with deep brain stimulation in the subthalamic nucleus (STN-DBS) is now considered the gold standard in fluctuating PD. Many patients experience a gain of weight following the surgery. The aim of this study was to identify possible mechanisms, which may contribute to body weight gain in patients with PD...

  16. Perturbation and Nonlinear Dynamic Analysis of Acoustic Phonatory Signal in Parkinsonian Patients Receiving Deep Brain Stimulation

    Science.gov (United States)

    Lee, Victoria S.; Zhou, Xiao Ping; Rahn, Douglas A., III; Wang, Emily Q.; Jiang, Jack J.

    2008-01-01

    Nineteen PD patients who received deep brain stimulation (DBS), 10 non-surgical (control) PD patients, and 11 non-pathologic age- and gender-matched subjects performed sustained vowel phonations. The following acoustic measures were obtained on the sustained vowel phonations: correlation dimension (D[subscript 2]), percent jitter, percent shimmer,…

  17. Nucleus accumbens deep brain stimulation as treatment option for binge eating disorder?

    NARCIS (Netherlands)

    Lok, R.; Verhagen, M.; Staal, L.; Van Dijk, J.; Van Beek, A.; Temel, Y.; Jahanshahi, A.; Staal, M.; Van Dijk, G.

    2014-01-01

    Introduction: Binge eating disorder (BED) has been postulated to arise from mesolimbic dopaminergic system changes, presumably homologous to those seen in drug addiction. Deep Brain Stimulation (DBS) is regarded as a relatively novel but promising surgical treatment of addiction. Because of

  18. Subthalamic Nucleus Deep Brain Stimulation Changes Velopharyngeal Control in Parkinson's Disease

    Science.gov (United States)

    Hammer, Michael J.; Barlow, Steven M.; Lyons, Kelly E.; Pahwa, Rajesh

    2011-01-01

    Purpose: Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal…

  19. Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson's disease

    NARCIS (Netherlands)

    Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir; Brown, Peter

    2016-01-01

    Oswal et al. characterise the effect of deep brain stimulation (DBS) on STN-cortical synchronisation in Parkinson-s disease. They propose that cortical driving of the STN in beta frequencies is subdivided anatomically and spectrally, corresponding to the hyperdirect and indirect pathways. DBS

  20. A novel lead design enables selective deep brain stimulation of neural populations in the subthalamic region

    NARCIS (Netherlands)

    van Dijk, Kees J.; Verhagen, Rens; Chaturvedi, Ashutosh; McIntyre, Cameron C.; Bour, Lo J.; Heida, Ciska; Veltink, Peter H.

    2015-01-01

    The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) as a treatment for Parkinson's disease are sensitive to the location of the DBS lead within the STN. New high density (HD) lead designs have been created which are hypothesized to provide additional degrees of

  1. A novel lead design enables selective deep brain stimulation of neural populations in the subthalamic region

    NARCIS (Netherlands)

    van Dijk, Kees J.; Verhagen, Rens; Chaturvedi, Ashutosh; McIntyre, Cameron C.; Bour, Lo J.; Heida, Tjitske; Veltink, Peter H.

    2015-01-01

    Objective. The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) as a treatment for Parkinson's disease are sensitive to the location of the DBS lead within the STN. New high density (HD) lead designs have been created which are hypothesized to provide additional

  2. Rest and action tremor in Parkinson's disease: effects of Deep Brain Stimulation

    NARCIS (Netherlands)

    Heida, Tjitske; Wentink, E.C.

    2010-01-01

    One of the cardinal symptoms of Parkinson’s disease is rest tremor. While rest tremor generally disappears during sleep and voluntary movement, action tremor may be triggered by voluntary movement, and may even be more disabling than rest tremor. Deep brain stimulation (DBS) in the subthalamic

  3. The application of deep brain stimulation in the treatment of psychiatric disorders

    NARCIS (Netherlands)

    Graat, Ilse; Figee, Martijn; Denys, D.

    2017-01-01

    Deep brain stimulation (DBS) is a last-resort treatment for neurological and psychiatric disorders that are refractory to standard treatment. Over the last decades, the progress of DBS in psychiatry has been slower than in neurology, in part owing to the heterogenic symptomatology and complex

  4. Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

    NARCIS (Netherlands)

    Boel, Judith A.; Odekerken, Vincent J. J.; Geurtsen, Gert J.; Schmand, Ben A.; Cath, Danielle C.; Figee, Martijn; van den Munckhof, Pepijn; de Haan, Rob J.; Schuurman, P. Richard; de Bie, Rob M. A.; van Dijk, J. Marc C.; Staal, Michael

    BackgroundThe aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). MethodsWe randomly assigned patients to receive GPi DBS

  5. Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

    NARCIS (Netherlands)

    Boel, J.A.; Odekerken, V.J.J.; Geurtsen, G.J.; Schmand, B.A.; Cath, D.C.; Figee, M.; van den Munckhof, P.; de Haan, R.J.; Schuurman, P.R.; de Bie, R.M.A.

    BACKGROUND: The aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). METHODS: We randomly assigned patients to receive GPi

  6. Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

    NARCIS (Netherlands)

    Boel, Judith A.; Odekerken, Vincent J. J.; Geurtsen, Gert J.; Schmand, Ben A.; Cath, Danielle C.; Figee, Martijn; van den Munckhof, Pepijn; de Haan, Rob J.; Schuurman, P. Richard; de Bie, Rob M. A.; van Laar, Teus; van Dijk, J. Marc C.; Mosch, Arne; Hoffmann, Carel F. E.; Nijssen, Peter C. G.; Beute, Guus N.; van Vugt, Jeroen P. P.; Lenders, Mathieu W. P. M.; Contarino, M. Fiorella; Bour, Lo J.

    2016-01-01

    The aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). We randomly assigned patients to receive GPi DBS (n = 65) or STN

  7. Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

    NARCIS (Netherlands)

    Boel, Judith A; Odekerken, Vincent J J; Geurtsen, Gert J; Schmand, Ben A; Cath, Danielle C; Figee, Martijn; van den Munckhof, Pepijn; de Haan, Rob J; Schuurman, P Richard; de Bie, Rob M A

    2016-01-01

    BACKGROUND: The aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). METHODS: We randomly assigned patients to receive GPi

  8. Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation

    Science.gov (United States)

    2015-10-01

    currently investigating the effects of CG stimulation in subjects with debilitating pain due to cervical or thoracic SCI. This study stemmed from...had a low thoracic injury and pain in lumbar dermatomes, whereas Subject 1 had mainly mid- cervical pain that responded minimally to DBS and matched...AWARD NUMBER: W81XWH-12-1-0559 TITLE: Treatment of Pain and Autonomic Dysreflexia in Spinal Cord Injury with Deep Brain Stimulation PRINCIPAL

  9. Potential predictors for the amount of intra-operative brain shift during deep brain stimulation surgery

    Science.gov (United States)

    Datteri, Ryan; Pallavaram, Srivatsan; Konrad, Peter E.; Neimat, Joseph S.; D'Haese, Pierre-François; Dawant, Benoit M.

    2011-03-01

    A number of groups have reported on the occurrence of intra-operative brain shift during deep brain stimulation (DBS) surgery. This has a number of implications for the procedure including an increased chance of intra-cranial bleeding and complications due to the need for more exploratory electrodes to account for the brain shift. It has been reported that the amount of pneumocephalus or air invasion into the cranial cavity due to the opening of the dura correlates with intraoperative brain shift. Therefore, pre-operatively predicting the amount of pneumocephalus expected during surgery is of interest toward accounting for brain shift. In this study, we used 64 DBS patients who received bilateral electrode implantations and had a post-operative CT scan acquired immediately after surgery (CT-PI). For each patient, the volumes of the pneumocephalus, left ventricle, right ventricle, third ventricle, white matter, grey matter, and cerebral spinal fluid were calculated. The pneumocephalus was calculated from the CT-PI utilizing a region growing technique that was initialized with an atlas-based image registration method. A multi-atlas-based image segmentation method was used to segment out the ventricles of each patient. The Statistical Parametric Mapping (SPM) software package was utilized to calculate the volumes of the cerebral spinal fluid (CSF), white matter and grey matter. The volume of individual structures had a moderate correlation with pneumocephalus. Utilizing a multi-linear regression between the volume of the pneumocephalus and the statistically relevant individual structures a Pearson's coefficient of r = 0.4123 (p = 0.0103) was found. This study shows preliminary results that could be used to develop a method to predict the amount of pneumocephalus ahead of the surgery.

  10. Deep brain stimulation results in local glutamate and adenosine release: investigation into the role of astrocytes.

    Science.gov (United States)

    Tawfik, Vivianne L; Chang, Su-Youne; Hitti, Frederick L; Roberts, David W; Leiter, James C; Jovanovic, Svetlana; Lee, Kendall H

    2010-08-01

    Several neurological disorders are treated with deep brain stimulation; however, the mechanism underlying its ability to abolish oscillatory phenomena associated with diseases as diverse as Parkinson's disease and epilepsy remain largely unknown. To investigate the role of specific neurotransmitters in deep brain stimulation and determine the role of non-neuronal cells in its mechanism of action. We used the ferret thalamic slice preparation in vitro, which exhibits spontaneous spindle oscillations, to determine the effect of high-frequency stimulation on neurotransmitter release. We then performed experiments using an in vitro astrocyte culture to investigate the role of glial transmitter release in high-frequency stimulation-mediated abolishment of spindle oscillations. In this series of experiments, we demonstrated that glutamate and adenosine release in ferret slices was able to abolish spontaneous spindle oscillations. The glutamate release was still evoked in the presence of the Na channel blocker tetrodotoxin, but was eliminated with the vesicular H-ATPase inhibitor bafilomycin and the calcium chelator 2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester. Furthermore, electrical stimulation of purified primary astrocytic cultures was able to evoke intracellular calcium transients and glutamate release, and bath application of 2-bis (2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester inhibited glutamate release in this setting. Vesicular astrocytic neurotransmitter release may be an important mechanism by which deep brain stimulation is able to achieve clinical benefits.

  11. Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry.

    Science.gov (United States)

    Martinez-Ramirez, Daniel; Jimenez-Shahed, Joohi; Leckman, James Frederick; Porta, Mauro; Servello, Domenico; Meng, Fan-Gang; Kuhn, Jens; Huys, Daniel; Baldermann, Juan Carlos; Foltynie, Thomas; Hariz, Marwan I; Joyce, Eileen M; Zrinzo, Ludvic; Kefalopoulou, Zinovia; Silburn, Peter; Coyne, Terry; Mogilner, Alon Y; Pourfar, Michael H; Khandhar, Suketu M; Auyeung, Man; Ostrem, Jill Louise; Visser-Vandewalle, Veerle; Welter, Marie-Laure; Mallet, Luc; Karachi, Carine; Houeto, Jean Luc; Klassen, Bryan Timothy; Ackermans, Linda; Kaido, Takanobu; Temel, Yasin; Gross, Robert E; Walker, Harrison C; Lozano, Andres M; Walter, Benjamin L; Mari, Zoltan; Anderson, William S; Changizi, Barbara Kelly; Moro, Elena; Zauber, Sarah Elizabeth; Schrock, Lauren E; Zhang, Jian-Guo; Hu, Wei; Rizer, Kyle; Monari, Erin H; Foote, Kelly D; Malaty, Irene A; Deeb, Wissam; Gunduz, Aysegul; Okun, Michael S

    2018-03-01

    Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide. Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]). Scores on the Yale Global Tic Severity Scale and adverse events. The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.

  12. Me, Myself and My Brain Implant: Deep Brain Stimulation Raises Questions of Personal Authenticity and Alienation.

    Science.gov (United States)

    Kraemer, Felicitas

    2013-01-01

    In this article, I explore select case studies of Parkinson patients treated with deep brain stimulation (DBS) in light of the notions of alienation and authenticity. While the literature on DBS has so far neglected the issues of authenticity and alienation, I argue that interpreting these cases in terms of these concepts raises new issues for not only the philosophical discussion of neuro-ethics of DBS, but also for the psychological and medical approach to patients under DBS. In particular, I suggest that the experience of alienation and authenticity varies from patient to patient with DBS. For some, alienation can be brought about by neurointerventions because patients no longer feel like themselves. But, on the other hand, it seems alienation can also be cured by DBS as other patients experience their state of mind as authentic under treatment and retrospectively regard their former lives without stimulation as alienated. I argue that we must do further research on the relevance of authenticity and alienation to patients treated with DBS in order to gain a deeper philosophical understanding, and to develop the best evaluative criterion for the behavior of DBS patients.

  13. Camptocormia and deep brain stimulation: The interesting overlapping etiologies and the therapeutic role of subthalamic nucleus-deep brain stimulation in Parkinson disease with camptocormia.

    Science.gov (United States)

    Ekmekci, Hakan; Kaptan, Hulagu

    2016-01-01

    Camptocormia is known as "bent spine syndrome" and defined as a forward hyperflexion. The most common etiologic factor is related with the movement disorders, mainly in Parkinson's disease (PD). We present the case of a 51-year-old woman who has been followed with PD for the last 10 years, and also under the therapy for PD. An unappreciated correlation low back pain with camptocormia developed. She underwent deep brain stimulation (DBS) in the subthalamic nucleus bilaterally and improved her bending posture. The relationship between the DBS and camptocormia is discussed in this unique condition.

  14. Neuropsychiatric Outcome of an Adolescent Who Received Deep Brain Stimulation for Tourette's Syndrome

    Directory of Open Access Journals (Sweden)

    S. J. Pullen

    2011-01-01

    Full Text Available This case study followed one adolescent patient who underwent bilateral deep brain stimulation of the centromedian parafascicular complex (CM-Pf for debilitating, treatment refractory Tourette's syndrome for a period of 1.5 years. Neurocognitive testing showed no significant changes between baseline and follow-up assessments. Psychiatric assessment revealed positive outcomes in overall adaptive functioning and reduction in psychotropic medication load in this patient. Furthermore, despite significant baseline psychiatric comorbidity, this patient reported no suicidal ideation following electrode implantation. Deep brain stimulation is increasingly being used in children and adolescents. This case reports on the positive neurologic and neuropsychiatric outcome of an adolescent male with bilateral CM-Pf stimulation.

  15. Intraoperative functional MRI as a new approach to monitor deep brain stimulation in Parkinson's disease

    International Nuclear Information System (INIS)

    Hesselmann, Volker; Sorger, Bettina; Girnus, Ralf; Lasek, Kathrin; Schulte, Oliver; Krug, Barbara; Lackner, Klaus; Maarouf, Mohammad; Sturm, Volker; Wedekind, Christoph; Bunke, Juergen

    2004-01-01

    This article deals with technical aspects of intraoperative functional magnetic resonance imaging (fMRI) for monitoring the effect of deep brain stimulation (DBS) in a patient with Parkinson's disease. Under motor activation, therapeutic high-frequency stimulation of the subthalamic nucleus was accompanied by an activation decrease in the contralateral primary sensorimotor cortex and the ipsilateral cerebellum. Furthermore, an activation increase in the contralateral basal ganglia and insula region were detected. These findings demonstrate that fMRI constitutes a promising clinical application for investigating brain activity changes induced by DBS. (orig.)

  16. Probabilistic mapping of deep brain stimulation effects in essential tremor

    Directory of Open Access Journals (Sweden)

    Till A Dembek

    2017-01-01

    Discussion: Our results support the assumption, that the ZI might be a very effective target for tremor suppression. However stimulation inside the ZI and in its close vicinity was also related to the occurrence of stimulation-induced side-effects, so it remains unclear whether the VIM or the ZI is the overall better target. The study demonstrates the use of PSMs for target selection and evaluation. While their accuracy has to be carefully discussed, they can improve the understanding of DBS effects and can be of use for other DBS targets in the therapy of neurological or psychiatric disorders as well. Furthermore they provide a priori information about expected DBS effects in a certain region and might be helpful to clinicians in programming DBS devices in the future.

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

    Science.gov (United States)

    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.

  18. Subthalamic deep brain stimulation modulates small fiber-dependent sensory thresholds in Parkinson's disease.

    Science.gov (United States)

    Ciampi de Andrade, Daniel; Lefaucheur, Jean-Pascal; Galhardoni, Ricardo; Ferreira, Karine S L; Brandão Paiva, Anderson Rodrigues; Bor-Seng-Shu, Edson; Alvarenga, Luciana; Myczkowski, Martin L; Marcolin, Marco Antonio; de Siqueira, Silvia R D T; Fonoff, Erich; Barbosa, Egberto Reis; Teixeira, Manoel Jacobsen

    2012-05-01

    The effects of deep brain stimulation of the subthalamic nucleus on nonmotor symptoms of Parkinson's disease (PD) rarely have been investigated. Among these, sensory disturbances, including chronic pain (CP), are frequent in these patients. The aim of this study was to evaluate the changes induced by deep brain stimulation in the perception of sensory stimuli, either noxious or innocuous, mediated by small or large nerve fibers. Sensory detection and pain thresholds were assessed in 25 PD patients all in the off-medication condition with the stimulator turned on or off (on- and off-stimulation conditions, respectively). The relationship between the changes induced by surgery on quantitative sensory testing, spontaneous CP, and motor abilities were studied. Quantitative sensory test results obtained in PD patients were compared with those of age-matched healthy subjects. Chronic pain was present in 72% of patients before vs 36% after surgery (P=.019). Compared with healthy subjects, PD patients had an increased sensitivity to innocuous thermal stimuli and mechanical pain, but a reduced sensitivity to innocuous mechanical stimuli. In addition, they had an increased pain rating when painful thermal stimuli were applied, particularly in the off-stimulation condition. In the on-stimulation condition, there was an increased sensitivity to innocuous thermal stimuli but a reduced sensitivity to mechanical or thermal pain. Pain provoked by thermal stimuli was reduced when the stimulator was turned on. Motor improvement positively correlated with changes in warm detection and heat pain thresholds. Subthalamic nucleus deep brain stimulation contributes to relieve pain associated with PD and specifically modulates small fiber-mediated sensations. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  19. Oscillatory activity in the basal ganglia and deep brain stimulation.

    Science.gov (United States)

    Guridi, Jorge; Alegre, Manuel

    2017-01-01

    Over the past 10 years, research into the neurophysiology of the basal ganglia has provided new insights into the pathophysiology of movement disorders. The presence of pathological oscillations at specific frequencies has been linked to different signs and symptoms in PD and dystonia, suggesting a new model to explain basal ganglia dysfunction. These advances occurred in parallel with improvements in imaging and neurosurgical techniques, both of which having facilitated the more widespread use of DBS to modulate dysfunctional circuits. High-frequency stimulation is thought to disrupt pathological activity in the motor cortex/basal ganglia network; however, it is not easy to explain all of its effects based only on changes in network oscillations. In this viewpoint, we suggest that a return to classic anatomical concepts might help to understand some apparently paradoxical findings. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  20. Deep Brain Stimulation for Pantothenate Kinase-Associated Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Pedro J. Garcia-Ruiz

    2015-01-01

    Full Text Available Pantothenate kinase-associated neurodegeneration (PKAN is usually associated with dystonia, which is typically severe and progressive over time. Pallidal stimulation (GPi DBS has been carried out in selected cases of PKAN with drug-resistant dystonia with variable results. We report a 30-month follow-up study of a 30-year-old woman with PKAN-related dystonia treated with GPi DBS. Postoperatively, the benefit quickly became evident, as the patient exhibited a marked improvement in her dystonia, including her writing difficulty. This result has been maintained up to the present. GPi DBS should be considered in dystonic PKAN patients provided fixed contractures and/or pyramidal symptoms are not present.

  1. Programming Deep Brain Stimulation for Parkinson's Disease: The Toronto Western Hospital Algorithms.

    Science.gov (United States)

    Picillo, Marina; Lozano, Andres M; Kou, Nancy; Puppi Munhoz, Renato; Fasano, Alfonso

    2016-01-01

    Deep brain stimulation (DBS) is an established and effective treatment for Parkinson's disease (PD). After surgery, a number of extensive programming sessions are performed to define the most optimal stimulation parameters. Programming sessions mainly rely only on neurologist's experience. As a result, patients often undergo inconsistent and inefficient stimulation changes, as well as unnecessary visits. We reviewed the literature on initial and follow-up DBS programming procedures and integrated our current practice at Toronto Western Hospital (TWH) to develop standardized DBS programming protocols. We propose four algorithms including the initial programming and specific algorithms tailored to symptoms experienced by patients following DBS: speech disturbances, stimulation-induced dyskinesia and gait impairment. We conducted a literature search of PubMed from inception to July 2014 with the keywords "deep brain stimulation", "festination", "freezing", "initial programming", "Parkinson's disease", "postural instability", "speech disturbances", and "stimulation induced dyskinesia". Seventy papers were considered for this review. Based on the literature review and our experience at TWH, we refined four algorithms for: (1) the initial programming stage, and management of symptoms following DBS, particularly addressing (2) speech disturbances, (3) stimulation-induced dyskinesia, and (4) gait impairment. We propose four algorithms tailored to an individualized approach to managing symptoms associated with DBS and disease progression in patients with PD. We encourage established as well as new DBS centers to test the clinical usefulness of these algorithms in supplementing the current standards of care. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Deep brain stimulation, brain maps and personalized medicine: lessons from the human genome project.

    Science.gov (United States)

    Fins, Joseph J; Shapiro, Zachary E

    2014-01-01

    Although the appellation of personalized medicine is generally attributed to advanced therapeutics in molecular medicine, deep brain stimulation (DBS) can also be so categorized. Like its medical counterpart, DBS is a highly personalized intervention that needs to be tailored to a patient's individual anatomy. And because of this, DBS like more conventional personalized medicine, can be highly specific where the object of care is an N = 1. But that is where the similarities end. Besides their differing medical and surgical provenances, these two varieties of personalized medicine have had strikingly different impacts. The molecular variant, though of a more recent vintage has thrived and is experiencing explosive growth, while DBS still struggles to find a sustainable therapeutic niche. Despite its promise, and success as a vetted treatment for drug resistant Parkinson's Disease, DBS has lagged in broadening its development, often encountering regulatory hurdles and financial barriers necessary to mount an adequate number of quality trials. In this paper we will consider why DBS-or better yet neuromodulation-has encountered these challenges and contrast this experience with the more successful advance of personalized medicine. We will suggest that personalized medicine and DBS's differential performance can be explained as a matter of timing and complexity. We believe that DBS has struggled because it has been a journey of scientific exploration conducted without a map. In contrast to molecular personalized medicine which followed the mapping of the human genome and the Human Genome Project, DBS preceded plans for the mapping of the human brain. We believe that this sequence has given personalized medicine a distinct advantage and that the fullest potential of DBS will be realized both as a cartographical or electrophysiological probe and as a modality of personalized medicine.

  3. The effect of deep brain stimulation on the speech motor system.

    Science.gov (United States)

    Mücke, Doris; Becker, Johannes; Barbe, Michael T; Meister, Ingo; Liebhart, Lena; Roettger, Timo B; Dembek, Till; Timmermann, Lars; Grice, Martine

    2014-08-01

    Chronic deep brain stimulation of the nucleus ventralis intermedius is an effective treatment for individuals with medication-resistant essential tremor. However, these individuals report that stimulation has a deleterious effect on their speech. The present study investigates one important factor leading to these effects: the coordination of oral and glottal articulation. Sixteen native-speaking German adults with essential tremor, between 26 and 86 years old, with and without chronic deep brain stimulation of the nucleus ventralis intermedius and 12 healthy, age-matched subjects were recorded performing a fast syllable repetition task (/papapa/, /tatata/, /kakaka/). Syllable duration and voicing-to-syllable ratio as well as parameters related directly to consonant production, voicing during constriction, and frication during constriction were measured. Voicing during constriction was greater in subjects with essential tremor than in controls, indicating a perseveration of voicing into the voiceless consonant. Stimulation led to fewer voiceless intervals (voicing-to-syllable ratio), indicating a reduced degree of glottal abduction during the entire syllable cycle. Stimulation also induced incomplete oral closures (frication during constriction), indicating imprecise oral articulation. The detrimental effect of stimulation on the speech motor system can be quantified using acoustic measures at the subsyllabic level.

  4. Subthalamic Nucleus Deep Brain Stimulation Alters Prefrontal Correlates of Emotion Induction.

    Science.gov (United States)

    Bick, Sarah K B; Folley, Bradley S; Mayer, Jutta S; Park, Sohee; Charles, P David; Camalier, Corrie R; Pallavaram, Srivatsan; Konrad, Peter E; Neimat, Joseph S

    2017-04-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in advanced Parkinson's disease. STN DBS may also affect emotion, possibly by impacting a parallel limbic cortico-striatal circuit. The objective of this study was to investigate changes in prefrontal cortical activity related to DBS during an emotion induction task. We used near infrared spectroscopy to monitor prefrontal cortex hemodynamic changes during an emotion induction task. Seven DBS patients were tested sequentially in the stimulation-on and stimulation-off states while on dopaminergic medication. Patients watched a series of positive, negative, and neutral videos. The general linear model was used to compare prefrontal oxygenated hemoglobin concentration between DBS states. Deep brain stimulation was correlated with prefrontal oxygenated hemoglobin changes relative to the stimulation off state in response to both positive and negative videos. These changes were specific to emotional stimuli and were not seen during neutral stimuli. These results suggest that STN stimulation influences the prefrontal cortical representation of positive and negative emotion induction. © 2016 International Neuromodulation Society.

  5. Effect of Deep Brain Stimulation on Speech Performance in Parkinson's Disease

    OpenAIRE

    Skodda, Sabine

    2012-01-01

    Deep brain stimulation (DBS) has been reported to be successful in relieving the core motor symptoms of Parkinson's disease (PD) and motor fluctuations in the more advanced stages of the disease. However, data on the effects of DBS on speech performance are inconsistent. While there are some series of patients documenting that speech function was relatively unaffected by DBS of the nucleus subthalamicus (STN), other investigators reported on improvements of distinct parameters of oral control...

  6. Deep Brain Stimulation Salvages a Flourishing Dental Practice: A Dentist with Essential Tremor Recounts his Experience

    OpenAIRE

    Giacopuzzi, Guy; Lising, Melanie; Halpern, Casey H

    2016-01-01

    In recounting his experience with deep brain stimulation (DBS), a practicing dentist challenged with long-standing bilateral essential tremor of the hands?shares insights into his diagnosis, treatments, and ultimately successful DBS surgery at Stanford University Medical Center, CA, USA. Now nearly one year after his surgery, his practice continues to flourish and he encourages others in his profession to consider the possibility of DBS as a definitive?treatment for tremors of the hand, which...

  7. Globus Pallidus Interna Deep Brain Stimulation in a Patient with Medically Intractable Meige Syndrome

    Directory of Open Access Journals (Sweden)

    Dae-Woong Bae

    2014-10-01

    Full Text Available Medical therapies in patients with Meige syndrome, including botulinum toxin injection, have been limited because of incomplete response or adverse side effects. We evaluated a patient with Meige syndrome who was successfully treated with deep brain stimulation (DBS in the globus pallidus interna (GPi. This case report and other previous reports suggest that bilateral GPi DBS may be an effective treatment for medically refractory Meige syndrome, without significant adverse effects.

  8. Deep Brain Stimulation in Huntington’s Disease—Preliminary Evidence on Pathophysiology, Efficacy and Safety

    Directory of Open Access Journals (Sweden)

    Lars Wojtecki

    2016-08-01

    Full Text Available Huntington’s disease (HD is one of the most disabling degenerative movement disorders, as it not only affects the motor system but also leads to cognitive disabilities and psychiatric symptoms. Deep brain stimulation (DBS of the pallidum is a promising symptomatic treatment targeting the core motor symptom: chorea. This article gives an overview of preliminary evidence on pathophysiology, safety and efficacy of DBS in HD.

  9. Two-step tunneling technique of deep brain stimulation extension wires-a description.

    Science.gov (United States)

    Fontaine, Denys; Vandersteen, Clair; Saleh, Christian; von Langsdorff, Daniel; Poissonnet, Gilles

    2013-12-01

    While a significant body of literature exists on the intracranial part of deep brain stimulation surgery, the equally important second part of the intervention related to the subcutaneous tunneling of deep brain stimulation extension wires is rarely described. The tunneling strategy can consist of a single passage of the extension wires from the frontal incision site to the subclavicular area, or of a two-step approach that adds a retro-auricular counter-incision. Each technique harbors the risk of intraoperative and postoperative complications. At our center, we perform a two-step tunneling procedure that we developed based on a cadaveric study. In 125 consecutive patients operated since 2002, we did not encounter any complication related to our tunneling method. Insufficient data exist to fully evaluate the advantages and disadvantages of each tunneling technique. It is of critical importance that authors detail their tunneling modus operandi and report the presence or absence of complications. This gathered data pool may help to formulate a definitive conclusions on the safest method for subcutaneous tunneling of extension wires in deep brain stimulation.

  10. Scientific and ethical issues related to deep brain stimulation for disorders of mood, behavior, and thought.

    Science.gov (United States)

    Rabins, Peter; Appleby, Brian S; Brandt, Jason; DeLong, Mahlon R; Dunn, Laura B; Gabriëls, Loes; Greenberg, Benjamin D; Haber, Suzanne N; Holtzheimer, Paul E; Mari, Zoltan; Mayberg, Helen S; McCann, Evelyn; Mink, Sallie P; Rasmussen, Steven; Schlaepfer, Thomas E; Vawter, Dorothy E; Vitek, Jerrold L; Walkup, John; Mathews, Debra J H

    2009-09-01

    A 2-day consensus conference was held to examine scientific and ethical issues in the application of deep brain stimulation for treating mood and behavioral disorders, such as major depression, obsessive-compulsive disorder, and Tourette syndrome. The primary objectives of the conference were to (1) establish consensus among participants about the design of future clinical trials of deep brain stimulation for disorders of mood, behavior, and thought and (2) develop standards for the protection of human subjects participating in such studies. Conference participants identified 16 key points for guiding research in this growing field. The adoption of the described guidelines would help to protect the safety and rights of research subjects who participate in clinical trials of deep brain stimulation for disorders of mood, behavior, and thought and have further potential to benefit other stakeholders in the research process, including clinical researchers and device manufactures. That said, the adoption of the guidelines will require broad and substantial commitment from many of these same stakeholders.

  11. Near-infrared deep brain stimulation via upconversion nanoparticle–mediated optogenetics

    Science.gov (United States)

    Chen, Shuo; Weitemier, Adam Z.; Zeng, Xiao; He, Linmeng; Wang, Xiyu; Tao, Yanqiu; Huang, Arthur J. Y.; Hashimotodani, Yuki; Kano, Masanobu; Iwasaki, Hirohide; Parajuli, Laxmi Kumar; Okabe, Shigeo; Teh, Daniel B. Loong; All, Angelo H.; Tsutsui-Kimura, Iku; Tanaka, Kenji F.; Liu, Xiaogang; McHugh, Thomas J.

    2018-02-01

    Optogenetics has revolutionized the experimental interrogation of neural circuits and holds promise for the treatment of neurological disorders. It is limited, however, because visible light cannot penetrate deep inside brain tissue. Upconversion nanoparticles (UCNPs) absorb tissue-penetrating near-infrared (NIR) light and emit wavelength-specific visible light. Here, we demonstrate that molecularly tailored UCNPs can serve as optogenetic actuators of transcranial NIR light to stimulate deep brain neurons. Transcranial NIR UCNP-mediated optogenetics evoked dopamine release from genetically tagged neurons in the ventral tegmental area, induced brain oscillations through activation of inhibitory neurons in the medial septum, silenced seizure by inhibition of hippocampal excitatory cells, and triggered memory recall. UCNP technology will enable less-invasive optical neuronal activity manipulation with the potential for remote therapy.

  12. Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism.

    Science.gov (United States)

    Tronnier, V M; Domingo, A; Moll, C K; Rasche, D; Mohr, C; Rosales, R; Capetian, P; Jamora, R D; Lee, L V; Münchau, A; Diesta, C C; Tadic, V; Klein, C; Brüggemann, N; Moser, A

    2015-08-01

    Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30 min and during 25/30 min of high-frequency GPi stimulation. While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231 ± 102% in comparison to baseline values), a decrease was observed in the GPe (22 ± 10%). Extracellular glutamate levels largely remained unchanged. Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Stuttering in Parkinson's disease after deep brain stimulation: A note on dystonia and low-frequency stimulation.

    Science.gov (United States)

    Mendonça, Marcelo D; Barbosa, Raquel; Seromenho-Santos, Alexandra; Reizinho, Carla; Bugalho, Paulo

    2018-04-01

    Stuttering, a speech fluency disorder, is a rare complication of Deep Brain Stimulation (DBS) in Parkinson's Disease (PD). We report a 61 years-old patient with PD, afflicted by severe On and Off dystonia, treated with Subthalamic Nucleus DBS that developed post-DBS stuttering while on 130 Hz stimulation. Stuttering reduction was noted when frequency was changed to 80 Hz, but the previously observed dystonia improvement was lost. There are no reports in literature on patients developing stuttering with low-frequency stimulation. We question if low-frequency stimulation could have a role for managing PD's post-DBS stuttering, and notice that stuttering improvement was associated with dystonia worsening suggesting that they are distinct phenomena. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Treatment of movement disorders using deep brain stimulation – illustrative case reports and technical notes

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    Tadej Strojnik

    2012-05-01

    Full Text Available Operative neuromodulation is the field of electrically or chemically altering the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks to produce therapeutic effects. Deep brain stimulation (DBS is an important component of the therapy of movement disorders and has almost completely replaced high-frequency coagulation of brain tissue in stereotactic neurosurgery. This article presents the first DBS cases in Slovenia. In the article the technical features and adjustments of magnetic resonance (MR imaging and development of a new microdrive, which was clinically successfully tested, are described and discussed.

  15. The Emerging Role of Tractography in Deep Brain Stimulation: Basic Principles and Current Applications

    Directory of Open Access Journals (Sweden)

    Nelson B. Rodrigues

    2018-01-01

    Full Text Available Diffusion tensor imaging (DTI is an MRI-based technique that delineates white matter tracts in the brain by tracking the diffusion of water in neural tissue. This methodology, known as “tractography”, has been extensively applied in clinical neuroscience to explore nervous system architecture and diseases. More recently, tractography has been used to assist with neurosurgical targeting in functional neurosurgery. This review provides an overview of DTI principles, and discusses current applications of tractography for improving and helping develop novel deep brain stimulation (DBS targets.

  16. From Parkinsonian thalamic activity to restoring thalamic relay using deep brain stimulation: new insights from computational modeling

    NARCIS (Netherlands)

    Meijer, Hil Gaétan Ellart; Krupa, M.; Cagnan, H.; Lourens, Marcel Antonius Johannes; Heida, Tjitske; Martens, H.C.F.; Bour, L.J.; van Gils, Stephanus A.

    2011-01-01

    We present a computational model of a thalamocortical relay neuron for exploring basal ganglia thalamocortical loop behavior in relation to Parkinson's disease and deep brain stimulation (DBS). Previous microelectrode, single-unit recording studies demonstrated that oscillatory interaction within

  17. Deep brain stimulation of the subthalamic nucleus: effectiveness in advanced Parkinson's disease patients previously reliant on apomorphine

    OpenAIRE

    Varma, T; Fox, S; Eldridge, P; Littlechild, P; Byrne, P; Forster, A; Marshall, A; Cameron, H; McIver, K; Fletcher, N; Steiger, M

    2003-01-01

    Objectives: To assess the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced Parkinson's disease previously reliant on apomorphine as their main antiparkinsonian medication.

  18. Deep brain stimulation and treatment-resistant obsessive-compulsive disorder: A systematic review.

    Science.gov (United States)

    Vázquez-Bourgon, Javier; Martino, Juan; Sierra Peña, María; Infante Ceberio, Jon; Martínez Martínez, M Ángeles; Ocón, Roberto; Menchón, José Manuel; Crespo Facorro, Benedicto; Vázquez-Barquero, Alfonso

    2017-07-01

    At least 10% of patients with Obsessive-compulsive Disorder (OCD) are refractory to psychopharmacological treatment. The emergence of new technologies for the modulation of altered neuronal activity in Neurosurgery, deep brain stimulation (DBS), has enabled its use in severe and refractory OCD cases. The objective of this article is to review the current scientific evidence on the effectiveness and applicability of this technique to refractory OCD. We systematically reviewed the literature to identify the main characteristics of deep brain stimulation, its use and applicability as treatment for obsessive-compulsive disorder. Therefore, we reviewed PubMed/Medline, Embase and PsycINFO databases, combining the key-words 'Deep brain stimulation', 'DBS' and 'Obsessive-compulsive disorder' 'OCS'. The articles were selected by two of the authors independently, based on the abstracts, and if they described any of the main characteristics of the therapy referring to OCD: applicability; mechanism of action; brain therapeutic targets; efficacy; side-effects; co-therapies. All the information was subsequently extracted and analysed. The critical analysis of the evidence shows that the use of DBS in treatment-resistant OCD is providing satisfactory results regarding efficacy, with assumable side-effects. However, there is insufficient evidence to support the use of any single brain target over another. Patient selection has to be done following analyses of risks/benefits, being advisable to individualize the decision of continuing with concomitant psychopharmacological and psychological treatments. The use of DBS is still considered to be in the field of research, although it is increasingly used in refractory-OCD, producing in the majority of studies significant improvements in symptomatology, and in functionality and quality of life. It is essential to implement random and controlled studies regarding its long-term efficacy, cost-risk analyses and cost/benefit. Copyright

  19. Shielded battery syndrome: a new hardware complication of deep brain stimulation.

    Science.gov (United States)

    Chelvarajah, Ramesh; Lumsden, Daniel; Kaminska, Margaret; Samuel, Michael; Hulse, Natasha; Selway, Richard P; Lin, Jean-Pierre; Ashkan, Keyoumars

    2012-01-01

    Deep brain stimulation hardware is constantly advancing. The last few years have seen the introduction of rechargeable cell technology into the implanted pulse generator design, allowing for longer battery life and fewer replacement operations. The Medtronic® system requires an additional pocket adaptor when revising a non-rechargeable battery such as their Kinetra® to their rechargeable Activa® RC. This additional hardware item can, if it migrates superficially, become an impediment to the recharging of the battery and negate the intended technological advance. To report the emergence of the 'shielded battery syndrome', which has not been previously described. We reviewed our deep brain stimulation database to identify cases of recharging difficulties reported by patients with Activa RC implanted pulse generators. Two cases of shielded battery syndrome were identified. The first required surgery to reposition the adaptor to the deep aspect of the subcutaneous pocket. In the second case, it was possible to perform external manual manipulation to restore the adaptor to its original position deep to the battery. We describe strategies to minimise the occurrence of the shielded battery syndrome and advise vigilance in all patients who experience difficulty with recharging after replacement surgery of this type for the implanted pulse generator. Copyright © 2012 S. Karger AG, Basel.

  20. Brain activation associated with deep brain stimulation causing dissociation in a patient with Tourette's syndrome.

    Science.gov (United States)

    Goethals, Ingeborg; Jacobs, Filip; Van der Linden, Chris; Caemaert, Jacques; Audenaert, Kurt

    2008-01-01

    Dissociation involves a disruption in the integrated functions of consciousness, memory, identity, or perception of the environment. Attempts at localizing dissociative responses have yielded contradictory results regarding brain activation, laterality, and regional involvement. Here, we used a single-day split-dose activation paradigm with single photon emission computed tomography and 99m-Tc ethylcysteinatedimer as a brain perfusion tracer in a patient with Tourette's syndrome undergoing bilateral high-frequency thalamic stimulation for the treatment of tics who developed an alternate personality state during right thalamic stimulation. We documented increased regional cerebral blood flow in bilateral prefrontal and left temporal brain areas during the alternate identity state. We conclude that our findings support the temporal lobe as well as the frontolimbic disconnection hypotheses of dissociation.

  1. Deep Brain Stimulation for Essential Tremor: Aligning Thalamic and Posterior Subthalamic Targets in 1 Surgical Trajectory.

    Science.gov (United States)

    Bot, Maarten; van Rootselaar, Fleur; Contarino, Maria Fiorella; Odekerken, Vincent; Dijk, Joke; de Bie, Rob; Schuurman, Richard; van den Munckhof, Pepijn

    2017-12-21

    Ventral intermediate nucleus (VIM) deep brain stimulation (DBS) and posterior subthalamic area (PSA) DBS suppress tremor in essential tremor (ET) patients, but it is not clear which target is optimal. Aligning both targets in 1 surgical trajectory would facilitate exploring stimulation of either target in a single patient. To evaluate aligning VIM and PSA in 1 surgical trajectory for DBS in ET. Technical aspects of trajectories, intraoperative stimulation findings, final electrode placement, target used for chronic stimulation, and adverse and beneficial effects were evaluated. In 17 patients representing 33 trajectories, we successfully aligned VIM and PSA targets in 26 trajectories. Trajectory distance between targets averaged 7.2 (range 6-10) mm. In all but 4 aligned trajectories, optimal intraoperative tremor suppression was obtained in the PSA. During follow-up, active electrode contacts were located in PSA in the majority of cases. Overall, successful tremor control was achieved in 69% of patients. Stimulation-induced dysarthria or gait ataxia occurred in, respectively, 56% and 44% of patients. Neither difference in tremor suppression or side effects was noted between aligned and nonaligned leads nor between the different locations of chronic stimulation. Alignment of VIM and PSA for DBS in ET is feasible and enables intraoperative exploration of both targets in 1 trajectory. This facilitates positioning of electrode contacts in both areas, where multiple effective points of stimulation can be found. In the majority of aligned leads, optimal intraoperative and chronic stimulation were located in the PSA. Copyright © 2017 by the Congress of Neurological Surgeons

  2. Endoventricular Deep Brain Stimulation of the Third Ventricle: Proof of Concept and Application to Cluster Headache.

    Science.gov (United States)

    Chabardès, Stéphan; Carron, Romain; Seigneuret, Eric; Torres, Napoleon; Goetz, Laurent; Krainik, Alexandre; Piallat, Brigitte; Pham, Pascale; David, Olivier; Giraud, Pierrick; Benabid, Alim Louis

    2016-12-01

    The third ventricle (3rd V) is surrounded by centers related to satiety, homeostasis, hormones, sleep, memory, and pain. Stimulation of the wall of the 3rd V could be useful to treat disorders related to dysfunction of the hypothalamus. To assess safety and efficacy of endoventricular electrical stimulation of the hypothalamus using a floating deep brain stimulation (DBS) lead laid on the floor of the 3rd V to treat refractory cluster headaches (CH). Seven patients, aged 24 to 60 years, experiencing chronic CH (mean chronic duration 5.8 ± 2.5 years) were enrolled in this pilot, prospective, open study assessing the safety and potential efficacy of chronic DBS of the 3rd V. Number of attacks was collected during baseline and was compared with those occurring at 3, 6, and 12 months postoperation. Any side effects that occurred during or after surgery were reported. Effect on mood was assessed using the Hospital Anxiety and Depression scale during baseline and at 6 and 12 months postoperation. Insertion of the lead into the posterior 3rd V and chronic stimulation was feasible and safe in all patients. The voltage ranged from 0.9 to 2.3 volts. The most common side effect was transient trembling vision during stimulation. At 12 months, 3 of 7 patients were pain free, 2 had 90% improvement, 1 of 7 had 75% improvement, and 1 of 7 was not significantly improved. This proof of concept demonstrates the feasibility, safety, and potential efficacy of 3rd V DBS using an endoventricular road that could be applied to treat various diseases involving hypothalamic areas. CCH, chronic cluster headacheCH, cluster headacheDBS, deep brain stimulationHAD, hospital anxiety depressionONS, occipital nerve stimulationPAG, periaqueductal gray matterPH, posterior hypothalamusPVG, periventricular gray matter3rd V, third ventricle.

  3. Electromagnetic interference of GSM mobile phones with the implantable deep brain stimulator, ITREL-III

    Directory of Open Access Journals (Sweden)

    Alesch François

    2003-05-01

    Full Text Available Abstract Background The purpose was to investigate mobile phone interference with implantable deep brain stimulators by means of 10 different 900 Mega Hertz (MHz and 10 different 1800 MHz GSM (Global System for Mobile Communications mobile phones. Methods All tests were performed in vitro using a phantom especially developed for testing with deep brain stimulators. The phantom was filled with liquid phantom materials simulating brain and muscle tissue. All examinations were carried out inside an anechoic chamber on two implants of the same type of deep brain stimulator: ITREL-III from Medtronic Inc., USA. Results Despite a maximum transmitted peak power of mobile phones of 1 Watt (W at 1800 MHz and 2 W at 900 MHz respectively, no influence on the ITREL-III was found. Neither the shape of the pulse form changed nor did single pulses fail. Tests with increased transmitted power using CW signals and broadband dipoles have shown that inhibition of the ITREL-III occurs at frequency dependent power levels which are below the emissions of GSM mobile phones. The ITREL-III is essentially more sensitive at 1800 MHz than at 900 MHz. Particularly the frequency range around 1500 MHz shows a very low interference threshold. Conclusion These investigations do not indicate a direct risk for ITREL-III patients using the tested GSM phones. Based on the interference levels found with CW signals, which are below the mobile phone emissions, we recommend similar precautions as for patients with cardiac pacemakers: 1. The phone should be used at the ear at the opposite side of the implant and 2. The patient should avoid carrying the phone close to the implant.

  4. Anaesthetic management of shoulder arthroscopic repair in Parkinson′s disease with deep brain stimulator

    Directory of Open Access Journals (Sweden)

    Ranju Gandhi

    2014-01-01

    Full Text Available 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.

  5. Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization

    Science.gov (United States)

    Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P.; Johnson, G. Allan

    2015-01-01

    Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved 3D reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate accurate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. PMID:26043869

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

    Directory of Open Access Journals (Sweden)

    Christopher Dromey

    2011-01-01

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

  7. [The role of neurologists in deep brain stimulation for Parkinson disease: a neurosurgical perspective].

    Science.gov (United States)

    Umemura, Atsushi

    2012-01-01

    Deep brain stimulation (DBS) has been accepted as an effective treatment for medically refractory Parkinson disease (PD). Appropriate patient selection, safe and precise surgery, and proper postoperative adjustment of stimulation and medication, are essential for the success of DBS. Patient selection is the most important role for the neurologist in DBS treatment. Neurologists treating PD should understand the correct indications and contraindications for DBS, and introduce it in a timely manner to patients who can be expected to benefit substantially from it. For long term treatment of PD, ideally the neurologist in charge of the patient should adjust both the stimulation parameters and medication. Neurologists engaged in this treatment should also have a comprehensive understanding of the probable complications and how to avoid them.

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

    Science.gov (United States)

    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.

  9. Deep Brain Stimulation for Tourette-Syndrome: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Baldermann, Juan Carlos; Schüller, Thomas; Huys, Daniel; Becker, Ingrid; Timmermann, Lars; Jessen, Frank; Visser-Vandewalle, Veerle; Kuhn, Jens

    2016-01-01

    A significant proportion of patients with Tourette syndrome (TS) continue to experience symptoms across adulthood that in severe cases fail to respond to standard therapies. For these cases, deep brain stimulation (DBS) is emerging as a promising treatment option. We conducted a systematic literature review to evaluate the efficacy of DBS for GTS. Individual data of case reports and series were pooled; the Yale Global Tic Severity Scale (YGTSS) was chosen as primary outcome parameter. In total, 57 studies were eligible, including 156 cases. Overall, DBS resulted in a significant improvement of 52.68% (IQR = 40.74, p < 0.001) in the YGTSS. Analysis of controlled studies significantly favored stimulation versus off stimulation with a standardized mean difference of 0.96 (95% CI: 0.36-1.56). Disentangling different target points revealed significant YGTSS reductions after stimulation of the thalamus, the posteroventrolateral part and the anteromedial part of the globus pallidus internus, the anterior limb of the internal capsule and nucleus accumbens with no significant difference between these targets. A significant negative correlation of preoperative tic scores with the outcome of thalamic stimulation was found. Despite small patient numbers, we conclude that DBS for GTS is a valid option for medically intractable patients. Different brain targets resulted in comparable improvement rates, indicating a modulation of a common network. Future studies might focus on a better characterization of the clinical effects of distinct regions, rather than searching for a unique target. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Deep brain stimulation for severe treatment-resistant obsessive-compulsive disorder: An open-label case series.

    Science.gov (United States)

    Farrand, Sarah; Evans, Andrew H; Mangelsdorf, Simone; Loi, Samantha M; Mocellin, Ramon; Borham, Adam; Bevilacqua, JoAnne; Blair-West, Scott; Walterfang, Mark A; Bittar, Richard G; Velakoulis, Dennis

    2017-09-01

    Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8-54 months). The sample included four females and three males, with a mean age of 46 years (range, 37-59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15-38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Deep

  11. Long-term outcome of thalamic deep brain stimulation in two patients with Tourette syndrome.

    Science.gov (United States)

    Ackermans, Linda; Duits, Annelien; Temel, Yasin; Winogrodzka, Ania; Peeters, Frenk; Beuls, Emile A M; Visser-Vandewalle, Veerle

    2010-10-01

    Thalamic deep brain stimulation for intractable Tourette Syndrome was introduced in 1999 by Vandewalle et al. In this follow-up study, the authors report on the long-term (6 and 10 years) outcome in terms of tic reduction, cognition, mood and side effects of medial thalamic deep brain stimulation in two previously described Tourette patients. The authors compared the outcome of two patients at 6 and 10 years after surgery with their preoperative status and after 8 months and 5 years of treatment, respectively. Standardised video recordings were scored by three independent investigators. Both patients underwent (neuro)psychological assessment at all time points of follow-up. Tic improvement observed at 5 years in patient 1 (90.1%) was maintained at 10 years (92.6%). In patient 2, the tic improvement at 8 months (82%) was slightly decreased at 6 years (78%). During follow-up, case 1 revealed no changes in cognition, but case 2 showed a decrease in verbal fluency and learning which was in line with his subjective reports. Case 2 showed a slight decrease in depression, but overall psychopathology was still high at 6 years after surgery with an increase in anger and aggression together with difficulties in social adaptation. Besides temporary hardware-related complications, no distressing adverse effects were observed. Bilateral thalamic stimulation may provide sustained tic benefit after at least 6 years, but to maximise overall outcome, attention is needed for postoperative psychosocial adaptation, already prior to surgery.

  12. New Insights Offered by a Computational Model of Deep Brain Stimulation

    DEFF Research Database (Denmark)

    Modolo, J.; Mosekilde, Erik; Beuter, A.

    2007-01-01

    Deep brain stimulation (DBS) is a standard neurosurgical procedure used to treat motor symptoms in about 5% of patients with Parkinson's disease (PD). Despite the indisputable success of this procedure, the biological mechanisms underlying the clinical benefits of DBS have not yet been fully...... and exploring the physiological mechanisms which respond to this treatment strategy (i.e., DBS). Finally, we present new insights into the ways this computational model may help to elucidate the dynamic network effects produced in a cerebral structure when DBS is applied. (C) 2007 Elsevier Ltd. All rights...

  13. The Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies

    Directory of Open Access Journals (Sweden)

    P. Justin eRossi

    2016-04-01

    Full Text Available This review summarizes 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; these advances were presented at the 3rd Annual Deep Brain Stimulation Think Tank. 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.

  14. Olfactory Functioning in Parkinson's Disease: The Effects of Deep Brain Stimulation

    DEFF Research Database (Denmark)

    van Hartevelt, Tim Johannes

    2014-01-01

    The sense of smell is vital for species survival in terms of food selection and detection as well as procreation. Disorders of the sense of smell are not uncommon and can have a significant effect on general health and well-being including quality of life. In Parkinson's disease (PD), the loss...... of sense of smell is one of the most common and earliest symptoms, appearing approximately 5 years prior to any motor symptoms. Deep brain stimulation (DBS) has proven remarkably effective in alleviating the symptoms of PD including olfactory dysfunction. This remains a difficult area to research with many...

  15. Deep Brain Stimulation for the Treatment of Tremor and Ataxia Associated with Abetalipoproteinemia

    Directory of Open Access Journals (Sweden)

    Antonios Mammis

    2012-07-01

    Full Text Available Background: Abetalipoproteinemia is a rare disorder of fat absorption, characterized by vitamin deficiency, acanthocytosis, and neurologic symptoms including ataxia and tremor.Case Report: A 41-year-old male with abetalipoproteinemia is presented. He underwent staged bilateral thalamic deep brain stimulation (DBS for the treatment of his tremors. After DBS, the patient achieved significant improvements in his tremors, ataxia, and quality of life.Discussion: Thalamic DBS proved to be both safe and efficacious in the management of ataxia and tremors in a patient with abetalipoproteinemia. This is the first report of DBS in abetalipoproteinemia in the literature. 

  16. Deep Brain Stimulation Salvages a Flourishing Dental Practice: A Dentist with Essential Tremor Recounts his Experience.

    Science.gov (United States)

    Giacopuzzi, Guy; Lising, Melanie; Halpern, Casey H

    2016-10-22

    In recounting his experience with deep brain stimulation (DBS), a practicing dentist challenged with long-standing bilateral essential tremor of the hands shares insights into his diagnosis, treatments, and ultimately successful DBS surgery at Stanford University Medical Center, CA, USA. Now nearly one year after his surgery, his practice continues to flourish and he encourages others in his profession to consider the possibility of DBS as a definitive treatment for tremors of the hand, which may salvage their practice.

  17. Evaluation of deep brain stimulation for Parkinson's disease by using FDG PET

    International Nuclear Information System (INIS)

    Guan, Y.H.; Zuo, C.T.; Zhao, J.; Lin, X.T.; Sun, B.M.

    2002-01-01

    Objective: Patients are effectively treated with medication in their initial phases of Parkinson's disease. However, the drugs become less effective and the adverse effects revealed. Recent years, the chronic deep brain stimulation is becoming an important treatment for patients with patients with Parkinson's disease. It has shown that the Parkinson's state is characterized by pathological neural activity in the motor system including the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN). The chronic deep brain stimulation can make benefits in the patients by intermediate the pathological neural activity. It needs an external method to evaluate the mechanism of therapy and to monitor the effect of treatment. The objective of our study is to observe the regional glucose metabolism changes in the motor loops and demonstrate the mechanism of therapy and how to monitor the treatment. Patients and Methods: Employing FDG PET, we had studied 7 patients who suffered from Parkinson's disease all the patients were failing medical therapy.the electrodes were implanted in the brain by the direction of MRI.The target of DBS is STN. Resting FDG PET were performed on and off STN stimulation. Metabolic changes with DBS were correlated with clinical improvement as measured by changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor ratings off medication. PET imaging was read by visual interpretation in blind method and calculated by semi-quantitative analysis. The statistic data was analysis after FDG PET imaging. Results: Through the research, regional cerebral glucose metabolic changes with DBS on and off were correlated with clinical improvement as measured by changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor ratings. STN DBS improved UPDRS motor ratings (33%, P<0.001) and significantly increased regional glucose metabolism in the frontal lobe, temporal lobe, Parietal lobe cortex ipsilateral to stimulation. The heighten

  18. Assessing the direct effects of deep brain stimulation using embedded axon models

    Science.gov (United States)

    Sotiropoulos, Stamatios N.; Steinmetz, Peter N.

    2007-06-01

    To better understand the spatial extent of the direct effects of deep brain stimulation (DBS) on neurons, we implemented a geometrically realistic finite element electrical model incorporating anisotropic and inhomogenous conductivities. The model included the subthalamic nucleus (STN), substantia nigra (SN), zona incerta (ZI), fields of Forel H2 (FF), internal capsule (IC) and Medtronic 3387/3389 electrode. To quantify the effects of stimulation, we extended previous studies by using multi-compartment axon models with geometry and orientation consistent with anatomical features of the brain regions of interest. Simulation of axonal firing produced a map of relative changes in axonal activation. Voltage-controlled stimulation, with clinically typical parameters at the dorso-lateral STN, caused axon activation up to 4 mm from the target. This activation occurred within the FF, IC, SN and ZI with current intensities close to the average injected during DBS (3 mA). A sensitivity analysis of model parameters (fiber size, fiber orientation, degree of inhomogeneity, degree of anisotropy, electrode configuration) revealed that the FF and IC were consistently activated. Direct activation of axons outside the STN suggests that other brain regions may be involved in the beneficial effects of DBS when treating Parkinsonian symptoms.

  19. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

    Directory of Open Access Journals (Sweden)

    Alik S. Widge

    2018-03-01

    Full Text Available Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial “failures” are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this “valley of disillusionment,” DBS may be nearing a “slope of enlightenment.” Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI, the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.

  20. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

    Science.gov (United States)

    Widge, Alik S.; Malone, Donald A.; Dougherty, Darin D.

    2018-01-01

    Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial “failures” are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this “valley of disillusionment,” DBS may be nearing a “slope of enlightenment.” Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care. PMID:29618967

  1. Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression.

    Science.gov (United States)

    Widge, Alik S; Malone, Donald A; Dougherty, Darin D

    2018-01-01

    Major depressive episodes are the largest cause of psychiatric disability, and can often resist treatment with medication and psychotherapy. Advances in the understanding of the neural circuit basis of depression, combined with the success of deep brain stimulation (DBS) in movement disorders, spurred several groups to test DBS for treatment-resistant depression. Multiple brain sites have now been stimulated in open-label and blinded studies. Initial open-label results were dramatic, but follow-on controlled/blinded clinical trials produced inconsistent results, with both successes and failures to meet endpoints. Data from follow-on studies suggest that this is because DBS in these trials was not targeted to achieve physiologic responses. We review these results within a technology-lifecycle framework, in which these early trial "failures" are a natural consequence of over-enthusiasm for an immature technology. That framework predicts that from this "valley of disillusionment," DBS may be nearing a "slope of enlightenment." Specifically, by combining recent mechanistic insights and the maturing technology of brain-computer interfaces (BCI), the next generation of trials will be better able to target pathophysiology. Key to that will be the development of closed-loop systems that semi-autonomously alter stimulation strategies based on a patient's individual phenotype. Such next-generation DBS approaches hold great promise for improving psychiatric care.

  2. Time and frequency-dependent modulation of local field potential synchronization by deep brain stimulation.

    Directory of Open Access Journals (Sweden)

    Clinton B McCracken

    Full Text Available 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

  3. From miracle to reconciliation: a hermeneutic phenomenological study exploring the experience of living with Parkinson's disease following deep brain stimulation.

    Science.gov (United States)

    Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Ostergaard, Karen

    2010-10-01

    Deep Brain Stimulation for Parkinson's disease is a promising treatment for patients who can no longer be treated satisfactorily with L-dopa. Deep Brain Stimulation is known to relieve motor symptoms of Parkinson's disease and improve quality of life. Focusing on how patients experience life when treated with Deep Brain Stimulation can provide essential information on the process patients go through when receiving a treatment that alters the body and changes the illness trajectory. The aim of this study was to explore and describe the experience of living with Parkinson's disease when treated with Deep Brain Stimulation. The study was designed as a longitudinal study and data were gathered through qualitative in-depth interviews three times during the first year of treatment. Nine patients participated in the study. They were included when they had accepted treatment with Deep Brain Stimulation for Parkinson's disease. Data collection and data analysis were inspired by the hermeneutic phenomenological methodology of Van Manen. The treatment had a major impact on the body. Participants experienced great bodily changes and went through a process of adjustment in three phases during the first year of treatment with Deep Brain Stimulation. These stages were; being liberated: a kind of miracle, changes as a challenge: decline or opportunity and reconciliation: re-defining life with Parkinson's disease. The course of the process was unique for each participant, but dominant was that difficulties during the adjustment of stimulation and medication did affect the re-defining process. Patients go through a dramatic process of change following Deep Brain Stimulation. A changing body affects their entire lifeworld. Some adjust smoothly to changes while others are affected by loss of control, uncertainty and loss of everyday life as they knew it. These experiences affect the process of adjusting to life with Deep Brain Stimulation and re-define life with Parkinson's disease

  4. Hitting the right target : noninvasive localization of the subthalamic nucleus motor part for specific deep brain stimulation

    NARCIS (Netherlands)

    Brunenberg, E.J.L.

    2011-01-01

    Deep brain stimulation of the subthalamic nucleus (STN) has gained momentum as a therapy for advanced Parkinson’s disease. The stimulation effectively alleviates the patients’ typical motor symptoms on a long term, but can give rise to cognitive and psychiatric adverse effects as well. Based on

  5. Impact of deep brain stimulation of the ventral anterior limb of the internal capsule on cognition in depression

    NARCIS (Netherlands)

    Bergfeld, Isidoor O.; Mantione, Mariska; Hoogendoorn, M L C; Ruhe, H. G.; Horst, Ferdinand; Notten, P; van Laarhoven, J; van den Munckhof, M. P.; Beute, G. N.; Schuurman, P R; Denys, D

    Background. Preliminary studies report no negative and a possible positive impact of deep brain stimulation (DBS) on cognition of patients with treatment-resistant depression (TRD). However, these studies neither controlled for practice effects nor compared active with sham stimulation. Method. To

  6. Impact of deep brain stimulation of the ventral anterior limb of the internal capsule on cognition in depression

    NARCIS (Netherlands)

    Bergfeld, I O; Mantione, M; Hoogendoorn, M L C; Ruhé, H G; Horst, F; Notten, P; van Laarhoven, J; van den Munckhof, P; Beute, G; Schuurman, P R; Denys, D

    2017-01-01

    BACKGROUND: Preliminary studies report no negative and a possible positive impact of deep brain stimulation (DBS) on cognition of patients with treatment-resistant depression (TRD). However, these studies neither controlled for practice effects nor compared active with sham stimulation. METHOD: To

  7. Impact of deep brain stimulation of the ventral anterior limb of the internal capsule on cognition in depression

    NARCIS (Netherlands)

    Bergfeld, I. O.; Mantione, M.; Hoogendoorn, M. L. C.; Ruhé, H. G.; Horst, F.; Notten, P.; van Laarhoven, J.; van den Munckhof, P.; Beute, G.; Schuurman, P. R.; Denys, D.

    2017-01-01

    Background. Preliminary studies report no negative and a possible positive impact of deep brain stimulation (DBS) on cognition of patients with treatment-resistant depression (TRD). However, these studies neither controlled for practice effects nor compared active with sham stimulation. Method. To

  8. Deep Brain Stimulation of the internal globus pallidus in refractory Tourette Syndrome.

    Science.gov (United States)

    Smeets, A Y J M; Duits, A A; Plantinga, B R; Leentjens, A F G; Oosterloo, M; Visser-Vandewalle, V; Temel, Y; Ackermans, L

    2016-03-01

    Deep Brain Stimulation in psychiatric disorders is becoming an increasingly performed surgery. At present, seven different targets have been stimulated in Tourette Syndrome, including the internal globus pallidus. We describe the effects on tics and comorbid behavioral disorders of Deep Brain Stimulation of the anterior internal globus pallidus in five patients with refractory Tourette Syndrome. This study was performed as an open label study with follow-up assessment between 12 and 38 months. Patients were evaluated twice, one month before surgery and at long-term follow-up. Primary outcome was tic severity, assessed by several scales. Secondary outcomes were comorbid behavioral disorders, mood and cognition. The final position of the active contacts of the implanted electrodes was investigated and side effects were reported. Three males and two females were included with a mean age of 41.6 years (SD 9.7). The total post-operative score on the Yale Global Tic Severity Scale was significantly lower than the pre-operative score (42.2±4.8 versus 12.8±3.8, P=0.043). There was also a significant reduction on the modified Rush Video-Based Tic Rating Scale (13.0±2.0 versus 7.0±1.6, P=0.041) and in the total number of video-rated tics (259.6±107.3 versus 49.6±24.8, P=0.043). No significant difference on the secondary outcomes was found, however, there was an improvement on an individual level for obsessive-compulsive behavior. The final position of the active contacts was variable in our sample and no relationship between position and stimulation effects could be established. Our study suggests that Deep Brain Stimulation of the anterior internal globus pallidus is effective in reducing tic severity, and possibly also obsessive-compulsive behavior, in refractory Tourette patients without serious adverse events or side-effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. European clinical guidelines for Tourette syndrome and other tic disorders. Part IV: deep brain stimulation

    DEFF Research Database (Denmark)

    Müller-Vahl, Kirsten R; Cath, Danielle C; Cavanna, Andrea E

    2011-01-01

    Ten years ago deep brain stimulation (DBS) has been introduced as an alternative and promising treatment option for patients suffering from severe Tourette syndrome (TS). It seemed timely to develop a European guideline on DBS by a working group of the European Society for the Study of Tourette......, randomized controlled studies including a larger number of patients are still lacking. Although persistent serious adverse effects (AEs) have hardly been reported, surgery-related (e.g., bleeding, infection) as well as stimulation-related AEs (e.g., sedation, anxiety, altered mood, changes in sexual function......) may occur. At present time, DBS in TS is still in its infancy. Due to both different legality and practical facilities in different European countries these guidelines, therefore, have to be understood as recommendations of experts. However, among the ESSTS working group on DBS in TS there is general...

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

    Science.gov (United States)

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

    2015-01-01

    Twiddler's syndrome is a rare complication associated with implantable electrical stimulation devices. First described in a patient with a pacemaker, it is a known complication in the field of cardiology. However, it is not so recognised in the world of neurosurgery, in which it has been described in relation to deep brain stimulation (DBS) devices. Characterised by manipulating either consciously or unconsciously the generator of such devices, which causes it to rotate on itself, the syndrome causes the coiling of the wiring of these systems and can lead to their rupture or the displacement of intracranial electrodes. We describe a case of twiddler's syndrome in a patient treated with DBS for obsessive-compulsive disorder, in which clinical deterioration presented after a good initial response. Control radiographs revealed rotation of the wiring system and displacement of the intracranial electrodes. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Christian eIneichen

    2014-09-01

    Full Text Available 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. 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.

  12. Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation.

    Science.gov (United States)

    Quinn, Emma J; Blumenfeld, Zack; Velisar, Anca; Koop, Mandy Miller; Shreve, Lauren A; Trager, Megan H; Hill, Bruce C; Kilbane, Camilla; Henderson, Jaimie M; Brontë-Stewart, Helen

    2015-11-01

    Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P closed-loop DBS. © 2015 International Parkinson and Movement Disorder Society.

  13. The impact of multichannel microelectrode recording (MER) in deep brain stimulation of the basal ganglia.

    Science.gov (United States)

    Kinfe, Thomas M; Vesper, Jan

    2013-01-01

    Deep brain stimulation (DBS) of the basal ganglia (Ncl. subthalamicus, Ncl. ventralis intermedius thalami, globus pallidus internus) has become an evidence-based and well-established treatment option in otherwise refractory movement disorders. The Ncl. subthalamicus (STN) is the target of choice in Parkinson's disease.However, a considerable discussion is currently ongoing with regard to the necessity for micro-electrode recording (MER) in DBS surgery.The present review provides an overview on deep brain stimulation and (MER) of the STN in patients with Parkinson's disease. Detailed description is given concerning the multichannel MER systems nowadays available for DBS of the basal ganglia, especially of the STN, as a useful tool for target refinement. Furthermore, an overview is given of the historical aspects, spatial mapping of the STN by MER, and its impact for accuracy and precision in current functional stereotactic neurosurgery.The pros concerning target refinement by MER means on the one hand, and cons including increased bleeding risk, increased operation time, local or general anesthesia, and single versus multichannel microelectrode recording are discussed in detail. Finally, the authors favor the use of MER with intraoperative testing combined with imaging to achieve a more precise electrode placement, aiming to ameliorate clinical outcome in therapy-resistant movement disorders.

  14. Oscillations in Pedunculopontine Nucleus in Parkinson's disease and its relationship with deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Min eLi

    2015-09-01

    Full Text Available The recent development of deep brain stimulation (DBS of the pedunculopontine nucleus (PPN for the treatment of parkinsonian patients, particularly those in advanced stages with axial symptoms, has ignited interest into the study of this brain nucleus. In contrast to the extensively studied alterations of neural activity that occur in the basal ganglia in Parkinson’s disease (PD, our understanding of the activity of the PPN remains insufficient. In recent years, however, a series of studies recording oscillatory activity in the PPN of parkinsonian patients have made important findings. Here, we briefly review recent studies that explore the different kinds of oscillations observed in the PPN of parkinsonian patients, and how they underlie the pathophysiology of PD and the efficacy of PPN DBS in these disorders.

  15. Lightning may pose a danger to patients receiving deep brain stimulation: case report.

    Science.gov (United States)

    Prezelj, Neža; Trošt, Maja; Georgiev, Dejan; Flisar, Dušan

    2018-05-01

    Deep brain stimulation (DBS) is an established treatment option for advanced stages of Parkinson's disease and other movement disorders. It is known that DBS is susceptible to strong electromagnetic fields (EMFs) that can be generated by various electrical devices at work, home, and in medical environments. EMFs can interfere with the proper functioning of implantable pulse generators (IPGs). Very strong EMFs can generate induction currents in implanted electrodes and even damage the brain. Manufacturers of DBS devices have issued a list of warnings on how to avoid this danger. Strong EMFs can result from natural forces as well. The authors present the case of a 66-year-old woman who was being treated with a rechargeable DBS system for neck dystonia when her apartment was struck by lightning. Domestic electronic devices that were operating during the event were burned and destroyed. The woman's IPG switched off but remained undamaged, and she suffered no neurological consequences.

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

    Science.gov (United States)

    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.

  17. Analysis of Oscillatory Neural Activity in Series Network Models of Parkinson's Disease During Deep Brain Stimulation.

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    Davidson, Clare M; de Paor, Annraoi M; Cagnan, Hayriye; Lowery, Madeleine M

    2016-01-01

    Parkinson's disease is a progressive, neurodegenerative disorder, characterized by hallmark motor symptoms. It is associated with pathological, oscillatory neural activity in the basal ganglia. Deep brain stimulation (DBS) is often successfully used to treat medically refractive Parkinson's disease. However, the selection of stimulation parameters is based on qualitative assessment of the patient, which can result in a lengthy tuning period and a suboptimal choice of parameters. This study explores fourth-order, control theory-based models of oscillatory activity in the basal ganglia. Describing function analysis is applied to examine possible mechanisms for the generation of oscillations in interacting nuclei and to investigate the suppression of oscillations with high-frequency stimulation. The theoretical results for the suppression of the oscillatory activity obtained using both the fourth-order model, and a previously described second-order model, are optimized to fit clinically recorded local field potential data obtained from Parkinsonian patients with implanted DBS. Close agreement between the power of oscillations recorded for a range of stimulation amplitudes is observed ( R(2)=0.69-0.99 ). The results suggest that the behavior of the system and the suppression of pathological neural oscillations with DBS is well described by the macroscopic models presented. The results also demonstrate that in this instance, a second-order model is sufficient to model the clinical data, without the need for added complexity. Describing the system behavior with computationally efficient models could aid in the identification of optimal stimulation parameters for patients in a clinical environment.

  18. Subthalamic deep brain stimulation and dopaminergic medication in Parkinson's disease: Impact on inter-limb coupling.

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    Daneault, Jean-François; Carignan, Benoit; Sadikot, Abbas F; Duval, Christian

    2016-10-29

    Patients with Parkinson's disease (PD) often present with bimanual coordination deficits whose exact origins remain unclear. One aspect of bimanual coordination is inter-limb coupling. This is characterized by the harmonization of movement parameters between limbs. We assessed different aspects of bimanual coordination in patients with PD, including inter-limb coupling, and determined whether they are altered by subthalamic (STN) deep brain stimulation (DBS) or dopaminergic medication. Twenty PD patients were tested before STN DBS surgery; with and without medication. Post- surgery, patients were tested with their stimulators on and off as well as with and without medication. Patients were asked to perform a unimanual and bimanual rapid repetitive diadochokinesis task. The difference in mean amplitude and mean duration of cycles between hands was computed in order to assess inter-limb coupling. Also, mean angular velocity of both hands and structural coupling were computed for the bimanual task. There was a positive effect of medication and stimulation on mean angular velocity, which relates to clinical improvement. PD patients exhibited temporal inter-limb coupling that was not altered by either medication or STN stimulation. However, PD patients did not exhibit spatial inter-limb coupling. Again, this was not altered by medication or stimulation. Collectively, the results suggest that structures independent of the dopaminergic system and basal ganglia may mediate temporal and spatial inter-limb coupling. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Deep Brain Stimulation of the Pedunculopontine Tegmental Nucleus (PPN Influences Visual Contrast Sensitivity in Human Observers.

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    Hendrik Strumpf

    Full Text Available The parapontine nucleus of the thalamus (PPN is a neuromodulatory midbrain structure with widespread connectivity to cortical and subcortical motor structures, as well as the spinal cord. The PPN also projects to the thalamus, including visual relay nuclei like the LGN and the pulvinar. Moreover, there is intense connectivity with sensory structures of the tegmentum in particular with the superior colliculus (SC. Given the existence and abundance of projections to visual sensory structures, it is likely that activity in the PPN has some modulatory influence on visual sensory selection. Here we address this possibility by measuring the visual discrimination performance (luminance contrast thresholds in a group of patients with Parkinson's Disease (PD treated with deep-brain stimulation (DBS of the PPN to control gait and postural motor deficits. In each patient we measured the luminance-contrast threshold of being able to discriminate an orientation-target (Gabor-grating as a function of stimulation frequency (high 60Hz, low 8/10, no stimulation. Thresholds were determined using a standard staircase-protocol that is based on parameter estimation by sequential testing (PEST. We observed that under low frequency stimulation thresholds increased relative to no and high frequency stimulation in five out of six patients, suggesting that DBS of the PPN has a frequency-dependent impact on visual selection processes at a rather elementary perceptual level.

  20. Syncope Associated with Subthalamic Nucleus Deep Brain Stimulation in a Patient with Parkinson’s Disease

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    Dursun Aygun

    2013-01-01

    Full Text Available In advanced Parkinson's disease (PD, deep brain stimulation (DBS may be an alternative option for the treatment of motor symptoms. Side effects associated with subthalamic nucleus (STN DBS in patients with PD are emerging as the most frequent sensory and motor symptoms. DBS-related syncope is reported as extremely rare. We wanted to discuss the mechanisms of syncope associated with STN DBS in a patient with Parkinson's disease. Case report. Sixty-three-year-old female patient is followed up with diagnosis of idiopathic Parkinson's disease for 6 years in our clinic. The patient has undergone STN DBS due to painful dystonia and drug resistant tremor. During the operation, when the left STN was stimulated at 5 milliampere (mAmp, the patient developed presyncopal symptoms. However, when the stimulation was stopped symptoms improved. During the early period after the operation, when the right STN was stimulated at 1.3 millivolts (mV, she developed the pre-yncopal symptoms and then syncope. Our case shows that STN DBS may lead to directly autonomic symptoms resulting in syncope during stimulation-on (stim-on.

  1. Programming Deep Brain Stimulation for Tremor and Dystonia: The Toronto Western Hospital Algorithms.

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    Picillo, Marina; Lozano, Andres M; Kou, Nancy; Munhoz, Renato Puppi; Fasano, Alfonso

    2016-01-01

    Deep brain stimulation (DBS) is an effective treatment for essential tremor (ET) and dystonia. After surgery, a number of extensive programming sessions are performed, mainly relying on neurologist's personal experience as no programming guidelines have been provided so far, with the exception of recommendations provided by groups of experts. Finally, fewer information is available for the management of DBS in ET and dystonia compared with Parkinson's disease. Our aim is to review the literature on initial and follow-up DBS programming procedures for ET and dystonia and integrate the results with our current practice at Toronto Western Hospital (TWH) to develop standardized DBS programming protocols. We conducted a literature search of PubMed from inception to July 2014 with the keywords "balance", "bradykinesia", "deep brain stimulation", "dysarthria", "dystonia", "gait disturbances", "initial programming", "loss of benefit", "micrographia", "speech", "speech difficulties" and "tremor". Seventy-six papers were considered for this review. Based on the literature review and our experience at TWH, we refined three algorithms for management of ET, including: (1) initial programming, (2) management of balance and speech issues and (3) loss of stimulation benefit. We also depicted algorithms for the management of dystonia, including: (1) initial programming and (2) management of stimulation-induced hypokinesia (shuffling gait, micrographia and speech impairment). We propose five algorithms tailored to an individualized approach to managing ET and dystonia patients with DBS. We encourage the application of these algorithms to supplement current standards of care in established as well as new DBS centers to test the clinical usefulness of these algorithms in supplementing the current standards of care. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Thalamic deep brain stimulation for neuropathic pain after amputation or brachial plexus avulsion.

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    Pereira, Erlick A C; Boccard, Sandra G; Linhares, Paulo; Chamadoira, Clara; Rosas, Maria José; Abreu, Pedro; Rebelo, Virgínia; Vaz, Rui; Aziz, Tipu Z

    2013-09-01

    Fifteen hundred patients have received deep brain stimulation (DBS) to treat neuropathic pain refractory to pharmacotherapy over the last half-century, but few during the last decade. Deep brain stimulation for neuropathic pain has shown variable outcomes and gained consensus approval in Europe but not the US. This study prospectively evaluated the efficacy at 1 year of DBS for phantom limb pain after amputation, and deafferentation pain after brachial plexus avulsion (BPA), in a single-center case series. Patient-reported outcome measures were collated before and after surgery, using a visual analog scale (VAS) score, 36-Item Short-Form Health Survey (SF-36), Brief Pain Inventory (BPI), and University of Washington Neuropathic Pain Score (UWNPS). Twelve patients were treated over 29 months, receiving contralateral, ventroposterolateral sensory thalamic DBS. Five patients were amputees and 7 had BPAs, all from traumas. A postoperative trial of externalized DBS failed in 1 patient with BPA. Eleven patients proceeded to implantation and gained improvement in pain scores at 12 months. No surgical complications or stimulation side effects were noted. In the amputation group, after 12 months the mean VAS score improved by 90.0% ± 10.0% (p = 0.001), SF-36 by 57.5% ± 97.9% (p = 0.127), UWNPS by 80.4% ± 12.7% (p stimulation demonstrated efficacy at 1 year for chronic neuropathic pain after traumatic amputation and BPA. Clinical trials that retain patients in long-term follow-up are desirable to confirm findings from prospectively assessed case series.

  3. Motor and Nonmotor Circuitry Activation Induced by Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease: Intraoperative Functional Magnetic Resonance Imaging for Deep Brain Stimulation.

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    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

    2015-06-01

    To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease would affect the activity of motor and nonmotor networks, we applied intraoperative functional magnetic resonance imaging (fMRI) to patients receiving DBS. Ten patients receiving STN DBS for Parkinson disease underwent intraoperative 1.5-T fMRI during high-frequency stimulation delivered via an external pulse generator. The study was conducted between January 1, 2013, and September 30, 2014. We observed blood oxygen level-dependent (BOLD) signal changes (false discovery rate <0.001) in the motor circuitry (including the primary motor, premotor, and supplementary motor cortices; thalamus; pedunculopontine nucleus; and cerebellum) and in the limbic circuitry (including the cingulate and insular cortices). Activation of the motor network was observed also after applying a Bonferroni correction (P<.001) to the data set, suggesting that across patients, BOLD changes in the motor circuitry are more consistent compared with those occurring in the nonmotor network. These findings support the modulatory role of STN DBS on the activity of motor and nonmotor networks and suggest complex mechanisms as the basis of the efficacy of this treatment modality. Furthermore, these results suggest that across patients, BOLD changes in the motor circuitry are more consistent than those in the nonmotor 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. clinicaltrials.gov Identifier: NCT01809613. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  4. Failure of delayed feedback deep brain stimulation for intermittent pathological synchronization in Parkinson's disease.

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    Andrey Dovzhenok

    Full Text Available Suppression of excessively synchronous beta-band oscillatory activity in the brain is believed to suppress hypokinetic motor symptoms of Parkinson's disease. Recently, a lot of interest has been devoted to desynchronizing delayed feedback deep brain stimulation (DBS. This type of synchrony control was shown to destabilize the synchronized state in networks of simple model oscillators as well as in networks of coupled model neurons. However, the dynamics of the neural activity in Parkinson's disease exhibits complex intermittent synchronous patterns, far from the idealized synchronous dynamics used to study the delayed feedback stimulation. This study explores the action of delayed feedback stimulation on partially synchronized oscillatory dynamics, similar to what one observes experimentally in parkinsonian patients. We employ a computational model of the basal ganglia networks which reproduces experimentally observed fine temporal structure of the synchronous dynamics. When the parameters of our model are such that the synchrony is unphysiologically strong, the feedback exerts a desynchronizing action. However, when the network is tuned to reproduce the highly variable temporal patterns observed experimentally, the same kind of delayed feedback may actually increase the synchrony. As network parameters are changed from the range which produces complete synchrony to those favoring less synchronous dynamics, desynchronizing delayed feedback may gradually turn into synchronizing stimulation. This suggests that delayed feedback DBS in Parkinson's disease may boost rather than suppress synchronization and is unlikely to be clinically successful. The study also indicates that delayed feedback stimulation may not necessarily exhibit a desynchronization effect when acting on a physiologically realistic partially synchronous dynamics, and provides an example of how to estimate the stimulation effect.

  5. Deep brain stimulation of the bilateral nucleus accumbens in normal rhesus monkey.

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    Li, Nan; Gao, Li; Wang, Xue-lian; Chen, Lei; Fang, Wei; Ge, Shun-nan; Gao, Guo-dong

    2013-01-09

    The nucleus accumbens (NAc) has been considered as a novel target of deep brain stimulation (DBS) for intractable psychiatric disorders. Quite a few questions exist about this new treatment, and might be explored in nonhuman primate models. There are several reports on DBS of brain nucleus other than NAc in nonhuman primates. Therefore, we stereotactically implanted the electrodes into bilateral NAc under the guidance of MRI using a clinical Leksell stereotactic system in normal rhesus monkeys. NAc could be recognized as the area of continuity between the caudate nucleus and putamen in the coronal sections, which is beneath the internal capsule, and the gray matter nucleus between the ventromedial prefrontal cortex and anterior commissure in axial sections, which is medial to the putamen. NAc is mainly at a point 2.0-3.0 mm inferior, 3.0-4.0 mm anterior, and 4.5-5.5 mm lateral to the anterior commissure. The electrodes were implanted accurately and connected to an implantable pulse generator subcutaneously. After recovery from surgery, stimulation with a variety of parameters was trialed, and continuous stimulation at 90 μs, 3.5 V, 160, or 60 Hz was administered individually for 7 days. The behaviors and spontaneous locomotor activity of the animals did not change significantly during stimulation. This is the first report on DBS of NAc in nonhuman primates to the best of our knowledge. Bilateral electrical stimulation of NAc is a safe treatment. This model could be helpful in further studies on the clinical use of NAc stimulation for psychiatric disorders and for a better understanding of the functions of this nucleus.

  6. [Emotion and basal ganglia (II): what can we learn from subthalamic nucleus deep brain stimulation in Parkinson's disease?].

    Science.gov (United States)

    Péron, J; Dondaine, T

    2012-01-01

    The subthalamic nucleus deep-brain stimulation Parkinson's disease patient model seems to represent a unique opportunity for studying the functional role of the basal ganglia and notably the subthalamic nucleus in human emotional processing. Indeed, in addition to constituting a therapeutic advance for severely disabled Parkinson's disease patients, deep brain stimulation is a technique, which selectively modulates the activity of focal structures targeted by surgery. There is growing evidence of a link between emotional impairments and deep-brain stimulation of the subthalamic nucleus. In this context, according to the definition of emotional processing exposed in the companion paper available in this issue, the aim of the present review will consist in providing a synopsis of the studies that investigated the emotional disturbances observed in subthalamic nucleus deep brain stimulation Parkinson's disease patients. This review leads to the conclusion that several emotional components would be disrupted after subthalamic nucleus deep brain stimulation in Parkinson's disease: subjective feeling, neurophysiological activation, and motor expression. Finally, after a description of the limitations of this study model, we discuss the functional role of the subthalamic nucleus (and the striato-thalamo-cortical circuits in which it is involved) in emotional processing. It seems reasonable to conclude that the striato-thalamo-cortical circuits are indeed involved in emotional processing and that the subthalamic nucleus plays a central in role the human emotional architecture. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

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

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    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

  8. Numerical Characterization of Intraoperative and Chronic Electrodes in Deep Brain Stimulation

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    Alessandra ePaffi

    2015-02-01

    Full Text Available Intraoperative electrode is used in the Deep Brain stimulation (DBS technique to pinpoint the brain target and to choose the best parameters for the stimulating signal. However, when the intraoperative electrode is replaced with the chronic one, the observed effects do not always coincide with predictions.To investigate the causes of such discrepancies, in this work, 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 on the electric potential and the activating function along neuronal fibers show that the different geometries and sizes of the two electrodes do not change shapes and polarities of these functions, but only the amplitudes. A similar effect is caused by the presence of different tissue layers (edema or glial tissue in the peri-electrode space. On the contrary, a not accurate positioning of the chronic electrode with respect to the intraoperative one (electric centers not coincident may induce a complete different electric stimulation on some groups of fibers.

  9. Ethical safety of deep brain stimulation: A study on moral decision-making in Parkinson's disease.

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    Fumagalli, Manuela; Marceglia, Sara; Cogiamanian, Filippo; Ardolino, Gianluca; Picascia, Marta; Barbieri, Sergio; Pravettoni, Gabriella; Pacchetti, Claudio; Priori, Alberto

    2015-07-01

    The possibility that deep brain stimulation (DBS) in Parkinson's disease (PD) alters patients' decisions and actions, even temporarily, raises important clinical, ethical and legal questions. Abnormal moral decision-making can lead to ethical rules violations. Previous experiments demonstrated the subthalamic (STN) activation during moral decision-making. Here we aim to study whether STN DBS can affect moral decision-making in PD patients. Eleven patients with PD and bilateral STN DBS implant performed a computerized moral task in ON and OFF stimulation conditions. A control group of PD patients without DBS implant performed the same experimental protocol. All patients underwent motor, cognitive and psychological assessments. STN stimulation was not able to modify neither reaction times nor responses to moral task both when we compared the ON and the OFF state in the same patient (reaction times, p = .416) and when we compared DBS patients with those treated only with the best medical treatment (reaction times: p = .408, responses: p = .776). Moral judgment is the result of a complex process, requiring cognitive executive functions, problem-solving, anticipations of consequences of an action, conflict processing, emotional evaluation of context and of possible outcomes, and involving different brain areas and neural circuits. Our data show that STN DBS leaves unaffected moral decisions thus implying relevant clinical and ethical implications for DBS consequences on patients' behavior, on decision-making and on judgment ability. In conclusion, the technique can be considered safe on moral behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Central thalamic deep brain stimulation for support of forebrain arousal regulation in the minimally conscious state.

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    Schiff, Nicholas D

    2013-01-01

    This chapter considers the use of central thalamic deep brain stimulation (CT/DBS) to support arousal regulation mechanisms in the minimally conscious state (MCS). CT/DBS for selected patients in a MCS is first placed in the historical context of prior efforts to use thalamic electrical brain stimulation to treat the unconscious clinical conditions of coma and vegetative state. These previous studies and a proof of concept result from a single-subject study of a patient in a MCS are reviewed against the background of new population data providing benchmarks of the natural history of vegetative and MCSs. The conceptual foundations for CT/DBS in selected patients in a MCS are then presented with consideration of both circuit and cellular mechanisms underlying recovery of consciousness identified from empirical studies. Directions for developing future generalizable criteria for CT/DBS that focus on the integrity of necessary brain systems and behavioral profiles in patients in a MCS that may optimally response to support of arousal regulation mechanisms are proposed. © 2013 Elsevier B.V. All rights reserved.

  11. And Then There Was Light: Perspectives of Optogenetics for Deep Brain Stimulation and Neuromodulation

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    Jean Delbeke

    2017-12-01

    Full Text Available Deep Brain Stimulation (DBS has evolved into a well-accepted add-on treatment for patients with severe Parkinsons disease as well as for other chronic neurological conditions. The focal action of electrical stimulation can yield better responses and it exposes the patient to fewer side effects compared to pharmaceuticals distributed throughout the body toward the brain. On the other hand, the current practice of DBS is hampered by the relatively coarse level of neuromodulation achieved. Optogenetics, in contrast, offers the perspective of much more selective actions on the various physiological structures, provided that the stimulated cells are rendered sensitive to the action of light. Optogenetics has experienced tremendous progress since its first in vivo applications about 10 years ago. Recent advancements of viral vector technology for gene transfer substantially reduce vector-associated cytotoxicity and immune responses. This brings about the possibility to transfer this technology into the clinic as a possible alternative to DBS and neuromodulation. New paths could be opened toward a rich panel of clinical applications. Some technical issues still limit the long term use in humans but realistic perspectives quickly emerge. Despite a rapid accumulation of observations about patho-physiological mechanisms, it is still mostly serendipity and empiric adjustments that dictate clinical practice while more efficient logically designed interventions remain rather exceptional. Interestingly, it is also very much the neuro technology developed around optogenetics that offers the most promising tools to fill in the existing knowledge gaps about brain function in health and disease. The present review examines Parkinson's disease and refractory epilepsy as use cases for possible optogenetic stimulation therapies.

  12. Disruption in proprioception from long-term thalamic deep brain stimulation: A pilot study

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    Jennifer A Semrau

    2015-05-01

    Full Text Available 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

  13. Pallidal Deep Brain Stimulation Improves Higher Control of the Oculomotor System in Parkinson's Disease.

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    Antoniades, Chrystalina A; Rebelo, Pedro; Kennard, Christopher; Aziz, Tipu Z; Green, Alexander L; FitzGerald, James J

    2015-09-23

    The frontal cortex and basal ganglia form a set of parallel but mostly segregated circuits called cortico-basal ganglia loops. The oculomotor loop controls eye movements and can direct relatively simple movements, such as reflexive prosaccades, without external help but needs input from "higher" loops for more complex behaviors. The antisaccade task requires the dorsolateral prefrontal cortex, which is part of the prefrontal loop. Information flows from prefrontal to oculomotor circuits in the striatum, and directional errors in this task can be considered a measure of failure of prefrontal control over the oculomotor loop. The antisaccadic error rate (AER) is increased in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has no effect on the AER, but a previous case suggested that DBS of the globus pallidus interna (GPi) might. Our aim was to compare the effects of STN DBS and GPi DBS on the AER. We tested eye movements in 14 human DBS patients and 10 controls. GPi DBS substantially reduced the AER, restoring lost higher control over oculomotor function. Interloop information flow involves striatal neurons that receive cortical input and project to pallidum. They are normally silent when quiescent, but in PD they fire randomly, creating noise that may account for the degradation in interloop control. The reduced AER with GPi DBS could be explained by retrograde stimulation of striatopallidal axons with consequent activation of inhibitory collaterals and reduction in background striatal firing rates. This study may help explain aspects of PD pathophysiology and the mechanism of action of GPi DBS. Significance statement: Parkinson's disease causes symptoms including stiffness, slowness of movement, and tremor. Electrical stimulation of specific areas deep in the brain can effectively treat these symptoms, but exactly how is not fully understood. Part of the cause of such symptoms may be impairments in the way information flows

  14. Intraoperative neurophysiological responses in epileptic patients submitted to hippocampal and thalamic deep brain stimulation.

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    Cukiert, Arthur; Cukiert, Cristine Mella; Argentoni-Baldochi, Meire; Baise, Carla; Forster, Cássio Roberto; Mello, Valeria Antakli; Burattini, José Augusto; Lima, Alessandra Moura

    2011-12-01

    Deep brain stimulation (DBS) has been used in an increasing frequency for treatment of refractory epilepsy. Acute deep brain macrostimulation intraoperative findings were sparsely published in the literature. We report on our intraoperative macrostimulation findings during thalamic and hippocampal DBS implantation. Eighteen patients were studied. All patients underwent routine pre-operative evaluation that included clinical history, neurological examination, interictal and ictal EEG, high resolution 1.5T MRI and neuropsychological testing. Six patients with temporal lobe epilepsy were submitted to hippocampal DBS (Hip-DBS); 6 patients with focal epilepsy were submitted to anterior thalamic nucleus DBS (AN-DBS) and 6 patients with generalized epilepsy were submitted to centro-median thalamic nucleus DBS (CM-DBS). Age ranged from 9 to 40 years (11 males). All patients were submitted to bilateral quadripolar DBS electrode implantation in a single procedure, under general anesthesia, and intraoperative scalp EEG monitoring. Final electrode's position was checked postoperatively using volumetric CT scanning. Bipolar stimulation using the more proximal and distal electrodes was performed. Final standard stimulation parameters were 6Hz, 4V, 300μs (low frequency range: LF) or 130Hz, 4V, 300μs (high frequency range: HF). Bilateral recruiting response (RR) was obtained after unilateral stimulation in all patients submitted to AN and CM-DBS using LF stimulation. RR was widespread but prevailed over the fronto-temporal region bilaterally, and over the stimulated hemisphere. HF stimulation led to background slowing and a DC shift. The mean voltage for the appearance of RR was 4V (CM) and 3V (AN). CM and AN-DBS did not alter inter-ictal spiking frequency or morphology. RR obtained after LF Hip-DBS was restricted to the stimulated temporal lobe and no contralateral activation was noted. HF stimulation yielded no visually recognizable EEG modification. Mean intensity for initial

  15. Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation

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    Baumgarten, C.; Zhao, Y.; Sauleau, P.; Malrain, C.; Jannin, P.; Haegelen, C.

    2016-03-01

    Deep brain stimulation of the medial globus pallidus is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The lack of side-effect predictive model leads the neurologist to secure an optimal electrode placement by iterating clinical testing on an awake patient during the surgical procedure. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning based method called PyMAN (for Pyramidal tract side effect Model based on Artificial Neural network) that accounted for the current of the stimulation, the 3D electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the medial globus pallidus have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was .78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

  16. [Obsessive-compulsive disorder, a new model of basal ganglia dysfunction? Elements from deep brain stimulation studies].

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    Haynes, W I A; Millet, B; Mallet, L

    2012-01-01

    Deep brain stimulation was first developed for movement disorders but is now being offered as a therapeutic alternative in severe psychiatric disorders after the failure of conventional therapies. One of such pathologies is obsessive-compulsive disorder. This disorder which associates intrusive thoughts (obsessions) and repetitive irrepressible rituals (compulsions) is characterized by a dysfunction of a cortico-subcortical loop. After having reviewed the pathophysiological evidence to show why deep brain stimulation was an interesting path to take for severe and resistant cases of obsessive-compulsive disorder, we will present the results of the different clinical trials. Finally, we will provide possible mechanisms for the effects of deep brain stimulation in this pathology. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  17. Optical coherence tomography and optical coherence domain reflectometry for deep brain stimulation probe guidance

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    Jeon, Sung W.; Shure, Mark A.; Baker, Kenneth B.; Chahlavi, Ali; Hatoum, Nagi; Turbay, Massud; Rollins, Andrew M.; Rezai, Ali R.; Huang, David

    2005-04-01

    Deep Brain Stimulation (DBS) is FDA-approved for the treatment of Parkinson's disease and essential tremor. Currently, placement of DBS leads is guided through a combination of anatomical targeting and intraoperative microelectrode recordings. The physiological mapping process requires several hours, and each pass of the microelectrode into the brain increases the risk of hemorrhage. Optical Coherence Domain Reflectometry (OCDR) in combination with current methodologies could reduce surgical time and increase accuracy and safety by providing data on structures some distance ahead of the probe. For this preliminary study, we scanned a rat brain in vitro using polarization-insensitive Optical Coherence Tomography (OCT). For accurate measurement of intensity and attenuation, polarization effects arising from tissue birefringence are removed by polarization diversity detection. A fresh rat brain was sectioned along the coronal plane and immersed in a 5 mm cuvette with saline solution. OCT images from a 1294 nm light source showed depth profiles up to 2 mm. Light intensity and attenuation rate distinguished various tissue structures such as hippocampus, cortex, external capsule, internal capsule, and optic tract. Attenuation coefficient is determined by linear fitting of the single scattering regime in averaged A-scans where Beer"s law is applicable. Histology showed very good correlation with OCT images. From the preliminary study using OCT, we conclude that OCDR is a promising approach for guiding DBS probe placement.

  18. Resting state cortical oscillations of patients with Parkinson disease and with and without subthalamic deep brain stimulation: a magnetoencephalography study.

    Science.gov (United States)

    Cao, Chunyan; Li, Dianyou; Jiang, Tianxiao; Ince, Nuri Firat; Zhan, Shikun; Zhang, Jing; Sha, Zhiyi; Sun, Bomin

    2015-04-01

    In this study, we investigate the modification to cortical oscillations of patients with Parkinson disease (PD) by subthalamic deep brain stimulation (STN-DBS). Spontaneous cortical oscillations of patients with PD were recorded with magnetoencephalography during on and off subthalamic nucleus deep brain stimulation states. Several features such as average frequency, average power, and relative subband power in regions of interest were extracted in the frequency domain, and these features were correlated with Unified Parkinson Disease Rating Scale III evaluation. The same features were also investigated in patients with PD without surgery and healthy controls. Patients with Parkinson disease without surgery compared with healthy controls had a significantly lower average frequency and an increased average power in 1 to 48 Hz range in whole cortex. Higher relative power in theta and simultaneous decrease in beta and gamma over temporal and occipital were also observed in patients with PD. The Unified Parkinson Disease Rating Scale III rigidity score correlated with the average frequency and with the relative power of beta and gamma in frontal areas. During subthalamic nucleus deep brain stimulation, the average frequency increased significantly when stimulation was on compared with off state. In addition, the relative power dropped in delta, whereas it rose in beta over the whole cortex. Through the course of stimulation, the Unified Parkinson Disease Rating Scale III rigidity and tremor scores correlated with the relative power of alpha over left parietal. Subthalamic nucleus deep brain stimulation improves the symptoms of PD by suppressing the synchronization of alpha rhythm in somatomotor region.

  19. Comparison of dysphagia before and after deep brain stimulation in Parkinson's disease.

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    Silbergleit, Alice K; LeWitt, Peter; Junn, Fred; Schultz, Lonni R; Collins, Denise; Beardsley, Tausha; Hubert, Meghan; Trosch, Richard; Schwalb, Jason M

    2012-12-01

    Although dysphagia is a common problem for many Parkinson's disease (PD) patients, the effect of deep brain stimulation (DBS) on swallowing is unclear. Fourteen subjects with advanced PD underwent videofluorographic swallowing studies prior to bilateral DBS of the subthalamic nucleus (STN) and at 3 and 12 months postprocedure. They were tested under several stimulation and medication conditions. Subjects completed the Dysphagia Handicap Index at each time. There was a strong trend toward improved swallowing response for solid intake in the medication-free condition with the stimulator on compared with the stimulator off (P = .0107). Also, there was a trend toward improved oral preparation of thin liquids (P = .0368) in the medication-free condition when the stimulator was on versus off 12 months later. The remaining swallowing parameters showed no change or worsening of swallowing function regardless of stimulator or medication status. Results of the Dysphagia Handicap Index revealed significant improvement in subject self-perception of swallowing 3 and 12 months following the procedure compared with baseline on the functional subscale (P = .020 and P = .010, respectively), the emotional subscale (P = .013 and P = .003, respectively), and the total score (P = .025 and P = .003, respectively). These data suggest that bilateral STN-DBS does not substantively impair swallowing in PD. In addition, it may improve motor sequencing of the oropharyngeal swallow for solid consistencies (which are known to provide increased sensory feedback to assist motor planning of the oropharyngeal swallow). Subjects with advanced PD who are undergoing DBS may perceive significant improvement in swallowing ability despite the lack of objective improvements in swallowing function. Copyright © 2012 Movement Disorder Society.

  20. Dr. Robert G. Heath: a controversial figure in the history of deep brain stimulation.

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    O'Neal, Christen M; Baker, Cordell M; Glenn, Chad A; Conner, Andrew K; Sughrue, Michael E

    2017-09-01

    The history of psychosurgery is filled with tales of researchers pushing the boundaries of science and ethics. These stories often create a dark historical framework for some of the most important medical and surgical advancements. Dr. Robert G. Heath, a board-certified neurologist, psychiatrist, and psychoanalyst, holds a debated position within this framework and is most notably remembered for his research on schizophrenia. Dr. Heath was one of the first physicians to implant electrodes in deep cortical structures as a psychosurgical intervention. He used electrical stimulation in an attempt to cure patients with schizophrenia and as a method of conversion therapy in a homosexual man. This research was highly controversial, even prior to the implementation of current ethics standards for clinical research and often goes unmentioned within the historical narrative of deep brain stimulation (DBS). While distinction between the modern practice of DBS and its controversial origins is necessary, it is important to examine Dr. Heath's work as it allows for reflection on current neurosurgical practices and questioning the ethical implication of these advancements.

  1. Deep brain stimulation for the treatment of childhood dystonic cerebral palsy.

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    Keen, Joseph R; Przekop, Allison; Olaya, Joffre E; Zouros, Alexander; Hsu, Frank P K

    2014-12-01

    Deep brain stimulation (DBS) for dystonic cerebral palsy (CP) has rarely been reported, and its efficacy, though modest when compared with that for primary dystonia, remains unclear, especially in the pediatric population. The authors present a small series of children with dystonic CP who underwent bilateral pallidal DBS, to evaluate the treatment's efficacy and safety in the pediatric dystonic CP population. The authors conducted a retrospective review of patients (under the age of 18 years) with dystonic CP who had undergone DBS of the bilateral globus pallidus internus between 2010 and 2012. Two of the authors independently assessed outcomes using the Barry-Albright Dystonia Scale (BADS) and the Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFMDRS-M). Five children were diagnosed with dystonic CP due to insults occurring before the age of 1 year. Mean age at surgery was 11 years (range 8-17 years), and the mean follow-up was 26.6 months (range 2-42 months). The mean target position was 20.6 mm lateral to the midcommissural point. The mean preoperative and postoperative BADS scores were 23.8 ± 4.9 (range 18.5-29.0) and 20.0 ± 5.5 (range 14.5-28.0), respectively, with a mean overall percent improvement of 16.0% (p = 0.14). The mean preoperative and postoperative BFMDRS-M scores were 73.3 ± 26.6 (range 38.5-102.0) and 52.4 ± 21.5 (range 34.0-80.0), respectively, with a mean overall percent improvement of 28.5% (p = 0.10). Those stimulated at least 23 months (4 patients) improved 18.3% (p = 0.14) on the BADS and 30.5% (p = 0.07) on the BFMDRS-M. The percentage improvement per body region yielded conflicting results between rating scales; however, BFMDRS-M scores for speech showed some of the greatest improvements. Two patients required hardware removal (1 complete system, 1 unilateral electrode) within 4 months after implantation because of infections that resolved with antibiotics. All postoperative dystonia rating scale scores improved with pallidal

  2. High Frequency Deep Brain Stimulation and Neural Rhythms in Parkinson's Disease.

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    Blumenfeld, Zack; Brontë-Stewart, Helen

    2015-12-01

    High frequency (HF) deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson's disease (PD). It effectively treats the cardinal motor signs of PD, including tremor, bradykinesia, and rigidity. The most common neural target is the subthalamic nucleus, located within the basal ganglia, the region most acutely affected by PD pathology. Using chronically-implanted DBS electrodes, researchers have been able to record underlying neural rhythms from several nodes in the PD network as well as perturb it using DBS to measure the ensuing neural and behavioral effects, both acutely and over time. In this review, we provide an overview of the PD neural network, focusing on the pathophysiological signals that have been recorded from PD patients as well as the mechanisms underlying the therapeutic benefits of HF DBS. We then discuss evidence for the relationship between specific neural oscillations and symptoms of PD, including the aberrant relationships potentially underlying functional connectivity in PD as well as the use of different frequencies of stimulation to more specifically target certain symptoms. Finally, we briefly describe several current areas of investigation and how the ability to record neural data in ecologically-valid settings may allow researchers to explore the relationship between brain and behavior in an unprecedented manner, culminating in the future automation of neurostimulation therapy for the treatment of a variety of neuropsychiatric diseases.

  3. Patients' expectations in subthalamic nucleus deep brain stimulation surgery for Parkinson disease.

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    Hasegawa, Harutomo; Samuel, Michael; Douiri, Abdel; Ashkan, Keyoumars

    2014-12-01

    Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson disease. However, some patients feel less satisfied with the outcome of surgery. We sought to study the relationship between expectations, satisfaction, and outcome in STN DBS for Parkinson disease. Twenty-two consecutive patients undergoing STN DBS completed a modified 39-item Parkinson disease questionnaire (PDQ-39) preoperatively and 6 months postoperatively. A satisfaction questionnaire accompanied the postoperative questionnaire. Patients expected a significant improvement from surgery preoperatively: preoperative score (median PDQ-39 summary score [interquartile range]): 37.0 (9.5), expected postoperative score: 13.0 (8.0), P Parkinson disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Deep brain stimulation of the subthalamic nucleus improves pain in Parkinson's disease.

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    Pellaprat, Jean; Ory-Magne, Fabienne; Canivet, Cindy; Simonetta-Moreau, Marion; Lotterie, Jean-Albert; Radji, Fatai; Arbus, Christophe; Gerdelat, Angélique; Chaynes, Patrick; Brefel-Courbon, Christine

    2014-06-01

    In Parkinson's disease (PD), chronic pain is a common symptom which markedly affects the quality of life. Some physiological arguments proposed that Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) could improve pain in PD. We investigated in 58 PD patients the effect of STN-DBS on pain using the short McGill Pain Questionnaire and other pain parameters such as the Bodily discomfort subscore of the Parkinson's disease Questionnaire 39 and the Unified Parkinson's Disease Rating Scale section II (UPDRS II) item 17. All pain scores were significantly improved 12 months after STN-DBS. This improvement was not correlated with motor improvement, depression scores or L-Dopa reduction. STN-DBS induced a substantial beneficial effect on pain in PD, independently of its motor effects and mood status of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Deep Brain Stimulation of the H Fields of Forel Alleviates Tics in Tourette Syndrome

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    Clemens Neudorfer

    2017-06-01

    Full Text Available The current rationale for target selection in Tourette syndrome revolves around the notion of cortico-basal ganglia circuit involvement in the pathophysiology of the disease. However, despite extensive research, the ideal target for deep brain stimulation (DBS is still under debate, with many structures being neglected and underexplored. Based on clinical observations and taking into account the prevailing hypotheses of network processing in Tourette syndrome, we chose the fields of Forel, namely field H1, as a target for DBS. The fields of Forel constitute the main link between the striatopallidal system and the thalamocortical network, relaying pallidothalamic projections from core anatomical structures to the thalamic ventral nuclear group. In a retrospective study we investigated two patients suffering from chronic, medically intractable Tourette syndrome who underwent bilateral lead implantation in field H1 of Forel. Clinical scales revealed significant alleviation of tics and comorbid symptoms, namely depression and anxiety, in the postoperative course in both patients.

  6. Malignant Neuroleptic Syndrome following Deep Brain Stimulation Surgery of Globus Pallidus Pars Internus in Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Jae Meen Lee

    2016-02-01

    Full Text Available Neuroleptic malignant syndrome (NMS is a rare but potentially lethal outcome caused by sudden discontinuation or dose reduction of dopaminergic agents. We report an extremely rare case of NMS after deep brain stimulation (DBS surgery in a cerebral palsy (CP patient without the withdrawal of dopaminergic agents. A 19-year-old girl with CP was admitted for DBS due to medically refractory dystonia and rigidity. Dopaminergic agents were not stopped preoperatively. DBS was performed uneventfully under monitored anesthesia. Dopaminergic medication was continued during the postoperative period. She manifested spasticity and muscle rigidity, and was high fever resistant to anti-pyretic drugs at 2 h postoperative. At postoperative 20 h, she suffered cardiac arrest and expired, despite vigorous cardiopulmonary resuscitation. NMS should be considered for hyperthermia and severe spasticity in CP patients after DBS surgery, irrespective of continued dopaminergic medication.

  7. Therapeutic deep brain stimulation worsening dysprosody in Parkinson’s disease – an unexplored entity

    Directory of Open Access Journals (Sweden)

    Shoaib M

    2018-03-01

    Full Text Available Maria Shoaib,1 Muhammad Taimoor Khan2 1Department of Medicine, Dow Medical College, Karachi, Pakistan; 2Department of Neurology, Charleston Area Medical Center/West Virginia University, Charleston, WV, USA  We read this article, “Altered emotional recognition and expression in patients with Parkinson’s disease” by Jin et al1 with great interest and appreciate the novel information provided on altered emotional processing in pre-deep brain stimulation (DBS Parkinson’s disease (PD patients and we would like to add our feedback on the role of DBS on nonmotor and emotional components of PD.View the original paper by Jin and colleagues. 

  8. Deep brain stimulation for the treatment of Alzheimer disease and dementias.

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    Laxton, Adrian W; Lozano, Andres M

    2013-01-01

    To review the use of deep brain stimulation (DBS) for treatment of dementia. A PubMed literature search was conducted to identify all studies that have investigated the use of DBS for treatment of dementia. Three studies examined the use of DBS for dementia. One study involved fornix DBS for Alzheimer disease (AD), and two studies involved DBS of the nucleus basalis of Meynert, one to treat AD and one to treat Parkinson disease dementia. Evidence for the use of DBS to treat dementia is preliminary and limited. Fornix and nucleus basalis of Meynert DBS can influence activity in the pathologic neural circuits that underlie AD and Parkinson disease dementia. Further investigation into the potential clinical effects of DBS for dementia is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex.

    Science.gov (United States)

    Li, Qian; Ke, Ya; Chan, Danny C W; Qian, Zhong-Ming; Yung, Ken K L; Ko, Ho; Arbuthnott, Gordon W; Yung, Wing-Ho

    2012-12-06

    Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimulation, it had been assumed that its action is on the nucleus itself. By means of simultaneous recordings of the firing activities from populations of neurons and the local field potentials in the motor cortex of freely moving Parkinsonian rats, this study casts doubt on this assumption. Instead, we found evidence that the corrective action is upon the cortex, where stochastic antidromic spikes originating from the STN directly modify the firing probability of the corticofugal projection neurons, destroy the dominance of beta rhythm, and thus restore motor control to the subjects, be they patients or rodents. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Swallowing and deep brain stimulation in Parkinson’s disease: A systematic review

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    Troche, Michelle S.; Brandimore, Alexandra E.; Foote, Kelly D.; Okun, Michael S.

    2013-01-01

    The purpose of this review is to assess the current state of the literature on the topic of deep brain stimulation (DBS) and its effects on swallowing function in Parkinson’s disease (PD). Pubmed, Cochrane review, and web of science searches were completed on all articles addressing DBS that contained a swallowing outcome measure. Outcome measures included the penetration/aspiration scale, pharyngeal transit time, oropharyngeal residue, drooling, aspiration pneumonia, death, hyolaryngeal excursion, epiglottic inversion, UPDRS scores, and presence of coughing/throat clearing during meals. The search identified 13 studies specifically addressing the effects of DBS on swallowing. Critical assessment of the 13 identified peer-reviewed publications revealed nine studies employing an experimental design, (e.g. “on” vs. “off”, pre- vs. post-DBS) and four case reports. None of the nine experimental studies were found to identify clinically significant improvement or decline in swallowing function with DBS. Despite these findings, several common threads were identified across experimental studies and will be examined in this review. Additionally, available data demonstrate that, although subthalamic nucleus (STN) stimulation has been considered to cause more impairment to swallowing function than globus pallidus internus (GPi) stimulation, there are no experimental studies directly comparing swallowing function in STN vs. GPi. Moreover, there has been no comparison of unilateral vs. bilateral DBS surgery and the coincident effects on swallowing function. This review includes a critical analysis of all experimental studies and discusses methodological issues that should be addressed in future studies. PMID:23726461

  11. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    Science.gov (United States)

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  12. Simulation of cortico-basal ganglia oscillations and their suppression by closed loop deep brain stimulation.

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    Grant, Peadar F; Lowery, Madeleine M

    2013-07-01

    A new model of deep brain stimulation (DBS) is presented that integrates volume conduction effects with a neural model of pathological beta-band oscillations in the cortico-basal ganglia network. The model is used to test the clinical hypothesis that closed-loop control of the amplitude of DBS may be possible, based on the average rectified value of beta-band oscillations in the local field potential. Simulation of closed-loop high-frequency DBS was shown to yield energy savings, with the magnitude of the energy saved dependent on the strength of coupling between the subthalamic nucleus and the remainder of the cortico-basal ganglia network. When closed-loop DBS was applied to a strongly coupled cortico-basal ganglia network, the stimulation energy delivered over a 480 s period was reduced by up to 42%. Greater energy reductions were observed for weakly coupled networks, as the stimulation amplitude reduced to zero once the initial desynchronization had occurred. The results provide support for the application of closed-loop high-frequency DBS based on electrophysiological biomarkers.

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

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    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.

  14. Simultaneous bilateral stereotactic procedure for deep brain stimulation implants: a significant step for reducing operation time.

    Science.gov (United States)

    Fonoff, Erich Talamoni; Azevedo, Angelo; Angelos, Jairo Silva Dos; Martinez, Raquel Chacon Ruiz; Navarro, Jessie; Reis, Paul Rodrigo; Sepulveda, Miguel Ernesto San Martin; Cury, Rubens Gisbert; Ghilardi, Maria Gabriela Dos Santos; Teixeira, Manoel Jacobsen; Lopez, William Omar Contreras

    2016-07-01

    OBJECT Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads. METHODS Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson's disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared. RESULTS Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 ± 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 ± 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off-medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% ± 9.5% improvement in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% ± 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa-equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time. CONCLUSIONS A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional

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

    Directory of Open Access Journals (Sweden)

    Peter Jonas Grahn

    2014-06-01

    Full Text Available 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

  16. Thalamic Deep Brain Stimulation for Essential Tremor Also Reduces Voice Tremor.

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    Kundu, Bornali; Schrock, Lauren; Davis, Tyler; House, Paul A

    2017-12-12

    Voice tremor is a common feature of essential tremor (ET) that is difficult to treat medically and significantly affects quality of life. Deep brain stimulation (DBS) of the ventral intermediate nucleus (Vim) of the thalamus is effective in improving contralateral distal limb tremor and has been shown in limited studies to affect voice tremor. Our objective was to retrospectively evaluate whether Vim-DBS used to treat patients with essential motor tremor also effectively treated underlying concurrent voice tremor and assess whether particular lead locations were favorable for treating vocal tremor. In this retrospective cohort study, patients had unilateral or bilateral lead placement and were monitored for up to 12 months. We used the Fahn-Tolosa-Marin (FTM) subscore to assess vocal tremor. Changes in vocal tremor before and after stimulation and over several sessions were assessed. Of the 77 patients who met the inclusion criteria and were treated for essential tremor, 20 (26%) patients had vocal tremor prior to stimulation. Active Vim-DBS decreased the amplitude of voice tremor by 80% (p centroid of stimulation showed that Vim thalamic stimulation that is more anterior on average yielded better voice tremor control, significantly so on the left side (p < 0.05). Additionally, there was improvement in head, tongue, and face tremor scores (p < 0.05). Unilateral and bilateral Vim-DBS targeted to treat the motor component of essential tremor also dramatically decreased the amplitude of voice tremor in this group of patients, suggesting a potential benefit of this treatment for affected patients. © 2017 International Neuromodulation Society.

  17. Hemispheric dissociation of reward processing in humans: insights from deep brain stimulation.

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    Palminteri, Stefano; Serra, Giulia; Buot, Anne; Schmidt, Liane; Welter, Marie-Laure; Pessiglione, Mathias

    2013-01-01

    Rewards have various effects on human behavior and multiple representations in the human brain. Behaviorally, rewards notably enhance response vigor in incentive motivation paradigms and bias subsequent choices in instrumental learning paradigms. Neurally, rewards affect activity in different fronto-striatal regions attached to different motor effectors, for instance in left and right hemispheres for the two hands. Here we address the question of whether manipulating reward-related brain activity has local or general effects, with respect to behavioral paradigms and motor effectors. Neuronal activity was manipulated in a single hemisphere using unilateral deep brain stimulation (DBS) in patients with Parkinson's disease. Results suggest that DBS amplifies the representation of reward magnitude within the targeted hemisphere, so as to affect the behavior of the contralateral hand specifically. These unilateral DBS effects on behavior include both boosting incentive motivation and biasing instrumental choices. Furthermore, using computational modeling we show that DBS effects on incentive motivation can predict DBS effects on instrumental learning (or vice versa). Thus, we demonstrate the feasibility of causally manipulating reward-related neuronal activity in humans, in a manner that is specific to a class of motor effectors but that generalizes to different computational processes. As these findings proved independent from therapeutic effects on parkinsonian motor symptoms, they might provide insight into DBS impact on non-motor disorders, such as apathy or hypomania. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  19. Effects of STN and GPi deep brain stimulation on impulse control disorders and dopamine dysregulation syndrome.

    Directory of Open Access Journals (Sweden)

    Sarah J Moum

    Full Text Available Impulse control disorders (ICDs and dopamine dysregulation syndrome (DDS are important behavioral problems that affect a subpopulation of patients with Parkinson's disease (PD and typically result in markedly diminished quality of life for patients and their caregivers. We aimed to investigate the effects of subthalamic nucleus (STN and internal globus pallidus (GPi deep brain stimulation (DBS on ICD/DDS frequency and dopaminergic medication usage.A retrospective chart review was performed on 159 individuals who underwent unilateral or bilateral PD DBS surgery in either STN or GPi. According to published criteria, pre- and post-operative records were reviewed to categorize patients both pre- and post-operatively as having ICD, DDS, both ICD and DDS, or neither ICD nor DDS. Group differences in patient demographics, clinical presentations, levodopa equivalent dose (LED, and change in diagnosis following unilateral/bilateral by brain target (STN or GPi DBS placement were examined.28 patients met diagnostic criteria for ICD or DDS pre- or post-operatively. ICD or DDS classification did not differ by GPi or STN target stimulation. There was no change in DDS diagnosis after unilateral or bilateral stimulation. For ICD, diagnosis resolved in 2 of 7 individuals after unilateral or bilateral DBS. Post-operative development of these syndromes was significant; 17 patients developed ICD diagnoses post-operatively with 2 patients with pre-operative ICD developing DDS post-operatively.Unilateral or bilateral DBS did not significantly treat DDS or ICD in our sample, even though a few cases of ICD resolved post-operatively. Rather, our study provides preliminary evidence that DDS and ICD diagnoses may emerge following DBS surgery.

  20. Posterolateral Trajectories Favor a Longer Motor Domain in Subthalamic Nucleus Deep Brain Stimulation for Parkinson Disease.

    Science.gov (United States)

    Tamir, Idit; Marmor-Levin, Odeya; Eitan, Renana; Bergman, Hagai; Israel, Zvi

    2017-10-01

    The clinical outcome of patients with Parkinson disease (PD) who undergo subthalamic nucleus (STN) deep brain stimulation (DBS) is, in part, determined by the length of the electrode trajectory through the motor STN domain, the dorsolateral oscillatory region (DLOR). Trajectory length has been found to correlate with the stimulation-related improvement in patients' motor function (estimated by part III of the United Parkinson's Disease Rating Scale [UPDRS]). Therefore, it seems that ideally trajectories should have maximal DLOR length. We retrospectively studied the influence of various anatomic aspects of the brains of patients with PD and the geometry of trajectories planned on the length of the DLOR and STN recorded during DBS surgery. We examined 212 trajectories and 424 microelectrode recording tracks in 115 patients operated on in our center between 2010 and 2015. We found a strong correlation between the length of the recorded DLOR and STN. Trajectories that were more lateral and/or posterior in orientation had a longer STN and DLOR pass, although the DLOR/STN fraction length remained constant. The STN target was more lateral when the third ventricle was wider, and the latter correlated with older age and male gender. Trajectory angles correlate with the recorded STN and DLOR lengths, and should be altered toward a more posterolateral angle in older patients and atrophied brains to compensate for the changes in STN location and geometry. These fine adjustments should yield a longer motor domain pass, thereby improving the patient's predicted outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Effect of low-frequency deep brain stimulation on sensory thresholds in Parkinson's disease.

    Science.gov (United States)

    Belasen, Abigail; Rizvi, Khizer; Gee, Lucy E; Yeung, Philip; Prusik, Julia; Ramirez-Zamora, Adolfo; Hanspal, Era; Paiva, Priscilla; Durphy, Jennifer; Argoff, Charles E; Pilitsis, Julie G

    2017-02-01

    OBJECTIVE Chronic pain is a major distressing symptom of Parkinson's disease (PD) that is often undertreated. Subthalamic nucleus (STN) deep brain stimulation (DBS) delivers high-frequency stimulation (HFS) to patients with PD and has been effective in pain relief in a subset of these patients. However, up to 74% of patients develop new pain concerns while receiving STN DBS. Here the authors explore whether altering the frequency of STN DBS changes pain perception as measured through quantitative sensory testing (QST). METHODS Using QST, the authors measured thermal and mechanical detection and pain thresholds in 19 patients undergoing DBS via HFS, low-frequency stimulation (LFS), and off conditions in a randomized order. Testing was performed in the region of the body with the most pain and in the lower back in patients without chronic pain. RESULTS In the patients with chronic pain, LFS significantly reduced heat detection thresholds as compared with thresholds following HFS (p = 0.029) and in the off state (p = 0.010). Moreover, LFS resulted in increased detection thresholds for mechanical pressure (p = 0.020) and vibration (p = 0.040) compared with these thresholds following HFS. Neither LFS nor HFS led to changes in other mechanical thresholds. In patients without chronic pain, LFS significantly increased mechanical pain thresholds in response to the 40-g pinprick compared with thresholds following HFS (p = 0.032). CONCLUSIONS Recent literature has suggested that STN LFS can be useful in treating nonmotor symptoms of PD. Here the authors demonstrated that LFS modulates thermal and mechanical detection to a greater extent than HFS. Low-frequency stimulation is an innovative means of modulating chronic pain in PD patients receiving STN DBS. The authors suggest that STN LFS may be a future option to consider when treating Parkinson's patients in whom pain remains the predominant complaint.

  2. Intensive Voice Treatment (LSVT[R]LOUD) for Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus

    Science.gov (United States)

    Spielman, Jennifer; Mahler, Leslie; Halpern, Angela; Gilley, Phllip; Klepitskaya, Olga; Ramig, Lorraine

    2011-01-01

    Purpose: Intensive voice therapy (LSVT[R]LOUD) can effectively manage voice and speech symptoms associated with idiopathic Parkinson disease (PD). This small-group study evaluated voice and speech in individuals with and without deep brain stimulation of the subthalamic nucleus (STN-DBS) before and after LSVT LOUD, to determine whether outcomes…

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

    Science.gov (United States)

    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…

  4. Episodic memory following deep brain stimulation of the ventral anterior limb of the internal capsule and electroconvulsive therapy

    NARCIS (Netherlands)

    Bergfeld, Isidoor O; Mantione, Mariska; Hoogendoorn, Mechteld L C; Horst, Ferdinand; Notten, Peter; Schuurman, P Richard; Denys, D.

    2017-01-01

    BACKGROUND: Electroconvulsive Therapy (ECT) and Deep Brain Stimulation (DBS) are effective treatments for patients with treatment-resistant depression (TRD). However, a common side effect of ECT is autobiographical memory loss (e.g., personal experiences), whereas the impact of DBS on

  5. Episodic memory following deep brain stimulation of the ventral anterior limb of the internal capsule and electroconvulsive therapy

    NARCIS (Netherlands)

    Bergfeld, Isidoor O.; Mantione, Mariska; Hoogendoorn, Mechteld L. C.; Horst, Ferdinand; Notten, Peter; Schuurman, P. Richard; Denys, Damiaan

    2017-01-01

    Background: Electroconvulsive Therapy (ECT) and Deep Brain Stimulation (DBS) are effective treatments for patients with treatment-resistant depression (TRD). However, a common side effect of ECT is autobiographical memory loss (e.g., personal experiences), whereas the impact of DBS on

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

    NARCIS (Netherlands)

    Deeb, Wissam; Giordano, James J.; Rossi, Peter J.; Mogilner, Alon Y.; Gunduz, Aysegul; Judy, Jack W.; Klassen, Bryan T.; Butson, Christopher R.; van Horne, Craig; Deny, Damiaan; Dougherty, Darin D.; Rowell, David; Gerhardt, Greg A.; Smith, Gwenn S.; Ponce, Francisco A.; Walker, Harrison C.; Bronte-Stewart, Helen M.; Mayberg, Helen S.; Chizeck, Howard J.; Langevin, Jean-Philippe; Volkmann, Jens; Ostrem, Jill L.; Shute, Jonathan B.; Jimenez-Shahed, Joohi; Foote, Kelly D.; Wagle Shukla, Aparna; Rossi, Marvin A.; Oh, Michael; Pourfar, Michael; Rosenberg, Paul B.; Silburn, Peter A.; de Hemptine, Coralie; Starr, Philip A.; Denison, Timothy; Akbar, Umer; Grill, Warren M.; Okun, Michael S.

    2016-01-01

    This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with

  7. The added value of semimicroelectrode recording in deep brain stimulation of the subthalamic nucleus for Parkinson disease

    NARCIS (Netherlands)

    Jonker, Pascal K. C.; van Dijk, J. Marc C.; van Hulzen, Arjen L. J.; van Laar, Teus; Staal, Michiel J.; Journee, H. Louis

    2013-01-01

    Object. Accurate placement of the leads is crucial in deep brain stimulation (DBS). To optimize the surgical positioning of the lead, a combination of anatomical targeting on MRI, electrophysiological mapping, and clinical testing is applied during the procedure. Electrophysiological mapping is

  8. Deep brain stimulation of the subthalamic nucleus improves reward-based decision-learning in Parkinson's disease

    NARCIS (Netherlands)

    van Wouwe, N.C.; Ridderinkhof, K.R.; van den Wildenberg, W.P.M.; Band, G.P.H.; Abisogun, A.; Elias, W.J.; Frysinger, R.; Wylie, S.A.

    2011-01-01

    Recently, the subthalamic nucleus (STN) has been shown to be critically involved in decision-making, action selection, and motor control. Here we investigate the effect of deep brain stimulation (DBS) of the STN on reward-based decision-learning in patients diagnosed with Parkinson's disease (PD).

  9. Deep brain stimulation of the subthalamic nucleus improves reward-based decision-learning in Parkinson’s disease

    NARCIS (Netherlands)

    Wouwe, N.C. van; Ridderinkhof, K.R.; Wildenberg, W.P.M. van den; Band, G.P.H.; Abisogun, A.; Elias, W.J.; Frysinger, R.; Wylie, S.A.

    2011-01-01

    Recently, the subthalamic nucleus (STN) has been shown to be critically involved in decision-making, action selection, and motor control. Here we investigate the effect of deep brain stimulation (DBS) of the STN on reward-based decision-learning in patients diagnosed with Parkinson’s disease (PD).

  10. Use of dexmedetomidine during deep brain stimulation for Tourette Syndrome : a case report and review of the literature

    NARCIS (Netherlands)

    Bos, Michael; Janssen, Mark; Temel, Yasin; van Zundert, André; Ackermans, Linda

    2017-01-01

    Deep brain stimulation is invasive and used in selected patients with intractable Tourette Syndrome. The anaesthetic technique of first choice during implantation of the electrodes is an awake technique with local anaesthetics and conscious sedation. The anaesthetic management can be challenging,

  11. Long-term effects of pallidal or subthalamic deep brain stimulation on quality of life in Parkinson's disease

    NARCIS (Netherlands)

    Volkmann, Jens; Albanese, Alberto; Kulisevsky, Jaime; Tornqvist, Aana-Lena; Houeto, Jean-Luc; Pidoux, Bernard; Bonnet, Anne-Marie; Mendes, Alexandre; Benabid, Alim-Louis; Fraix, Valerie; van Blercom, Nadege; Xie, Jing; Obeso, José; Rodriguez-Oroz, Maria Cruz; Guridi, Jurge; Schnitzler, Alfons; Timmermann, Lars; Gironell, Alexandre A.; Molet, Juan; Pascual-Sedano, Benta; Rehncrona, Stig; Moro, Elena; Lang, Anthony C.; Lozano, Andres M.; Bentivoglio, Anna Rita; Scerrati, Massimo; Contarino, Maria Fiorella; Romito, Luigi; Janssens, Marc; Agid, Yves

    2009-01-01

    We assessed the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) or internal pallidum (GPi-DBS) on health-related quality of life (HrQoL) in patients with advanced Parkinson's disease participating in a previously reported multicenter trial. Sickness Impact Profile (SIP)

  12. Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output

    OpenAIRE

    Humphries, Mark D.; Gurney, Kevin

    2012-01-01

    Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contr...

  13. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease.

    Science.gov (United States)

    Hacker, Mallory L; DeLong, Mahlon R; Turchan, Maxim; Heusinkveld, Lauren E; Ostrem, Jill L; Molinari, Anna L; Currie, Amanda D; Konrad, Peter E; Davis, Thomas L; Phibbs, Fenna T; Hedera, Peter; Cannard, Kevin R; Drye, Lea T; Sternberg, Alice L; Shade, David M; Tonascia, James; Charles, David

    2018-06-29

    To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT ( p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy ( p will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor. © 2018 American Academy of Neurology.

  14. European clinical guidelines for Tourette syndrome and other tic disorders. Part IV: deep brain stimulation.

    Science.gov (United States)

    Müller-Vahl, Kirsten R; Cath, Danielle C; Cavanna, Andrea E; Dehning, Sandra; Porta, Mauro; Robertson, Mary M; Visser-Vandewalle, Veerle

    2011-04-01

    Ten years ago deep brain stimulation (DBS) has been introduced as an alternative and promising treatment option for patients suffering from severe Tourette syndrome (TS). It seemed timely to develop a European guideline on DBS by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). For a narrative review a systematic literature search was conducted and expert opinions of the guidelines group contributed also to the suggestions. Of 63 patients reported so far in the literature 59 had a beneficial outcome following DBS with moderate to marked tic improvement. However, randomized controlled studies including a larger number of patients are still lacking. Although persistent serious adverse effects (AEs) have hardly been reported, surgery-related (e.g., bleeding, infection) as well as stimulation-related AEs (e.g., sedation, anxiety, altered mood, changes in sexual function) may occur. At present time, DBS in TS is still in its infancy. Due to both different legality and practical facilities in different European countries these guidelines, therefore, have to be understood as recommendations of experts. However, among the ESSTS working group on DBS in TS there is general agreement that, at present time, DBS should only be used in adult, treatment resistant, and severely affected patients. It is highly recommended to perform DBS in the context of controlled trials.

  15. Evaluation of the efficacy of deep brain stimulation in the surgical treatment of cervical dystonia.

    Science.gov (United States)

    Calheiros-Trigo, Francisca; Linhares, Paulo

    2014-01-01

    Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a promising therapeutic option for patients with medically refractory dystonia. We present the results after 1 year of DBS of the GPi in 4 patients with cervical dystonia. Four patients with medically refractory cervical dystonia who underwent stereotactic pallidal DBS surgery between June 2010 and November 2011 were included in this retrospective study. Preoperative and postoperative evaluations at 3, 6 and 12 months after surgery were performed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). The 4 patients experienced a sustained improvement, with a mean TWSTRS reduction of 74.25%, at 12 months follow-up. Disability improved by 80.5% (mean) at 1 year follow-up. No stimulation-related side effects were reported. Pallidal DBS is a valid and effective second-line treatment for patients with cervical focal dystonia. Our results support its use in patients with an insufficient response to medical treatment. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  16. Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients.

    Science.gov (United States)

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

    2016-01-01

    Reduced verbal fluency (VF) has been reported in patients with Parkinson's disease (PD), especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS). To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS. Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., 'clusters' as correlates of automatic activation spread within lexical fields) from slower cluster transitions (i.e., 'switches' reflecting set-shifting towards new lexical fields). The results were compared to those of eleven healthy control subjects. PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls. Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones.

  17. Deep Brain Stimulation of the Subthalamic Nucleus Improves Lexical Switching in Parkinsons Disease Patients.

    Directory of Open Access Journals (Sweden)

    Isabelle Vonberg

    Full Text Available Reduced verbal fluency (VF has been reported in patients with Parkinson's disease (PD, especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS. To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS.Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., 'clusters' as correlates of automatic activation spread within lexical fields from slower cluster transitions (i.e., 'switches' reflecting set-shifting towards new lexical fields. The results were compared to those of eleven healthy control subjects.PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls.Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones.

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

    Science.gov (United States)

    Iriki, Atsushi; Isoda, Masaki

    2015-01-01

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

  19. Deep brain stimulation changes basal ganglia output nuclei firing pattern in the dystonic hamster.

    Science.gov (United States)

    Leblois, Arthur; Reese, René; Labarre, David; Hamann, Melanie; Richter, Angelika; Boraud, Thomas; Meissner, Wassilios G

    2010-05-01

    Dystonia is a heterogeneous syndrome of movement disorders characterized by involuntary muscle contractions leading to abnormal movements and postures. While medical treatment is often ineffective, deep brain stimulation (DBS) of the internal pallidum improves dystonia. Here, we studied the impact of DBS in the entopeduncular nucleus (EP), the rodent equivalent of the human globus pallidus internus, on basal ganglia output in the dt(sz)-hamster, a well-characterized model of dystonia by extracellular recordings. Previous work has shown that EP-DBS improves dystonic symptoms in dt(sz)-hamsters. We report that EP-DBS changes firing pattern in the EP, most neurons switching to a less regular firing pattern during DBS. In contrast, EP-DBS did not change the average firing rate of EP neurons. EP neurons display multiphasic responses to each stimulation impulse, likely underlying the disruption of their firing rhythm. Finally, neurons in the substantia nigra pars reticulata display similar responses to EP-DBS, supporting the idea that EP-DBS affects basal ganglia output activity through the activation of common afferent fibers. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Effect of Deep Brain Stimulation on Speech Performance in Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Sabine Skodda

    2012-01-01

    Full Text Available Deep brain stimulation (DBS has been reported to be successful in relieving the core motor symptoms of Parkinson's disease (PD and motor fluctuations in the more advanced stages of the disease. However, data on the effects of DBS on speech performance are inconsistent. While there are some series of patients documenting that speech function was relatively unaffected by DBS of the nucleus subthalamicus (STN, other investigators reported on improvements of distinct parameters of oral control and voice. Though, these ameliorations of single speech modalities were not always accompanied by an improvement of overall speech intelligibility. On the other hand, there are also indications for an induction of dysarthria as an adverse effect of STN-DBS occurring at least in some patients with PD. Since a deterioration of speech function has more often been observed under high stimulation amplitudes, this phenomenon has been ascribed to a spread of current-to-adjacent pathways which might also be the reason for the sporadic observation of an onset of dysarthria under DBS of other basal ganglia targets (e.g., globus pallidus internus/GPi or thalamus/Vim. The aim of this paper is to review and evaluate reports in the literature on the effects of DBS on speech function in PD.

  1. Effects of deep brain stimulation of the cerebellothalamic pathways on the sense of smell.

    Science.gov (United States)

    Kronenbuerger, M; Zobel, S; Ilgner, J; Finkelmeyer, A; Reinacher, P; Coenen, V A; Wilms, H; Kloss, M; Kiening, K; Daniels, C; Falk, D; Schulz, J B; Deuschl, G; Hummel, T

    2010-03-01

    The cerebellum and the motor thalamus, connected by cerebellothalamic pathways, are traditionally considered part of the motor-control system. Yet, functional imaging studies and clinical studies including patients with cerebellar disease suggest an involvement of the cerebellum in olfaction. Additionally, there are anecdotal clinical reports of olfactory disturbances elicited by electrical stimulation of the motor thalamus and its neighbouring subthalamic region. Deep brain stimulation (DBS) targeting the cerebellothalamic pathways is an effective treatment for essential tremor (ET), which also offers the possibility to explore the involvement of cerebellothalamic pathways in the sense of smell. This may be important for patient care given the increased use of DBS for the treatment of tremor disorders. Therefore, 21 none-medicated patients with ET treated with DBS (13 bilateral, 8 unilateral) were examined with "Sniffin' Sticks," an established and reliable method for olfactory testing. Patients were studied either with DBS switched on and then off or in reversed order. DBS impaired odor threshold and, to a lesser extent, odor discrimination. These effects were sub-clinical as none of the patients reported changes in olfactory function. The findings, however, demonstrate that olfaction can be modulated in a circumscribed area of the posterior (sub-) thalamic region. We propose that the impairment of the odor threshold with DBS is related to effects on an olfacto-motor loop, while disturbed odor discrimination may be related to effects of DBS on short-term memory. Copyright 2009 Elsevier Inc. All rights reserved.

  2. Improvement of Isolated Myoclonus Phenotype in Myoclonus Dystonia after Pallidal Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Ritesh Ramdhani

    2016-03-01

    Full Text Available Background: Myoclonus–dystonia is a condition that manifests predominantly as myoclonic jerks with focal dystonia. It is genetically heterogeneous with most mutations in the epsilon sarcoglycan gene (SGCE. In medically refractory cases, deep brain stimulation (DBS has been shown to provide marked sustainable clinical improvement, especially in SGCE-positive patients. We present two patients with myoclonus–dystonia (one SGCE positive and the other SGCE negative who have the isolated myoclonus phenotype and had DBS leads implanted in the bilateral globus pallidus internus (GPi. Methods: We review their longitudinal Unified Myoclonus Rating Scale scores along with their DBS programming parameters and compare them with published cases in the literature. Results: Both patients demonstrated complete amelioration of all aspects of myoclonus within 6–12 months after surgery. The patient with the SGCE-negative mutation responded just as well as the patient who was SGCE positive. High-frequency stimulation (130 Hz with amplitudes greater than 2.5 V provided therapeutic benefit. Discussion: This case series demonstrates that high frequency GPi-DBS is effective in treating isolated myoclonus in myoclonus–dystonia, regardless of the presence of SGCE mutation.

  3. Surgical neuroanatomy and programming in deep brain stimulation for obsessive compulsive disorder.

    Science.gov (United States)

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

    2014-06-01

    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 anatomic 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. 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 anatomic targets, programming details, and the outcomes. 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. 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 neuroanatomic 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. © 2013 International Neuromodulation Society.

  4. Subthalamic nucleus deep brain stimulation affects distractor interference in auditory working memory.

    Science.gov (United States)

    Camalier, Corrie R; Wang, Alice Y; McIntosh, Lindsey G; Park, Sohee; Neimat, Joseph S

    2017-03-01

    Computational and theoretical accounts hypothesize the basal ganglia play a supramodal "gating" role in the maintenance of working memory representations, especially in preservation from distractor interference. There are currently two major limitations to this account. The first is that supporting experiments have focused exclusively on the visuospatial domain, leaving questions as to whether such "gating" is domain-specific. The second is that current evidence relies on correlational measures, as it is extremely difficult to causally and reversibly manipulate subcortical structures in humans. To address these shortcomings, we examined non-spatial, auditory working memory performance during reversible modulation of the basal ganglia, an approach afforded by deep brain stimulation of the subthalamic nucleus. We found that subthalamic nucleus stimulation impaired auditory working memory performance, specifically in the group tested in the presence of distractors, even though the distractors were predictable and completely irrelevant to the encoding of the task stimuli. This study provides key causal evidence that the basal ganglia act as a supramodal filter in working memory processes, further adding to our growing understanding of their role in cognition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Quantitative methods for evaluating the efficacy of thalamic deep brain stimulation in patients with essential tremor.

    Science.gov (United States)

    Wastensson, Gunilla; Holmberg, Björn; Johnels, Bo; Barregard, Lars

    2013-01-01

    Deep brain stimulation (DBS) of the thalamus is a safe and efficient method for treatment of disabling tremor in patient with essential tremor (ET). However, successful tremor suppression after surgery requires careful selection of stimulus parameters. Our aim was to examine the possible use of certain quantitative methods for evaluating the efficacy of thalamic DBS in ET patients in clinical practice, and to compare these methods with traditional clinical tests. We examined 22 patients using the Essential Tremor Rating Scale (ETRS) and quantitative assessment of tremor with the stimulator both activated and deactivated. We used an accelerometer (CATSYS tremor Pen) for quantitative measurement of postural tremor, and a eurythmokinesimeter (EKM) to evaluate kinetic tremor in a rapid pointing task. The efficacy of DBS on tremor suppression was prominent irrespective of the method used. The agreement between clinical rating of postural tremor and tremor intensity as measured by the CATSYS tremor pen was relatively high (rs = 0.74). The agreement between kinetic tremor as assessed by the ETRS and the main outcome variable from the EKM test was low (rs = 0.34). The lack of agreement indicates that the EKM test is not comparable with the clinical test. Quantitative methods, such as the CATSYS tremor pen, could be a useful complement to clinical tremor assessment in evaluating the efficacy of DBS in clinical practice. Future studies should evaluate the precision of these methods and long-term impact on tremor suppression, activities of daily living (ADL) function and quality of life.

  6. The impact of Parkinson's disease and subthalamic deep brain stimulation on reward processing.

    Science.gov (United States)

    Evens, Ricarda; Stankevich, Yuliya; Dshemuchadse, Maja; Storch, Alexander; Wolz, Martin; Reichmann, Heinz; Schlaepfer, Thomas E; Goschke, Thomas; Lueken, Ulrike

    2015-08-01

    Due to its position in cortico-subthalamic and cortico-striatal pathways, the subthalamic nucleus (STN) is considered to play a crucial role not only in motor, but also in cognitive and motivational functions. In the present study we aimed to characterize how different aspects of reward processing are affected by disease and deep brain stimulation of the STN (DBS-STN) in patients with idiopathic Parkinson's disease (PD). We compared 33 PD patients treated with DBS-STN under best medical treatment (DBS-on, medication-on) to 33 PD patients without DBS, but optimized pharmacological treatment and 34 age-matched healthy controls. We then investigated DBS-STN effects using a postoperative stimulation-on/ -off design. The task set included a delay discounting task, a task to assess changes in incentive salience attribution, and the Iowa Gambling Task. The presence of PD was associated with increased incentive salience attribution and devaluation of delayed rewards. Acute DBS-STN increased risky choices in the Iowa Gambling Task under DBS-on condition, but did not further affect incentive salience attribution or the evaluation of delayed rewards. Findings indicate that acute DBS-STN affects specific aspects of reward processing, including the weighting of gains and losses, while larger-scale effects of disease or medication are predominant in others reward-related functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Differentiated effects of deep brain stimulation and medication on somatosensory processing in Parkinson's disease.

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    Sridharan, Kousik Sarathy; Højlund, Andreas; Johnsen, Erik Lisbjerg; Sunde, Niels Aagaard; Johansen, Lars Gottfried; Beniczky, Sándor; Østergaard, Karen

    2017-07-01

    Deep brain stimulation (DBS) and dopaminergic medication effectively alleviate the motor symptoms in Parkinson's disease (PD) patients, but their effects on the sensory symptoms of PD are still not well understood. To explore early somatosensory processing in PD, we recorded magnetoencephalography (MEG) from thirteen DBS-treated PD patients and ten healthy controls during median nerve stimulation. PD patients were measured during DBS-treated, untreated and dopaminergic-medicated states. We focused on early cortical somatosensory processing as indexed by N20m, induced gamma augmentation (31-45Hz and 55-100Hz) and induced beta suppression (13-30Hz). PD patients' motor symptoms were assessed by UPDRS-III. Using Bayesian statistics, we found positive evidence for differentiated effects of treatments on the induced gamma augmentation (31-45Hz) with highest gamma in the dopaminergic-medicated state and lowest in the DBS-treated and untreated states. In contrast, UPDRS-III scores showed beneficial effects of both DBS and dopaminergic medication on the patients' motor symptoms. Furthermore, treatments did not affect the amplitude of N20m. Our results suggest differentiated effects of DBS and dopaminergic medication on cortical somatosensory processing in PD patients despite consistent ameliorating effects of both treatments on PD motor symptoms. The differentiated effect suggests differences in the effect mechanisms of the two treatments. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

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

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    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.

  9. Investigating Irregularly Patterned Deep Brain Stimulation Signal Design Using Biophysical Models

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    Samantha Rose Summerson

    2015-06-01

    Full Text Available Parkinson’s disease (PD is a neurodegenerative disorder which follows from cell loss of dopaminergic neurons in the substantia nigra pars compacta (SNc, a nucleus in the basal ganglia (BG. Deep brain stimulation (DBS is an electrical therapy that modulates the pathological activity to treat the motor symptoms of PD. Although this therapy is currently used in clinical practice, the sufficient conditions for therapeutic efficacy are unknown. In this work we develop a model of critical motor circuit structures in the brain using biophysical cell models as the base components and then evaluate performance of different DBS signals in this model to perform comparative studies of their efficacy. Biological models are an important tool for gaining insights into neural function and, in this case, serve as effective tools for investigating innovative new DBS paradigms. Experiments were performed using the hemi-parkinsonian rodent model to test the same set of signals, verifying the obedience of the model to physiological trends. We show that antidromic spiking from DBS of the subthalamic nucleus (STN has a significant impact on cortical neural activity, which is frequency dependent and additionally modulated by the regularity of the stimulus pulse train used. Irregular spacing between stimulus pulses, where the amount of variability added is bounded, is shown to increase diversification of response of basal ganglia neurons and reduce entropic noise in cortical neurons, which may be fundamentally important to restoration of information flow in the motor circuit.

  10. Diffusion tensor imaging and neuromodulation: DTI as key technology for deep brain stimulation.

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    Coenen, Volker Arnd; Schlaepfer, Thomas E; Allert, Niels; Mädler, Burkhard

    2012-01-01

    Diffusion tensor imaging (DTI) is more than just a useful adjunct to invasive techniques like optogenetics which recently have tremendously influenced our understanding of the mechanisms of deep brain stimulation (DBS). In combination with other technologies, DTI helps us to understand which parts of the brain tissue are connected to others and which ones are truly influenced with neuromodulation. The complex interaction of DBS with the surrounding tissues-scrutinized with DTI-allows to create testable hypotheses that can explain network interactions. Those interactions are vital for our understanding of the net effects of neuromodulation. This work naturally was first done in the field of movement disorder surgery, where a lot of experience regarding therapeutic effects and only a short latency between initiation of neuromodulation and alleviation of symptoms exist. This chapter shows the journey over the past 10 years with first applications in DBS toward current research in affect regulating network balances and their therapeutic alterations with the neuromodulation technology. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Targeting the brain: considerations in 332 consecutive patients treated by deep brain stimulation (DBS) for severe neurological diseases.

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    Franzini, Angelo; Cordella, Roberto; Messina, Giuseppe; Marras, Carlo Efisio; Romito, Luigi Michele; Albanese, Alberto; Rizzi, Michele; Nardocci, Nardo; Zorzi, Giovanna; Zekaj, Edvin; Villani, Flavio; Leone, Massimo; Gambini, Orsola; Broggi, Giovanni

    2012-12-01

    Deep brain stimulation (DBS) extends the treatment of some severe neurological diseases beyond pharmacological and conservative therapy. Our experience extends the field of DBS beyond the treatment of Parkinson disease and dystonia, including several other diseases such as cluster headache and disruptive behavior. Since 1993, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan, 580 deep brain electrodes were implanted in 332 patients. The DBS targets include Stn, GPi, Voa, Vop, Vim, CM-pf, pHyp, cZi, Nacc, IC, PPN, and Brodmann areas 24 and 25. Three hundred patients are still available for follow-up and therapeutic considerations. DBS gave a new therapeutic chance to these patients affected by severe neurological diseases and in some cases controlled life-threatening pathological conditions, which would otherwise result in the death of the patient such as in status dystonicus, status epilepticus and post-stroke hemiballismus. The balance of DBS in severe neurological disease is strongly positive even if further investigations and studies are needed to search for new applications and refine the selection criteria for the actual indications.

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

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    William P Melega

    Full Text Available 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.

  13. Constant Current versus Constant Voltage Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease.

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    Ramirez de Noriega, Fernando; Eitan, Renana; Marmor, Odeya; Lavi, Adi; Linetzky, Eduard; Bergman, Hagai; Israel, Zvi

    2015-02-18

    Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established therapy for advanced Parkinson's disease (PD). Motor efficacy and safety have been established for constant voltage (CV) devices and more recently for constant current (CC) devices. CC devices adjust output voltage to provide CC stimulation irrespective of impedance fluctuation, while the current applied by CV stimulation depends on the impedance that may change over time. No study has directly compared the clinical effects of these two stimulation modalities. Objective: To compare the safety and clinical impact of CC STN DBS to CV STN DBS in patients with advanced PD 2 years after surgery. Methods: Patients were eligible for inclusion if they had undergone STN DBS surgery for idiopathic PD, had been implanted with a Medtronic Activa PC and if their stimulation program and medication had been stable for at least 1 year. This single-center trial was designed as a double-blind, randomized, prospective study with crossover after 2 weeks. Motor equivalence of the 2 modalities was confirmed utilizing part III of the Unified Parkinson's Disease Rating Scale (UPDRS). PD diaries and multiple subjective and objective evaluations of quality of life, depression, cognition and emotional processing were evaluated on both CV and on CC stimulation. Analysis using the paired t test with Bonferroni correction for multiple comparisons was performed to identify any significant difference between the stimulation modalities. Results: 8 patients were recruited (6 men, 2 women); 1 patient did not complete the study. The average age at surgery was 56.7 years (range 47-63). Disease duration at the time of surgery was 7.5 years (range 3-12). Patients were recruited 23.8 months (range 22.5-24) after surgery. At the postoperative study baseline, this patient group showed an average motor improvement of 69% (range 51-97) as measured by the change in UPDRS part III with stimulation alone. Levodopa equivalent

  14. Comparison of the Battery Life of Nonrechargeable Generators for Deep Brain Stimulation.

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    Helmers, Ann-Kristin; Lübbing, Isabel; Deuschl, Günther; Witt, Karsten; Synowitz, Michael; Mehdorn, Hubertus Maximilian; Falk, Daniela

    2017-11-03

    Nonrechargeable deep brain stimulation (DBS) generators must be replaced when the battery capacity is exhausted. Battery life depends on many factors and differs between generator models. A new nonrechargeable generator model replaced the previous model in 2008. Our clinical impression is that the earlier model had a longer battery life than the new one. We conducted this study to substantiate this. We determined the battery life of every DBS generator that had been implanted between 2005 and 2012 in our department for the treatment of Parkinson's disease, and compared the battery lives of the both devices. We calculated the current used by estimating the total electrical energy delivered (TEED) based on the stimulation parameters in use one year after electrode implantation. One hundred ninety-two patients were included in the study; 105 with the old and 86 with the new model generators. The mean battery life in the older model was significantly longer (5.44 ± 0.20 years) than that in the new model (4.44 ± 0.17 years) (p = 0.023). The mean TEED without impedance was 219.9 ± 121.5 mW * Ω in the older model and 145.1 ± 72.7 mW * Ω in the new one, which indicated significantly lower stimulation parameters in the new model (p = 0.00038). The battery life of the new model was significantly shorter than that of the previous model. A lower battery capacity is the most likely reason, since current consumption was similar in both groups. © 2017 International Neuromodulation Society.

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

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    Scott F Lempka

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

  16. Motor outcome and electrode location in deep brain stimulation in Parkinson's disease.

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    Koivu, Maija; Huotarinen, Antti; Scheperjans, Filip; Laakso, Aki; Kivisaari, Riku; Pekkonen, Eero

    2018-05-30

    To evaluate the efficacy and adverse effects of subthalamic deep brain stimulation (STN-DBS) in patients with advanced Parkinson's disease (PD) and the possible correlation between electrode location and clinical outcome. We retrospectively reviewed 87 PD-related STN-DBS operations at Helsinki University Hospital (HUH) from 2007 to 2014. The changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, Hoehn & Yahr stage, antiparkinson medication, and adverse effects were studied. We estimated the active electrode location in three different coordinate systems: direct visual analysis of MRI correlated to brain atlas, location in relation to the nucleus borders and location in relation to the midcommisural point. At 6 months after operation, both levodopa equivalent doses (LEDs; 35%, Wilcoxon signed-rank test = 0.000) and UPDRS part III scores significantly decreased (38%, Wilcoxon signed-rank test = 0.000). Four patients (5%) suffered from moderate DBS-related dysarthria. The generator and electrodes had to be removed in one patient due to infection (1%). Electrode coordinates in the three coordinate systems correlated well with each other. On the left side, more ventral location of the active contact was associated with greater LED decrease. STN-DBS improves motor function and enables the reduction in antiparkinson medication with an acceptable adverse effect profile. More ventral location of the active contact may allow stronger LED reduction. Further research on the correlation between contact location, clinical outcome, and LED reduction is warranted. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

  17. Comparison of bispectral index and entropy monitoring in patients undergoing internalisation of deep brain stimulators

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    Suparna Bharadwaj

    2016-01-01

    Full Text Available Introduction: Depth of anaesthesia (DOA monitors are shown to reduce the intra-operative dose of anaesthetic agents, provide haemodynamic stability and shorten emergence times. Electroencephalography (EEG based DOA monitors such as bispectral index (BIS and entropy have been calibrated and validated in healthy subjects. Hence the clinical effectiveness of these monitors may be affected when monitoring patients with neurological disorders (e.g., epilepsy, dystonia, dementia and Parkinson's disease. The aim of this study was to determine whether BIS and entropy correlate with each other and with clinical indices of DOA in patients with movement disorders under general anaesthesia (GA. Materials and Methods: We conducted a prospective, observational study in patients with movement disorders undergoing internalization of deep brain stimulators. All patients received standard GA with age-adjusted mean alveolar concentration (aaMAC of an inhalational agent between 0.7 and 1.1. BIS and entropy sensors were applied on the patient's left forehead. Data collected included clinical parameters and EEG-based DOA indices. Correlation analysis was performed between entropy, BIS and the clinical indices of DOA. Bland Altman analysis was performed to determine the agreement between BIS and entropy. Results: Thirty patients were studied (mean age was 58.4 ± 11 years, male: female 18:12 and weight 79.2 ± 17 kg. Indications for deep brain stimulation were Parkinson's disease (n = 25, essential tremors (n = 2 and dystonia (n = 3. There was a very strong positive correlation between BIS and response entropy (RE (r = 0.932 and BIS and state entropy (SE (r = 0.950 and a strong negative correlation among aaMAC and BIS, RE and SE with r values of −0.686, −0.788 and −0.732, respectively. However, there was no correlation between BIS, RE, SE and haemodynamic values. Conclusion: Our study showed that BIS and entropy perform well in patients with movement disorders

  18. Neuropsychological profile of Parkinson's disease patients selected for deep brain stimulation surgery

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    Flavia Amaral Machado

    Full Text Available ABSTRACT Background: Parkinson's disease (PD shows symptoms involving motor and non-motor complications, including cognitive and behavioral changes, such changes might to contraindicate deep brain stimulation surgery (DBS. Objective: The aim of study was to investigate the neuropsychological profile of patients with PD in a waiting list for DBS. Methods: The neuropsychological evaluation was held in 30 patients of the ISCMPA Movement Disorders Clinic, with surgical indication based on the criteria of the responsible neurologists, in the period of 12 months. Instruments used: MMSE, FAB, MoCA, BDI, Semantic Verbal Fluency, PDQ-39, PDSS; and the UPDRS and Hoehn-Yahr scale. Results: The patients were mostly male (66.7% with a mean age of 59.37 (SD 10.60 and disease duration 9.33 (SD 4.08. There was cognitive impairment in 56.7% of patients by FAB and 76.7% by MoCA. Conclusion: Even in the earliest stages of the disease, there is the incidence of non-motor symptoms, especially in those subjects who had an early onset of the disease.

  19. Aspects of oral communication in patients with Parkinson's disease submitted to Deep Brain Stimulation.

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    Cruz, Aline Nunes da; Beber, Bárbara Costa; Olchik, Maira Rozenfeld; Chaves, Márcia Lorena Fagundes; Rieder, Carlos Roberto de Mello; Dornelles, Sílvia

    2016-01-01

    Deep Brain Stimulation (DBS) has been satisfactorily used to control the cardinal motor symptoms of Parkinson's disease (PD), but little is known about its impact on communication. This study aimed to characterize the aspects of cognition, language, speech, voice, and self-perception in two patients with PD, pre- and post- DBS implant surgery. The patients were assessed using a cognitive screening test, a brief language evaluation, a self-declared protocol, and an analysis of the aspects of voice and speech, which was conducted by a specialized Speech-language Therapist who was blinded for the study. At the pre-surgery assessment, Case I showed impairment regarding the aspects of cognition, language and voice, whereas Case II showed impairment only with respect to the voice aspect. The post-surgery evaluation of the cases showed an opposite pattern of the effect of DBS after analysis of the communication data: Case I, who presented greater impairment before the surgery, showed improvement in some aspects; Case II, who presented lower communicative impairment before the surgery, showed worsening in other aspects. This study shows that DBS may influence different communication aspects both positively and negatively. Factors associated with the different effects caused by DBS on the communication of patients with PD need to be further investigated.

  20. Evaluation of electrode position in deep brain stimulation by image fusion (MRI and CT)

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    Barnaure, I.; Lovblad, K.O.; Vargas, M.I. [Geneva University Hospital, Department of Neuroradiology, Geneva 14 (Switzerland); Pollak, P.; Horvath, J.; Boex, C.; Burkhard, P. [Geneva University Hospital, Department of Neurology, Geneva (Switzerland); Momjian, S. [Geneva University Hospital, Department of Neurosurgery, Geneva (Switzerland); Remuinan, J. [Geneva University Hospital, Department of Radiology, Geneva (Switzerland)

    2015-09-15

    Imaging has an essential role in the evaluation of correct positioning of electrodes implanted for deep brain stimulation (DBS). Although MRI offers superior anatomic visualization of target sites, there are safety concerns in patients with implanted material; imaging guidelines are inconsistent and vary. The fusion of postoperative CT with preoperative MRI images can be an alternative for the assessment of electrode positioning. The purpose of this study was to assess the accuracy of measurements realized on fused images (acquired without a stereotactic frame) using a manufacturer-provided software. Data from 23 Parkinson's disease patients who underwent bilateral electrode placement for subthalamic nucleus (STN) DBS were acquired. Preoperative high-resolution T2-weighted sequences at 3 T, and postoperative CT series were fused using a commercially available software. Electrode tip position was measured on the obtained images in three directions (in relation to the midline, the AC-PC line and an AC-PC line orthogonal, respectively) and assessed in relation to measures realized on postoperative 3D T1 images acquired at 1.5 T. Mean differences between measures carried out on fused images and on postoperative MRI lay between 0.17 and 0.97 mm. Fusion of CT and MRI images provides a safe and fast technique for postoperative assessment of electrode position in DBS. (orig.)

  1. Secondary chronic cluster headache treated by posterior hypothalamic deep brain stimulation: first reported case.

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    Messina, Giuseppe; Rizzi, Michele; Cordella, Roberto; Caraceni, Augusto; Zecca, Ernesto; Bussone, Gennaro; Franzini, Angelo; Leone, Massimo

    2013-01-01

    Deep brain stimulation (DBS) of the posterior hypothalamus (pHyp) has been reported as an effective treatment for primary, drug-refractory and chronic cluster headache (CCH). We here describe the use of such a procedure for the treatment of secondary CCH due to a neoplasm affecting the soft tissues of the right hemiface. A 27-year-old man affected by infiltrating angiomyolipoma of the right hemiface who subsequently developed drug refractory homolateral CCH underwent DBS of the right pHyp region at the Fondazione IRCCS Istituto Nazionale Neurologico Carlo Besta. After surgery, the patient presented a significant reduction in frequency of pain bouts. However, because of a subsequent infection, the entire system was removed. After re-implantation of the system, successful outcome was observed at 2 years follow-up. This brief report shows the feasibility of pHyp DBS in secondary drug-refractory CCH syndromes; future reports are needed in order to confirm our positive result.

  2. Deep brain stimulation for movement disorders. Considerations on 276 consecutive patients.

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    Franzini, Angelo; Cordella, Roberto; Messina, Giuseppe; Marras, Carlo Efisio; Romito, Luigi Michele; Carella, Francesco; Albanese, Alberto; Rizzi, Michele; Nardocci, Nardo; Zorzi, Giovanna; Zekay, Edvin; Broggi, Giovanni

    2011-10-01

    The links between Stn DBS and advanced Parkinson disease, and between GPi DBS and dystonia are nearly universally accepted by the neurologists and neurosurgeons. Nevertheless, in some conditions, targets such as the ventral thalamus and the Zona Incerta may be considered to optimize the results and avoid the side effects. Positive and negative aspects of current DBS treatments justify the research of new targets, new stimulation programs and new hardware. Since 1993, at the Istituto Nazionale Neurologico "Carlo Besta" in Milan, 580 deep brain electrodes were implanted in 332 patients. 276 patients were affected by movement disorders. The DBS targets included Stn, GPi, Voa, Vop, Vim, CM-pf, cZi, IC. The long-term follow-up is reported and related to the chosen target. DBS gave a new therapeutic option to patients affected by severe movement disorders, and in some cases resolved life-threatening pathological conditions that would otherwise result in the death of the patient, such as in status dystonicus, and post-stroke hemiballismus. Nevertheless, the potential occurrence of severe complications still limit a wider use of DBS. At today, the use of DBS in severe movement disorders is strongly positive even if further investigations and studies are needed to unveil potential new applications, and to refine the selection criteria for the actual indications and targets. The experience of different targets may be useful to guide and tailor the target choice to the individual clinical condition.

  3. Impulse control behaviors and subthalamic deep brain stimulation in Parkinson disease.

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    Merola, Aristide; Romagnolo, Alberto; Rizzi, Laura; Rizzone, Mario Giorgio; Zibetti, Maurizio; Lanotte, Michele; Mandybur, George; Duker, Andrew P; Espay, Alberto J; Lopiano, Leonardo

    2017-01-01

    To determine the clinical and demographic correlates of persistent, remitting, and new-onset impulse control behaviors (ICBs) before and after subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD). We compared the pre- and post-surgical prevalence of ICBs, classified as impulse control disorders (ICD), dopamine dysregulation syndrome (DDS), and punding in 150 consecutive PD STN-DBS-treated patients and determined the association with motor, cognitive, neuropsychological, and neuropsychiatric endpoints. At baseline (before STN-DBS), ICBs were associated with younger age (p = 0.045) and male gender (85 %; p = 0.001). Over an average follow-up of 4.3 ± 2.1 years of chronic STN-DBS there was an overall trend for reduction in ICBs (from 17.3 to 12.7 %; p = 0.095) with significant improvement in hypersexuality (12-8.0 %; p = 0.047), gambling (10.7-5.3 %; p = 0.033), and DDS (4.7-0 %; p disorders; persistent ICB in those with obsessive-compulsive traits. PD-related ICBs exhibit a complex outcome after STN-DBS, with a tendency for overall reduction but with age, gender, dopaminergic therapy, and neuropsychiatric features exerting independent effects.

  4. Experience with "Fast track" postoperative care after deep brain stimulation surgery.

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    Martín, Nuria; Valero, Ricard; Hurtado, Paola; Gracia, Isabel; Fernández, Carla; Rumià, Jordi; Valldeoriola, Francesc; Carrero, Enrique J; Tercero, Francisco Javier; de Riva, Nicolás; Fàbregas, Neus

    A 24-h-stay in the post-anesthesia care unit (PACU) is a common postoperative procedure after deep brain stimulation surgery (DBS). We evaluated the impact of a fast-track (FT) postoperative care protocol. An analysis was performed on all patients who underwent DBS in 2 periods: 2006, overnight monitored care (OMC group), and 2007-2013, FT care (FT group). The study included 19 patients in OMC and 95 patients in FT. Intraoperative complications occurred in 26.3% patients in OMC vs. 35.8% in FT. Post-operatively, one patient in OMC developed hemiparesis, and agitation in 2 patients. In FT, two patients with intraoperative hemiparesis were transferred to the ICU. While on the ward, 3 patients from the FT developed hemiparesis, two of them 48h after the procedure. Thirty eight percent of FT had an MRI scan, while the remaining 62% and all patients of OMC had a CT-scan performed on their transfer to the ward. One patient in OMC had a subthalamic hematoma. Two patients in FT had a pallidal hematoma, and 3 a bleeding along the electrode. A FT discharge protocol is a safe postoperative care after DBS. There are a small percentage of complications after DBS, which mainly occur within the first 6h. Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Cognitive outcome and reliable change indices two years following bilateral subthalamic nucleus deep brain stimulation.

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    Williams, Amy E; Arzola, Gladys Marina; Strutt, Adriana M; Simpson, Richard; Jankovic, Joseph; York, Michele K

    2011-06-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) is currently the treatment of choice for medication-resistant levodopa-related motor complications in patients with Parkinson's disease (PD). While STN-DBS often results in meaningful motor improvements, consensus regarding long-term neuropsychological outcome continues to be debated. We assessed the cognitive outcomes of 19 STN-DBS patients compared to a group of 18 medically-managed PD patients on a comprehensive neuropsychological battery at baseline and two years post-surgery. Patients did not demonstrate changes in global cognitive functioning on screening measures. However, neuropsychological results revealed impairments in nonverbal recall, oral information processing speed, and lexical and semantic fluency in STN-DBS patients compared to PD controls 2 years post-surgery in these preliminary analyses. Additionally, reliable change indices revealed that approximately 50% of STN-DBS patients demonstrated significant declines in nonverbal memory and oral information processing speed compared to 25-30% of PD controls, and 26% of STN-DBS patients declined on lexical fluency compared to 11% of PD patients. Approximately 30% of both groups declined on semantic fluency. The number of STN-DBS patients who converted to dementia 2 years following surgery was not significantly different from the PD participants (32% versus 16%, respectively). Our results suggest that neuropsychological evaluations may identify possible mild cognitive changes following surgery. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Subthalamic deep brain stimulation modulates conscious perception of sensory function in Parkinson's disease.

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    Cury, Rubens G; Galhardoni, Ricardo; Teixeira, Manoel J; Dos Santos Ghilardi, Maria G; Silva, Valquiria; Myczkowski, Martin L; Marcolin, Marco A; Barbosa, Egberto R; Fonoff, Erich T; Ciampi de Andrade, Daniel

    2016-12-01

    Subthalamic deep brain stimulation (STN-DBS) is used to treat refractory motor complications in Parkinson disease (PD), but its effects on nonmotor symptoms remain uncertain. Up to 80% of patients with PD may have pain relief after STN-DBS, but it is unknown whether its analgesic properties are related to potential effects on sensory thresholds or secondary to motor improvement. We have previously reported significant and long-lasting pain relief after DBS, which did not correlate with motor symptomatic control. Here we present secondary data exploring the effects of DBS on sensory thresholds in a controlled way and have explored the relationship between these changes and clinical pain and motor improvement after surgery. Thirty-seven patients were prospectively evaluated before STN-DBS and 12 months after the procedure compared with healthy controls. Compared with baseline, patients with PD showed lower thermal and mechanical detection and higher cold pain thresholds after surgery. There were no changes in heat and mechanical pain thresholds. Compared with baseline values in healthy controls, patients with PD had higher thermal and mechanical detection thresholds, which decreased after surgery toward normalization. These sensory changes had no correlation with motor or clinical pain improvement after surgery. These data confirm the existence of sensory abnormalities in PD and suggest that STN-DBS mainly influenced the detection thresholds rather than painful sensations. However, these changes may depend on the specific effects of DBS on somatosensory loops with no correlation to motor or clinical pain improvement.

  7. Personality Changes after Deep Brain Stimulation in Parkinson’s Disease

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    Uyen Pham

    2015-01-01

    Full Text Available Objectives. Deep brain stimulation of the subthalamic nucleus (STN-DBS is a recognized therapy that improves motor symptoms in advanced Parkinson’s disease (PD. However, little is known about its impact on personality. To address this topic, we have assessed personality traits before and after STN-DBS in PD patients. Methods. Forty patients with advanced PD were assessed with the Temperament and Character Inventory (TCI: the Urgency, Premeditation, Perseverance, Sensation Seeking impulsive behaviour scale (UPPS, and the Neuroticism and Lie subscales of the Eysenck Personality Questionnaire (EPQ-N, EPQ-L before surgery and after three months of STN-DBS. Collateral information obtained from the UPPS was also reported. Results. Despite improvement in motor function and reduction in dopaminergic dosage patients reported lower score on the TCI Persistence and Self-Transcendence scales, after three months of STN-DBS, compared to baseline (P=0.006; P=0.024. Relatives reported significantly increased scores on the UPPS Lack of Premeditation scale at follow-up (P=0.027. Conclusion. STN-DBS in PD patients is associated with personality changes in the direction of increased impulsivity.

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

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    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.

  9. Toward sophisiticated basal ganglia neuromodulation: review on basal gaglia deep brain stimulation

    Science.gov (United States)

    Da Cunha, Claudio; Boschen, Suelen L.; Gómez-A, Alexander; Ross, Erika K.; Gibson, William S. J.; Min, Hoon-Ki; Lee, Kendall H.; Blaha, Charles D.

    2015-01-01

    This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson’s disease, Huntington’s disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. PMID:25684727

  10. Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation.

    Science.gov (United States)

    Da Cunha, Claudio; Boschen, Suelen L; Gómez-A, Alexander; Ross, Erika K; Gibson, William S J; Min, Hoon-Ki; Lee, Kendall H; Blaha, Charles D

    2015-11-01

    This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Deep brain stimulation and responsiveness of the Persian version of Parkinson's disease questionnaire with 39-items.

    Science.gov (United States)

    Shahidi, Gholam Ali; Ghaempanah, Zeinab; Khalili, Yasaman; Nojomi, Marzieh

    2014-10-06

    Assessment of quality-of-life (QOF) as an outcome measure after deep brain stimulation (DBS) surgery in patients with Parkinson's disease (PD) need a valid, reliable and responsive instrument. The aim of the current study was to determine responsiveness of validated Persian version of PD questionnaire with 39-items (PDQ-39) after DBS surgery in patients with PD. Eleven patients with PD, who were candidate for DBS operation between May 2012 and June 2013 were assessed. PDQ-39 and short-form questionnaire with 36-items (SF-36) were used. To assess responsiveness of PDQ-39 standardized response mean (SRM) was used. Mean age was 51.8 (8.8) and all of the patients, but just one were male (10 patients). Mean duration of the disease was 8.7 (2.1) years. Eight patients were categorized as moderate using Hoehn and Yahr (H and Y) classification. All patients had a better H and Y score compared with the baseline evaluation (3.09 vs. 0.79). The amount of SRM was above 0.70 for all domains means a large responsiveness for PDQ-39. Persian version of PDQ-39 has an acceptable responsiveness and could be used to assess as an outcome measure to evaluate the effect of therapies on PD.

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

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    Nelson Hwynn

    2011-01-01

    Full Text Available 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, =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, =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.

  13. Clinical, neuropsychological, and pre-stimulus dorsomedial thalamic nucleus electrophysiological data in deep brain stimulation patients

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    Catherine M. Sweeney-Reed

    2016-09-01

    Full Text Available The data presented here comprise clinical, neuropsychological, and intrathalamic electrophysiological data from 7 patients with pharmacoresistant focal epilepsy and are related to the article “Pre-stimulus thalamic theta power predicts human memory formation” C.M. Sweeney-Reed, T. Zaehle, J. Voges, F.C. Schmitt, L. Buentjen, K. Kopitzki, et al. (2016 [1]. The patients participated in a memory paradigm after receiving electrodes implanted in the DMTN due to the surgical approach taken in electrode insertion for deep brain stimulation of the anterior thalamic nucleus. Epilepsy duration and pre-operative neuropsychological tests provide an indication of the profile of patients receiving intrathalamic electrode implantation and the memory capabilities in such a patient group. The electrophysiological data were recorded from the right DMTN preceding stimulus presentation during intentional memory encoding. The patients viewed a series of photographic scenes, which they judged as indoors or outdoors. The 900 ms epochs prior to stimulus presentation were labeled as preceding successful or unsuccessful subsequent memory formation according to a subsequent memory test for the items. The difference between theta power preceding successful versus unsuccessful subsequent memory formation is shown against time for each patient individually. Keywords: Memory encoding, Dorsomedial thalamic nucleus, Pre-stimulus theta

  14. Anaesthetic management and perioperative complications during deep brain stimulation surgery: Our institutional experience

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    Renu Bala

    2016-01-01

    Full Text Available Background: Deep brain stimulation (DBS surgery is an established therapeutic option for alleviating movement disorders. It represents unique challenges for anaesthesiologists. We retrospectively reviewed the patients, who underwent this surgery at our institution, to study anaesthetic management and perioperative complications. Materials and Methods: After taking approval from the Institutional Ethics Committee, medical, surgical and anaesthesia records of 67 patients who were admitted to undergo DBS surgery during 11 years period (January 2001 to December 2011 were retrieved and reviewed. Sixty-five patients underwent the procedure. Various anaesthetic events and perioperative complications were noted and appropriate statistical analysis was carried out to analyse the data. Results: Electrode placement under monitored anaesthesia care (MAC was the most commonly used technique (86% of patients. Intra-operative complications occurred in 16 patients (24% whereas post-operative complication occurred in 10 patients (15.4%. There was one mortality. Though age >60 years and American Society of Anesthesiologists status > II were found to be the risk factors for post-operative complications in the bivariate analysis; they were not significant in multivariate analysis. Conclusions: We report our experience of DBS surgery, which was performed using MAC in majority of patients, though general anaesthesia is also feasible. Further prospective randomised studies comprising large number of patients are warranted to corroborate our finding and to find out the most suitable sedative agent.

  15. Outcomes of Interventional-MRI Versus Microelectrode Recording-Guided Subthalamic Deep Brain Stimulation

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    Philip S. Lee

    2018-04-01

    Full Text Available In deep brain stimulation (DBS of the subthalamic nucleus (STN for Parkinson’s disease (PD, there is debate concerning the use of neuroimaging alone to confirm correct anatomic placement of the DBS lead into the STN, versus the use of microelectrode recording (MER to confirm functional placement. We performed a retrospective study of a contemporaneous cohort of 45 consecutive patients who underwent either interventional-MRI (iMRI or MER-guided DBS lead implantation. We compared radial lead error, motor and sensory side effect, and clinical benefit programming thresholds, and pre- and post-operative unified PD rating scale scores, and levodopa equivalent dosages. MER-guided surgery was associated with greater radial error compared to the intended target. In general, side effect thresholds during initial programming were slightly lower in the MER group, but clinical benefit thresholds were similar. No significant difference in the reduction of clinical symptoms or medication dosage was observed. In summary, iMRI lead implantation occurred with greater anatomic accuracy, in locations demonstrated to be the appropriate functional region of the STN, based on the observation of similar programming side effect and benefit thresholds obtained with MER. The production of equivalent clinical outcomes suggests that surgeon and patient preference can be used to guide the decision of whether to recommend iMRI or MER-guided DBS lead implantation to appropriate patients with PD.

  16. Deep brain stimulation in Gilles de la Tourette syndrome: killing several birds with one stone?

    Science.gov (United States)

    Hartmann, Andreas

    2016-01-01

    In patients with severe, treatment-refractory Gilles de la Tourette syndrome (GTS), deep brain stimulation (DBS) of various targets has been increasingly explored over the past 15 years. The multiplicity of surgical targets is intriguing and may be partly due to the complexity of GTS, specifically the various and frequent associated psychiatric comorbidities in this disorder. Thus, the target choice may not only be aimed at reducing tics but also comorbidities. While this approach is laudable, it also carries the risk to increase confounding factors in DBS trials and patient evaluation. Moreover, I question whether DBS should really be expected to alleviate multiple symptoms at a time. Rather, I argue that tic reduction should remain our primary objective in severe GTS patients and that this intervention may subsequently allow an improved psychotherapeutic and/or pharmacological treatment of comorbidities. Thus, I consider DBS in GTS not as a single solution for all our patients’ ailments but as a stepping stone to improved holistic care made possible by tic reduction. PMID:27746910

  17. Deep brain stimulation in tourette syndrome: a description of 3 patients with excellent outcome.

    Science.gov (United States)

    Savica, Rodolfo; Stead, Matt; Mack, Kenneth J; Lee, Kendall H; Klassen, Bryan T

    2012-01-01

    Tourette syndrome (TS) is a complex neuropsychiatric disorder often starting in childhood and characterized by the presence of multiple motor and vocal tics and psychiatric comorbidities. Patients with TS usually respond to medical treatment, and the condition often improves during adolescence; however, surgery has been considered a possible approach for the subset of patients with ongoing medically refractory disease. Ablative procedures have been associated with unsatisfactory results and major adverse effects, prompting trials of deep brain stimulation (DBS) as an alternative therapy. It remains unclear which of the various nuclear targets is most effective in TS. We describe 3 patients with TS who underwent DBS targeting the bilateral thalamic centromedian/parafascicular complex (CM/Pf) with an excellent clinical outcome. At 1-year follow-up, the mean reduction in the total Yale Global Tic Severity Scale score in the 3 patients was 70% (range, 60%-80%).Our study further supports the role of the CM/Pf DBS target in medically intractable TS. Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  18. Apathy following Bilateral Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease: A Meta-Analysis

    Science.gov (United States)

    Zhang, Xiaona

    2018-01-01

    Bilateral deep brain stimulation of subthalamic nucleus (STN-DBS) has proven effective in improving motor symptoms in Parkinson's disease (PD) patients. However, psychiatric changes after surgery are controversial. In this study, we specifically analyzed apathy following bilateral STN-DBS in PD patients using a meta-analysis. Relevant articles utilized for this study were obtained through literature search on PubMed, ScienceDirect, and Embase databases. The articles included were those contained both pre- and postsurgery apathy data acquired using the Starkstein Apathy Scale or Apathy Evaluation Scale with patient follow-up of at least three months. A total of 9 out of 86 articles were included in our study through this strict screening process. Standardized mean difference (SMD), that is, Cohen's d, with a 95% confidence interval (CI) was calculated to show the change. We found a significant difference between the presurgery stage and the postsurgery stage scores (SMD = 0.35, 95% CI: 0.17∼0.52, P < 0.001). STN-DBS seems to relatively worsen the condition of apathy, which may result from both the surgery target (subthalamic nucleus) and the reduction of dopaminergic medication. Further studies should focus on the exact mechanisms of possible postoperative apathy in the future.

  19. Neuroversion: using electroconvulsive therapy as a bridge to deep brain stimulation implantation.

    Science.gov (United States)

    Williams, Nolan R; Sahlem, Greg; Pannu, Jaspreet; Takacs, Istvan; Short, Baron; Revuelta, Gonzalo; George, Mark S

    2017-02-01

    Parkinson's disease (PD) is a movement disorder with significant neuropsychiatric comorbidities. Electroconvulsive therapy (ECT) is effective in treating these neuropsychiatric symptoms; however, clinicians are reluctant to use ECT in patients with deep brain stimulation (DBS) implantations for fear of damaging the device, as well as potential cognitive side effects. Right unilateral ultra-brief pulse (RUL UBP) ECT has a more favorable cognitive side-effect profile yet has never been reported in PD patients with DBS implants. We present a case series of three patients with a history of PD that all presented with psychiatric decompensation immediately prior to planned DBS surgery. All three patients had DBS electrode(s) in place at the time and an acute course of ECT was utilized in a novel method to "bridge" these individuals to neurosurgery. The patients all experienced symptom resolution (psychosis and/or depression and/or anxiety) without apparent cognitive side effects. This case series not only illustrates that right unilateral ultra-brief pulse can be utilized in patients with DBS electrodes but also illustrates that this intervention can be utilized as a neuromodulatory "bridge", where nonoperative surgical candidates with unstable psychiatric symptoms can be converted to operative candidates in a manner similar to electrical cardioversion.

  20. Deep Brain Stimulation Can Preserve Working Status in Parkinson’s Disease

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    Gabriella Deli

    2015-01-01

    Full Text Available Objectives. Our investigation aimed at evaluating if bilateral subthalamic deep brain stimulation (DBS could preserve working capability in Parkinson’s disease (PD. Materials. We reviewed the data of 40 young (<60 year-old PD patients who underwent DBS implantation and had at least 2 years of follow-up. Patients were categorized based on their working capability at time of surgery: “active job” group (n=20 and “no job” group (n=20. Baseline characteristics were comparable. Quality of life (EQ-5D and presence of active job were evaluated preoperatively and 2 years postoperatively. Results. Although similar (approximately 50% improvement was achieved in the severity of motor and major nonmotor symptoms in both groups, the postoperative quality of life was significantly better in the “active job” group (0.687 versus 0.587, medians, p<0.05. Majority (80% of “active job” group members were able to preserve their job 2 years after the operation. However, only a minimal portion (5% of the “no job” group members was able to return to the world of active employees (p<0.01. Conclusions. Although our study has several limitations, our results suggest that in patients with active job the appropriately “early” usage of DBS might help preserve working capability and gain higher improvement in quality of life.

  1. Self-guided training for deep brain stimulation planning using objective assessment.

    Science.gov (United States)

    Holden, Matthew S; Zhao, Yulong; Haegelen, Claire; Essert, Caroline; Fernandez-Vidal, Sara; Bardinet, Eric; Ungi, Tamas; Fichtinger, Gabor; Jannin, Pierre

    2018-04-04

    Deep brain stimulation (DBS) is an increasingly common treatment for neurodegenerative diseases. Neurosurgeons must have thorough procedural, anatomical, and functional knowledge to plan electrode trajectories and thus ensure treatment efficacy and patient safety. Developing this knowledge requires extensive training. We propose a training approach with objective assessment of neurosurgeon proficiency in DBS planning. To assess proficiency, we propose analyzing both the viability of the planned trajectory and the manner in which the operator arrived at the trajectory. To improve understanding, we suggest a self-guided training course for DBS planning using real-time feedback. To validate the proposed measures of proficiency and training course, two experts and six novices followed the training course, and we monitored their proficiency measures throughout. At baseline, experts planned higher quality trajectories and did so more efficiently. As novices progressed through the training course, their proficiency measures increased significantly, trending toward expert measures. We developed and validated measures which reliably discriminate proficiency levels. These measures are integrated into a training course, which quantitatively improves trainee performance. The proposed training course can be used to improve trainees' proficiency, and the quantitative measures allow trainees' progress to be monitored.

  2. PyDBS: an automated image processing workflow for deep brain stimulation surgery.

    Science.gov (United States)

    D'Albis, Tiziano; Haegelen, Claire; Essert, Caroline; Fernández-Vidal, Sara; Lalys, Florent; Jannin, Pierre

    2015-02-01

    Deep brain stimulation (DBS) is a surgical procedure for treating motor-related neurological disorders. DBS clinical efficacy hinges on precise surgical planning and accurate electrode placement, which in turn call upon several image processing and visualization tasks, such as image registration, image segmentation, image fusion, and 3D visualization. These tasks are often performed by a heterogeneous set of software tools, which adopt differing formats and geometrical conventions and require patient-specific parameterization or interactive tuning. To overcome these issues, we introduce in this article PyDBS, a fully integrated and automated image processing workflow for DBS surgery. PyDBS consists of three image processing pipelines and three visualization modules assisting clinicians through the entire DBS surgical workflow, from the preoperative planning of electrode trajectories to the postoperative assessment of electrode placement. The system's robustness, speed, and accuracy were assessed by means of a retrospective validation, based on 92 clinical cases. The complete PyDBS workflow achieved satisfactory results in 92 % of tested cases, with a median processing time of 28 min per patient. The results obtained are compatible with the adoption of PyDBS in clinical practice.

  3. Design of a Small Modified Minkowski Fractal Antenna for Passive Deep Brain Stimulation Implants

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    Sara Manafi

    2014-01-01

    Full Text Available A small planar modified Minkowski fractal antenna is designed and simulated in dual frequency bands (2.4 and 5.8 GHz for wireless energy harvesting by deep brain stimulation (DBS devices. The designed antenna, physically being confined inside a miniaturized structure, can efficiently convert the wireless signals in dual ISM frequency bands to the energy source to recharge the DBS battery or power the pulse generator directly. The performance metrics such as the return loss, the specific absorption rate (SAR, and the radiation pattern within skin and muscle-fat-skin tissues are evaluated for the designed antenna. The gain of the proposed antenna is 3.2 dBi at 2.4 GHz and 4.7 dBi at 5.8 GHz; also the averaged SAR of the antenna in human body tissue is found to be well below the legally allowed limit at both frequency bands. The link budget shows the received power at the distance of 25 cm at 2.4 GHz and 5.8 GHz are around 0.4 mW and 0.04 mW, which can empower the DBS implant. The large operational bandwidth, the physical compactness, and the efficiency in wireless signal reception make this antenna suitable in being used in implanted biomedical devices such as DBS pulse generators.

  4. Exploring risk factors for stuttering development in Parkinson disease after deep brain stimulation.

    Science.gov (United States)

    Picillo, Marina; Vincos, Gustavo B; Sammartino, Francesco; Lozano, Andres M; Fasano, Alfonso

    2017-05-01

    Stuttering is a speech disorder with disruption of verbal fluency, occasionally present in Parkinson's disease (PD). PD co-incident stuttering may either worsen or improve after Deep Brain Stimulation (DBS). Sixteen out of 453 PD patients (3.5%) exhibited stuttering after DBS (PD-S) and were compared with a group of patients without stuttering (PD-NS) using non-parametric statistics. After DBS, stuttering worsened in 3 out of 4 patients with co-incidental stuttering. Most PD-S underwent subthalamic (STN) DBS, but 4 were implanted in the globus pallidus (GPi). Nine out of 16 PD-S (56.3%) reported a positive familial history for stuttering compared to none of the PD-NS. PD-S were mainly male (81.3%) with slight worse motor features compared to PD-NS. Herein, we describe a group of PD patients developing stuttering after DBS and report the presence of a positive familial history for stuttering as the most relevant risk factor, suggesting a possible underlying genetic cause. The fact that stuttering occurred after either STN or GPi DBS is an argument against the impact of medication reduction on stuttering. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Mental Health-Related Healthcare Use Following Bilateral Deep Brain Stimulation For Parkinson's Disease.

    Science.gov (United States)

    Westbay, Lauren C; Cao, Lishan; Burnett-Zeigler, Inger; Reizine, Natalie; Barton, Brandon; Ippolito, Dolores; Weaver, Frances M; Stroupe, Kevin T

    2015-01-01

    The subthalamic nucleus (STN) and the globus pallidus internus (GPi) are both effective targets for deep brain stimulation (DBS) to relieve motor symptoms of Parkinson's disease. However, studies have reported varied effects on mental health-related adverse events and depressed mood following DBS. The current observational study sought to compare mental health healthcare utilization and costs for three years following STN or GPi DBS. For a cohort of Veterans (n = 161) with Parkinson's disease who participated in a larger multi-site randomized trial, we compared mental health outpatient visits, medication use, inpatient admissions, and associated costs by DBS target site (STN vs. GPi). Neither group nor time differences were significant for mental health outpatient or inpatient utilization following DBS. Overall costs associated with mental health visits and medications did not differ by time or by group. However, the percentage of patients with mental health medication use increased in the 6-month and 6 to 12 month periods post-surgery. The STN group had significantly greater increase in medication use at 6 to 12 months post-surgery compared to the GPi group (p use following surgery, this study suggests that mental health healthcare use and costs are stable over time and similar between DBS targets. Prior research findings of mental health-related adverse events and mood following DBS did not translate to greater mental health service utilization in our cohort. The changes seen in the year following surgery may reflect temporary adjustments with stabilization over time.

  6. Modulating affect, cognition and behavior – prospects of deep brain stimulation for treatment resistant psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Thomas E. Schlaepfer

    2011-06-01

    Full Text Available Most patients suffering from psychiatric disorders respond to combina-tions of psycho- and psychopharmacotherapy, however there are patients who profit little if anything even after many years of treatment. Since about a decade different modalities of targeted neuromodulation – among them most prominently – Deep Brain Stimulation (DBS - are being actively researched as putative approaches to very treatment resistant forms of those disorders. Recently, promising pilot data have been re-ported both for Major Depression (MD and Obsessive-Compulsive Disor-der (OCD. Given the fact that patients studied had been treated unsuc-cessfully for many years renders these findings remarkable. Remarkable is the fact, that in case of the long-term studies underway for MD, patients show a stable response. This gives hope to a substantial percentage of therapy-resistant psychiatric patients requiring new therapy approaches. There are no fundamental ethic objections to its use in psychiatric disor-ders, but until substantial clinical data is available, mandatory standards are needed. DBS is a unique and very promising method for the treat-ment of therapy-resistant psychiatric patients. The method allows ma-nipulating pathological neuronal networks in a very precise way.

  7. Oscillatory neural representations in the sensory thalamus predict neuropathic pain relief by deep brain stimulation.

    Science.gov (United States)

    Huang, Yongzhi; Green, Alexander L; Hyam, Jonathan; Fitzgerald, James; Aziz, Tipu Z; Wang, Shouyan

    2018-01-01

    Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Square biphasic pulse deep brain stimulation for essential tremor: The BiP tremor study.

    Science.gov (United States)

    De Jesus, Sol; Almeida, Leonardo; Shahgholi, Leili; Martinez-Ramirez, Daniel; Roper, Jaimie; Hass, Chris J; Akbar, Umer; Wagle Shukla, Aparna; Raike, Robert S; Okun, Michael S

    2018-01-01

    Conventional deep brain stimulation (DBS) utilizes regular, high frequency pulses to treat medication-refractory symptoms in essential tremor (ET). Modifications of DBS pulse shape to achieve improved effectiveness is a promising approach. The current study assessed the safety, tolerability and effectiveness of square biphasic pulse shaping as an alternative to conventional ET DBS. This pilot study compared biphasic pulses (BiP) versus conventional DBS pulses (ClinDBS). Eleven ET subjects with clinically optimized ventralis intermedius nucleus DBS were enrolled. Objective measures were obtained over 3 h while ON BiP stimulation. There was observed benefit in the Fahn-Tolosa Tremor Rating Scale (TRS) for BiP conditions when compared to the DBS off condition and to ClinDBS setting. Total TRS scores during the DBS OFF condition (28.5 IQR = 24.5-35.25) were significantly higher than the other time points. Following active DBS, TRS improved to (20 IQR = 13.8-24.3) at ClinDBS setting and to (16.5 IQR = 12-20.75) at the 3 h period ON BiP stimulation (p = 0.001). Accelerometer recordings revealed improvement in tremor at rest (χ 2  = 16.1, p = 0.006), posture (χ 2  = 15.9, p = 0.007) and with action (χ 2  = 32.1, p=<0.001) when comparing median total scores at ClinDBS and OFF DBS conditions to 3 h ON BiP stimulation. There were no adverse effects and gait was not impacted. BiP was safe, tolerable and effective on the tremor symptoms when tested up to 3 h. This study demonstrated the feasibility of applying a novel DBS waveform in the clinic setting. Larger prospective studies with longer clinical follow-up will be required. Copyright © 2017. Published by Elsevier Ltd.

  9. Non-stationary discharge patterns in motor cortex under subthalamic nucleus deep brain stimulation.

    Science.gov (United States)

    Santaniello, Sabato; Montgomery, Erwin B; Gale, John T; Sarma, Sridevi V

    2012-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) directly modulates the basal ganglia (BG), but how such stimulation impacts the cortex upstream is largely unknown. There is evidence of cortical activation in 6-hydroxydopamine (OHDA)-lesioned rodents and facilitation of motor evoked potentials in Parkinson's disease (PD) patients, but the impact of the DBS settings on the cortical activity in normal vs. Parkinsonian conditions is still debated. We use point process models to analyze non-stationary activation patterns and inter-neuronal dependencies in the motor and sensory cortices of two non-human primates during STN DBS. These features are enhanced after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes a consistent PD-like motor impairment, while high-frequency (HF) DBS (i.e., ≥100 Hz) strongly reduces the short-term patterns (period: 3-7 ms) both before and after MPTP treatment, and elicits a short-latency post-stimulus activation. Low-frequency DBS (i.e., ≤50 Hz), instead, has negligible effects on the non-stationary features. Finally, by using tools from the information theory [i.e., receiver operating characteristic (ROC) curve and information rate (IR)], we show that the predictive power of these models is dependent on the DBS settings, i.e., the probability of spiking of the cortical neurons (which is captured by the point process models) is significantly conditioned on the timely delivery of the DBS input. This dependency increases with the DBS frequency and is significantly larger for high- vs. low-frequency DBS. Overall, the selective suppression of non-stationary features and the increased modulation of the spike probability suggest that HF STN DBS enhances the neuronal activation in motor and sensory cortices, presumably because of reinforcement mechanisms, which perhaps involve the overlap between feedback antidromic and feed-forward orthodromic responses along the BG-thalamo-cortical loop.

  10. Skin complications in deep brain stimulation for Parkinson's disease: frequency, time course, and risk factors.

    Science.gov (United States)

    Sixel-Döring, Friederike; Trenkwalder, Claudia; Kappus, Christoph; Hellwig, Dieter

    2010-02-01

    Deep brain stimulation (DBS) has been recognized as an efficacious treatment for movement disorders. Its beneficial effects however may be lost due to skin complications such as erosions or infections over the implanted foreign material. We sought to document skin complications in the entire Parkinson's disease patient population who received a DBS system at the Marburg/Kassel implantation centre since the start of our DBS program in January 2002 to analyze frequency, time course, and possible risk factors. We investigated 85 consecutive patients with Parkinson's disease (PD) from a single center/single surgeon DBS series for the occurrence of skin complications and analyzed localization, time course, and possible risk factors. Mean follow-up was 3 years (range 1-7 years). In total, 21/85 patients (24.7%) suffered a total of 30 single skin complications. Sixty percent of all incidents occurred within the first post-operative year. Forty percent of all incidents occurred later than the first year following primary implantation. Complications involved the burr hole cap in 37%, the course of the cables in 33%, and the impulse generator (IPG) site in 30%. Six of 21 patients suffered recurring skin complications. Eight patients permanently lost their DBS system. Factor analysis for age, gender, disease duration, disease severity, the incidence of hypertension or diabetes as well as a 2-day period with externalized electrodes for continuous test stimulation did not have any statistically significant impact on skin complications. We conclude that (1) PD patients have a risk for skin complications after DBS as long as the system remains in situ and (2) there are at present no identifiable risk factors for skin complications after DBS, other than PD itself.

  11. Deep brain stimulation for Parkinson's disease: defining the optimal location within the subthalamic nucleus.

    Science.gov (United States)

    Bot, Maarten; Schuurman, P Richard; Odekerken, Vincent J J; Verhagen, Rens; Contarino, Fiorella Maria; De Bie, Rob M A; van den Munckhof, Pepijn

    2018-05-01

    Individual motor improvement after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease (PD) varies considerably. Stereotactic targeting of the dorsolateral sensorimotor part of the STN is considered paramount for maximising effectiveness, but studies employing the midcommissural point (MCP) as anatomical reference failed to show correlation between DBS location and motor improvement. The medial border of the STN as reference may provide better insight in the relationship between DBS location and clinical outcome. Motor improvement after 12 months of 65 STN DBS electrodes was categorised into non-responding, responding and optimally responding body-sides. Stereotactic coordinates of optimal electrode contacts relative to both medial STN border and MCP served to define theoretic DBS 'hotspots'. Using the medial STN border as reference, significant negative correlation (Pearson's correlation -0.52, P<0.01) was found between the Euclidean distance from the centre of stimulation to this DBS hotspot and motor improvement. This hotspot was located at 2.8 mm lateral, 1.7 mm anterior and 2.5 mm superior relative to the medial STN border. Using MCP as reference, no correlation was found. The medial STN border proved superior compared with MCP as anatomical reference for correlation of DBS location and motor improvement, and enabled defining an optimal DBS location within the nucleus. We therefore propose the medial STN border as a better individual reference point than the currently used MCP on preoperative stereotactic imaging, in order to obtain optimal and thus less variable motor improvement for individual patients with PD following STN DBS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Diane eWhitmer

    2012-06-01

    Full Text Available Parkinson’s disease (PD is marked by excessive synchronous activity in the beta (8-35 Hz band throughout the cortico-basal ganglia network. The optimal location of high frequency deep brain stimulation (HF DBS within the subthalamic nucleus (STN region and the location of maximal beta hypersynchrony are currently matters of debate. Additionally, the effect of STN HF DBS on neural synchrony in functionally connected regions of motor cortex is unknown and of great interest. Scalp EEG studies demonstrated that stimulation of the STN can activate motor cortex antidromically, but the spatial specificity of this effect has not been examined. The present study examined the effect of STN HF DBS on neural synchrony within the cortico-basal ganglia network in patients with PD. We measured local field potentials dorsal to and within the STN of PD patients, and additionally in the motor cortex in a subset of these patients. We used diffusion tensor imaging (DTI to guide the placement of subdural cortical surface electrodes over the DTI-identified origin of the hyperdirect pathway between motor cortex and the STN. The results demonstrated that local beta power was attenuated during HF DBS both dorsal to and within the STN. The degree of attenuation was monotonic with increased DBS voltages in both locations, but this voltage-dependent effect was greater in the central STN than dorsal to the STN (p < 0.05. Cortical signals over the estimated origin of the hyperdirect pathway also demonstrated attenuation of beta hypersynchrony during DBS dorsal to or within STN, whereas signals from non-specific regions of motor cortex were not attenuated. The spatially specific suppression of beta synchrony in the motor cortex support the hypothesis that DBS may treat Parkinsonism by reducing excessive synchrony in the functionally connected sensorimotor network.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Subthalamic deep brain stimulation improves auditory sensory gating deficit in Parkinson's disease.

    Science.gov (United States)

    Gulberti, A; Hamel, W; Buhmann, C; Boelmans, K; Zittel, S; Gerloff, C; Westphal, M; Engel, A K; Schneider, T R; Moll, C K E

    2015-03-01

    While motor effects of dopaminergic medication and subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients are well explored, their effects on sensory processing are less well understood. Here, we studied the impact of levodopa and STN-DBS on auditory processing. Rhythmic auditory stimulation (RAS) was presented at frequencies between 1 and 6Hz in a passive listening paradigm. High-density EEG-recordings were obtained before (levodopa ON/OFF) and 5months following STN-surgery (ON/OFF STN-DBS). We compared auditory evoked potentials (AEPs) elicited by RAS in 12 PD patients to those in age-matched controls. Tempo-dependent amplitude suppression of the auditory P1/N1-complex was used as an indicator of auditory gating. Parkinsonian patients showed significantly larger AEP-amplitudes (P1, N1) and longer AEP-latencies (N1) compared to controls. Neither interruption of dopaminergic medication nor of STN-DBS had an immediate effect on these AEPs. However, chronic STN-DBS had a significant effect on abnormal auditory gating characteristics of parkinsonian patients and restored a physiological P1/N1-amplitude attenuation profile in response to RAS with increasing stimulus rates. This differential treatment effect suggests a divergent mode of action of levodopa and STN-DBS on auditory processing. STN-DBS may improve early attentive filtering processes of redundant auditory stimuli, possibly at the level of the frontal cortex. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  16. Combining cell transplants or gene therapy with deep brain stimulation for Parkinson's disease.

    Science.gov (United States)

    Rowland, Nathan C; Starr, Philip A; Larson, Paul S; Ostrem, Jill L; Marks, William J; Lim, Daniel A

    2015-02-01

    Cell transplantation and gene therapy each show promise to enhance the treatment of Parkinson's disease (PD). However, because cell transplantation and gene therapy generally require direct delivery to the central nervous system, clinical trial design involves unique scientific, ethical, and financial concerns related to the invasive nature of the procedure. Typically, such biologics have been tested in PD patients who have not received any neurosurgical intervention. Here, we suggest that PD patients undergoing deep brain stimulation (DBS) device implantation are an ideal patient population for the clinical evaluation of cell transplantation and gene therapy. Randomizing subjects to an experimental group that receives the biologic concurrently with the DBS implantation-or to a control group that receives the DBS treatment alone-has several compelling advantages. First, this study design enables the participation of patients likely to benefit from DBS, many of whom simultaneously meet the inclusion criteria of biologic studies. Second, the need for a sham neurosurgical procedure is eliminated, which may reduce ethical concerns, promote patient recruitment, and enhance the blinding of surgical trials. Third, testing the biologic by "piggybacking" onto an established, reimbursable procedure should reduce the cost of clinical trials, which may allow a greater number of biologics to reach this critical stage of research translation. Finally, this clinical trial design may lead to combinatorial treatment strategies that provide PD patients with more durable control over disabling motor symptoms. By combining neuromodulation with biologics, we may also reveal important treatment paradigms relevant to other diseases of the brain. © 2014 International Parkinson and Movement Disorder Society.

  17. CMOS Image Sensor and System for Imaging Hemodynamic Changes in Response to Deep Brain Stimulation.

    Science.gov (United States)

    Zhang, Xiao; Noor, Muhammad S; McCracken, Clinton B; Kiss, Zelma H T; Yadid-Pecht, Orly; Murari, Kartikeya

    2016-06-01

    Deep brain stimulation (DBS) is a therapeutic intervention used for a variety of neurological and psychiatric disorders, but its mechanism of action is not well understood. It is known that DBS modulates neural activity which changes metabolic demands and thus the cerebral circulation state. However, it is unclear whether there are correlations between electrophysiological, hemodynamic and behavioral changes and whether they have any implications for clinical benefits. In order to investigate these questions, we present a miniaturized system for spectroscopic imaging of brain hemodynamics. The system consists of a 144 ×144, [Formula: see text] pixel pitch, high-sensitivity, analog-output CMOS imager fabricated in a standard 0.35 μm CMOS process, along with a miniaturized imaging system comprising illumination, focusing, analog-to-digital conversion and μSD card based data storage. This enables stand alone operation without a computer, nor electrical or fiberoptic tethers. To achieve high sensitivity, the pixel uses a capacitive transimpedance amplifier (CTIA). The nMOS transistors are in the pixel while pMOS transistors are column-parallel, resulting in a fill factor (FF) of 26%. Running at 60 fps and exposed to 470 nm light, the CMOS imager has a minimum detectable intensity of 2.3 nW/cm(2) , a maximum signal-to-noise ratio (SNR) of 49 dB at 2.45 μW/cm(2) leading to a dynamic range (DR) of 61 dB while consuming 167 μA from a 3.3 V supply. In anesthetized rats, the system was able to detect temporal, spatial and spectral hemodynamic changes in response to DBS.

  18. Deep brain stimulation for Tourette’s syndrome: the case for targeting the thalamic centromedian-parafascicular complex.

    Directory of Open Access Journals (Sweden)

    Paola Testini

    2016-11-01

    Full Text Available Tourette syndrome is a neurologic condition characterized by both motor and phonic tics and is typically associated with psychiatric comorbidities, including obsessive-compulsive disorder/behavior and attention deficit hyperactivity disorder and can be psychologically and socially debilitating. It is considered a disorder of the cortico-striato-thalamo-cortical circuitry, as suggested by pathophysiology studies and therapeutic options. Among these, deep brain stimulation of the centromedian-parafascicular nuclear complex (CM-Pf of the thalamus is emerging as a valuable treatment modality for patients affected by severe, treatment resistant TS. Here we review the most recent experimental evidence for the pivotal role of CM-Pf in the pathophysiology of Tourette syndrome, discuss potential mechanisms of action that may mediate the effects of CM-Pf deep brain stimulation in Tourette syndrome, and summarize its clinical efficacy.

  19. Basal ganglia, movement disorders and deep brain stimulation: advances made through non-human primate research.

    Science.gov (United States)

    Wichmann, Thomas; Bergman, Hagai; DeLong, Mahlon R

    2018-03-01

    Studies in non-human primates (NHPs) have led to major advances in our understanding of the function of the basal ganglia and of the pathophysiologic mechanisms of hypokinetic movement disorders such as Parkinson's disease and hyperkinetic disorders such as chorea and dystonia. Since the brains of NHPs are anatomically very close to those of humans, disease states and the effects of medical and surgical approaches, such as deep brain stimulation (DBS), can be more faithfully modeled in NHPs than in other species. According to the current model of the basal ganglia circuitry, which was strongly influenced by studies in NHPs, the basal ganglia are viewed as components of segregated networks that emanate from specific cortical areas, traverse the basal ganglia, and ventral thalamus, and return to the frontal cortex. Based on the presumed functional domains of the different cortical areas involved, these networks are designated as 'motor', 'oculomotor', 'associative' and 'limbic' circuits. The functions of these networks are strongly modulated by the release of dopamine in the striatum. Striatal dopamine release alters the activity of striatal projection neurons which, in turn, influences the (inhibitory) basal ganglia output. In parkinsonism, the loss of striatal dopamine results in the emergence of oscillatory burst patterns of firing of basal ganglia output neurons, increased synchrony of the discharge of neighboring basal ganglia neurons, and an overall increase in basal ganglia output. The relevance of these findings is supported by the demonstration, in NHP models of parkinsonism, of the antiparkinsonian effects of inactivation of the motor circuit at the level of the subthalamic nucleus, one of the major components of the basal ganglia. This finding also contributed strongly to the revival of the use of surgical interventions to treat patients with Parkinson's disease. While ablative procedures were first used for this purpose, they have now been largely

  20. Are Patients Ready for ?EARLYSTIM?? Attitudes towards Deep Brain Stimulation among Female and Male Patients with Moderately Advanced Parkinson's Disease

    OpenAIRE

    Sperens, Maria; Hamberg, Katarina; Hariz, Gun-Marie

    2017-01-01

    Objective. To explore, in female and male patients with medically treated, moderately advanced Parkinson's disease (PD), their knowledge and reasoning about Deep Brain Stimulation (DBS). Methods. 23 patients with PD (10 women), aged 46- 70, were interviewed at a mean of 8 years after diagnosis, with open-ended questions concerning their reflections and considerations about DBS. The interviews were transcribed verbatim and analysed according to the difference and similarity technique in Ground...

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

    OpenAIRE

    Deeb, Wissam; Giordano, James J.; Rossi, Peter J.; Mogilner, Alon Y.; Gunduz, Aysegul; Judy, Jack W.; Klassen, Bryan T.; Butson, Christopher R.; Van Horne, Craig; Deny, Damiaan; Dougherty, Darin D.; Rowell, David; Gerhardt, Greg A.; Smith, Gwenn S.; Ponce, Francisco A.

    2016-01-01

    This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinica...

  2. Implementation of a smartphone wireless accelerometer platform for establishing deep brain stimulation treatment efficacy of essential tremor with machine learning.

    Science.gov (United States)

    LeMoyne, Robert; Tomycz, Nestor; Mastroianni, Timothy; McCandless, Cyrus; Cozza, Michael; Peduto, David

    2015-01-01

    Essential tremor (ET) is a highly prevalent movement disorder. Patients with ET exhibit a complex progressive and disabling tremor, and medical management often fails. Deep brain stimulation (DBS) has been successfully applied to this disorder, however there has been no quantifiable way to measure tremor severity or treatment efficacy in this patient population. The quantified amelioration of kinetic tremor via DBS is herein demonstrated through the application of a smartphone (iPhone) as a wireless accelerometer platform. The recorded acceleration signal can be obtained at a setting of the subject's convenience and conveyed by wireless transmission through the Internet for post-processing anywhere in the world. Further post-processing of the acceleration signal can be classified through a machine learning application, such as the support vector machine. Preliminary application of deep brain stimulation with a smartphone for acquisition of a feature set and machine learning for classification has been successfully applied. The support vector machine achieved 100% classification between deep brain stimulation in `on' and `off' mode based on the recording of an accelerometer signal through a smartphone as a wireless accelerometer platform.

  3. Deep brain stimulation for patients with Parkinson's disease: Effect on caregiver burden.

    Science.gov (United States)

    Crespo-Burillo, J A; Rivero-Celada, D; Saenz-de Cabezón, A; Casado-Pellejero, J; Alberdi-Viñas, J; Alarcia-Alejos, R

    2018-04-01

    Our aim is to assess the burden on caregivers of patients with Parkinson's disease treated with deep brain stimulation (DBS) compared to those caring for patients at advanced stages and undergoing other treatments. We have also assessed the variables associated with presence of caregiver overload. We included consecutive patients with Parkinson's disease treated with DBS. Our control group included patients in advanced stages of Parkinson's disease undergoing other treatments. Patients were assessed with the following scales: UPDRS-II, UPDRS-III, UPDRS-IV, Hoehn and Yahr, Schwab & England, Barthel, PDQ-39, MoCA, Apathy Evaluation Scale, HADS, and the abbreviated QUIP. Caregiver burden was evaluated with the Zarit caregiver burden interview and their moods were assessed with the HADS scale. We included 11 patients treated with DBS and 11 with other treatments. For patients treated with DBS, we observed a better quality of life according to the PDQ-39 questionnaire (P=.028), and a lower score on the HADS anxiety subscale (P=.010). Caregiver overload was observed in 54.5% of the caregivers of patients in both groups (P=1.000); Zarit scores were similar (P=.835). Caregiver overload was associated with higher scores on the caregiver's Apathy Evaluation Scale (P=.048) and on the HADS anxiety subscale (P=.006). According to our results, treatment with DBS is not associated with lower caregiver burden. Apathy in patients and anxiety in caregivers are factors associated with the appearance of overload. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Optimized programming algorithm for cylindrical and directional deep brain stimulation electrodes.

    Science.gov (United States)

    Anderson, Daria Nesterovich; Osting, Braxton; Vorwerk, Johannes; Dorval, Alan D; Butson, Christopher R

    2018-04-01

    Deep brain stimulation (DBS) is a growing treatment option for movement and psychiatric disorders. As DBS technology moves toward directional leads with increased numbers of smaller electrode contacts, trial-and-error methods of manual DBS programming are becoming too time-consuming for clinical feasibility. We propose an algorithm to automate DBS programming in near real-time for a wide range of DBS lead designs. Magnetic resonance imaging and diffusion tensor imaging are used to build finite element models that include anisotropic conductivity. The algorithm maximizes activation of target tissue and utilizes the Hessian matrix of the electric potential to approximate activation of neurons in all directions. We demonstrate our algorithm's ability in an example programming case that targets the subthalamic nucleus (STN) for the treatment of Parkinson's disease for three lead designs: the Medtronic 3389 (four cylindrical contacts), the direct STNAcute (two cylindrical contacts, six directional contacts), and the Medtronic-Sapiens lead (40 directional contacts). The optimization algorithm returns patient-specific contact configurations in near real-time-less than 10 s for even the most complex leads. When the lead was placed centrally in the target STN, the directional leads were able to activate over 50% of the region, whereas the Medtronic 3389 could activate only 40%. When the lead was placed 2 mm lateral to the target, the directional leads performed as well as they did in the central position, but the Medtronic 3389 activated only 2.9% of the STN. This DBS programming algorithm can be applied to cylindrical electrodes as well as novel directional leads that are too complex with modern technology to be manually programmed. This algorithm may reduce clinical programming time and encourage the use of directional leads, since they activate a larger volume of the target area than cylindrical electrodes in central and off-target lead placements.

  5. Long-Term Clinical Outcome of Internal Globus Pallidus Deep Brain Stimulation for Dystonia.

    Directory of Open Access Journals (Sweden)

    Hye Ran Park

    Full Text Available GPi (Internal globus pallidus DBS (deep brain stimulation is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia.This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital.Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12-84.The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006. The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073. When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement.GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center.

  6. Subthalamic nucleus deep brain stimulation impacts language in early Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Lara Phillips

    Full Text Available Although deep brain stimulation (DBS of the basal ganglia improves motor outcomes in Parkinson's disease (PD, its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars and lexical (irregulars processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor and non-manipulated (non-motor objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor but not non-manipulated (non-motor objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar but not irregulars (lexicon, as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar remain to be elucidated.

  7. Complications of Impulse Generator Exchange Surgery for Deep Brain Stimulation: A Single-Center, Retrospective Study.

    Science.gov (United States)

    Helmers, Ann-Kristin; Lübbing, Isabel; Birkenfeld, Falk; Witt, Karsten; Synowitz, Michael; Mehdorn, Hubertus Maximilian; Falk, Daniela

    2018-05-01

    Nonrechargeable deep brain stimulation impulse generators (IGs) with low or empty battery status require surgical IG exchange several years after initial implantation. The aim of this study was to investigate complication rates after IG exchange surgery and identify risk factors. We retrospectively analyzed complications following IG exchange surgery from 2008 to 2015 in our department. Medical records of all patients who underwent IG exchange surgery were systematically reviewed. The shortest follow-up time was 19 months. From 2008 to 2015, 438 IGs were exchanged in 319 patients. Overall complication rate was 8.90%. Infection developed in 12 patients (2.74%). Six patients (1.37%) experienced local wound erosions. Hardware malfunctions were present in 11 patients (2.51%), and local hemorrhage was observed in 3 cases (0.68%). Repeated fixation of the IG was required in 2 patients (0.46%). Traction of the connecting cables necessitated surgical revision in 2 patients (0.46%). In 2 cases (0.46%), the IG was placed abdominally or exchanged for a smaller device owing to patient discomfort resulting from the initial positioning. One 80-year-old patient (0.23%) had severely worsening heart failure and died 4 days after IG exchange surgery. IG exchange surgery, although often considered a minor surgery, was associated with a complication rate of approximately 9% in our center. Patients and physicians should understand the complication rates associated with IG exchange surgery because this information might facilitate selection of a rechargeable IG. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. RF rectifiers for EM power harvesting in a Deep Brain Stimulating device.

    Science.gov (United States)

    Hosain, Md Kamal; Kouzani, Abbas Z; Tye, Susannah; Kaynak, Akif; Berk, Michael

    2015-03-01

    A passive deep brain stimulation (DBS) device can be equipped with a rectenna, consisting of an antenna and a rectifier, to harvest energy from electromagnetic fields for its operation. This paper presents optimization of radio frequency rectifier circuits for wireless energy harvesting in a passive head-mountable DBS device. The aim is to achieve a compact size, high conversion efficiency, and high output voltage rectifier. Four different rectifiers based on the Delon doubler, Greinacher voltage tripler, Delon voltage quadrupler, and 2-stage charge pumped architectures are designed, simulated, fabricated, and evaluated. The design and simulation are conducted using Agilent Genesys at operating frequency of 915 MHz. A dielectric substrate of FR-4 with thickness of 1.6 mm, and surface mount devices (SMD) components are used to fabricate the designed rectifiers. The performance of the fabricated rectifiers is evaluated using a 915 MHz radio frequency (RF) energy source. The maximum measured conversion efficiency of the Delon doubler, Greinacher tripler, Delon quadrupler, and 2-stage charge pumped rectifiers are 78, 75, 73, and 76 % at -5 dBm input power and for load resistances of 5-15 kΩ. The conversion efficiency of the rectifiers decreases significantly with the increase in the input power level. The Delon doubler rectifier provides the highest efficiency at both -5 and 5 dBm input power levels, whereas the Delon quadrupler rectifier gives the lowest efficiency for the same inputs. By considering both efficiency and DC output voltage, the charge pump rectifier outperforms the other three rectifiers. Accordingly, the optimised 2-stage charge pumped rectifier is used together with an antenna to harvest energy in our DBS device.

  9. Analyzing 7000 texts on Deep Brain Stimulation: what do they tell us?

    Directory of Open Access Journals (Sweden)

    Christian eIneichen

    2015-10-01

    Full Text Available The enormous increase in numbers of scientific publications in the last decades requires quantitative methods for obtaining a better understanding of topics and developments in various fields. In this exploratory study, we investigate the emergence, trends and connections of topics within the whole text corpus of the deep brain stimulation (DBS literature based on more than 7000 papers (title and abstracts published between 1991 to 2014 using a network approach. Taking the co-occurrence of basic terms that represent important topics within DBS as starting position, we outline the statistics of interconnections between DBS indications, targets, positive and negative effects, as well as methodological, technological and economic issues. This quantitative approach confirms known trends within the literature (e.g., regarding the emergence of psychiatric indications. The data also reflect an increased discussion about complex issues such as personality connected tightly to the ethical context, as well as an apparent focus on depression as important DBS indication, whereas the co-occurrence of terms related to negative effects is low both for the indication as well as the related targets. We also discuss consequences of the analysis from a bioethical perspective, i.e. how such a quantitative analysis could uncover hidden subject matters that have ethical relevance. For example, we find that hardware-related issues in DBS are far more robustly connected to an ethical context compared to impulsivity, concrete side-effects or death/suicide. Our contribution also outlines the methodology of quantitative text analysis that combines statistical approaches with expert knowledge. It thus serves as an example how innovative quantitative tools can be made useful for gaining a better understanding in the field of DBS.

  10. Moving forward: advances in the treatment of movement disorders with deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Terry K Schiefer

    2011-11-01

    Full Text Available 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 Parkinson’s disease 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. Our search criteria for PubMed included combinations of the following terms: DBS, neuromodulation, movement disorders, PD, tremor, dystonia, and history. Dates were not restricted.

  11. Deep Brain Stimulation of the Dentato-Rubro-Thalamic Tract: Outcomes of Direct Targeting for Tremor.

    Science.gov (United States)

    Fenoy, Albert J; Schiess, Mya C

    2017-07-01

    Targeting the dentato-rubro-thalamic tract (DRTt) has been suggested to be efficacious in deep brain stimulation (DBS) for tremor suppression, both in case reports and post-hoc analyses. This prospective observational study sought to analyze outcomes after directly targeting the DRTt in tremor patients. 20 consecutively enrolled intention tremor patients obtained pre-operative MRI with diffusion tensor (dTi) sequences. Mean baseline tremor amplitude based on The Essential Tremor Rating Assessment Scale was recorded. The DRTt was drawn for each individual on StealthViz software (Medtronic) using the dentate nucleus as the seed region and the ipsilateral pre-central gyrus as the end region and then directly targeted during surgery. Intraoperative testing confirmed successful tremor control. Post-operative analysis of electrode position relative to the DRTt was performed, as was post-operative assessment of tremor improvement. The mean age of patients was 66.8 years; mean duration of tremor was 16 years. Mean voltage for the L electrode = 3.4 V; R = 2.6 V. Mean distance from the center of the active electrode contact to the DRTt was 0.9 mm on the L, and 0.8 mm on the R. Improvement in arm tremor amplitude from baseline after DBS was significant (P tremor suppression. Accounting for hardware, software, and model limitations, depiction of the DRTt allows for placement of electrode contacts directly within the fiber tract for modulation despite any anatomical variation, which reproducibly resulted in good tremor control. © 2017 International Neuromodulation Society.

  12. Factors predicting incremental administration of antihypertensive boluses during deep brain stimulator placement for Parkinson's disease.

    Science.gov (United States)

    Rajan, Shobana; Deogaonkar, Milind; Kaw, Roop; Nada, Eman Ms; Hernandez, Adrian V; Ebrahim, Zeyd; Avitsian, Rafi

    2014-10-01

    Hypertension is common in deep brain stimulator (DBS) placement predisposing to intracranial hemorrhage. This retrospective review evaluates factors predicting incremental antihypertensive use intraoperatively. Medical records of Parkinson's disease (PD) patients undergoing DBS procedure between 2008-2011 were reviewed after Institutional Review Board approval. Anesthesia medication, preoperative levodopa dose, age, preoperative use of antihypertensive medications, diabetes mellitus, anxiety, motor part of the Unified Parkinson's Disease Rating Scale score and PD duration were collected. Univariate and multivariate analysis was done between each patient characteristic and the number of antihypertensive boluses. From the 136 patients included 60 were hypertensive, of whom 32 were on angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), told to hold on the morning of surgery. Antihypertensive medications were given to 130 patients intraoperatively. Age (relative risk [RR] 1.01; 95% confidence interval [CI] 1.00-1.02; p=0.005), high Joint National Committee (JNC) class (p10 years (RR 1.2; 95%CI 1.1-1.3; p=0.001) were independent predictors for antihypertensive use. No difference was noted in the mean dose of levodopa (p=0.1) and levodopa equivalent dose (p=0.4) between the low (I/II) and high severity (III/IV) JNC groups. Addition of dexmedetomidine to propofol did not influence antihypertensive boluses required (p=0.38). Intraoperative hypertension during DBS surgery is associated with higher age group, hypertensive, diabetic patients and longer duration of PD. Withholding ACEI or ARB is an independent predictor of hypertension requiring more aggressive therapy. Levodopa withdrawal and choice of anesthetic agent is not associated with higher intraoperative antihypertensive medications. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Deep brain stimulation of the antero-medial globus pallidus interna for Tourette syndrome.

    Directory of Open Access Journals (Sweden)

    Perminder S Sachdev

    Full Text Available BACKGROUND: We have previously reported the results of Deep Brain Stimulation (DBS of the antero-medial globus pallidus interna (GPi for severe Tourette Syndrome (TS in 11 patients. We extend this case series to 17 patients and a longer follow-up to a maximum of 46 months. METHODS: 17 patients (14 male; mean age 29.1 years, range 17-51 years with severe and medically intractable TS were implanted with Medtronic quadripolar electrodes bilaterally in the antero-medial GPi. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS. Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, Hamilton Depression Rating Scale, Gilles de la Tourette Quality of Life Scale and Global Assessment of Functioning. Follow up was at one month, three months and finally at a mean 24.1 months (range 8-46 months following surgery. RESULTS: Overall, there was a 48.3% reduction in motor tics and a 41.3% reduction in phonic tics at one month, and this improvement was maintained at final follow-up. 12 out of 17 (70.6% patients had a>50% reduction in YGTSS score at final follow up. Only 8 patients required ongoing pharmacotherapy for tics post-surgery. Patients improved significantly on all secondary measures. Adverse consequences included lead breakage in 4 patients, infection (1, transient anxiety (2, dizziness (1, poor balance (1 and worsening of stuttering (1. CONCLUSIONS: This case series provides further support that antero-medial GPi DBS is an effective and well tolerated treatment for a subgroup of severe TS, with benefits sustained up to 4 years.

  14. Deep brain stimulation in uncommon tremor disorders: indications, targets, and programming.

    Science.gov (United States)

    Artusi, Carlo Alberto; Farooqi, Ashar; Romagnolo, Alberto; Marsili, Luca; Balestrino, Roberta; Sokol, Leonard L; Wang, Lily L; Zibetti, Maurizio; Duker, Andrew P; Mandybur, George T; Lopiano, Leonardo; Merola, Aristide

    2018-03-06

    In uncommon tremor disorders, clinical efficacy and optimal anatomical targets for deep brain stimulation (DBS) remain inadequately studied and insufficiently quantified. We performed a systematic review of PubMed.gov and ClinicalTrials.gov. Relevant articles were identified using the following keywords: "tremor", "Holmes tremor", "orthostatic tremor", "multiple sclerosis", "multiple sclerosis tremor", "neuropathy", "neuropathic tremor", "fragile X-associated tremor/ataxia syndrome", and "fragile X." We identified a total of 263 cases treated with DBS for uncommon tremor disorders. Of these, 44 had Holmes tremor (HT), 18 orthostatic tremor (OT), 177 multiple sclerosis (MS)-associated tremor, 14 neuropathy-associated tremor, and 10 fragile X-associated tremor/ataxia syndrome (FXTAS). DBS resulted in favorable, albeit partial, clinical improvements in HT cases receiving Vim-DBS alone or in combination with additional targets. A sustained improvement was reported in OT cases treated with bilateral Vim-DBS, while the two cases treated with unilateral Vim-DBS demonstrated only a transient effect. MS-associated tremor responded to dual-target Vim-/VO-DBS, but the inability to account for the progression of MS-associated disability impeded the assessment of its long-term clinical efficacy. Neuropathy-associated tremor substantially improved with Vim-DBS. In FXTAS patients, while Vim-DBS was effective in improving tremor, equivocal results were observed in those with ataxia. DBS of select targets may represent an effective therapeutic strategy for uncommon tremor disorders, although the level of evidence is currently in its incipient form and based on single cases or limited case series. An international registry is, therefore, warranted to clarify selection criteria, long-term results, and optimal surgical targets.

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

    Science.gov (United States)

    Li, J; Andrews, R J

    2007-01-01

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

  16. Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze.

    Science.gov (United States)

    Jeong, Da Un; Lee, Jihyeon; Chang, Won Seok; Chang, Jin Woo

    2017-03-07

    The possibility of using deep brain stimulation (DBS) for memory enhancement has recently been reported, but the precise underlying mechanisms of its effects remain unknown. Our previous study suggested that spatial memory improvement by medial septum (MS)-DBS may be associated with cholinergic regulation and neurogenesis. However, the affected stage of memory could not be distinguished because the stimulation was delivered during the execution of all memory processes. Therefore, this study was performed to determine the stage of memory affected by MS-DBS. Rats were administered 192 IgG-saporin to lesion cholinergic neurons. Stimulation was delivered at different times in different groups of rats: 5 days before the Morris water maze test (pre-stimulation), 5 days during the training phase of the Morris water maze test (training-stimulation), and 2 h before the Morris water maze probe test (probe-stimulation). A fourth group of rats was lesioned but received no stimulation. These four groups were compared with a normal (control) group. The most effective memory restoration occurred in the pre-stimulation group. Moreover, the pre-stimulation group exhibited better recall of the platform position than the other stimulation groups. An increase in the level of brain derived neurotrophic factor (BDNF) was observed in the pre-stimulation group; this increase was maintained for 1 week. However, acetylcholinesterase activity in the pre-stimulation group was not significantly different from the lesion group. Memory impairment due to cholinergic denervation can be improved by DBS. The improvement is significantly correlated with the up-regulation of BDNF expression and neurogenesis. Based on the results of this study, the use of MS-DBS during the early stage of disease may restore spatial memory impairment.

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

    Science.gov (United States)

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

    2015-04-21

    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.

  18. Deep Brain Stimulation Target Selection in an Advanced Parkinson's Disease Patient with Significant Tremor and Comorbid Depression

    Directory of Open Access Journals (Sweden)

    Amar S. Patel

    2017-04-01

    Full Text Available Clinical Vignette: A 67-year-old female with advanced Parkinson's disease (PD, medically refractory tremor, and a history of significant depression presents for evaluation of deep brain stimulation (DBS candidacy.  Clinical Dilemma: Traditionally, stimulation of the subthalamic nucleus (STN has been the preferred target for patients with significant PD tremor. However, STN stimulation is avoided in patients with a significant pre-surgical history of mood disorder.  Clinical Solution: Bilateral DBS of the globus pallidus interna led to significant short term improvement in PD motor symptoms, including significant tremor reduction.  Gap in Knowledge: There is insufficient evidence to support or refute clinicians' traditional preference for STN stimulation in treating refractory PD tremor. Similarly, the available evidence for risk of worsening depression and/or suicidality after STN DBS is mixed. Both questions require further clarification to guide patient and clinician decision-making.

  19. Deep Brain Stimulation as a Treatment for Refractory Epilepsy: Review of the Current State-of-the-Art.

    Science.gov (United States)

    Ganguli, Malika P; Upton, Adrian R M; Kamath, Markad V

    2017-01-01

    Epilepsy affects ∼ 1% of the global population, and 33% of patients are nonresponsive to medication and must seek alternative treatment options. Alternative options such as surgery and ablation exist but are not appropriate treatment plans for some patients. Neurostimulation methods such as vagal nerve stimulation, responsive neural stimulation, and deep brain stimulation (DBS) are viable alternatives for medically refractory patients. DBS stimulation has been used in the treatment of Parkinson's disease, dystonia, and pain management. For the treatment of epilepsy, DBS has been found to be an effective treatment plan, with promising results of reduced seizure frequency and intensity. In this review, we discuss DBS surgery and equipment, mechanisms of DBS for epilepsy, and efficacy, technological specifications, and suggestions for future research. We also review a historical summary of experiments involving DBS for epilepsy. Our literature review suggests that further studies are warranted for medically refractory epilepsy using DBS.

  20. Tic related local field potentials in the thalamus and the effect of deep brain stimulation in Tourette syndrome : Report of three cases

    NARCIS (Netherlands)

    Bour, L. J.; Ackermans, L.; Foncke, E. M. J.; Cath, D.; van der Linden, C.; Vandewalle, V. Visser; Tijssen, M. A.

    Objective: Three patients with intractable Tourette syndrome (TS) underwent thalamic deep brain stimulation (DBS). To investigate the role of thalamic electrical activity in tic generation, local field potentials (LFP), EEG and EMG simultaneously were recorded. Methods: Event related potentials and

  1. Smile and laughter induction and intraoperative predictors of response to deep brain stimulation for obsessive-compulsive disorder.

    Science.gov (United States)

    Haq, Ihtsham U; Foote, Kelly D; Goodman, Wayne G; Wu, Samuel S; Sudhyadhom, Atchar; Ricciuti, Nicola; Siddiqui, Mustafa S; Bowers, Dawn; Jacobson, Charles E; Ward, Herbert; Okun, Michael S

    2011-01-01

    We recently treated six patients for OCD utilizing deep brain stimulation (DBS) of the anterior limb of the internal capsule and the nucleus accumbens region (ALIC-NA). We individually tested leads via a scripted intraoperative protocol designed to determine DBS-induced side effects and mood changes. We previously published qualitative data regarding our observations of induced emotional behaviors in our first five subjects. We have now studied these same behaviors in the full cohort of six patients over 2 years of follow-up and have examined the relationship of these behaviors to intraoperative mood changes and postoperative clinical outcomes. Five patients experienced at least one smile response during testing. At higher voltages of stimulation, some of these smiles progressed to natural laughter. Smiles and laughter were associated with mood elevation. At stimulation locations at which smiles were observed, voltage and mood were significantly correlated (p=0.0004 for right brain and plaughter-inducing sites were located relatively medial, posterior, and deep in the ALIC-NA. The presence of stimulation induced laughter predicted improvement in OCD symptoms at 2 years. The higher the percentage of laugh conditions experienced in an individual patient, the greater the reduction in YBOCS (24 months, p=0.034). Other correlations between clinical outcomes and percent of smile/laugh conditions were not significant. These stimulation-induced behaviors were less frequently observed with 1 and 2-month postoperative test stimulation and were not observed at subsequent test stimulation sessions. Intraoperative stimulation-induced laughter may predict long-term OCD response to DBS. Identifying other potential response predictors for OCD will become increasingly important as more patients are implanted with DBS devices. A larger study is needed to better delineate the relationship between induced intraoperative and postoperative emotional behavior and clinical outcome in

  2. Smile and Laughter Induction and Intraoperative Predictors of Response to Deep Brain Stimulation for Obsessive Compulsive Disorder

    Science.gov (United States)

    Haq, Ihtsham U; Foote, Kelly D; Goodman, Wayne G; Wu, Samuel S; Sudhyadhom, Atchar; Ricciutti, Nicola; Siddiqui, Mustafa S.; Bowers, Dawn; Jacobson, Charles E; Ward, Herbert; Okun, Michael S

    2010-01-01

    We recently treated six patients for OCD utilizing deep brain stimulation (DBS) of the anterior limb of the internal capsule and the nucleus accumbens region (ALIC-NA). We individually tested leads via a scripted intraoperative protocol designed to determine DBS-induced side effects and mood changes. We previously published qualitative data regarding our observations of induced emotional behaviors in our first five subjects. We have now studied these same behaviors in the full cohort of six patients over two years of follow-up and have examined the relationship of these behaviors to intraoperative mood changes and postoperative clinical outcomes. Five patients experienced at least one smile response during testing. At higher voltages of stimulation some of these smiles progressed to natural laughter. Smiles and laughter were associated with mood elevation. At stimulation locations at which smiles were observed, voltage and mood were significantly correlated (p=0.0004 for right brain and plaughter-inducing sites were located relatively medial, posterior, and deep in the ALIC-NA. The presence of stimulation induced laughter predicted improvement in OCD symptoms at two years. The higher the percentage of laugh conditions experienced in an individual patient, the greater the reduction in YBOCS (24 months, p=0.034). Other correlations between clinical outcomes and percent of smile/laugh conditions were not significant. These stimulation-induced behaviors were less frequently observed with one and two-month postoperative test stimulation and were not observed at subsequent test stimulation sessions. Intraoperative stimulation-induced laughter may predict long-term OCD response to DBS. Identifying other potential response predictors for OCD will become increasingly important as more patients are implanted with DBS devices. A larger study is needed to better delineate the relationship between induced intraoperative and postoperative emotional behavior and clinical outcome

  3. Interleaving subthalamic nucleus deep brain stimulation to avoid side effects while achieving satisfactory motor benefits in Parkinson disease

    Science.gov (United States)

    Zhang, Shizhen; Zhou, Peizhi; Jiang, Shu; Wang, Wei; Li, Peng

    2016-01-01

    Abstract Background: Deep brain stimulation (DBS) of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD). However, achieving ideal outcomes by conventional programming can be difficult in some patients, resulting in suboptimal control of PD symptoms and stimulation-induced adverse effects. Interleaving stimulation (ILS) is a newer programming technique that can individually optimize the stimulation area, thereby improving control of PD symptoms while alleviating stimulation-induced side effects after conventional programming fails to achieve the desired results. Methods: We retrospectively reviewed PD patients who received DBS programming during the previous 4 years in our hospital. We collected clinical and demographic data from 12 patients who received ILS because of incomplete alleviation of PD symptoms or stimulation-induced adverse effects after conventional programming had proven ineffective or intolerable. Appropriate lead location was confirmed with postoperative reconstruction images. The rationale and clinical efficacy of ILS was analyzed. Results: We divided our patients into 4 groups based on the following symptoms: stimulation-induced dysarthria and choreoathetoid dyskinesias, gait disturbance, and incomplete control of parkinsonism. After treatment with ILS, patients showed satisfactory improvement in PD symptoms and alleviation of stimulation-induced side effects, with a mean improvement in Unified PD Rating Scale motor scores of 26.9%. Conclusions: ILS is a newer choice and effective programming strategy to maximize symptom control in PD while decreasing stimulation-induced adverse effects when conventional programming fails to achieve satisfactory outcome. However, we should keep in mind that most DBS patients are routinely treated with conventional stimulation and that not all patients benefit from ILS. ILS is not recommended as the first choice of programming, and it is recommended only when patients have

  4. Validation of a Portable Low-Power Deep Brain Stimulation Device Through Anxiolytic Effects in a Laboratory Rat Model.

    Science.gov (United States)

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

    2017-09-01

    Deep brain stimulation (DBS) devices deliver electrical pulses to neural tissue through an electrode. To study the mechanisms and therapeutic benefits of deep brain stimulation, murine preclinical research is necessary. However, conducting naturalistic long-term, uninterrupted animal behavioral experiments can be difficult with bench-top systems. The reduction of size, weight, power consumption, and cost of DBS devices can assist the progress of this research in animal studies. A low power, low weight, miniature DBS device is presented in this paper. This device consists of electronic hardware and software components including a low-power microcontroller, an adjustable current source, an n-channel metal-oxide-semiconductor field-effect transistor, a coin-cell battery, electrode wires and a software program to operate the device. Evaluation of the performance of the device in terms of battery lifetime and device functionality through bench and in vivo tests was conducted. The bench test revealed that this device can deliver continuous stimulation current pulses of strength [Formula: see text], width [Formula: see text], and frequency 130 Hz for over 22 days. The in vivo tests demonstrated that chronic stimulation of the nucleus accumbens (NAc) with this device significantly increased psychomotor activity, together with a dramatic reduction in anxiety-like behavior in the elevated zero-maze test.

  5. Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

    Directory of Open Access Journals (Sweden)

    Tomasz Fundament

    Full Text Available Parkinson's disease (PD is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT, among PD patients with early onset of motor complications, from a United Kingdom (UK payer perspective.We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY. One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty.Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs, resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values.These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental

  6. Realistic modeling of deep brain stimulation implants for electromagnetic MRI safety studies.

    Science.gov (United States)

    Guerin, Bastien; Serano, Peter; Iacono, Maria Ida; Herrington, Todd M; Widge, Alik S; Dougherty, Darin D; Bonmassar, Giorgio; Angelone, Leonardo M; Wald, Lawrence L

    2018-05-04

    We propose a framework for electromagnetic (EM) simulation of deep brain stimulation (DBS) patients in radiofrequency (RF) coils. We generated a model of a DBS patient using post-operative head and neck computed tomography (CT) images stitched together into a 'virtual CT' image covering the entire length of the implant. The body was modeled as homogeneous. The implant path extracted from the CT data contained self-intersections, which we corrected automatically using an optimization procedure. Using the CT-derived DBS path, we built a model of the implant including electrodes, helicoidal internal conductor wires, loops, extension cables, and the implanted pulse generator. We also built four simplified models with straight wires, no extension cables and no loops to assess the impact of these simplifications on safety predictions. We simulated EM fields induced by the RF birdcage body coil in the body model, including at the DBS lead tip at both 1.5 Tesla (64 MHz) and 3 Tesla (123 MHz). We also assessed the robustness of our simulation results by systematically varying the EM properties of the body model and the position and length of the DBS implant (sensitivity analysis). The topology correction algorithm corrected all self-intersection and curvature violations of the initial path while introducing minimal deformations (open-source code available at http://ptx.martinos.org/index.php/Main_Page). The unaveraged lead-tip peak SAR predicted by the five DBS models (0.1 mm resolution grid) ranged from 12.8 kW kg -1 (full model, helicoidal conductors) to 43.6 kW kg -1 (no loops, straight conductors) at 1.5 T (3.4-fold variation) and 18.6 kW kg -1 (full model, straight conductors) to 73.8 kW kg -1 (no loops, straight conductors) at 3 T (4.0-fold variation). At 1.5 T and 3 T, the variability of lead-tip peak SAR with respect to the conductivity ranged between 18% and 30%. Variability with respect to the position and length of the DBS implant ranged between 9.5% and 27.6%.

  7. Realistic modeling of deep brain stimulation implants for electromagnetic MRI safety studies

    Science.gov (United States)

    Guerin, Bastien; Serano, Peter; Iacono, Maria Ida; Herrington, Todd M.; Widge, Alik S.; Dougherty, Darin D.; Bonmassar, Giorgio; Angelone, Leonardo M.; Wald, Lawrence L.

    2018-05-01

    We propose a framework for electromagnetic (EM) simulation of deep brain stimulation (DBS) patients in radiofrequency (RF) coils. We generated a model of a DBS patient using post-operative head and neck computed tomography (CT) images stitched together into a ‘virtual CT’ image covering the entire length of the implant. The body was modeled as homogeneous. The implant path extracted from the CT data contained self-intersections, which we corrected automatically using an optimization procedure. Using the CT-derived DBS path, we built a model of the implant including electrodes, helicoidal internal conductor wires, loops, extension cables, and the implanted pulse generator. We also built four simplified models with straight wires, no extension cables and no loops to assess the impact of these simplifications on safety predictions. We simulated EM fields induced by the RF birdcage body coil in the body model, including at the DBS lead tip at both 1.5 Tesla (64 MHz) and 3 Tesla (123 MHz). We also assessed the robustness of our simulation results by systematically varying the EM properties of the body model and the position and length of the DBS implant (sensitivity analysis). The topology correction algorithm corrected all self-intersection and curvature violations of the initial path while introducing minimal deformations (open-source code available at http://ptx.martinos.org/index.php/Main_Page). The unaveraged lead-tip peak SAR predicted by the five DBS models (0.1 mm resolution grid) ranged from 12.8 kW kg‑1 (full model, helicoidal conductors) to 43.6 kW kg‑1 (no loops, straight conductors) at 1.5 T (3.4-fold variation) and 18.6 kW kg‑1 (full model, straight conductors) to 73.8 kW kg‑1 (no loops, straight conductors) at 3 T (4.0-fold variation). At 1.5 T and 3 T, the variability of lead-tip peak SAR with respect to the conductivity ranged between 18% and 30%. Variability with respect to the position and length of the DBS implant ranged between 9

  8. Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease.

    Science.gov (United States)

    Brodsky, Matthew A; Anderson, Shannon; Murchison, Charles; Seier, Mara; Wilhelm, Jennifer; Vederman, Aaron; Burchiel, Kim J

    2017-11-07

    To compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement. DBS candidates with PD referred to Oregon Health & Science University underwent asleep DBS with imaging guidance. Six-month outcomes were compared to those of patients who previously underwent awake DBS by the same surgeon and center. Assessments included an "off"-levodopa Unified Parkinson's Disease Rating Scale (UPDRS) II and III, the 39-item Parkinson's Disease Questionnaire, motor diaries, and speech fluency. Thirty participants underwent asleep DBS and 39 underwent awake DBS. No difference was observed in improvement of UPDRS III (+14.8 ± 8.9 vs +17.6 ± 12.3 points, p = 0.19) or UPDRS II (+9.3 ± 2.7 vs +7.4 ± 5.8 points, p = 0.16). Improvement in "on" time without dyskinesia was superior in asleep DBS (+6.4 ± 3.0 h/d vs +1.7 ± 1.2 h/d, p = 0.002). Quality of life scores improved in both groups (+18.8 ± 9.4 in awake, +8.9 ± 11.5 in asleep). Improvement in summary index ( p = 0.004) and subscores for cognition ( p = 0.011) and communication ( p < 0.001) were superior in asleep DBS. Speech outcomes were superior in asleep DBS, both in category (+2.77 ± 4.3 points vs -6.31 ± 9.7 points ( p = 0.0012) and phonemic fluency (+1.0 ± 8.2 points vs -5.5 ± 9.6 points, p = 0.038). Asleep DBS for PD improved motor outcomes over 6 months on par with or better than awake DBS, was superior with regard to speech fluency and quality of life, and should be an option considered for all patients who are candidates for this treatment. NCT01703598. This study provides Class III evidence that for patients with PD undergoing DBS, asleep intraoperative CT imaging-guided implantation is not significantly different from awake microelectrode recording-guided implantation in improving motor outcomes at 6 months. © 2017

  9. Stimulation Induced Electrographic Seizures in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Do Not Preclude a Subsequent Favorable Treatment Response.

    Science.gov (United States)

    Nora, Tommi; Heinonen, Hanna; Tenhunen, Mirja; Rainesalo, Sirpa; Järvenpää, Soila; Lehtimäki, Kai; Peltola, Jukka

    2018-01-01

    Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient's seizures in long-term follow-up. We therefore hypothesize that the occurrence of stimulation induced seizures at the onset of DBS therapy should not be considered as a failure in the DBS therapy, and the possibility of a subsequent favorable response to the treatment still exists.

  10. Stimulation Induced Electrographic Seizures in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Do Not Preclude a Subsequent Favorable Treatment Response

    Directory of Open Access Journals (Sweden)

    Tommi Nora

    2018-02-01

    Full Text Available Deep brain stimulation (DBS of the anterior nucleus of the thalamus (ANT is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient’s seizures in long-term follow-up. We therefore hypothesize that the occurrence of stimulation induced seizures at the onset of DBS therapy should not be considered as a failure in the DBS therapy, and the possibility of a subsequent favorable response to the treatment still exists.

  11. Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach.

    Directory of Open Access Journals (Sweden)

    Sofia D Karamintziou

    Full Text Available Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson's disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications.

  12. Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach.

    Science.gov (United States)

    Karamintziou, Sofia D; Custódio, Ana Luísa; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stéphan; Stathis, Pantelis G; Tagaris, George A; Sakas, Damianos E; Polychronaki, Georgia E; Tsirogiannis, George L; David, Olivier; Nikita, Konstantina S

    2017-01-01

    Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson's disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications.

  13. Nonlinear predictive control for adaptive adjustments of deep brain stimulation parameters in basal ganglia-thalamic network.

    Science.gov (United States)

    Su, Fei; Wang, Jiang; Niu, Shuangxia; Li, Huiyan; Deng, Bin; Liu, Chen; Wei, Xile

    2018-02-01

    The efficacy of deep brain stimulation (DBS) for Parkinson's disease (PD) depends in part on the post-operative programming of stimulation parameters. Closed-loop stimulation is one method to realize the frequent adjustment of stimulation parameters. This paper introduced the nonlinear predictive control method into the online adjustment of DBS amplitude and frequency. This approach was tested in a computational model of basal ganglia-thalamic network. The autoregressive Volterra model was used to identify the process model based on physiological data. Simulation results illustrated the efficiency of closed-loop stimulation methods (amplitude adjustment and frequency adjustment) in improving the relay reliability of thalamic neurons compared with the PD state. Besides, compared with the 130Hz constant DBS the closed-loop stimulation methods can significantly reduce the energy consumption. Through the analysis of inter-spike-intervals (ISIs) distribution of basal ganglia neurons, the evoked network activity by the closed-loop frequency adjustment stimulation was closer to the normal state. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Deep brain stimulation of the subthalamic nucleus modulates sensitivity to decision outcome value in Parkinson’s disease

    Science.gov (United States)

    Seymour, Ben; Barbe, Michael; Dayan, Peter; Shiner, Tamara; Dolan, Ray; Fink, Gereon R.

    2016-09-01

    Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson’s disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson’s Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson’s disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought.

  15. The role of deep brain stimulation in Parkinson’s disease: an overview and update on new developments

    Directory of Open Access Journals (Sweden)

    Fang JY

    2017-03-01

    Full Text Available John Y Fang, Christopher Tolleson Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA Abstract: Parkinson’s disease (PD is a progressive neurodegenerative disorder characterized by the loss of neuronal dopamine production in the brain. Oral therapies primarily augment the dopaminergic pathway. As the disease progresses, more continuous delivery of therapy is commonly needed. Deep brain stimulation (DBS has become an effective therapy option for several different neurologic and psychiatric conditions, including PD. It currently has US Food and Drug Administration approval for PD and essential tremor, as well as a humanitarian device exception for dystonia and obsessive-compulsive disorder. For PD treatment, it is currently approved specifically for those patients suffering from complications of pharmacotherapy, including motor fluctuations or dyskinesias, and a disease process of at least 4 years of duration. Studies have demonstrated superiority of DBS and medical management compared to medical management alone in selected PD patients. Optimal patient selection criteria, choice of target, and programming methods for PD and the other indications for DBS are important topics that continue to be explored and remain works in progress. In addition, new hardware options, such as different types of leads, and different software options have recently become available, increasing the potential for greater efficacy and/or reduced side effects. This review gives an overview of therapeutic management in PD, specifically highlighting DBS and some of the recent changes with surgical therapy. Keywords: Parkinson’s disease, deep brain stimulation, functional neurosurgery 

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

    Science.gov (United States)

    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

  17. Cortical Plasticity Induction by Pairing Subthalamic Nucleus Deep-Brain Stimulation and Primary Motor Cortical Transcranial Magnetic Stimulation in Parkinson's Disease.

    Science.gov (United States)

    Udupa, Kaviraja; Bahl, Nina; Ni, Zhen; Gunraj, Carolyn; Mazzella, Filomena; Moro, Elena; Hodaie, Mojgan; Lozano, Andres M; Lang, Anthony E; Chen, Robert

    2016-01-13

    Noninvasive brain stimulation studies have shown abnormal motor cortical plasticity in Parkinson's disease (PD). These studies used peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) to primary motor cortex (M1) at specific intervals to induce plasticity. Induction of cortical plasticity through stimulation of the basal ganglia (BG)-M1 connections has not been studied. In the present study, we used a novel technique of plasticity induction by repeated pairing of deep-brain stimulation (DBS) of the BG with M1 stimulation using TMS. We hypothesize that repeated pairing of subthalamic nucleus (STN)-DBS and M1-TMS at specific time intervals will lead to plasticity in the M1. Ten PD human patients with STN-DBS were studied in the on-medication state with DBS set to 3 Hz. The interstimulus intervals (ISIs) between STN-DBS and TMS that produced cortical facilitation were determined individually for each patient. Three plasticity induction conditions with repeated pairings (180 times) at specific ISIs (∼ 3 and ∼ 23 ms) that produced cortical facilitation and a control ISI of 167 ms were tested in random order. Repeated pairing of STN-DBS and M1-TMS at short (∼ 3 ms) and medium (∼ 23 ms) latencies increased M1 excitability that lasted for at least 45 min, whereas the control condition (fixed ISI of 167 ms) had no effect. There were no specific changes in motor thresholds, intracortical circuits, or recruitment curves. Our results indicate that paired-associative cortical plasticity can be induced by repeated STN and M1 stimulation at specific intervals. These results show that STN-DBS can modulate cortical plasticity. We introduced a new experimental paradigm to test the hypothesis that pairing subthalamic nucleus deep-brain stimulation (STN-DBS) with motor cortical transcranial magnetic stimulation (M1-TMS) at specific times can induce cortical plasticity in patients with Parkinson's disease (PD). We found that repeated pairing of STN

  18. Serial 1H-MRS of thalamus during deep brain stimulation of bilateral globus pallidus internus for primary generalized dystonia

    International Nuclear Information System (INIS)

    Chernov, Mikhail F.; Iseki, Hiroshi; Takakura, Kintomo; Ochiai, Taku; Taira, Takaomi; Hori, Tomokatsu; Ono, Yuko; Nakamura, Ryoichi; Muragaki, Yoshihiro

    2008-01-01

    The physiological mechanisms of deep brain stimulation (DBS) are not completely clear. Our understanding of them may be facilitated with the use of proton magnetic resonance spectroscopy ( 1 H-MRS). Serial 1 H-MRS of both thalami was performed during the course of DBS of bilateral globus pallidus internus in a patient with primary generalized dystonia. Two days after microelectrode implantation, a pulse frequency of 185 Hz was applied for stimulation. It resulted in relief of symptoms and a decrease of Burke-Fahn-Marsden dystonia rating scale (BFMDRS) scores, and was accompanied by a prominent increase of N-acetylaspartate (NAA)/choline-containing compounds (Cho) ratio, a mild increase of NAA/creatine (Cr) ratio, and a moderate decrease of Cho/Cr ratio. Two weeks later, for a search of the optimal stimulation mode, the pulse frequency was switched to 60 Hz, which resulted in clinical deterioration and significant increase of BFMDRS scores. At that time, all investigated 1 H-MRS-detected metabolic parameters had nearly returned to the pretreatment levels. Use of serial 1 H-MRS investigations of various brain structures during DBS in cases of movement disorders permits detailed evaluation of the treatment response, has a potential for its possible prediction, and may facilitate understanding of the physiological mechanisms of stimulation. (orig.)

  19. Long-term implantation of deep brain stimulation electrodes in the pontine micturition centre of the Göttingen minipig.

    Science.gov (United States)

    Jensen, Kristian N; Deding, Dorthe; Sørensen, Jens Christian; Bjarkam, Carsten R

    2009-07-01

    To implant deep brain stimulation (DBS) electrodes in the porcine pontine micturition centre (PMC) in order to establish a large animal model of PMC-DBS. Brain stems from four Göttingen minipigs were sectioned coronally into 40-mum-thick histological sections and stained with Nissl, auto-metallographic myelin stain, tyrosine hydroxylase and corticotrophin-releasing factor immunohistochemistry in order to identify the porcine PMC. DBS electrodes were then stereotaxically implanted on the right side into the PMC in four Göttingen minipigs, and the bladder response to electrical stimulation was evaluated by subsequent cystometry performed immediately after the operation and several weeks later. A paired CRF-dense area homologous to the PMC in other species was encountered in the rostral pontine tegmentum medial to the locus coeruleus and ventral to the floor of the fourth ventricle. Electrical stimulation of the CRF-dense area resulted in an increased detrusor pressure followed by visible voiding in some instances. The pigs were allowed to survive between 14 and 55 days, and electrical stimulation resulting in an increased detrusor pressure was performed on more than one occasion without affecting consciousness or general thriving. None of the pigs developed postoperative infections or died prematurely. DBS electrodes can be implanted for several weeks in the identified CRF-dense area resulting in a useful large animal model for basic research on micturition and the future clinical use of this treatment modality in neurogenic supra-pontine voiding disorders.

  20. Deep Brain Stimulation of the Subthalamic Nucleus Parameter Optimization for Vowel Acoustics and Speech Intelligibility in Parkinson's Disease

    Science.gov (United States)

    Knowles, Thea; Adams, Scott; Abeyesekera, Anita; Mancinelli, Cynthia; Gilmore, Greydon; Jog, Mandar

    2018-01-01

    Purpose: The settings of 3 electrical stimulation parameters were adjusted in 12 speakers with Parkinson's disease (PD) with deep brain stimulation of the subthalamic nucleus (STN-DBS) to examine their effects on vowel acoustics and speech intelligibility. Method: Participants were tested under permutations of low, mid, and high STN-DBS frequency,…

  1. Deep brain stimulation of the subthalamic nucleus alters frontal activity during spatial working memory maintenance of patients with Parkinson's disease.

    Science.gov (United States)

    Mayer, Jutta S; Neimat, Joseph; Folley, Bradley S; Bourne, Sarah K; Konrad, Peter E; Charles, David; Park, Sohee

    2016-08-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). The STN may represent an important relay station not only in the motor but also the associative cortico-striato-thalamocortical pathway. Therefore, STN stimulation may alter cognitive functions, such as working memory (WM). We examined cortical effects of STN-DBS on WM in early PD patients using functional near-infrared spectroscopy. The effects of dopaminergic medication on WM were also examined. Lateral frontal activity during WM maintenance was greater when patients were taking dopaminergic medication. STN-DBS led to a trend-level worsening of WM performance, accompanied by increased lateral frontal activity during WM maintenance. These findings suggest that STN-DBS in PD might lead to functional modifications of the basal ganglia-thalamocortical pathway during WM maintenance.

  2. Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank - A Review of Emerging Issues and Technologies

    Directory of Open Access Journals (Sweden)

    Wissam Deeb

    2016-11-01

    Full Text Available This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual Deep Brain Stimulation Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson’s disease, essential tremor, Alzheimer’s disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year’s international Think Tank, with a view toward current and near future advancement of the field.

  3. Effects of deep brain stimulation on balance and gait in patients with Parkinson's disease: A systematic neurophysiological review.

    Science.gov (United States)

    Collomb-Clerc, A; Welter, M-L

    2015-11-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) provides an efficient treatment for the alleviation of motor signs in patients with Parkinson's disease. The effects of DBS on gait and balance disorders are less successful and may even lead to an aggravation of freezing of gait and imbalance. The identification of a substantia nigra pars reticulata (SNr)-mesencephalic locomotor region (MLR) network in the control of locomotion and postural control and of its dysfunction/lesion in PD patients with gait and balance disorders led to suggestion that DBS should be targeting the SNr and the pedunculopontine nucleus (part of the MLR) for PD patients with these disabling axial motor signs. However, the clinical results to date have been disappointing. In this review, we discuss the effects of DBS of these basal ganglia and brainstem structures on the neurophysiological parameters of gait and balance control in PD patients. Overall, the data suggest that both STN and GPi-DBS improve gait parameters and quiet standing postural control in PD patients, but have no effect or may even aggravate dynamic postural control, in particular with STN-DBS. Conversely, DBS of the SNr and PPN has no effect on gait parameters but improves anticipatory postural adjustments and gait postural control. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  4. Decline in verbal fluency after subthalamic nucleus deep brain stimulation in Parkinson's disease: a microlesion effect of the electrode trajectory?

    Science.gov (United States)

    Le Goff, Floriane; Derrey, Stéphane; Lefaucheur, Romain; Borden, Alaina; Fetter, Damien; Jan, Maryvonne; Wallon, David; Maltête, David

    2015-01-01

    Decline in verbal fluency (VF) is frequently reported after chronic deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson disease (PD). We investigated whether the trajectory of the implanted electrode correlate with the VF decline 6 months after surgery. We retrospectively analysed 59 PD patients (mean age, 61.9 ± 7; mean disease duration, 13 ± 4.6) who underwent bilateral STN-DBS. The percentage of VF decline 6 months after STN-DBS in the on-drug/on-stimulation condition was determined in respect of the preoperative on-drug condition. The patients were categorised into two groups (decline and stable) for each VF. Cortical entry angles, intersection with deep grey nuclei (caudate, thalamic or pallidum), and anatomical extent of the STN affected by the electrode pathway, were compared between groups. A significant decline of both semantic and phonemic VF was found after surgery, respectively 14.9% ± 22.1 (P < 0.05) and 14.2% ± 30.3 (P < 0.05). Patients who declined in semantic VF (n = 44) had a left trajectory with a more anterior cortical entry point (56 ± 53 versus 60 ± 55 degree, P = 0.01) passing less frequently trough the thalamus (P = 0.03). Microlesion of left brain regions may contribute to subtle cognitive impairment following STN-DBS in PD.

  5. Development of a Compact Rectenna for Wireless Powering of a Head-Mountable Deep Brain Stimulation Device.

    Science.gov (United States)

    Hosain, M D Kamal; Kouzani, Abbas Z; Tye, Susannah J; Abulseoud, Osama A; Amiet, Andrew; Galehdar, Amir; Kaynak, Akif; Berk, Michael

    2014-01-01

    Design of a rectangular spiral planar inverted-F antenna (PIFA) at 915 MHz for wireless power transmission applications is proposed. The antenna and rectifying circuitry form a rectenna, which can produce dc power from a distant radio frequency energy transmitter. The generated dc power is used to operate a low-power deep brain stimulation pulse generator. The proposed antenna has the dimensions of 10 mm [Formula: see text]12.5 mm [Formula: see text]1.5 mm and resonance frequency of 915 MHz with a measured bandwidth of 15 MHz at return loss of [Formula: see text]. A dielectric substrate of FR-4 of [Formula: see text] and [Formula: see text] with thickness of 1.5 mm is used for both antenna and rectifier circuit simulation and fabrication because of its availability and low cost. An L-section impedance matching circuit is used between the PIFA and voltage doubler rectifier. The impedance matching circuit also works as a low-pass filter for elimination of higher order harmonics. Maximum dc voltage at the rectenna output is 7.5 V in free space and this rectenna can drive a deep brain stimulation pulse generator at a distance of 30 cm from a radio frequency energy transmitter, which transmits power of 26.77 dBm.

  6. State of the Art for Deep Brain Stimulation Therapy in Movement Disorders: A Clinical and Technological Perspective.

    Science.gov (United States)

    Wagle Shukla, Aparna; Okun, Michael S

    2016-01-01

    Deep brain stimulation (DBS) therapy is a widely used brain surgery that can be applied for many neurological and psychiatric disorders. DBS is American Food and Drug Administration approved for medication refractory Parkinson's disease, essential tremor and dystonia. Although DBS has shown consistent success in many clinical trials, the therapy has limitations and there are well-recognized complications. Thus, only carefully selected patients are ideal candidates for this surgery. Over the last two decades, there have been significant advances in clinical knowledge on DBS. In addition, the surgical techniques and technology related to DBS has been rapidly evolving. The goal of this review is to describe the current status of DBS in the context of movement disorders, outline the mechanisms of action for DBS in brief, discuss the standard surgical and imaging techniques, discuss the patient selection and clinical outcomes in each of the movement disorders, and finally, introduce the recent advancements from a clinical and technological perspective.

  7. Effective deep brain stimulation suppresses low frequency network oscillations in the basal ganglia by regularizing neural firing patterns

    Science.gov (United States)

    McConnell, George C.; So, Rosa Q.; Hilliard, Justin D; Lopomo, Paola; Grill, Warren M.

    2012-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson’s disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90Hz) improve motor symptoms, while low frequencies (basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high frequency DBS reversed motor symptoms and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high frequency DBS, but not low frequency DBS, reduced pathological low frequency oscillations (~9Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low frequency band to the stimulation frequency during high frequency DBS, but not during low frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high frequency DBS is more effective than low frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low frequency network oscillations with a regularized pattern of neuronal firing. PMID:23136407

  8. Effective deep brain stimulation suppresses low-frequency network oscillations in the basal ganglia by regularizing neural firing patterns.

    Science.gov (United States)

    McConnell, George C; So, Rosa Q; Hilliard, Justin D; Lopomo, Paola; Grill, Warren M

    2012-11-07

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson's disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90 Hz) improve motor symptoms, while low frequencies (basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high-frequency DBS reversed motor symptoms, and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high-frequency DBS, but not low-frequency DBS, reduced pathological low-frequency oscillations (∼9 Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low-frequency band to the stimulation frequency during high-frequency DBS, but not during low-frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high-frequency DBS is more effective than low-frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low-frequency network oscillations with a regularized pattern of neuronal firing.

  9. The effects of unilateral versus bilateral subthalamic nucleus deep brain stimulation on prosaccades and antisaccades in Parkinson's disease.

    Science.gov (United States)

    Goelz, Lisa C; David, Fabian J; Sweeney, John A; Vaillancourt, David E; Poizner, Howard; Metman, Leonard Verhagen; Corcos, Daniel M

    2017-02-01

    Unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease improves skeletomotor function assessed clinically, and bilateral STN DBS improves motor function to a significantly greater extent. It is unknown whether unilateral STN DBS improves oculomotor function and whether bilateral STN DBS improves it to a greater extent. Further, it has also been shown that bilateral, but not unilateral, STN DBS is associated with some impaired cognitive-motor functions. The current study compared the effect of unilateral and bilateral STN DBS on sensorimotor and cognitive aspects of oculomotor control. Patients performed prosaccade and antisaccade tasks during no stimulation, unilateral stimulation, and bilateral stimulation. There were three sets of findings. First, for the prosaccade task, unilateral STN DBS had no effect on prosaccade latency and it reduced prosaccade gain; bilateral STN DBS reduced prosaccade latency and increased prosaccade gain. Second, for the antisaccade task, neither unilateral nor bilateral stimulation had an effect on antisaccade latency, unilateral STN DBS increased antisaccade gain, and bilateral STN DBS increased antisaccade gain to a greater extent. Third, bilateral STN DBS induced an increase in prosaccade errors in the antisaccade task. These findings suggest that while bilateral STN DBS benefits spatiotemporal aspects of oculomotor control, it may not be as beneficial for more complex cognitive aspects of oculomotor control. Our findings are discussed considering the strategic role the STN plays in modulating information in the basal ganglia oculomotor circuit.

  10. Thalamo–cortical network underlying deep brain stimulation of centromedian thalamic nuclei in intractable epilepsy: a multimodal imaging analysis

    Directory of Open Access Journals (Sweden)

    Kim SH

    2017-10-01

    Full Text Available Seong Hoon Kim,1 Sung Chul Lim,1 Dong Won Yang,1 Jeong Hee Cho,1 Byung-Chul Son,2 Jiyeon Kim,3 Seung Bong Hong,4 Young-Min Shon4 1Department of Neurology, 2Department of Neurosurgery, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, 3Department of Neurology, Korea University Ansan Hospital, College of Medicine, Korea University, Ansan, 4Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Objective: Deep brain stimulation (DBS of the centromedian thalamic nucleus (CM can be an alternative treatment option for intractable epilepsy patients. Since CM may be involved in widespread cortico-subcortical networks, identification of the cortical sub-networks specific to the target stimuli may provide further understanding on the underlying mechanisms of CM DBS. Several brain structures have distinguishing brain connections that may be related to the pivotal propagation and subsequent clinical effect of DBS.Methods: To explore core structures and their connections relevant to CM DBS, we applied electroencephalogram (EEG and diffusion tensor imaging (DTI to 10 medically intractable patients – three generalized epilepsy (GE and seven multifocal epilepsy (MFE patients unsuitable for resective surgery. Spatiotemporal activation pattern was mapped from scalp EEG by delivering low-frequency stimuli (5 Hz. Structural connections between the CM and the cortical activation spots were assessed using DTI.Results: We confirmed an average 72% seizure reduction after CM DBS and its clinical efficiency remained consistent during the observation period (mean 21 months. EEG data revealed sequential source propagation from the anterior cingulate, followed by the frontotemporal regions bilaterally. In addition, maximal activation was found in the left cingulate gyrus and the right medial frontal cortex during the right and left CM stimulation, respectively

  11. EDITORIAL: Deep brain stimulation, deontology and duty: the moral obligation of non-abandonment at the neural interface Deep brain stimulation, deontology and duty: the moral obligation of non-abandonment at the neural interface

    Science.gov (United States)

    Fins, Joseph J.; MD; FACP

    2009-10-01

    At the height of the psychosurgery debate the editors of The Lancet referenced the popular hesitancy to intervene surgically with the workings of the brain. They wrote that to do so `carries a peculiar penumbra of sacrilege' [1, 2]. Penumbra of sacrilege is a memorable, even strange phrase. It is one worth unpacking as we embark on an era which will see ever more border crossings at the blood-brain barrier. By invoking popular beliefs about a penumbra of sacrilege, the editors were suggesting that psychosurgery represented a gray zone in the shadows, a desecration or violation of a sacred space, the seat of the soul, the self. And as such, they were reflecting a cultural hesitancy, a lay reluctance to pursue this work. Fortunately for those with intractable neuropsychiatric disorders, neuromodulation has evolved beyond the primitive—and barbaric—sweep of the lobotomy, and with this advance, categorical resistance to this work has dissipated. And that is all to the good. But as the field progresses, and we implant more and more devices for therapeutic and investigational purposes, we must not let the placement of electrodes become too easy. It is a decision that should be made with full awareness of its implications for patients and families. Recently, I spoke to a friend who appeared to have early essential tremor. (Some non-essential aspects of this story have been changed to protect confidentiality.) He asked me, `Do you know anything about deep brain stimulation?' I indicated that I did. `Really?', he asked, seemingly unaware of my scholarly interest in the topic [3, 4, 5, 6] and involvement as a co-investigator in the use of deep brain stimulation in the minimally conscious state [7, 8, 9]. Satisfied that I might be a credible source for some free advice, he told me that his neurologist had sent him to a neurosurgeon to see about a stimulator. I asked him how disabling his condition was. As he competently drank a cup of soda, he told me it was a bit of a

  12. Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders

    Science.gov (United States)

    2014-01-01

    Background Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood. Results Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically. Conclusions Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models. PMID:24512669

  13. A wirelessly controlled implantable LED system for deep brain optogenetic stimulation

    Science.gov (United States)

    Rossi, Mark A.; Go, Vinson; Murphy, Tracy; Fu, Quanhai; Morizio, James; Yin, Henry H.

    2015-01-01

    In recent years optogenetics has rapidly become an essential technique in neuroscience. Its temporal and spatial specificity, combined with efficacy in manipulating neuronal activity, are especially useful in studying the behavior of awake behaving animals. Conventional optogenetics, however, requires the use of lasers and optic fibers, which can place considerable restrictions on behavior. Here we combined a wirelessly controlled interface and small implantable light-emitting diode (LED) that allows flexible and precise placement of light source to illuminate any brain area. We tested this wireless LED system in vivo, in transgenic mice expressing channelrhodopsin-2 in striatonigral neurons expressing D1-like dopamine receptors. In all mice tested, we were able to elicit movements reliably. The frequency of twitches induced by high power stimulation is proportional to the frequency of stimulation. At lower power, contraversive turning was observed. Moreover, the implanted LED remains effective over 50 days after surgery, demonstrating the long-term stability of the light source. Our results show that the wireless LED system can be used to manipulate neural activity chronically in behaving mice without impeding natural movements. PMID:25713516

  14. Deep Brain Stimulation of Caudal Zona Incerta and Subthalamic Nucleus in Patients with Parkinson's Disease: Effects on Voice Intensity

    Directory of Open Access Journals (Sweden)

    Sofie Lundgren

    2011-01-01

    Full Text Available Deep brain stimulation of the subthalamic nucleus (STN-DBS in patients with Parkinson's disease (PD affects speech inconsistently. Recently, stimulation of the caudal zona incerta (cZi-DBS has shown superior motor outcomes for PD patients, but effects on speech have not been systematically investigated. The aim of this study was to compare the effects of cZi-DBS and STN-DBS on voice intensity in PD patients. Mean intensity during reading and intensity decay during rapid syllable repetition were measured for STN-DBS and cZi-DBS patients (eight patients per group, before- and 12 months after-surgery on- and off-stimulation. For mean intensity, there were small significant differences on- versus off-stimulation in each group: 74.2 (2.0 dB contra 72.1 (2.2 dB (=.002 for STN-DBS, and 71.6 (4.1 dB contra 72.8 (3.4 dB (=.03 for cZi-DBS, with significant interaction (<.001. Intensity decay showed no significant changes. The subtle differences found for mean intensity suggest that STN-DBS and cZi-DBS may influence voice intensity differently.

  15. The effects of Thalamic Deep Brain Stimulation on speech dynamics in patients with Essential Tremor: An articulographic study.

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    Doris Mücke

    Full Text Available Acoustic studies have revealed that patients with Essential Tremor treated with thalamic Deep Brain Stimulation (DBS may suffer from speech deterioration in terms of imprecise oral articulation and reduced voicing control. Based on the acoustic signal one cannot infer, however, whether this deterioration is due to a general slowing down of the speech motor system (e.g., a target undershoot of a desired articulatory goal resulting from being too slow or disturbed coordination (e.g., a target undershoot caused by problems with the relative phasing of articulatory movements. To elucidate this issue further, we here investigated both acoustics and articulatory patterns of the labial and lingual system using Electromagnetic Articulography (EMA in twelve Essential Tremor patients treated with thalamic DBS and twelve age- and sex-matched controls. By comparing patients with activated (DBS-ON and inactivated stimulation (DBS-OFF with control speakers, we show that critical changes in speech dynamics occur on two levels: With inactivated stimulation (DBS-OFF, patients showed coordination problems of the labial and lingual system in terms of articulatory imprecision and slowness. These effects of articulatory discoordination worsened under activated stimulation, accompanied by an additional overall slowing down of the speech motor system. This leads to a poor performance of syllables on the acoustic surface, reflecting an aggravation either of pre-existing cerebellar deficits and/or the affection of the upper motor fibers of the internal capsule.

  16. From Parkinsonian thalamic activity to restoring thalamic relay using deep brain stimulation: new insights from computational modeling

    Science.gov (United States)

    Meijer, H. G. E.; Krupa, M.; Cagnan, H.; Lourens, M. A. J.; Heida, T.; Martens, H. C. F.; Bour, L. J.; van Gils, S. A.

    2011-10-01

    We present a computational model of a thalamocortical relay neuron for exploring basal ganglia thalamocortical loop behavior in relation to Parkinson's disease and deep brain stimulation (DBS). Previous microelectrode, single-unit recording studies demonstrated that oscillatory interaction within and between basal ganglia nuclei is very often accompanied by synchronization at Parkinsonian rest tremor frequencies (3-10 Hz). These oscillations have a profound influence on thalamic projections and impair the thalamic relaying of cortical input by generating rebound action potentials. Our model describes convergent inhibitory input received from basal ganglia by the thalamocortical cells based on characteristics of normal activity, and/or low-frequency oscillations (activity associated with Parkinson's disease). In addition to simulated input, we also used microelectrode recordings as inputs for the model. In the resting state, and without additional sensorimotor input, pathological rebound activity is generated for even mild Parkinsonian input. We have found a specific stimulation window of amplitudes and frequencies for periodic input, which corresponds to high-frequency DBS, and which also suppresses rebound activity for mild and even more prominent Parkinsonian input. When low-frequency pathological rebound activity disables the thalamocortical cell's ability to relay excitatory cortical input, a stimulation signal with parameter settings corresponding to our stimulation window can restore the thalamocortical cell's relay functionality.

  17. Evolving Concepts in Posterior Subthalamic Area Deep Brain Stimulation for Treatment of Tremor: Surgical Neuroanatomy and Practical Considerations.

    Science.gov (United States)

    Ramirez-Zamora, Adolfo; Smith, Heather; Kumar, Vignessh; Prusik, Julia; Phookan, Sujoy; Pilitsis, Julie G

    2016-01-01

    Although thalamic deep brain stimulation (DBS) has been established as an effective therapy for refractory tremor in Parkinson's disease and essential tremor, reports investigating the efficacy of posterior subthalamic area (PSA) DBS for severe, debilitating tremors continue to emerge. However, questions regarding the optimal anatomical target, surgical approach, programming paradigms and effectiveness compared to other targets remain. In this report, we aimed to review the current literature to assess different stereotactic techniques, anatomical considerations, adverse effects and stimulation settings in PSA DBS. A comprehensive literature review was performed searching for articles discussing tremors and PSA stimulation. We performed a quantitative analysis comparing different DBS tremor targets. Tremor improvement is consistently documented in most reports with an average reduction in tremor of 79% depending on the specific tremor syndrome. Tremor benefit in patients with multiple sclerosis (MS) tremor was significantly higher than for other stimulation targets. Transient paresthesias, imbalance, dizziness and dysarthria are the most common side effects with PSA DBS. PSA DBS is an effective and safe treatment for tremor control and should be considered in patients with refractory tremors with associated cerebellar or dystonic features, proximal tremors and MS tremor. © 2016 S. Karger AG, Basel.

  18. Hearing assessment during deep brain stimulation of the central nucleus of the inferior colliculus and dentate cerebellar nucleus in rat

    Directory of Open Access Journals (Sweden)

    Jasper V. Smit

    2017-10-01

    Full Text Available Background Recently it has been shown in animal studies that deep brain stimulation (DBS of auditory structures was able to reduce tinnitus-like behavior. However, the question arises whether hearing might be impaired when interfering in auditory-related network loops with DBS. Methods The auditory brainstem response (ABR was measured in rats during high frequency stimulation (HFS and low frequency stimulation (LFS in the central nucleus of the inferior colliculus (CIC, n = 5 or dentate cerebellar nucleus (DCBN, n = 5. Besides hearing thresholds using ABR, relative measures of latency and amplitude can be extracted from the ABR. In this study ABR thresholds, interpeak latencies (I–III, III–V, I–V and V/I amplitude ratio were measured during off-stimulation state and during LFS and HFS. Results In both the CIC and the CNBN groups, no significant differences were observed for all outcome measures. Discussion DBS in both the CIC and the CNBN did not have adverse effects on hearing measurements. These findings suggest that DBS does not hamper physiological processing in the auditory circuitry.

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

    Science.gov (United States)

    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.

  20. Opposite effects of ketamine and deep brain stimulation on rat thalamocortical information processing.

    Science.gov (United States)

    Kulikova, Sofya P; Tolmacheva, Elena A; Anderson, Paul; Gaudias, Julien; Adams, Brendan E; Zheng, Thomas; Pinault, Didier

    2012-11-01

    Sensory and cognitive deficits are common in schizophrenia. They are associated with abnormal brain rhythms, including disturbances in γ frequency (30-80 Hz) oscillations (GFO) in cortex-related networks. However, the underlying anatomofunctional mechanisms remain elusive. Clinical and experimental evidence suggests that these deficits result from a hyporegulation of glutamate N-methyl-D-aspartate receptors. Here we modeled these deficits in rats with ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist and a translational psychotomimetic substance at subanesthetic doses. We tested the hypothesis that ketamine-induced sensory deficits involve an impairment of the ability of the thalamocortical (TC) system to discriminate the relevant information from the baseline activity. Furthermore, we wanted to assess whether ketamine disrupts synaptic plasticity in TC systems. We conducted multisite network recordings in the rat somatosensory TC system, natural stimulation of the vibrissae and high-frequency electrical stimulation (HFS) of the thalamus. A single systemic injection of ketamine increased the amount of baseline GFO, reduced the amplitude of the sensory-evoked TC response and decreased the power of the sensory-evoked GFO. Furthermore, cortical application of ketamine elicited local and distant increases in baseline GFO. The ketamine effects were transient. Unexpectedly, HFS of the TC pathway had opposite actions. In conclusion, ketamine and thalamic HFS have opposite effects on the ability of the somatosensory TC system to discriminate the sensory-evoked response from the baseline GFO during information processing. Investigating the link between the state and function of the TC system may conceptually be a key strategy to design innovative therapies against neuropsychiatric disorders. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  1. Creating and parameterizing patient-specific deep brain stimulation pathway-activation models using the hyperdirect pathway as an example.

    Science.gov (United States)

    Gunalan, Kabilar; Chaturvedi, Ashutosh; Howell, Bryan; Duchin, Yuval; Lempka, Scott F; Patriat, Remi; Sapiro, Guillermo; Harel, Noam; McIntyre, Cameron C

    2017-01-01

    Deep brain stimulation (DBS) is an established clinical therapy and computational models have played an important role in advancing the technology. Patient-specific DBS models are now common tools in both academic and industrial research, as well as clinical software systems. However, the exact methodology for creating patient-specific DBS models can vary substantially and important technical details are often missing from published reports. Provide a detailed description of the assembly workflow and parameterization of a patient-specific DBS pathway-activation model (PAM) and predict the response of the hyperdirect pathway to clinical stimulation. Integration of multiple software tools (e.g. COMSOL, MATLAB, FSL, NEURON, Python) enables the creation and visualization of a DBS PAM. An example DBS PAM was developed using 7T magnetic resonance imaging data from a single unilaterally implanted patient with Parkinson's disease (PD). This detailed description implements our best computational practices and most elaborate parameterization steps, as defined from over a decade of technical evolution. Pathway recruitment curves and strength-duration relationships highlight the non-linear response of axons to changes in the DBS parameter settings. Parameterization of patient-specific DBS models can be highly detailed and constrained, thereby providing confidence in the simulation predictions, but at the expense of time demanding technical implementation steps. DBS PAMs represent new tools for investigating possible correlations between brain pathway activation patterns and clinical symptom modulation.

  2. Creating and parameterizing patient-specific deep brain stimulation pathway-activation models using the hyperdirect pathway as an example.

    Directory of Open Access Journals (Sweden)

    Kabilar Gunalan

    Full Text Available Deep brain stimulation (DBS is an established clinical therapy and computational models have played an important role in advancing the technology. Patient-specific DBS models are now common tools in both academic and industrial research, as well as clinical software systems. However, the exact methodology for creating patient-specific DBS models can vary substantially and important technical details are often missing from published reports.Provide a detailed description of the assembly workflow and parameterization of a patient-specific DBS pathway-activation model (PAM and predict the response of the hyperdirect pathway to clinical stimulation.Integration of multiple software tools (e.g. COMSOL, MATLAB, FSL, NEURON, Python enables the creation and visualization of a DBS PAM. An example DBS PAM was developed using 7T magnetic resonance imaging data from a single unilaterally implanted patient with Parkinson's disease (PD. This detailed description implements our best computational practices and most elaborate parameterization steps, as defined from over a decade of technical evolution.Pathway recruitment curves and strength-duration relationships highlight the non-linear response of axons to changes in the DBS parameter settings.Parameterization of patient-specific DBS models can be highly detailed and constrained, thereby providing confidence in the simulation predictions, but at the expense of time demanding technical implementation steps. DBS PAMs represent new tools for investigating possible correlations between brain pathway activation patterns and clinical symptom modulation.

  3. Restoring the basal ganglia in Parkinson's disease to normal via multi-input phase-shifted deep brain stimulation.

    Science.gov (United States)

    Agarwal, Rahul; Sarma, Sridevi V

    2010-01-01

    Deep brain stimulation (DBS) injects a high frequency current that effectively disables the diseased basal ganglia (BG) circuit in Parkinson's disease (PD) patients, leading to a reversal of motor symptoms. Though therapeutic, high frequency stimulation consumes significant power forcing frequent surgical battery replacements and causing widespread influence into other brain areas which may lead to adverse side effects. In this paper, we conducted a rigorous study to assess whether low frequency signals can restore behavior in PD patients by restoring neural activity in the BG to the normal state. We used a biophysical-based model of BG nuclei and motor thalamus whose parameters can be set to simulate the normal state and the PD state with and without DBS. We administered pulse train DBS waveforms to the subthalamic nucleus (STN) with frequencies ranging from 1-150Hz. For each DBS frequency, we computed statistics on the simulated neural activity to assess whether it is restored to the normal state. In particular, we searched for DBS waveforms that suppress pathological bursting, oscillations, correlations and synchronization prevalent in the PD state and that enable thalamic cells to relay cortical inputs reliably. We found that none of the tested waveforms restores neural activity to the normal state. However, our simulations led us to construct a novel DBS strategy involving low frequency multi-input phaseshifted DBS to be administered into the STN. This strategy successfully suppressed all pathological symptoms in the BG in addition to enabling thalamic cells to relay cortical inputs reliably.

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

    Directory of Open Access Journals (Sweden)

    Erwin B. Montgomery

    2016-08-01

    Full Text Available 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.

  5. Deep Brain Stimulation in Parkinson’s Disease: New and Emerging Targets for Refractory Motor and Nonmotor Symptoms

    Directory of Open Access Journals (Sweden)

    Dustin Anderson

    2017-01-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative condition characterized by bradykinesia, tremor, rigidity, and postural instability (PI, in addition to numerous nonmotor manifestations. Many pharmacological therapies now exist to successfully treat PD motor symptoms; however, as the disease progresses, it often becomes challenging to treat with medications alone. Deep brain stimulation (DBS has become a crucial player in PD treatment, particularly for patients who have disabling motor complications from medical treatment. Well-established DBS targets include the subthalamic nucleus (STN, the globus pallidus pars interna (GPi, and to a lesser degree the ventral intermediate nucleus (VIM of the thalamus. Studies of alternative DBS targets for PD are ongoing, the majority of which have shown some clinical benefit; however, more carefully designed and controlled studies are needed. In the present review, we discuss the role of these new and emerging DBS targets in treating refractory axial motor symptoms and other motor and nonmotor symptoms (NMS.

  6. Holmes’ Tremor with Shoulder Pain Treated by Deep Brain Stimulation of Unilateral Ventral Intermediate Thalamic Nucleus and Globus Pallidus Internus

    Directory of Open Access Journals (Sweden)

    Sabri Aydın

    2017-05-01

    Full Text Available A 21-year-old male was admitted with severe right arm and hand tremors after a thalamic hemorrhage caused by a traffic accident. He was also suffering from agonizing pain in his right shoulder that manifested after the tremor. Neurologic examination revealed a disabling, severe, and irregular kinetic and postural tremor in the right arm during target-directed movements. There was also an irregular ipsilateral rest tremor and dystonic movements in the distal part of the right arm. The amplitude was moderate at rest and extremely high during kinetic and intentional movements. The patient underwent left globus pallidum internus and ventral intermediate thalamic nucleus deep brain stimulation. The patient improved by more than 80% as rated by the Fahn-Tolosa-Marin Tremor Rating Scale and Visual Analog Scale six months after surgery.

  7. COMMUNICATION: Toward closed-loop optimization of deep brain stimulation for Parkinson's disease: concepts and lessons from a computational model

    Science.gov (United States)

    Feng, Xiao-jiang; Greenwald, Brian; Rabitz, Herschel; Shea-Brown, Eric; Kosut, Robert

    2007-06-01

    Deep brain stimulation (DBS) of the subthalamic nucleus with periodic, high-frequency pulse trains is an increasingly standard therapy for advanced Parkinson's disease. Here, we propose that a closed-loop global optimization algorithm may identify novel DBS waveforms that could be more effective than their high-frequency counterparts. We use results from a computational model of the Parkinsonian basal ganglia to illustrate general issues relevant to eventual clinical or experimental tests of such an algorithm. Specifically, while the relationship between DBS characteristics and performance is highly complex, global search methods appear able to identify novel and effective waveforms with convergence rates that are acceptably fast to merit further investigation in laboratory or clinical settings.

  8. Catatonia after deep brain stimulation successfully treated with lorazepam and right unilateral electroconvulsive therapy: a case report.

    Science.gov (United States)

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

    2014-09-01

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

  9. Deep brain stimulation: custom-made silicone-coated pulse-generator implantation after allergic reaction to generator compounds.

    Science.gov (United States)

    Anthofer, Judith; Herbst, Andreas; Janzen, Annettte; Lange, Max; Brawanski, Alexander; Schlaier, Juergen

    2018-02-01

    Deep brain stimulation for Parkinson's disease has become an established treatment option in recent years. The method and its application in clinical practice has proved to be safe and effective. Nevertheless, procedure-related and hardware-related complications occur. We present a rare case of a patient with an allergic reaction to the impulse generator. The patient suffered from delayed wound-healing deficits with several wound revisions and generator repositionings. After diagnosis of an allergic reaction to components of the generator, a custom-made silicon-coated model was implanted. Hereafter, no wound healing-deficit occurred throughout long-term follow-up. Allergic reaction to hardware components may lead to wound-healing deficits. In such cases, custom-made silicon-coated models may be an effective treatment option.

  10. Preoperative DTI and probabilistic tractography in an amputee with deep brain stimulation for lower limb stump pain.

    Science.gov (United States)

    Owen, S L F; Heath, J; Kringelbach, M L; Stein, J F; Aziz, T Z

    2007-10-01

    This study aimed to find out whether preoperative diffusion tensor imaging (DTI) and probabilistic tractography could help with surgical planning for deep brain stimulation in the periaqueductal/periventricular grey area (PAG/PVG) in a patient with lower leg stump pain. A preoperative DTI was obtained from the patient, who then received DBS surgery in the PAG/PVG area with good pain relief. The postoperative MRI scan showing electrode placement was used to calculate four seed areas to represent the contacts on the Medtronic 3387 electrode. Probabilistic tractography was then performed from the pre-operative DTI image. Tracts were seen to connect to many areas within the pain network from the four different contacts. These initial findings suggest that preoperative DTI scanning and probabilistic tractography may be able to assist surgical planning in the future.

  11. Successful deep brain stimulation surgery with intraoperative magnetic resonance imaging on a difficult neuroacanthocytosis case: case report.

    Science.gov (United States)

    Lim, Thien Thien; Fernandez, Hubert H; Cooper, Scott; Wilson, Kathryn Mary K; Machado, Andre G

    2013-07-01

    Chorea acanthocytosis is a progressive hereditary neurodegenerative disorder characterized by hyperkinetic movements, seizures, and acanthocytosis in the absence of any lipid abnormality. Medical treatment is typically limited and disappointing. We report on a 32-year-old patient with chorea acanthocytosis with a failed attempt at awake deep brain stimulation (DBS) surgery due to intraoperative seizures and postoperative intracranial hematoma. He then underwent a second DBS operation, but under general anesthesia and with intraoperative magnetic resonance imaging guidance. Marked improvement in his dystonia, chorea, and overall quality of life was noted 2 and 8 months postoperatively. DBS surgery of the bilateral globus pallidus pars interna may be useful in controlling the hyperkinetic movements in neuroacanthocytosis. Because of the high propensity for seizures in this disorder, DBS performed under general anesthesia, with intraoperative magnetic resonance imaging guidance, may allow successful implantation while maintaining accurate target localization.

  12. Effects of deep brain stimulation of the peduncolopontine area on working memory tasks in patients with Parkinson's disease.

    Science.gov (United States)

    Costa, Alberto; Carlesimo, Giovanni Augusto; Caltagirone, Carlo; Mazzone, Paolo; Pierantozzi, Mariangela; Stefani, Alessandro; Peppe, Antonella

    2010-01-01

    The present paper was aimed at investigating the effect of low-frequency electrical stimulation (25 Hz) of the peduncolopontine (PPN) area on working memory (WM) functioning in patients with Parkinson's disease (PD). Five PD patients who underwent simultaneous PPN area- and subthalamic nucleus-deep brain stimulation (DBS) implantation participated in the study. PD patients were evaluated in the morning at least 12 h after antiparkinsonian therapy withdrawal in two conditions: i) after continuous PPN area stimulation (Off Therapy/On PPN: "On" condition); ii) at least 120 min after PPN area had been switched "Off" (Off Ther/Off PPN: "Off" condition). The experimental WM task consisted of an n-back paradigm with verbal and visual-object stimuli. PD patients showed a consistent response time decrease on both the verbal and the visual-object tasks passing from the "Off" to the "On" condition (p processing of information in the content of WM, possibly through the modulation of the attentional resources.

  13. Network effects of subthalamic deep brain stimulation drive a unique mixture of responses in basal ganglia output.

    Science.gov (United States)

    Humphries, Mark D; Gurney, Kevin

    2012-07-01

    Deep brain stimulation (DBS) is a remarkably successful treatment for the motor symptoms of Parkinson's disease. High-frequency stimulation of the subthalamic nucleus (STN) within the basal ganglia is a main clinical target, but the physiological mechanisms of therapeutic STN DBS at the cellular and network level are unclear. We set out to begin to address the hypothesis that a mixture of responses in the basal ganglia output nuclei, combining regularized firing and inhibition, is a key contributor to the effectiveness of STN DBS. We used our computational model of the complete basal ganglia circuit to show how such a mixture of responses in basal ganglia output naturally arises from the network effects of STN DBS. We replicated the diversification of responses recorded in a primate STN DBS study to show that the model's predicted mixture of responses is consistent with therapeutic STN DBS. We then showed how this 'mixture of response' perspective suggests new ideas for DBS mechanisms: first, that the therapeutic frequency of STN DBS is above 100 Hz because the diversification of responses exhibits a step change above this frequency; and second, that optogenetic models of direct STN stimulation during DBS have proven therapeutically ineffective because they do not replicate the mixture of basal ganglia output responses evoked by electrical DBS. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  14. Mechanisms Underlying Decision-Making as Revealed by Deep-Brain Stimulation in Patients with Parkinson's Disease.

    Science.gov (United States)

    Herz, Damian M; Little, Simon; Pedrosa, David J; Tinkhauser, Gerd; Cheeran, Binith; Foltynie, Tom; Bogacz, Rafal; Brown, Peter

    2018-04-23

    To optimally balance opposing demands of speed and accuracy during decision-making, we must flexibly adapt how much evidence we require before making a choice. Such adjustments in decision thresholds have been linked to the subthalamic nucleus (STN), and therapeutic STN deep-brain stimulation (DBS) has been shown to interfere with this function. Here, we performed continuous as well as closed-loop DBS of the STN while Parkinson's disease patients performed a perceptual decision-making task. Closed-loop STN DBS allowed temporally patterned STN stimulation and simultaneous recordings of STN activity. This revealed that DBS only affected patients' ability to adjust decision thresholds if applied in a specific temporally confined time window during deliberation. Only stimulation in that window diminished the normal slowing of response times that occurred on difficult trials when DBS was turned off. Furthermore, DBS eliminated a relative, time-specific increase in STN beta oscillations and compromised its functional relationship with trial-by-trial adjustments in decision thresholds. Together, these results provide causal evidence that the STN is involved in adjusting decision thresholds in distinct, time-limited processing windows during deliberation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Choreatic Side Effects of Deep Brain Stimulation of the Anteromedial Subthalamic Nucleus for Treatment-Resistant Obsessive-Compulsive disorder.

    Science.gov (United States)

    Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin

    2017-08-01

    Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Long-range correlation properties in timing of skilled piano performance: the influence of auditory feedback and deep brain stimulation.

    Directory of Open Access Journals (Sweden)

    Maria eHerrojo Ruiz

    2014-09-01

    Full Text Available Unintentional timing deviations during musical performance can be conceived of as timing errors. However, recent research on humanizing computer-generated music has demonstrated that timing fluctuations that exhibit long-range temporal correlations (LRTC are preferred by human listeners. This preference can be accounted for by the ubiquitous presence of LRTC in human tapping and rhythmic performances. Interestingly, the manifestation of LRTC in tapping behavior seems to be driven in a subject-specific manner by the LRTC properties of resting-state background cortical oscillatory activity. In this framework, the current study aimed to investigate whether propagation of timing deviations during the skilled, memorized piano performance (without metronome of 17 professional pianists exhibits LRTC and whether the structure of the correlations is influenced by the presence or absence of auditory feedback.As an additional goal, we set out to investigate the influence of altering the dynamics along the cortico-basal-ganglia-thalamo-cortical network via deep brain stimulation (DBS on the LRTC properties of musical performance. Specifically, we investigated temporal deviations during the skilled piano performance of a non-professional pianist who was treated with subthalamic-deep brain stimulation (STN-DBS due to severe Parkinson's disease, with predominant tremor affecting his right upper extremity. In the tremor-affected right hand, the timing fluctuations of the performance exhibited random correlations with DBS OFF. By contrast, DBS restored long-range dependency in the temporal fluctuations, corresponding with the general motor improvement on DBS.Overall, the present investigations are the first to demonstrate the presence of LRTC in skilled piano performances, indicating that unintentional temporal deviations are correlated over a wide range of time scales. This phenomenon is stable after removal of the auditory feedback, but is altered by STN

  17. Toward defining deep brain stimulation targets in MNI space: A subcortical atlas based on multimodal MRI, histology and structural connectivity.

    Science.gov (United States)

    Ewert, Siobhan; Plettig, Philip; Li, Ningfei; Chakravarty, M Mallar; Collins, D Louis; Herrington, Todd M; Kühn, Andrea A; Horn, Andreas

    2018-04-15

    Three-dimensional atlases of subcortical brain structures are valuable tools to reference anatomy in neuroscience and neurology. For instance, they can be used to study the position and shape of the three most common deep brain stimulation (DBS) targets, the subthalamic nucleus (STN), internal part of the pallidum (GPi) and ventral intermediate nucleus of the thalamus (VIM) in spatial relationship to DBS electrodes. Here, we present a composite atlas based on manual segmentations of a multimodal high resolution brain template, histology and structural connectivity. In a first step, four key structures were defined on the template itself using a combination of multispectral image analysis and manual segmentation. Second, these structures were used as anchor points to coregister a detailed histological atlas into standard space. Results show that this approach significantly improved coregistration accuracy over previously published methods. Finally, a sub-segmentation of STN and GPi into functional zones was achieved based on structural connectivity. The result is a composite atlas that defines key nuclei on the template itself, fills the gaps between them using histology and further subdivides them using structural connectivity. We show that the atlas can be used to segment DBS targets in single subjects, yielding more accurate results compared to priorly published atlases. The atlas will be made publicly available and constitutes a resource to study DBS electrode localizations in combination with modern neuroimaging methods. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Effects of subthalamic nucleus deep brain stimulation on emotional working memory capacity and mood in patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Merkl A

    2017-06-01

    Full Text Available Angela Merkl,1,2 Eva Röck,1 Tanja Schmitz-Hübsch,1,3 Gerd-Helge Schneider,4 Andrea A Kühn1,3,5 1Department of Neurology, Charité – University Medicine Berlin, Campus Virchow Klinikum, 2Department of Psychiatry and Psychotherapy, Charité – University Medicine Berlin, Campus Benjamin Franklin, 3NeuroCure, Charité – University Medicine Berlin, 4Department of Neurosurgery, Charité – University Medicine Berlin, Campus Virchow Klinikum, 5Berlin School of Mind and Brain, Charité – University Medicine Berlin, Berlin, Germany Background: In Parkinson’s disease (PD, cognitive symptoms and mood changes may be even more distressing for the patient than motor symptoms.Objective: Our aim was to determine the effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS on working memory (WM and mood.Methods: Sixteen patients with PD were assessed with STN-DBS switched on (DBS-ON and with dopaminergic treatment (Med-ON compared to switched off (DBS-OFF and without dopaminergic treatment (Med-OFF. The primary outcome measures were a Visual Analog Mood Scale (VAMS and an emotional 2-back WM task at 12 months after DBS in the optimal DBS-ON/Med-ON setting compared to DBS-OFF/Med-OFF.Results: Comparison of DBS-OFF/Med-OFF to DBS-ON/Med-ON revealed a significant increase in alertness (meanoff/off =51.59±24.54; meanon/on =72.75; P=0.016 and contentedness (meanoff/off =38.73±24.41; meanon/on =79.01±17.66; P=0.001, n=16, and a trend for reduction in sedation (P=0.060, which was related to stimulation as shown in a subgroup of seven patients. The N-back task revealed a significant increase in accuracy with DBS-ON/Med-ON compared to DBS-OFF/Med-OFF (82.0% vs 76.0%, respectively (P=0.044, regardless of stimulus valence.Conclusion: In line with previous studies, we found that patients rated themselves subjectively as more alert, content, and less sedated during short-term DBS-ON. Accuracy in the WM task increased with the combination of

  19. Neuropsychological functions and rCBF SPECT in Parkinson's disease patients considered candidates for deep brain stimulation

    International Nuclear Information System (INIS)

    Paschali, Anna; Lakiotis, Velissarios; Vassilakos, Paulos; Messinis, Lambros; Lyros, Epameinondas; Papathanasopoulos, Panagiotis; Constantoyannis, Costas; Kefalopoulou, Zinovia

    2009-01-01

    In the present study, we examined relationships between neuropsychological functions and brain single photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) observed at presurgical evaluation for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD) patients. Twenty advanced non-demented PD patients, candidates for DBS surgery, underwent perfusion brain SPECT study and neuropsychological assessment prior to surgery (range: 30-50 days). Patients were further assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H and Y) scale. During all assessments patients were ''on'' standard medication. NeuroGam software, which permits voxel by voxel analysis, was used to compare the brain perfusion of PD patients with a normal database adjusted for sex and age. Neuropsychological scores were compared to age, education and sex-adjusted normative databases. Our results indicated that the distribution of rCBF showed significant differences when compared to an age- and sex-adjusted normative database. We found impaired blood flow in 17 (85%) of our patients in the left prefrontal lobe, in 14 (70%) in the right prefrontal lobe and in 11 (55%) in the left frontal and right parietal lobes. Neuropsychological testing revealed that 18 (90%) of our patients had significant impairments in measures of executive functions (set-shifting) and 15 (75%) in response inhibition. Furthermore, we found significant correlations between measures of visual attention, executive functions and the right frontal lobe region. The presence of widespread blood flow reduction was observed mainly in the frontal lobes of dementia-free patients with advanced PD. Furthermore, performance on specific cognitive measures was highly related to perfusion brain SPECT findings. (orig.)

  20. Neuropsychological functions and rCBF SPECT in Parkinson's disease patients considered candidates for deep brain stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Paschali, Anna; Lakiotis, Velissarios; Vassilakos, Paulos [University of Patras Medical School, Department of Nuclear Medicine, Patras (Greece); Messinis, Lambros; Lyros, Epameinondas; Papathanasopoulos, Panagiotis [University of Patras Medical School, Department of Neurology, Neuropsychology Section, Patras (Greece); Constantoyannis, Costas; Kefalopoulou, Zinovia [University of Patras Medical School, Department of Neurosurgery, Patras (Greece)

    2009-11-15

    In the present study, we examined relationships between neuropsychological functions and brain single photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) observed at presurgical evaluation for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD) patients. Twenty advanced non-demented PD patients, candidates for DBS surgery, underwent perfusion brain SPECT study and neuropsychological assessment prior to surgery (range: 30-50 days). Patients were further assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H and Y) scale. During all assessments patients were ''on'' standard medication. NeuroGam software, which permits voxel by voxel analysis, was used to compare the brain perfusion of PD patients with a normal database adjusted for sex and age. Neuropsychological scores were compared to age, education and sex-adjusted normative databases. Our results indicated that the distribution of rCBF showed significant differences when compared to an age- and sex-adjusted normative database. We found impaired blood flow in 17 (85%) of our patients in the left prefrontal lobe, in 14 (70%) in the right prefrontal lobe and in 11 (55%) in the left frontal and right parietal lobes. Neuropsychological testing revealed that 18 (90%) of our patients had significant impairments in measures of executive functions (set-shifting) and 15 (75%) in response inhibition. Furthermore, we found significant correlations between measures of visual attention, executive functions and the right frontal lobe region. The presence of widespread blood flow reduction was observed mainly in the frontal lobes of dementia-free patients with advanced PD. Furthermore, performance on specific cognitive measures was highly related to perfusion brain SPECT findings. (orig.)

  1. A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson’s disease—a pilot study

    Science.gov (United States)

    Gmel, Gerrit E.; Hamilton, Tara J.; Obradovic, Milan; Gorman, Robert B.; Single, Peter S.; Chenery, Helen J.; Coyne, Terry; Silburn, Peter A.; Parker, John L.

    2015-12-01

    Objective. Deep brain stimulation (DBS) has become the standard treatment for advanced stages of Parkinson’s disease (PD) and other motor disorders. Although the surgical procedure has improved in accuracy over the years thanks to imaging and microelectrode recordings, the underlying principles that render DBS effective are still debated today. The aim of this paper is to present initial findings around a new biomarker that is capable of assessing the efficacy of DBS treatment for PD which could be used both as a research tool, as well as in the context of a closed-loop stimulator. Approach. We have used a novel multi-channel stimulator and recording device capable of measuring the response of nervous tissue to stimulation very close to the stimulus site with minimal latency, rejecting most of the stimulus artefact usually found with commercial devices. We have recorded and analyzed the responses obtained intraoperatively in two patients undergoing DBS surgery in the subthalamic nucleus (STN) for advanced PD. Main results. We have identified a biomarker in the responses of the STN to DBS. The responses can be analyzed in two parts, an initial evoked compound action potential arising directly after the stimulus onset, and late responses (LRs), taking the form of positive peaks, that follow the initial response. We have observed a morphological change in the LRs coinciding with a decrease in the rigidity of the patients. Significance. These initial results could lead to a better characterization of the DBS therapy, and the design of adaptive DBS algorithms that could significantly improve existing therapies and help us gain insights into the functioning of the basal ganglia and DBS.

  2. A longitudinal study on deep brain stimulation of the medial forebrain bundle for treatment-resistant depression.

    Science.gov (United States)

    Fenoy, Albert J; Schulz, Paul E; Selvaraj, Sudhakar; Burrows, Christina L; Zunta-Soares, Giovanna; Durkin, Kathryn; Zanotti-Fregonara, Paolo; Quevedo, Joao; Soares, Jair C

    2018-06-04

    Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported to lead to rapid antidepressant effects. In this longitudinal study, we expand upon the initial results we reported at 26 weeks (Fenoy et al., 2016), showing sustained antidepressant effects of MFB DBS on six patients with treatment-resistant depression (TRD) over 1 year. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary assessment tool. Deterministic fiber tracking was used to individually map the target area; analysis was performed to compare modulated fiber tracts between patients. Intraoperatively, upon stimulation at target, responders reported immediate increases in energy and motivation. An insertional effect was seen during the 4-week sham stimulation phase from baseline (28% mean MADRS reduction, p = 0.02). However, after 1 week of initiating stimulation, three of six patients had a > 50% decrease in MADRS scores relative to baseline (43% mean MADRS reduction, p = 0.005). One patient withdrew from study participation. At 52 weeks, four of remaining five patients have > 70% decrease in MADRS scores relative to baseline (73% mean MADRS reduction, p = 0.007). Evaluation of modulated fiber tracts reveals significant common orbitofrontal connectivity to the target region in all responders. Neuropsychological testing and 18 F-fluoro-deoxyglucose-positron emission tomography cerebral metabolism evaluations performed at baseline and at 52 weeks showed minimal changes and verified safety. This longitudinal evaluation of MFB DBS demonstrated rapid antidepressant effects, as initially reported by Schlaepfer et al. (2013), and supports the use of DBS for TRD.

  3. Articulatory Closure Proficiency in Patients with Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus and Caudal Zona Incerta

    Science.gov (United States)

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

    2014-01-01

    Purpose: The present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on the proficiency in achieving oral closure and release during plosive production of people with Parkinson's disease. Method: Nineteen patients participated preoperatively and…

  4. Quantitative assessment of rest and action tremor and the effect of cueing in Parkinson’s disease patients treated with deep brain stimulation

    NARCIS (Netherlands)

    Heida, Tjitske; Wentink, E.C.; Marani, Enrico

    2011-01-01

    Introduction: In Parkinson’s disease rest and action tremor may occur. High frequency deep brain stimulation in basal ganglia nuclei has proved to be effective in the suppression of tremor. In addition, rhythmic auditory cues have shown to result in improved performance of repetitive movements,

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

    Science.gov (United States)

    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…

  6. [Deep brain stimulation - expectations and doubts. A nationwide questionnaire study of patients with Parkinson's disease and their family members].

    Science.gov (United States)

    Südmeyer, M; Volkmann, J; Wojtecki, L; Deuschl, G; Schnitzler, A; Möller, B

    2012-04-01

    The aim of this questionnaire-based study was to determine the decision-making motives from Parkinson's patients and their family members for deep brain stimulation (DBS), which are crucial for the attitude towards this therapy and which should be considered during the clinical interview. The questionnaire was sent out nationwide to members of the German Parkinson Association. Patient and family specific data as well as information sources, doubts and expectations with respect to DBS were assessed. A total of 582 patients and 476 family members answered the questionnaire, revealing that 96% of the patients and 91% of the family members already possessed information regarding DBS. While a large proportion of interviewees had specific expectations concerning DBS, more than two thirds expressed concerns regarding DBS; the most frequent with respect to intraoperative complications and stimulation-induced worsening of symptoms. The quantity of realistic patients and family expectations significantly correlated with a positive evaluation of DBS and doubts as well as unrealistic expectations of family members correlated with a negative attitude towards the operation. The findings suggest that patients and their relatives organized in support groups indeed possess detailed information regarding DBS. However, for the acceptance of the treatment a timely elucidation about DBS as well as responding to the individual concerns by the consulting physician is essential.

  7. Interaction of oscillations, and their suppression via deep brain stimulation, in a model of the cortico-basal ganglia network.

    Science.gov (United States)

    Kang, Guiyeom; Lowery, Madeleine M

    2013-03-01

    Growing evidence suggests that synchronized neural oscillations in the cortico-basal ganglia network may play a critical role in the pathophysiology of Parkinson's disease. In this study, a new model of the closed loop network is used to explore the generation and interaction of network oscillations and their suppression through deep brain stimulation (DBS). Under simulated dopamine depletion conditions, increased gain through the hyperdirect pathway resulted in the interaction of neural oscillations at different frequencies in the cortex and subthalamic nucleus (STN), leading to the emergence of synchronized oscillations at a new intermediate frequency. Further increases in synaptic gain resulted in the cortex driving synchronous oscillatory activity throughout the network. When DBS was added to the model a progressive reduction in STN power at the tremor and beta frequencies was observed as the frequency of stimulation was increased, with resonance effects occurring for low frequency DBS (40 Hz) in agreement with experimental observations. The results provide new insights into the mechanisms by which synchronous oscillations can arise within the network and how DBS may suppress unwanted oscillatory activity.

  8. Investigating Synchronous Oscillation and Deep Brain Stimulation Treatment in A Model of Cortico-Basal Ganglia Network.

    Science.gov (United States)

    Lu, Meili; Wei, Xile; Loparo, Kenneth A

    2017-11-01

    Altered firing properties and increased pathological oscillations in the basal ganglia have been proven to be hallmarks of Parkinson's disease (PD). Increasing evidence suggests that abnormal synchronous oscillations and suppression in the cortex may also play a critical role in the pathogenic process and treatment of PD. In this paper, a new closed-loop network including the cortex and basal ganglia using the Izhikevich models is proposed to investigate the synchrony and pathological oscillations in motor circuits and their modulation by deep brain stimulation (DBS). Results show that more coherent dynamics in the cortex may cause stronger effects on the synchrony and pathological oscillations of the subthalamic nucleus (STN). The pathological beta oscillations of the STN can both be efficiently suppressed with DBS applied directly to the STN or to cortical neurons, respectively, but the underlying mechanisms by which DBS suppresses the beta oscillations are different. This research helps to understand the dynamics of pathological oscillations in PD-related motor regions and supports the therapeutic potential of stimulation of cortical neurons.

  9. Increased thalamic gamma band activity correlates with symptom relief following deep brain stimulation in humans with Tourette's syndrome.

    Directory of Open Access Journals (Sweden)

    Nicholas Maling

    Full Text Available Tourette syndrome (TS is an idiopathic, childhood-onset neuropsychiatric disorder, which is marked by persistent multiple motor and phonic tics. The disorder is highly disruptive and in some cases completely debilitating. For those with severe, treatment-refractory TS, deep brain stimulation (DBS has emerged as a possible option, although its mechanism of action is not fully understood. We performed a longitudinal study of the effects of DBS on TS symptomatology while concomitantly examining neurophysiological dynamics. We present the first report of the clinical correlation between the presence of gamma band activity and decreased tic severity. Local field potential recordings from five subjects implanted in the centromedian nucleus (CM of the thalamus revealed a temporal correlation between the power of gamma band activity and the clinical metrics of symptomatology as measured by the Yale Global Tic Severity Scale and the Modified Rush Tic Rating Scale. Additional studies utilizing short-term stimulation also produced increases in gamma power. Our results suggest that modulation of gamma band activity in both long-term and short-term DBS of the CM is a key factor in mitigating the pathophysiology associated with TS.

  10. Weight gain after subthalamic nucleus deep brain stimulation in Parkinson's disease is influenced by dyskinesias' reduction and electrodes' position.

    Science.gov (United States)

    Balestrino, Roberta; Baroncini, Damiano; Fichera, Mario; Donofrio, Carmine Antonio; Franzin, Alberto; Mortini, Pietro; Comi, Giancarlo; Volontè, Maria Antonietta

    2017-12-01

    Parkinson's disease is a common neurodegenerative disease that can be treated with pharmacological or surgical therapy. Subthalamic nucleus (STN) deep brain stimulation is a commonly used surgical option. A reported side effect of STN-DBS is weight gain: the aim of our study was to find those factors that determine weight gain, through one year-long observation of 32 patients that underwent surgery in our centre. During the follow-up, we considered: anthropometric features, hormonal levels, motor outcome, neuropsychological and quality of life outcomes, therapeutic parameters and electrodes position. The majority (84%) of our patients gained weight (6.7 kg in 12 months); more than a half of the cohort became overweight. At 12th month, weight gain showed a correlation with dyskinesias reduction, electrodes voltage and distance on the lateral axis. In the multivariate regression analysis, the determinants of weight gain were dyskinesias reduction and electrodes position. In this study, we identified dyskinesias reduction and distance between the active electrodes and the third ventricle as determining factors of weight gain after STN-DBS implantation in PD patients. The first finding could be linked to a decrease in energy consumption, while the second one could be due to a lower stimulation of the lateral hypothalamic area, known for its important role in metabolism and body weight control. Weight gain is a common finding after STN-DBS implantation, and it should be carefully monitored given the potential harmful consequences of overweight.

  11. Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank

    Science.gov (United States)

    Ramirez-Zamora, Adolfo; Giordano, James J.; Gunduz, Aysegul; Brown, Peter; Sanchez, Justin C.; Foote, Kelly D.; Almeida, Leonardo; Starr, Philip A.; Bronte-Stewart, Helen M.; Hu, Wei; McIntyre, Cameron; Goodman, Wayne; Kumsa, Doe; Grill, Warren M.; Walker, Harrison C.; Johnson, Matthew D.; Vitek, Jerrold L.; Greene, David; Rizzuto, Daniel S.; Song, Dong; Berger, Theodore W.; Hampson, Robert E.; Deadwyler, Sam A.; Hochberg, Leigh R.; Schiff, Nicholas D.; Stypulkowski, Paul; Worrell, Greg; Tiruvadi, Vineet; Mayberg, Helen S.; Jimenez-Shahed, Joohi; Nanda, Pranav; Sheth, Sameer A.; Gross, Robert E.; Lempka, Scott F.; Li, Luming; Deeb, Wissam; Okun, Michael S.

    2018-01-01

    The annual Deep Brain Stimulation (DBS) Think Tank provides a focal opportunity for a multidisciplinary ensemble of experts in the field of neuromodulation to discuss advancements and forthcoming opportunities and challenges in the field. The proceedings of the fifth Think Tank summarize progress in neuromodulation neurotechnology and techniques for the treatment of a range of neuropsychiatric conditions including Parkinson's disease, dystonia, essential tremor, Tourette syndrome, obsessive compulsive disorder, epilepsy and cognitive, and motor disorders. Each section of this overview of the meeting provides insight to the critical elements of discussion, current challenges, and identified future directions of scientific and technological development and application. The report addresses key issues in developing, and emphasizes major innovations that have occurred during the past year. Specifically, this year's meeting focused on technical developments in DBS, design considerations for DBS electrodes, improved sensors, neuronal signal processing, advancements in development and uses of responsive DBS (closed-loop systems), updates on National Institutes of Health and DARPA DBS programs of the BRAIN initiative, and neuroethical and policy issues arising in and from DBS research and applications in practice. PMID:29416498

  12. Controlling the error on target motion through real-time mesh adaptation: Applications to deep brain stimulation.

    Science.gov (United States)

    Bui, Huu Phuoc; Tomar, Satyendra; Courtecuisse, Hadrien; Audette, Michel; Cotin, Stéphane; Bordas, Stéphane P A

    2018-05-01

    An error-controlled mesh refinement procedure for needle insertion simulations is presented. As an example, the procedure is applied for simulations of electrode implantation for deep brain stimulation. We take into account the brain shift phenomena occurring when a craniotomy is performed. We observe that the error in the computation of the displacement and stress fields is localised around the needle tip and the needle shaft during needle insertion simulation. By suitably and adaptively refining the mesh in this region, our approach enables to control, and thus to reduce, the error whilst maintaining a coarser mesh in other parts of the domain. Through academic and practical examples we demonstrate that our adaptive approach, as compared with a uniform coarse mesh, increases the accuracy of the displacement and stress fields around the needle shaft and, while for a given accuracy, saves computational time with respect to a uniform finer mesh. This facilitates real-time simulations. The proposed methodology has direct implications in increasing the accuracy, and controlling the computational expense of the simulation of percutaneous procedures such as biopsy, brachytherapy, regional anaesthesia, or cryotherapy. Moreover, the proposed approach can be helpful in the development of robotic surgeries because the simulation taking place in the control loop of a robot needs to be accurate, and to occur in real time. Copyright © 2018 John Wiley & Sons, Ltd.

  13. Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank

    Directory of Open Access Journals (Sweden)

    Adolfo Ramirez-Zamora

    2018-01-01

    Full Text Available The annual Deep Brain Stimulation (DBS Think Tank provides a focal opportunity for a multidisciplinary ensemble of experts in the field of neuromodulation to discuss advancements and forthcoming opportunities and challenges in the field. The proceedings of the fifth Think Tank summarize progress in neuromodulation neurotechnology and techniques for the treatment of a range of neuropsychiatric conditions including Parkinson's disease, dystonia, essential tremor, Tourette syndrome, obsessive compulsive disorder, epilepsy and cognitive, and motor disorders. Each section of this overview of the meeting provides insight to the critical elements of discussion, current challenges, and identified future directions of scientific and technological development and application. The report addresses key issues in developing, and emphasizes major innovations that have occurred during the past year. Specifically, this year's meeting focused on technical developments in DBS, design considerations for DBS electrodes, improved sensors, neuronal signal processing, advancements in development and uses of responsive DBS (closed-loop systems, updates on National Institutes of Health and DARPA DBS programs of the BRAIN initiative, and neuroethical and policy issues arising in and from DBS research and applications in practice.

  14. Effects of deformable registration algorithms on the creation of statistical maps for preoperative targeting in deep brain stimulation procedures

    Science.gov (United States)

    Liu, Yuan; D'Haese, Pierre-Francois; Dawant, Benoit M.

    2014-03-01

    Deep brain stimulation, which is used to treat various neurological disorders, involves implanting a permanent electrode into precise targets deep in the brain. Accurate pre-operative localization of the targets on pre-operative MRI sequence is challenging as these are typically located in homogenous regions with poor contrast. Population-based statistical atlases can assist with this process. Such atlases are created by acquiring the location of efficacious regions from numerous subjects and projecting them onto a common reference image volume using some normalization method. In previous work, we presented results concluding that non-rigid registration provided the best result for such normalization. However, this process could be biased by the choice of the reference image and/or registration approach. In this paper, we have qualitatively and quantitatively compared the performance of six recognized deformable registration methods at normalizing such data in poor contrasted regions onto three different reference volumes using a unique set of data from 100 patients. We study various metrics designed to measure the centroid, spread, and shape of the normalized data. This study leads to a total of 1800 deformable registrations and results show that statistical atlases constructed using different deformable registration methods share comparable centroids and spreads with marginal differences in their shape. Among the six methods being studied, Diffeomorphic Demons produces the largest spreads and centroids that are the furthest apart from the others in general. Among the three atlases, one atlas consistently outperforms the other two with smaller spreads for each algorithm. However, none of the differences in the spreads were found to be statistically significant, across different algorithms or across different atlases.

  15. 'Being in it together': living with a partner receiving deep brain stimulation for advanced Parkinson's disease--a hermeneutic phenomenological study.

    Science.gov (United States)

    Haahr, Anita; Kirkevold, Marit; Hall, Elisabeth O C; Østergaard, Karen

    2013-02-01

    This article is a report of an exploration of the lived experience of being a spouse to a person living with advanced Parkinson's disease, before and during the first year of deep brain stimulation. Parkinson's disease is a chronic progressive neurodegenerative disease. It has a profound impact on the everyday life for patients and spouses. Deep brain stimulation is offered with the aim of reducing symptoms of Parkinson's disease. The treatment is known to improve quality of life for patients, but little is known of how spouses experience life following their partners' treatment. A longitudinal interview study with a hermeneutic phenomenological approach. Ten spouses were included in the study. Data were gathered in 2007-2008, through qualitative in-depth interviews with spouses once before and three times during the first year of their partners' treatment with Deep Brain Stimulation. Data collection and data analysis were influenced by the hermeneutic phenomenological methodology of van Manen. The uniting theme 'Solidarity - the base for joined responsibility and concern' was the foundation for the relationship between spouses and their partners. Before treatment, the theme 'Living in partnership' was dominant. After treatment two dichotomous courses were described 'A sense of freedom embracing life' and 'The challenge of changes and constraint'. Spouses are deeply involved in their partners' illness and their experience of life is highly affected by their partners' illness, both before and after deep brain stimulation. The relationship is founded on solidarity and responsibility, which emphasizes spouses' need to be informed and involved in the process following Deep Brain Stimulation. © 2012 Blackwell Publishing Ltd.

  16. Central thalamic deep brain stimulation to promote recovery from chronic posttraumatic minimally conscious state: challenges and opportunities.

    Science.gov (United States)

    Giacino, Joseph; Fins, Joseph J; Machado, Andre; Schiff, Nicholas D

    2012-07-01

    Central thalamic deep brain stimulation (CT-DBS) may have therapeutic potential to improve behavioral functioning in patients with severe traumatic brain injury (TBI), but its use remains experimental. Current research suggests that the central thalamus plays a critical role in modulating arousal during tasks requiring sustained attention, working memory, and motor function. The aim of the current article is to review the methodology used in the CT-DBS protocol developed by our group, outline the challenges we encountered and offer suggestions for future DBS trials in this population. RATIONAL FOR CT-DBS IN TBI:  CT-DBS may therefore be able to stimulate these functions by eliciting action potentials that excite thalamocortical and thalamostriatal pathways. Because patients in chronic minimally conscious state (MCS) have a very low probability of regaining functional independence, yet often have significant sparing of cortical connectivity, they may represent a particularly appropriate target group for CT-DBS. PIlOT STUDY RESULTS:  We have conducted a series of single-subject studies of CT-DBS in patients with chronic posttraumatic MCS, with 24-month follow-up. Outcomes were measured using the Coma Recovery Scale-Revised as well as a battery of secondary outcome measures to capture more granular changes. Findings from our index case suggest that CT-DBS can significantly increase functional communication, motor performance, feeding, and object naming in the DBS on state, with performance in some domains remaining above baseline even after DBS was turned off. The use of CT-DBS in patients in MCS, however, presents challenges at almost every step, including during surgical planning, outcome measurement, and postoperative care. Additionally, given the difficulties of obtaining informed consent from patients in MCS and the experimental nature of the treatment, a robust, scientifically rooted ethical framework is resented for pursuing this line of work. © 2012

  17. Optimization of multiple coils immersed in a conducting liquid for half-hemisphere or whole-brain deep transcranial magnetic stimulation: a simulation study.

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    Sousa, Sónia C P; Almeida, Jorge; Cavaleiro Miranda, Pedro; Salvador, Ricardo; Silvestre, João; Simões, Hugo; Crespo, Paulo

    2014-01-01

    Transcranial magnetic stimulation (TMS) was proposed in 1985. Nevertheless, its wider use in the treatment of several neurologic diseases has been hindered by its inability to stimulate deep-brain regions. This is mainly due to the physical limiting effect arising from the presence of surface discontinuities, particularly between the scalp and air. Here, we present the optimization of a system of large multiple coils for whole-brain and half-hemisphere deep TMS, termed orthogonal configuration. COMSOL(®)-based simulations show that the system is capable of reaching the very center of a spherical brain phantom with 58% induction relative to surface maximum. Such penetration capability surpasses to the best of our knowledge that of existing state of the art TMS systems. This induction capability strongly relies on the immersion of the stimulating coils and part of the head of the patient in a conducting liquid (e.g. simple saline solution). We show the impact of the presence of this surrounding conducting liquid by comparing the performance of our system with and without such liquid. In addition, we also compare the performance of the proposed coil with that of a circular coil, a figure-eight coil, and the H-coil. Finally, in addition to its whole-brain stimulation capability (e.g. potentially useful for prophylaxis of epileptic patients) the system is also able to stimulate mainly one brain hemisphere, which may be useful in stroke rehabilitation, among other applications.

  18. Deep brain stimulation, histone deacetylase inhibitors and glutamatergic drugs rescue resistance to fear extinction in a genetic mouse model

    Science.gov (United States)

    Whittle, Nigel; Schmuckermair, Claudia; Gunduz Cinar, Ozge; Hauschild, Markus; Ferraguti, Francesco; Holmes, Andrew; Singewald, Nicolas

    2013-01-01

    Anxiety disorders are characterized by persistent, excessive fear. Therapeutic interventions that reverse deficits in fear extinction represent a tractable approach to treating these disorders. We previously reported that 129S1/SvImJ (S1) mice show no extinction learning following normal fear conditioning. We now demonstrate that weak fear conditioning does permit fear reduction during massed extinction training in S1 mice, but reveals specific deficiency in extinction memory consolidation/retrieval. Rescue of this impaired extinction consolidation/retrieval was achieved with d-cycloserine (N-methly-d-aspartate partial agonist) or MS-275 (histone deacetylase (HDAC) inhibitor), applied after extinction training. We next examined the ability of different drugs and non-pharmacological manipulations to rescue the extreme fear extinction deficit in S1 following normal fear conditioning with the ultimate aim to produce low fear levels in extinction retrieval tests. Results showed that deep brain stimulation (DBS) by applying high frequency stimulation to the nucleus accumbens (ventral striatum) during extinction training, indeed significantly reduced fear during extinction retrieval compared to sham stimulation controls. Rescue of both impaired extinction acquisition and deficient extinction consolidation/retrieval was achieved with prior extinction training administration of valproic acid (a GABAergic enhancer and HDAC inhibitor) or AMN082 [metabotropic glutamate receptor 7 (mGlu7) agonist], while MS-275 or PEPA (AMPA receptor potentiator) failed to affect extinction acquisition in S1 mice. Collectively, these data identify potential beneficial effects of DBS and various drug treatments, including those with HDAC inhibiting or mGlu7 agonism properties, as adjuncts to overcome treatment resistance in exposure-based therapies. This article is part of a Special Issue entitled ‘Cognitive Enhancers’. PMID:22722028

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

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    Mohammad Maarouf

    Full Text Available 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.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.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.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.

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

    Science.gov (United States)

    Maarouf, Mohammad; Neudorfer, Clemens; El Majdoub, Faycal; Lenartz, Doris; Kuhn, Jens; Sturm, Volker

    2016-01-01

    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. 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. 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. 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.

  1. A Noninvasive Imaging Approach to Understanding Speech Changes following Deep Brain Stimulation in Parkinson's Disease

    Science.gov (United States)

    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 noninvasive 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…

  2. Meta-analysis comparing deep brain stimulation of the globus pallidus and subthalamic nucleus to treat advanced Parkinson disease.

    Science.gov (United States)

    Liu, Yi; Li, Weina; Tan, Changhong; Liu, Xi; Wang, Xin; Gui, Yuejiang; Qin, Lu; Deng, Fen; Hu, Changlin; Chen, Lifen

    2014-09-01

    Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). The globus pallidus internus (GPi) and the subthalamic nucleus (STN) are commonly targeted by this procedure. The purpose of this meta-analysis was to compare the efficacy of DBS in each region. MEDLINE/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library were searched for English-language studies published before April 2013. of studies investigating the efficacy and clinical outcomes of DBS of the GPi and STN for PD were analyzed. Six eligible trials containing a total of 563 patients were included in the analysis. Deep brain stimulation of the GPi or STN equally improved motor function, measured by the Unified Parkinson's Disease Rating Scale Section III (UPDRSIII) (motor section, for patients in on- and off-medication phases), within 1 year postsurgery. The change score for the on-medication phase was 0.68 (95% CI - 2.12 to 3.47, p > 0.05; 5 studies, 518 patients) and for the off-medication phase was 1.83 (95% CI - 3.12 to 6.77, p > 0.05; 5 studies, 518 patients). The UPDRS Section II (activities of daily living) scores for patients on medication improved equally in both DBS groups (p = 0.97). STN DBS allowed medication dosages to be reduced more than GPi DBS (95% CI 129.27-316.64, p < 0.00001; 5 studies, 540 patients). Psychiatric symptoms, measured by Beck Depression Inventory, 2nd edition scores, showed greater improvement from baseline after GPi DBS than after STN DBS (standardized mean difference -2.28, 95% CI -3.73 to -0.84, p = 0.002; 3 studies, 382 patients). GPi and STN DBS improve motor function and activities of daily living for PD patients. Differences in therapeutic efficacy for PD were not observed between the 2 procedures. STN DBS allowed greater reduction in medication for patients, whereas GPi DBS provided greater relief from psychiatric symptoms. An understanding of other symptomatic aspects of targeting each region and long

  3. The Impact of Subthalamic Deep Brain Stimulation on Sleep-Wake Behavior: A Prospective Electrophysiological Study in 50 Parkinson Patients.

    Science.gov (United States)

    Baumann-Vogel, Heide; Imbach, Lukas L; Sürücü, Oguzkan; Stieglitz, Lennart; Waldvogel, Daniel; Baumann, Christian R; Werth, Esther

    2017-05-01

    This prospective observational study was designed to systematically examine the effect of subthalamic deep brain stimulation (DBS) on subjective and objective sleep-wake parameters in Parkinson patients. In 50 consecutive Parkinson patients undergoing subthalamic DBS, we assessed motor symptoms, medication, the position of DBS electrodes within the subthalamic nucleus (STN), subjective sleep-wake parameters, 2-week actigraphy, video-polysomnography studies, and sleep electroencepahalogram frequency and dynamics analyses before and 6 months after surgery. Subthalamic DBS improved not only motor symptoms and reduced daily intake of dopaminergic agents but also enhanced subjective sleep quality and reduced sleepiness (Epworth Sleepiness Scale: -2.1 ± 3.8, p sleep efficiency (+5.2 ± 17.6%, p = .005) and deep sleep (+11.2 ± 32.2 min, p = .017) and increased accumulation of slow-wave activity over the night (+41.0 ± 80.0%, p = .005). Rapid eye movement sleep features were refractory to subthalamic DBS, and the dynamics of sleep as assessed by state space analyses did not normalize. Increased sleep efficiency was associated with active electrode contact localization more distant from the ventral margin of the left subthalamic nucleus. Subthalamic DBS deepens and consolidates nocturnal sleep and improves daytime wakefulness in Parkinson patients, but several outcomes suggest that it does not normalize sleep. It remains elusive whether modulated activity in the STN directly contributes to changes in sleep-wake behavior, but dorsal positioning of electrodes within the STN is linked to improved sleep-wake outcomes. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  4. Deep brain stimulation in Gilles de la Tourette syndrome: killing several birds with one stone? [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Andreas Hartmann

    2016-09-01

    Full Text Available In patients with severe, treatment-refractory Gilles de la Tourette syndrome (GTS, deep brain stimulation (DBS of various targets has been increasingly explored over the past 15 years. The multiplicity of surgical targets is intriguing and may be partly due to the complexity of GTS, specifically the various and frequent associated psychiatric comorbidities in this disorder. Thus, the target choice may not only be aimed at reducing tics but also comorbidities. While this approach is laudable, it also carries the risk to increase confounding factors in DBS trials and patient evaluation. Moreover, I question whether DBS should really be expected to alleviate multiple symptoms at a time. Rather, I argue that tic reduction should remain our primary objective in severe GTS patients and that this intervention may subsequently allow an improved psychotherapeutic and/or pharmacological treatment of comorbidities. Thus, I consider DBS in GTS not as a single solution for all our patients’ ailments but as a stepping stone to improved holistic care made possible by tic reduction.

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

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    Fredrik Karlsson

    2011-01-01

    Full Text Available The hypokinetic dysarthria observed in Parkinson's disease (PD affects the range, speed, and accuracy of articulatory gestures in patients, reducing the perceived quality of speech acoustic output in continuous speech. Deep brain stimulation (DBS of the subthalamic nucleus (STN-DBS and of the caudal zona incerta (cZi-DBS are current surgical treatment options for PD. This study aimed at investigating the outcome of STN-DBS (7 patients and cZi-DBS (7 patients in two articulatory diadochokinesis tasks (AMR and SMR using measurements of articulation rate and quality of the plosive consonants (using the percent measurable VOT metric. The results indicate that patients receiving STN-DBS increased in articulation rate in the Stim-ON condition in the AMR task only, with no effect on production quality. Patients receiving cZi-DBS decreased in articulation rate in the Stim-ON condition and further showed a reduction in production quality. The data therefore suggest that cZi-DBS is more detrimental for extended articulatory movements than STN-DBS.

  6. Developing a Deep Brain Stimulation Neuromodulation Network for Parkinson Disease, Essential Tremor, and Dystonia: Report of a Quality Improvement Project.

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    Richard B Dewey

    Full Text Available To develop a process to improve patient outcomes from deep brain stimulation (DBS surgery for Parkinson disease (PD, essential tremor (ET, and dystonia.We employed standard quality improvement methodology using the Plan-Do-Study-Act process to improve patient selection, surgical DBS lead implantation, postoperative programming, and ongoing assessment of patient outcomes.The result of this quality improvement process was the development of a neuromodulation network. The key aspect of this program is rigorous patient assessment of both motor and non-motor outcomes tracked longitudinally using a REDCap database. We describe how this information is used to identify problems and to initiate Plan-Do-Study-Act cycles to address them. Preliminary outcomes data is presented for the cohort of PD and ET patients who have received surgery since the creation of the neuromodulation network.Careful outcomes tracking is essential to ensure quality in a complex therapeutic endeavor like DBS surgery for movement disorders. The REDCap database system is well suited to store outcomes data for the purpose of ongoing quality assurance monitoring.

  7. Subthalamic deep brain stimulation reduces pathological information transmission to the thalamus in a rat model of parkinsonism

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    Collin James Anderson

    2015-07-01

    Full Text Available The degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to parkinsonian motor symptoms via changes in electrophysiological activity throughout the basal ganglia. High-frequency deep brain stimulation (DBS partially treats these symptoms, but the mechanisms are unclear. We hypothesize that motor symptoms of Parkinson's disease are associated with increased information transmission from basal ganglia output neurons to motor thalamus input neurons, and that therapeutic DBS of the subthalamic nucleus (STN treats these symptoms by reducing this extraneous information transmission. We tested these hypotheses in a unilateral, 6-hydroxydopamine-lesioned rodent model of hemiparkinsonism. Information transfer between basal ganglia output neurons and motor thalamus input neurons increased in both the orthodromic and antidromic directions with hemiparkinsonian onset, and these changes were reversed by behaviorally therapeutic STN-DBS. Omnidirectional information increases in the parkinsonian state underscore the detrimental nature of that pathological information, and suggest a loss of information channel independence. Therapeutic STN-DBS reduced that pathological information, suggesting an effective increase in the number of independent information channels. We interpret these data with a model in which pathological information and fewer information channels diminishes the scope of possible motor activities, driving parkinsonian symptoms. In this model, STN-DBS restores information-channel independence by eliminating or masking the parkinsonism-associated information, and thus enlarges the scope of possible motor activities, alleviating parkinsonian symptoms.

  8. Tractographical model of the cortico-basal ganglia and corticothalamic connections: Improving Our Understanding of Deep Brain Stimulation.

    Science.gov (United States)

    Avecillas-Chasin, Josué M; Rascón-Ramírez, Fernando; Barcia, Juan A

    2016-05-01

    The cortico-basal ganglia and corticothalamic projections have been extensively studied in the context of neurological and psychiatric disorders. Deep brain stimulation (DBS) is known to modulate many of these pathways to produce the desired clinical effect. The aim of this work is to describe the anatomy of the main circuits of the basal ganglia using tractography in a surgical planning station. We used imaging studies of 20 patients who underwent DBS for movement and psychiatric disorders. We segmented the putamen, caudate nucleus (CN), thalamus, and subthalamic nucleus (STN), and we also segmented the cortical areas connected with these subcortical areas. We used tractography to define the subdivisions of the basal ganglia and thalamus through the generation of fibers from the cortical areas to the subcortical structures. We were able to generate the corticostriatal and corticothalamic connections involved in the motor, associative and limbic circuits. Furthermore, we were able to reconstruct the hyperdirect pathway through the corticosubthalamic connections and we found subregions in the STN. Finally, we reconstructed the cortico-subcortical connections of the ventral intermediate nucleus, the nucleus accumbens and the CN. We identified a feasible delineation of the basal ganglia and thalamus connections using tractography. These results could be potentially useful in DBS if the parcellations are used as targets during surgery. © 2016 Wiley Periodicals, Inc.

  9. Comparison of Globus Pallidus Interna and Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease: An Institutional Experience and Review

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    Shazia Mirza

    2017-01-01

    Full Text Available Deep Brain Stimulation (DBS has revolutionized the lives of patients of Parkinson disease, offering therapeutic options to those not benefiting entirely from medications alone. With its proven track record of outperforming the best medical management, the goal is to unlock the full potential of this therapy. Currently, the Globus Pallidus Interna (GPi and Subthalamic Nucleus (STN are both viable targets for DBS, and the choice of site should focus on the constellation of symptoms, both motor and nonmotor, which are key determinants to quality of life. Our article sheds light on the specific advantages and drawbacks of the two sites, highlighting the need for matching the inherent properties of a target with specific desired effects in patients. UT Southwestern Medical Center has a robust and constantly evolving DBS program and the narrative from our center provides invaluable insight into the practical realities of DBS. The ultimate decision in selecting a DBS target is complex, ideally made by a multidisciplinary team, tailored towards each patient’s profile and their expectations, by drawing upon scientific evidence coupled with experience. Ongoing research is expanding our knowledge base, which should be dynamically incorporated into an institute’s DBS paradigm to ensure that patients receive the optimal therapy.

  10. Are Patients Ready for "EARLYSTIM"? Attitudes towards Deep Brain Stimulation among Female and Male Patients with Moderately Advanced Parkinson's Disease.

    Science.gov (United States)

    Sperens, Maria; Hamberg, Katarina; Hariz, Gun-Marie

    2017-01-01

    Objective . To explore, in female and male patients with medically treated, moderately advanced Parkinson's disease (PD), their knowledge and reasoning about Deep Brain Stimulation (DBS). Methods . 23 patients with PD (10 women), aged 46-70, were interviewed at a mean of 8 years after diagnosis, with open-ended questions concerning their reflections and considerations about DBS. The interviews were transcribed verbatim and analysed according to the difference and similarity technique in Grounded Theory. Results . From the patients' narratives, the core category "Processing DBS: balancing symptoms, fears and hopes" was established. The patients were knowledgeable about DBS and expressed cautious and well considered attitudes towards its outcome but did not consider themselves ill enough to undergo DBS. They were aware of its potential side-effects. They considered DBS as the last option when oral medication is no longer sufficient. There was no difference between men and women in their reasoning and attitudes towards DBS. Conclusion . This study suggests that knowledge about the pros and cons of DBS exists among PD patients and that they have a cautious attitude towards DBS. Our patients did not seem to endorse an earlier implementation of DBS, and they considered that it should be the last resort when really needed.

  11. Radio frequency energy harvesting from a feeding source in a passive deep brain stimulation device for murine preclinical research.

    Science.gov (United States)

    Hosain, Md Kamal; Kouzani, Abbas Z; Tye, Susannah J; Samad, Mst Fateha; Kale, Rajas P; Bennet, Kevin E; Manciu, Felicia S; Berk, Michael

    2015-10-01

    This paper presents the development of an energy harvesting circuit for use with a head-mountable deep brain stimulation (DBS) device. It consists of a circular planar inverted-F antenna (PIFA) and a Schottky diode-based Cockcroft-Walton 4-voltage rectifier. The PIFA has the volume of π × 10(2) × 1.5 mm(3), resonance frequency of 915 MHz, and bandwidth of 16 MHz (909-925 MHz) at a return loss of -10 dB. The rectifier offers maximum efficiency of 78% for the input power of -5 dBm at a 5 kΩ load resistance. The developed rectenna operates efficiently at 915 MHz for the input power within -15 dBm to +5 dBm. For operating a DBS device, the DC voltage of 2 V is recorded from the rectenna terminal at a distance of 55 cm away from a 26.77 dBm transmitter in free space. An in-vitro test of the DBS device is presented. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

  12. Apathy following Bilateral Deep Brain Stimulation of Subthalamic Nucleus in Parkinson’s Disease: A Meta-Analysis

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    Ying Wang

    2018-01-01

    Full Text Available Bilateral deep brain stimulation of subthalamic nucleus (STN-DBS has proven effective in improving motor symptoms in Parkinson’s disease (PD patients. However, psychiatric changes after surgery are controversial. In this study, we specifically analyzed apathy following bilateral STN-DBS in PD patients using a meta-analysis. Relevant articles utilized for this study were obtained through literature search on PubMed, ScienceDirect, and Embase databases. The articles included were those contained both pre- and postsurgery apathy data acquired using the Starkstein Apathy Scale or Apathy Evaluation Scale with patient follow-up of at least three months. A total of 9 out of 86 articles were included in our study through this strict screening process. Standardized mean difference (SMD, that is, Cohen’s d, with a 95% confidence interval (CI was calculated to show the change. We found a significant difference between the presurgery stage and the postsurgery stage scores (SMD = 0.35, 95% CI: 0.17∼0.52, P<0.001. STN-DBS seems to relatively worsen the condition of apathy, which may result from both the surgery target (subthalamic nucleus and the reduction of dopaminergic medication. Further studies should focus on the exact mechanisms of possible postoperative apathy in the future.

  13. Factors predicting the instant effect of motor function after subthalamic nucleus deep brain stimulation in Parkinson's disease.

    Science.gov (United States)

    Su, Xin-Ling; Luo, Xiao-Guang; Lv, Hong; Wang, Jun; Ren, Yan; He, Zhi-Yi

    2017-01-01

    Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for Parkinson's disease (PD), the predictive effect of levodopa responsiveness on surgical outcomes was confirmed by some studies, however there were different conclusions about that through long- and short-term follow-ups. We aimed to investigate the factors which influence the predictive value of levodopa responsiveness, and discover more predictive factors of surgical outcomes. Twenty-three PD patients underwent bilateral STN-DBS and completed our follow-up. Clinical evaluations were performed 1 week before and 3 months after surgery. STN-DBS significantly improved motor function of PD patients after 3 months; preoperative levodopa responsiveness and disease subtype predicted the effect of DBS on motor function; gender, disease duration and duration of motor fluctuations modified the predictive effect of levodopa responsiveness on motor improvement; the duration of motor fluctuations and severity of preoperative motor symptoms modified the predictive effect of disease subtype on motor improvement. The intensity of levodopa responsiveness served as a predictor of motor improvement more accurately in female patients, patients with shorter disease duration or shorter motor fluctuations; PD patients with dominant axial symptoms benefit less from STN-DBS compared to those with limb-predominant symptoms, especially in their later disease stage.

  14. Chronic Deep Brain Stimulation of the Hypothalamic Nucleus in Wistar Rats Alters Circulatory Levels of Corticosterone and Proinflammatory Cytokines

    Science.gov (United States)

    Calleja-Castillo, Juan Manuel; De La Cruz-Aguilera, Dora Luz; Manjarrez, Joaquín; Velasco-Velázquez, Marco Antonio; Morales-Espinoza, Gabriel; Moreno-Aguilar, Julia; Hernández, Maria Eugenia; Aguirre-Cruz, Lucinda

    2013-01-01

    Deep brain stimulation (DBS) is a therapeutic option for several diseases, but its effects on HPA axis activity and systemic inflammation are unknown. This study aimed to detect circulatory variations of corticosterone and cytokines levels in Wistar rats, after 21 days of DBS-at the ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl), unilateral cervical vagotomy (UCVgX), or UCVgX plus DBS. We included the respective control (C) and sham (S) groups (n = 6 rats per group). DBS treated rats had higher levels of TNF-α (120%; P < 0.01) and IFN-γ (305%; P < 0.001) but lower corticosterone concentration (48%; P < 0.001) than C and S. UCVgX animals showed increased corticosterone levels (154%; P < 0.001) versus C and S. UCVgX plus DBS increased IL-1β (402%; P < 0.001), IL-6 (160%; P < 0.001), and corsticosterone (178%; P < 0.001 versus 48%; P < 0.001) compared with the C and S groups. Chronic DBS at VMHvl induced a systemic inflammatory response accompanied by a decrease of HPA axis function. UCVgX rats experienced HPA axis hyperactivity as result of vagus nerve injury; however, DBS was unable to block the HPA axis hyperactivity induced by unilateral cervical vagotomy. Further studies are necessary to explore these findings and their clinical implication. PMID:24235973

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

    Science.gov (United States)

    Deeb, Wissam; Giordano, James J.; Rossi, Peter J.; Mogilner, Alon Y.; Gunduz, Aysegul; Judy, Jack W.; Klassen, Bryan T.; Butson, Christopher R.; Van Horne, Craig; Deny, Damiaan; Dougherty, Darin D.; Rowell, David; Gerhardt, Greg A.; Smith, Gwenn S.; Ponce, Francisco A.; Walker, Harrison C.; Bronte-Stewart, Helen M.; Mayberg, Helen S.; Chizeck, Howard J.; Langevin, Jean-Philippe; Volkmann, Jens; Ostrem, Jill L.; Shute, Jonathan B.; Jimenez-Shahed, Joohi; Foote, Kelly D.; Wagle Shukla, Aparna; Rossi, Marvin A.; Oh, Michael; Pourfar, Michael; Rosenberg, Paul B.; Silburn, Peter A.; de Hemptine, Coralie; Starr, Philip A.; Denison, Timothy; Akbar, Umer; Grill, Warren M.; Okun, Michael S.

    2016-01-01

    This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field. PMID:27920671

  16. Informed consent for clinical trials of deep brain stimulation in psychiatric disease: challenges and implications for trial design.

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    Lipsman, Nir; Giacobbe, Peter; Bernstein, Mark; Lozano, Andres M

    2012-02-01

    Advances in neuromodulation and an improved understanding of the anatomy and circuitry of psychopathology have led to a resurgence of interest in surgery for psychiatric disease. Clinical trials exploring deep brain stimulation (DBS), a focally targeted, adjustable and reversible form of neurosurgery, are being developed to address the use of this technology in highly selected patient populations. Psychiatric patients deemed eligible for surgical intervention, such as DBS, typically meet stringent inclusion criteria, including demonstrated severity, chronicity and a failure of conventional therapy. Although a humanitarian device exemption by the US Food and Drug Administration exists for its use in obsessive-compulsive disorder, DBS remains a largely experimental treatment in the psychiatric context, with its use currently limited to clinical trials and investigative studies. The combination of a patient population at the limits of conventional therapy and a novel technology in a new indication poses interesting challenges to the informed consent process as it relates to clinical trial enrollment. These challenges can be divided into those that relate to the patient, their disease and the technology, with each illustrating how traditional conceptualisations of research consent may be inadequate in the surgical psychiatry context. With specific reference to risk analysis, patient autonomy, voluntariness and the duty of the clinician-researcher, this paper will discuss the unique challenges that clinical trials of surgery for refractory psychiatric disease present to the consent process. Recommendations are also made for an ethical approach to clinical trial consent acquisition in this unique patient population.

  17. Self-Reported Executive Functioning in Everyday Life in Parkinson's Disease after Three Months of Subthalamic Deep Brain Stimulation.

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    Pham, Uyen Ha Gia; Andersson, Stein; Toft, Mathias; Pripp, Are Hugo; Konglund, Ane Eidahl; Dietrichs, Espen; Malt, Ulrik Fredrik; Skogseid, Inger Marie; Haraldsen, Ira Ronit Hebolt; Solbakk, Anne-Kristin

    2015-01-01

    Objective. Studies on the effect of subthalamic deep brain stimulation (STN-DBS) on executive functioning in Parkinson's disease (PD) are still controversial. In this study we compared self-reported daily executive functioning in PD patients before and after three months of STN-DBS. We also examined whether executive functioning in everyday life was associated with motor symptoms, apathy, and psychiatric symptoms. Method. 40 PD patients were examined with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), the Symptom Checklist 90-Revised (SCL-90-R), and the Apathy Evaluation Scale (AES-S). Results. PD patients reported significant improvement in daily life executive functioning after 3 months of STN-DBS. Anxiety scores significantly declined, while other psychiatric symptoms remained unchanged. The improvement of self-reported executive functioning did not correlate with motor improvement after STN-DBS. Apathy scores remained unchanged after surgery. Only preoperative depressed mood had predictive value to the improvement of executive function and appears to prevent potentially favorable outcomes from STN-DBS on some aspects of executive function. Conclusion. PD patients being screened for STN-DBS surgery should be evaluated with regard to self-reported executive functioning. Depressive symptoms in presurgical PD patients should be treated. Complementary information about daily life executive functioning in PD patients might enhance further treatment planning of STN-DBS.

  18. Some Clinically Useful Information that Neuropsychology Provides Patients, Carepartners, Neurologists, and Neurosurgeons About Deep Brain Stimulation for Parkinson's Disease

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    Tröster, Alexander I

    2017-01-01

    Abstract Deep brain stimulation (DBS) is an effective (but non-curative) treatment for some of the motor symptoms and treatment complications associated with dopaminergic agents in Parkinson's disease (PD). DBS can be done relatively safely and is associated with quality of life gains. In most DBS centers, neuropsychological evaluations are performed routinely before surgery, and sometimes after surgery. The purpose of such evaluation is not to decide solely on its results whether or not to offer DBS to a given candidate, but to provide the patient and treatment team with the best available information to make reasonable risk-benefit assessments. This review provides information relevant to the questions often asked by patients and their carepartners, neurologists, and neurosurgeons about neuropsychological outcomes of DBS, including neuropsychological adverse event rates, magnitude of cognitive changes, outcomes after unilateral versus bilateral surgery directed at various targets, impact of mild cognitive impairment (MCI) on outcome, factors implicated in neurobehavioral outcomes, and safety of newer interventions or techniques such as asleep surgery and current steering. PMID:29077802

  19. Deep Brain Stimulation Utilizing Dexmedetomidine: A Clinical Report from theUniversity of Miami Miller School of Medicine

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    Derek B Covington

    2016-01-01

    Full Text Available Background: Deep brain stimulation (DBS is an increasingly utilized technique to treat symptoms of neurological movement disorders, most commonly, Parkinson′s Disease. Patients and surgeons alike appreciate the minimally invasive nature of this procedure, as well as its reversibility. As these surgeries are being performed more often, it is becoming increasingly important to optimize our anesthetic management during these cases. Methods: We conducted a retrospective review of the DBS procedures that have been performed at our institution utilizing monitored anaesthesia care (MAC via dexmedetomidine infusion to report on the frequency and type of perioperative complications as well as to assess the effectiveness of this technique. Results: A total of 150 patients and 174 lead placements were included in this study. Dexmedetomidine was the sole anaesthetic used in 85.6% of cases. The remaining cases used a combination of dexmedetomidine and adjuvant agents. A total of one perioperative complication was found in our series, resulting in a total complication rate percentage per patient of 0.6%. Conclusions: We found very few perioperative complications associated with the use of dexmedetomidine during these challenging cases. With its anxiolytic, sedative, and analgesic properties coupled with preservation of respiration and a short half-life, dexmedetomidine has ideal properties for DBS procedures.

  20. Deep Brain Stimulation for Tremor Associated with Underlying Ataxia Syndromes: A Case Series and Discussion of Issues

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    Genko Oyama

    2014-07-01

    Full Text Available Background: Deep brain stimulation (DBS has been utilized to treat various symptoms in patients suffering from movement disorders such as Parkinson's disease, dystonia, and essential tremor. Though ataxia syndromes have not been formally or frequently addressed with DBS, there are patients with ataxia and associated medication refractory tremor or dystonia who may potentially benefit from therapy.Methods: A retrospective database review was performed, searching for cases of ataxia where tremor and/or dystonia were addressed by utilizing DBS at the University of Florida Center for Movement Disorders and Neurorestoration between 2008 and 2011. Five patients were found who had DBS implantation to address either medication refractory tremor or dystonia. The patient's underlying diagnoses included spinocerebellar ataxia type 2 (SCA2, fragile X associated tremor ataxia syndrome (FXTAS, a case of idiopathic ataxia (ataxia not otherwise specified [NOS], spinocerebellar ataxia type 17 (SCA17, and a senataxin mutation (SETX.Results: DBS improved medication refractory tremor in the SCA2 and the ataxia NOS patients. The outcome for the FXTAS patient was poor. DBS improved dystonia in the SCA17 and SETX patients, although dystonia did not improve in the lower extremities of the SCA17 patient. All patients reported a transient gait dysfunction postoperatively, and there were no reports of improvement in ataxia‐related symptoms.Discussion: DBS may be an option to treat tremor, inclusive of dystonic tremor in patients with underlying ataxia; however, gait and other symptoms may possibly be worsened.Erratum published on July 27, 2016

  1. CranialVault and its CRAVE tools: a clinical computer assistance system for deep brain stimulation (DBS) therapy.

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

    2012-04-01

    A number of methods have been developed to assist surgeons at various stages of deep brain stimulation (DBS) therapy. These include construction of anatomical atlases, functional databases, and electrophysiological atlases and maps. But, a complete system that can be integrated into the clinical workflow has not been developed. In this paper we present a system designed to assist physicians in pre-operative target planning, intra-operative target refinement and implantation, and post-operative DBS lead programming. The purpose of this system is to centralize the data acquired a the various stages of the procedure, reduce the amount of time needed at each stage of the therapy, and maximize the efficiency of the entire process. The system consists of a central repository (CranialVault), of a suite of software modules called CRAnialVault Explorer (CRAVE) that permit data entry and data visualization at each stage of the therapy, and of a series of algorithms that permit the automatic processing of the data. The central repository contains image data for more than 400 patients with the related pre-operative plans and position of the final implants and about 10,550 electrophysiological data points (micro-electrode recordings or responses to stimulations) recorded from 222 of these patients. The system has reached the stage of a clinical prototype that is being evaluated clinically at our institution. A preliminary quantitative validation of the planning component of the system performed on 80 patients who underwent the procedure between January 2009 and December 2009 shows that the system provides both timely and valuable information. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Measurements of RF Heating during 3.0T MRI of a Pig Implanted with Deep Brain Stimulator

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    Gorny, Krzysztof R; Presti, Michael F; Goerss, Stephan J; Hwang, Sun C; Jang, Dong-Pyo; Kim, Inyong; Shu, Yunhong; Favazza, Christopher P; Lee, Kendall H; Bernstein, Matt A

    2012-01-01

    Purpose To present preliminary, in vivo temperature measurements during MRI of a pig implanted with a deep brain stimulation (DBS) system. Materials and Methods DBS system (Medtronic Inc., Minneapolis, MN) was implanted in the brain of an anesthetized pig. 3.0T MRI was performed with a T/R head coil using the low-SAR GRE EPI and IR-prepped GRE sequences (SAR: 0.42 W/kg and 0.39 W/kg, respectively), and the high-SAR 4-echo RF spin echo (SAR: 2.9 W/kg). Fluoroptic thermometry was used to directly measure RF-related heating at the DBS electrodes, and at the implantable pulse generator (IPG). For reference the measurements were repeated in the same pig at 1.5T and, at both field strengths, in a phantom. Results At 3.0T, the maximal temperature elevations at DBS electrodes were 0.46 °C and 2.3 °C, for the low- and high-SAR sequences, respectively. No heating was observed on the implanted IPG during any of the measurements. Measurements of in-vivo heating differed from those obtained in the phantom. Conclusion The 3.0T MRI using GRE EPI and IR-prepped GRE sequences resulted in local temperature elevations at DBS electrodes of no more than 0.46°C. Although no extrapolation should be made to human exams and much further study will be needed, these preliminary data are encouraging for the future use 3.0T MRI in patients with DBS. PMID:23228310

  3. Integration of sparse electrophysiological measurements with preoperative MRI using 3D surface estimation in deep brain stimulation surgery

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    Husch, Andreas; Gemmar, Peter; Thunberg, Johan; Hertel, Frank

    2017-03-01

    Intraoperative microelectrode recordings (MER) have been used for several decades to guide neurosurgeons during the implantation of Deep Brain Stimulation (DBS) electrodes, especially when targeting the subthalamic nucleus (STN) to suppress the symptoms of Parkinson's Disease. The standard approach is to use an array of up to five MER electrodes in a fixed configuration. Interpretation of the recorded signals yields a spatially very sparse set of information about the morphology of the respective brain structures in the targeted area. However, no aid is currently available for surgeons to intraoperatively integrate this information with other data available on the patient's individual morphology (e.g. MR imaging data used for surgical planning). This integration might allow surgeons to better determine the most probable position of the electrodes within the target structure during surgery. This paper suggests a method for reconstructing a surface patch from the sparse MER dataset utilizing additional a priori knowledge about the geometrical configuration of the measurement electrodes. The conventional representation of MER measurements as intervals of target region/non-target region is therefore transformed into an equivalent boundary set representation, allowing ecient point-based calculations. Subsequently, the problem is to integrate the resulting patch with a preoperative model of the target structure, which can be formulated as registration problem minimizing a distance measure between the two surfaces. When restricting this registration procedure to translations, which is reasonable given certain geometric considerations, the problem can be solved globally by employing an exhaustive search with arbitrary precision in polynomial time. The proposed method is demonstrated using bilateral STN/Substantia Nigra segmentation data from preoperative MRIs of 17 Patients with simulated MER electrode placement. When using simulated data of heavily perturbed electrodes

  4. Measurements of RF heating during 3.0-T MRI of a pig implanted with deep brain stimulator.

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    Gorny, Krzysztof R; Presti, Michael F; Goerss, Stephan J; Hwang, Sun C; Jang, Dong-Pyo; Kim, Inyong; Min, Hoon-Ki; Shu, Yunhong; Favazza, Christopher P; Lee, Kendall H; Bernstein, Matt A

    2013-06-01

    To present preliminary, in vivo temperature measurements during MRI of a pig implanted with a deep brain stimulation (DBS) system. DBS system (Medtronic Inc., Minneapolis, MN) was implanted in the brain of an anesthetized pig. 3.0-T MRI was performed with a T/R head coil using the low-SAR GRE EPI and IR-prepped GRE sequences (SAR: 0.42 and 0.39 W/kg, respectively), and the high-SAR 4-echo RF spin echo (SAR: 2.9 W/kg). Fluoroptic thermometry was used to directly measure RF-related heating at the DBS electrodes, and at the implantable pulse generator (IPG). For reference the measurements were repeated in the same pig at 1.5 T and, at both field strengths, in a phantom. At 3.0T, the maximal temperature elevations at DBS electrodes were 0.46 °C and 2.3 °C, for the low- and high-SAR sequences, respectively. No heating was observed on the implanted IPG during any of the measurements. Measurements of in vivo heating differed from those obtained in the phantom. The 3.0-T MRI using GRE EPI and IR-prepped GRE sequences resulted in local temperature elevations at DBS electrodes of no more than 0.46 °C. Although no extrapolation should be made to human exams and much further study will be needed, these preliminary data are encouraging for the future use 3.0-T MRI in patients with DBS. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. The International Deep Brain Stimulation Registry and Database for Gilles de la Tourette Syndrome: How Does it Work?

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    Wissam eDeeb

    2016-04-01

    Full Text Available Tourette Syndrome (TS is a neuropsychiatric disease characterized by a combination of motor and vocal tics. Deep brain stimulation (DBS, already widely utilized for Parkinson’s disease and other movement disorders, is an emerging therapy for select and severe cases of TS that are resistant to medication and behavioral therapy. Over the last two decades, DBS has been used experimentally to manage severe TS cases. The results of case reports and small case series have been variable but in general positive. The reported interventions have, however, been variable, and there remain non-standardized selection criteria, various brain targets, differences in hardware, as well as variability in the programming parameters utilized. DBS centers perform only a handful of TS DBS cases each year, making large-scale outcomes difficult to study and to interpret. These limitations, coupled with the variable effect of surgery, and the overall small numbers of TS patients with implanted DBS worldwide, have delayed regulatory agency approval (e.g. FDA and equivalent agencies around the world. The Tourette Association of America, in response to the worldwide need for a more organized and collaborative effort, launched an international TS DBS registry and database. The main goal of the project has been to share data, uncover best practices, improve outcomes, and to provide critical information to regulatory agencies. The international registry and database has improved the communication and collaboration among TS DBS centers worldwide. In this paper we will review some of the key operation details for the international TS DBS database and registry.

  6. Zolpidem improves neuropsychiatric symptoms and motor dysfunction in a patient with Parkinson's disease after deep brain stimulation.

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    Huang, Hung-Yu; Hsu, Yi-Ting; Wu, Yu-Chin; Chiou, Shang-Ming; Kao, Chia-Hung; Tsai, Mu-Chieh; Tsai, Chon-Haw

    2012-06-01

    To illustrate the beneficial effect of zolpidem on the neuropsychiatric and motor symptoms in a patient with Parkinson disease (PD) after bilateral subthalamic nucleus deep brain stimulation. The 61-year-old housewife was diagnosed to have PD for 12 years with initial presentation of clumsiness and rest tremor of right limbs. She was referred to our hospital in March 2009 due to shortening of drug beneficial period since 3 years ago and on-phase dyskinesia in recent 2 years. Bilateral STN DBS was conducted on 18 June, 2009. Fluctuating spells of mental confusion were developed on the next day after surgery. Electric stimuli via DBS electrodes were delivered with parameters of 2 volts, 60 μs, 130 Hz on bilateral STN 32 days after DBS. The incoherent behaviors and motor fluctuation remained to occur. The beneficial effect of zolpidem on her neuropsychiatric and motor symptoms was detected incidentally in early July 2009. She could chat normally with her caregiver and walk with assistance after taking zolpidem. The beneficial period may last for 2 hours. Zolpidem was then given in dosage of 10 mg three times per day. The neuropsychiatric inventory was scored 56 during zolpidem 'off' and 30 during zolpidem 'on'. To understand the intriguing feature, we conducted FDG-PET during 'off' and 'on' zolpidem conditions. The results revealed that the metabolism was decreased in the right frontal, parietal cortex and caudate nucleus during zolpidem 'off'. These cool spots can be partially restored by zolpidem. Zolpidem ameliorated the neuropsychiatric and parkinsonian motor symptom in the PD patient. Since GABAA benzodiazepine receptors are widely distributed throughout the central nervous system, zolpidem probably acts via modulating structures lying within the cortico-subcortical loop or by direct effect on these cortical regions.

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

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    Xiao-Hong Wang

    2015-01-01

    Full Text Available 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.

  8. Tackling psychosocial maladjustment in Parkinson's disease patients following subthalamic deep-brain stimulation: A randomised clinical trial.

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    Joao Flores Alves Dos Santos

    Full Text Available Subthalamic nucleus deep brain stimulation (STN-DBS is an effective treatment for the motor and non-motor signs of Parkinson's disease (PD, however, psychological disorders and social maladjustment have been reported in about one third of patients after STN-DBS. We propose here a perioperative psychoeducation programme to limit such social and familial disruption.Nineteen PD patients and carers were included in a randomised single blind study. Social adjustment scale (SAS scores from patients and carers that received the psychoeducation programme (n = 9 were compared, both 1 and 2 years after surgery, with patients and carers with usual care (n = 10. Depression, anxiety, cognitive status, apathy, coping, parkinsonian disability, quality-of-life, carers' anxiety and burden were also analysed.Seventeen patients completed the study, 2 were excluded from the final analysis because of adverse events. At 1 year, 2/7 patients with psychoeducation and 8/10 with usual care had an aggravation in at least one domain of the SAS (p = .058. At 2 years, only 1 patient with psychoeducation suffered persistent aggravated social adjustment as compared to 8 patients with usual care (p = .015. At 1 year, anxiety, depression and instrumental coping ratings improved more in the psychoeducation than in the usual care group (p = .038, p = .050 and p = .050, respectively. No significant differences were found between groups for quality of life, cognitive status, apathy or motor disability.Our results suggest that a perioperative psychoeducation programme prevents social maladjustment in PD patients following STN-DBS and improves anxiety and depression compared to usual care. These preliminary data need to be confirmed in larger studies.

  9. Episodic memory following deep brain stimulation of the ventral anterior limb of the internal capsule and electroconvulsive therapy.

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    Bergfeld, Isidoor O; Mantione, Mariska; Hoogendoorn, Mechteld L C; Horst, Ferdinand; Notten, Peter; Schuurman, P Richard; Denys, Damiaan

    Electroconvulsive Therapy (ECT) and Deep Brain Stimulation (DBS) are effective treatments for patients with treatment-resistant depression (TRD). However, a common side effect of ECT is autobiographical memory loss (e.g., personal experiences), whereas the impact of DBS on autobiographical memories has never been established. Comparing autobiographical memories following DBS and ECT. In two hospitals in The Netherlands, we interviewed 25 TRD patients treated with DBS of the ventral anterior limb of the internal capsule (vALIC), 14 TRD patients treated with ECT and 22 healthy controls (HC) with the Autobiographical Memory Inventory - Short Form (AMI-SF) in a prospective, longitudinal study between March 2010 and August 2016. Patients treated with DBS were interviewed before surgery, after surgery, and twice during treatment over 122.7 (SD: ±22.2) weeks. Patients treated with ECT were tested before ECT, after six right unilateral (RUL) ECT sessions and twice following ECT over 65.1 (±9.3) weeks. Controls were tested four times over 81.5 (±15.6) weeks. Compared to HC, the AMI-SF score decreased faster in both TRD groups (P ECT group was larger than both the DBS and HC groups. Both ECT and vALIC DBS result in a faster autobiographical memory decline compared to HC. DBS might have a negative impact on autobiographical memories, although less so than ECT. Future work should dissect whether DBS or characteristics of TRD cause this decline. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Acute changes in mood induced by subthalamic deep brain stimulation in Parkinson disease are modulated by psychiatric diagnosis.

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    Eisenstein, Sarah A; Dewispelaere, William B; Campbell, Meghan C; Lugar, Heather M; Perlmutter, Joel S; Black, Kevin J; Hershey, Tamara

    2014-01-01

    Deep brain stimulation of the subthalamic nucleus (STN DBS) reduces Parkinson disease (PD) motor symptoms but has unexplained, variable effects on mood. The study tested the hypothesis that pre-existing mood and/or anxiety disorders or increased symptom severity negatively affects mood response to STN DBS. Thirty-eight PD participants with bilateral STN DBS and on PD medications were interviewed with Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed Beck Depression Inventory (BDI) and Spielberger State Anxiety Inventory (SSAI) self-reports. Subsequently, during OFF and optimal ON (clinical settings) STN DBS conditions and while off PD medications, motor function was assessed with the United Parkinson Disease Rating Scale (UPDRS, part III), and participants rated their mood with Visual Analogue Scales (VAS), and again completed SSAI. VAS mood variables included anxiety, apathy, valence and emotional arousal. STN DBS improved UPDRS scores and mood. Unexpectedly, PD participants diagnosed with current anxiety or mood disorders experienced greater STN DBS-induced improvement in mood than those diagnosed with remitted disorders or who were deemed as having never met threshold criteria for diagnosis. BDI and SSAI scores did not modulate mood response to STN DBS, indicating that clinical categorical diagnosis better differentiates mood response to STN DBS than self-rated symptom severity. SCID diagnosis, BDI and SSAI scores did not modulate motor response to STN DBS. PD participants diagnosed with current mood or anxiety disorders are more sensitive to STN DBS-induced effects on mood, possibly indicating altered basal ganglia circuitry in this group. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Long-term follow-up study on the safety of deep brain stimulation for treating Parkinson's disease

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    Xi WU

    2015-10-01

    Full Text Available Objective To evaluate the safety of deep brain stimulation (DBS for treating Parkinson's disease (PD under long-term follow-up and modify the surgical procedure. Methods A total of 362 PD patients underwent DBS, and almost 613 electrodes were implanted into these patients. Both surgical and hardware-related complications of DBS were retrospectively analyzed. Results Perioperative complications included postoperative confusion or delirium in 21 cases (5.80%, intracranial hemorrhage in 4 cases (1.10%; 2 asymptomatic cortical microhemorrhage and 2 basal ganglia trajectory microhemorrhage, generalized tonic-clonic seizures (GTCS in 2 cases (0.55% , urinary tract infection in 4 cases (1.10% , pulmonary infection in 7 cases (1.93%, implantable pulse generator (IPG hematoma in 11 cases (3.04%, IPG seroma in 3 cases (0.83%. All these patients were cured. They were followed-up for 12-146 months (median 34 months. Hardware-related complications included infection of incisional wound and/or skin erosion (9 cases, 2.49% , extension wire fracture caused by IPG displacement (one case, 0.28% , IPG shifting to abdomen due to fixation wire fracture (one case, 0.28%, slightly migrated electrode due to fall (one case, 0.28%, and discomfort about occipital incision (one case, 0.28%. Conclusions The overall risk of both surgical and hardware-related adverse events of DBS for treating PD is acceptably low. DOI: 10.3969/j.issn.1672-6731.2015.10.005

  12. Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease.

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    Hacker, Mallory L; Tonascia, James; Turchan, Maxim; Currie, Amanda; Heusinkveld, Lauren; Konrad, Peter E; Davis, Thomas L; Neimat, Joseph S; Phibbs, Fenna T; Hedera, Peter; Wang, Lily; Shi, Yaping; Shade, David M; Sternberg, Alice L; Drye, Lea T; Charles, David

    2015-10-01

    The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39 scores significantly worsened in the ODT group after two years (p < 0.003), with no significant change in the DBS + ODT group. DBS + ODT in early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Impulsivity and decision-making in obsessive-compulsive disorder after effective deep brain stimulation or treatment as usual.

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    Grassi, Giacomo; Figee, Martijn; Ooms, Pieter; Righi, Lorenzo; Nakamae, Takashi; Pallanti, Stefano; Schuurman, Rick; Denys, Damiaan

    2018-06-04

    Impulsivity and impaired decision-making have been proposed as obsessive-compulsive disorder (OCD) endophenotypes, running in OCD and their healthy relatives independently of symptom severity and medication status. Deep brain stimulation (DBS) targeting the ventral limb of the internal capsule (vALIC) and the nucleus accumbens (Nacc) is an effective treatment strategy for treatment-refractory OCD. The effectiveness of vALIC-DBS for OCD has been linked to its effects on a frontostriatal network that is also implicated in reward, impulse control, and decision-making. While vALIC-DBS has been shown to restore reward dysfunction in OCD patients, little is known about the effects of vALIC-DBS on impulsivity and decision-making. The aim of the study was to compare cognitive impulsivity and decision-making between OCD patients undergoing effective vALIC-DBS or treatment as usual (TAU), and healthy controls. We used decision-making performances under ambiguity on the Iowa Gambling Task and reflection impulsivity on the Beads Task to compare 20 OCD patients effectively treated with vALIC-DBS, 40 matched OCD patients undergoing effective TAU (medication and/or cognitive behavioural therapy), and 40 healthy subjects. Effective treatment was defined as at least 35% improvement of OCD symptoms. OCD patients, irrespective of tr