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  1. Deep Brain Stimulation for Parkinson's Disease

    Science.gov (United States)

    ... Home » Disorders » All Disorders Deep Brain Stimulation for Parkinson's Disease Information Page Deep Brain Stimulation for Parkinson's Disease Information Page What research is being done? The ...

  2. Mechanisms of deep brain stimulation

    Science.gov (United States)

    Cheng, Jennifer J.; Eskandar, Emad N.

    2015-01-01

    Deep brain stimulation (DBS) is widely used for the treatment of movement disorders including Parkinson's disease, essential tremor, and dystonia and, to a lesser extent, certain treatment-resistant neuropsychiatric disorders including obsessive-compulsive disorder. Rather than a single unifying mechanism, DBS likely acts via several, nonexclusive mechanisms including local and network-wide electrical and neurochemical effects of stimulation, modulation of oscillatory activity, synaptic plasticity, and, potentially, neuroprotection and neurogenesis. These different mechanisms vary in importance depending on the condition being treated and the target being stimulated. Here we review each of these in turn and illustrate how an understanding of these mechanisms is inspiring next-generation approaches to DBS. PMID:26510756

  3. Anesthesia for Pediatric Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Joseph Sebeo

    2010-01-01

    Full Text Available In patients refractory to medical therapy, deep brain stimulations (DBSs have emerged as the treatment of movement disorders particularly Parkinson's disease. Their use has also been extended in pediatric and adult patients to treat epileptogenic foci. We here performed a retrospective chart review of anesthesia records from 28 pediatric cases of patients who underwent DBS implantation for dystonia using combinations of dexmedetomidine and propofol-based anesthesia. Complications with anesthetic techniques including airway and cardiovascular difficulties were analyzed.

  4. Deep brain stimulation in psychiatry.

    Science.gov (United States)

    Mohr, Pavel

    2008-11-01

    Deep brain stimulation (DBS) is a reversible surgical procedure that involves stereotactic implantation of electrodes into the targeted brain regions, with a subcutaneously placed pulse generator powering the electrodes via one or two leads. The mechanism of action can be explained by the stimulation-induced modulation of impaired network activity. So far, the main use of DBS has been for neurological conditions, such as essential tremor, motor symptoms in Parkinson's disease, dystonia, epilepsy, and chronic pain. In psychiatry, case series and open studies indicate treatment efficacy of DBS in Gilles de la Tourette syndrome, treatment-resistant obsessive-compulsive disorder, and refractory major depression. Neuroimaging studies have confirmed the effects of DBS on the brain regions implicated in specific neuropsychiatric disorders. It is a well-tolerated method with relatively few serious side effects. Additional well-designed and appropriately powered controlled clinical trials are needed to conclusively establish the efficacy and safety of DBS and to identify the patient population(s) who may benefit most. Ongoing research with stimulation techniques may also significantly contribute to our understanding of major neuropsychiatric disorders.

  5. Brain networks modulated by subthalamic nucleus deep brain stimulation.

    Science.gov (United States)

    Accolla, Ettore A; Herrojo Ruiz, Maria; Horn, Andreas; Schneider, Gerd-Helge; Schmitz-Hübsch, Tanja; Draganski, Bogdan; Kühn, Andrea A

    2016-09-01

    Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour. © The

  6. Orientation selective deep brain stimulation

    Science.gov (United States)

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

    2017-02-01

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

  7. Advanced research on deep brain stimulation in treating mental disorders.

    Science.gov (United States)

    Wang, Dongxin; Liu, Xuejun; Zhou, Bin; Kuang, Weiping; Guo, Tiansheng

    2018-01-01

    Deep brain stimulation is a method that involves using an electric stimulus on a specific target in the brain with stereotaxis. It is a minimally invasive, safe, adjustable and reversible nerve involvement technology. At present, this technique is widely applied to treat movement disorders and has produced promising effects on mental symptoms, including combined anxiety and depression. Deep brain stimulation has therefore been employed as a novel treatment for depression, obsessive-compulsive disorder, habituation, Tourette's syndrome, presenile dementia, anorexia nervosa and other refractory mental illnesses. Many encouraging results have been reported. The aim of the present review was to briefly describe the mechanisms, target selection, side effects, ethical arguments and risks associated with deep brain stimulation. Although deep brain stimulation is a developing and promising treatment, a large amount of research is still required to determine its curative effect, and the selection of patients and targets must be subjected to strict ethical standards.

  8. Advanced research on deep brain stimulation in treating mental disorders

    Science.gov (United States)

    Wang, Dongxin; Liu, Xuejun; Zhou, Bin; Kuang, Weiping; Guo, Tiansheng

    2018-01-01

    Deep brain stimulation is a method that involves using an electric stimulus on a specific target in the brain with stereotaxis. It is a minimally invasive, safe, adjustable and reversible nerve involvement technology. At present, this technique is widely applied to treat movement disorders and has produced promising effects on mental symptoms, including combined anxiety and depression. Deep brain stimulation has therefore been employed as a novel treatment for depression, obsessive-compulsive disorder, habituation, Tourette's syndrome, presenile dementia, anorexia nervosa and other refractory mental illnesses. Many encouraging results have been reported. The aim of the present review was to briefly describe the mechanisms, target selection, side effects, ethical arguments and risks associated with deep brain stimulation. Although deep brain stimulation is a developing and promising treatment, a large amount of research is still required to determine its curative effect, and the selection of patients and targets must be subjected to strict ethical standards. PMID:29250146

  9. Innovations in deep brain stimulation methodology.

    Science.gov (United States)

    Kühn, Andrea A; Volkmann, Jens

    2017-01-01

    Deep brain stimulation is a powerful clinical method for movement disorders that no longer respond satisfactorily to pharmacological management, but its progress has been hampered by stagnation in technological procedure solutions and device development. Recently, the combined research efforts of bioengineers, neuroscientists, and clinicians have helped to better understand the mechanisms of deep brain stimulation, and solutions for the translational roadblock are emerging. Here, we define the needs for methodological advances in deep brain stimulation from a neurophysiological perspective and describe technological solutions that are currently evaluated for near-term clinical application. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  10. Ethical issues in deep brain stimulation

    NARCIS (Netherlands)

    M.H.N. Schermer (Maartje)

    2011-01-01

    textabstractDeep brain stimulation (DBS) is currently used to treat neurological disorders like Parkinson's disease, essential tremor, and dystonia, and is explored as an experimental treatment for psychiatric disorders like major depression and obsessive compulsive disorder. This mini review

  11. MR anatomy of deep brain nuclei with special reference to specific diseases and deep brain stimulation localization.

    Science.gov (United States)

    Telford, Ryan; Vattoth, Surjith

    2014-02-01

    Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures.

  12. Tractography patterns of subthalamic nucleus deep brain stimulation.

    Science.gov (United States)

    Vanegas-Arroyave, Nora; Lauro, Peter M; Huang, Ling; Hallett, Mark; Horovitz, Silvina G; Zaghloul, Kareem A; Lungu, Codrin

    2016-04-01

    Deep brain stimulation therapy is an effective symptomatic treatment for Parkinson's disease, yet the precise mechanisms responsible for its therapeutic effects remain unclear. Although the targets of deep brain stimulation are grey matter structures, axonal modulation is known to play an important role in deep brain stimulation's therapeutic mechanism. Several white matter structures in proximity to the subthalamic nucleus have been implicated in the clinical benefits of deep brain stimulation for Parkinson's disease. We assessed the connectivity patterns that characterize clinically beneficial electrodes in Parkinson's disease patients, after deep brain stimulation of the subthalamic nucleus. We evaluated 22 patients with Parkinson's disease (11 females, age 57 ± 9.1 years, disease duration 13.3 ± 6.3 years) who received bilateral deep brain stimulation of the subthalamic nucleus at the National Institutes of Health. During an initial electrode screening session, one month after deep brain stimulation implantation, the clinical benefits of each contact were determined. The electrode was localized by coregistering preoperative magnetic resonance imaging and postoperative computer tomography images and the volume of tissue activated was estimated from stimulation voltage and impedance. Brain connectivity for the volume of tissue activated of deep brain stimulation contacts was assessed using probabilistic tractography with diffusion-tensor data. Areas most frequently connected to clinically effective contacts included the thalamus, substantia nigra, brainstem and superior frontal gyrus. A series of discriminant analyses demonstrated that the strength of connectivity to the superior frontal gyrus and the thalamus were positively associated with clinical effectiveness. The connectivity patterns observed in our study suggest that the modulation of white matter tracts directed to the superior frontal gyrus and the thalamus is associated with favourable clinical

  13. 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...

  14. Predicting sex from brain rhythms with deep learning.

    Science.gov (United States)

    van Putten, Michel J A M; Olbrich, Sebastian; Arns, Martijn

    2018-02-15

    We have excellent skills to extract sex from visual assessment of human faces, but assessing sex from human brain rhythms seems impossible. Using deep convolutional neural networks, with unique potential to find subtle differences in apparent similar patterns, we explore if brain rhythms from either sex contain sex specific information. Here we show, in a ground truth scenario, that a deep neural net can predict sex from scalp electroencephalograms with an accuracy of >80% (p deep net filter layers, showing that fast beta activity (20-25 Hz) and its spatial distribution is a main distinctive attribute. This demonstrates the ability of deep nets to detect features in spatiotemporal data unnoticed by visual assessment, and to assist in knowledge discovery. We anticipate that this approach may also be successfully applied to other specialties where spatiotemporal data is abundant, including neurology, cardiology and neuropsychology.

  15. Neuroethics: The Ethics and History Behind Deep Brain Stimulation

    OpenAIRE

    Simmonds, Matthew; Franck, Jannick

    2014-01-01

    In this Project we have tried to answer the Question: What is the history leading up to the development of Deep Brain Stimulation, and what are the ethical implications to the ethics of neuroscience? Has the historical background of psychosurgery affected the ethical climate now in regards to Deep Brain Stimulation, and are there any challenges to Deep Brain Stimulation’s future? We have gone through the historical background leading up to the use of Deep Brain Stimulation, and we discuss how...

  16. 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.

  17. 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.

  18. 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.

  19. Network effects of deep brain stimulation.

    Science.gov (United States)

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

    2015-10-01

    The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies. Copyright © 2015 the American Physiological Society.

  20. Network effects of deep brain stimulation

    Science.gov (United States)

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

    2015-01-01

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

  1. Novel applications of deep brain stimulation

    Science.gov (United States)

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

    2012-01-01

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

  2. Deep Brain Stimulation, Authenticity and Value.

    Science.gov (United States)

    Pugh, Jonathan; Maslen, Hannah; Savulescu, Julian

    2017-10-01

    Deep brain stimulation has been of considerable interest to bioethicists, in large part because of the effects that the intervention can occasionally have on central features of the recipient's personality. These effects raise questions regarding the philosophical concept of authenticity. In this article, we expand on our earlier work on the concept of authenticity in the context of deep brain stimulation by developing a diachronic, value-based account of authenticity. Our account draws on both existentialist and essentialist approaches to authenticity, and Laura Waddell Ekstrom's coherentist approach to personal autonomy. In developing our account, we respond to Sven Nyholm and Elizabeth O'Neill's synchronic approach to authenticity, and explain how the diachronic approach we defend can have practical utility, contrary to Alexandre Erler and Tony Hope's criticism of autonomy-based approaches to authenticity. Having drawn a distinction between the authenticity of an individual's traits and the authenticity of that person's values, we consider how our conception of authenticity applies to the context of anorexia nervosa in comparison to other prominent accounts of authenticity. We conclude with some reflections on the prudential value of authenticity, and by highlighting how the language of authenticity can be invoked to justify covert forms of paternalism that run contrary to the value of individuality that seems to be at the heart of authenticity.

  3. Stereotactic minimally invasive tubular retractor system for deep brain lesions.

    Science.gov (United States)

    Greenfield, Jeffrey P; Cobb, William S; Tsouris, A John; Schwartz, Theodore H

    2008-10-01

    Deep-seated supratentorial intraparenchymal and intraventricular brain lesions can be difficult to access without causing significant trauma to the overlying cortex and intervening white matter tracts. Traditional brain retractors use multiple blades, which do not exert pressure in an equally distributed fashion. Tubular retractors offer an advantage. Although a commercially available frame-based tubular retractor system is on the market (COMPASS; Compass, Inc., Rochester, MN), we modified existing off-the-shelf equipment at our institution into a frameless tubular brain retractor. We used 14- to 22-mm METRx (Medtronic, Minneapolis, MN) tubular retractors in combination with a frameless stereotactic navigation system to remove 10 deep lesions. Histological findings included 6 periventricular metastases, 1 insular glioblastoma multiforme, 1 periventricular glioblastoma multiforme, 1 intraventricular meningioma, and 1 hippocampal cavernous malformation. Radiographic gross total resection was achieved in all patients. One patient experienced a transient worsening of an existing preoperative Wernicke's aphasia; otherwise, there were no intra- or postoperative complications. One patient with radiographic gross total resection of a metastatic lesion experienced a local recurrence of disease, requiring stereotactic radiosurgery. A frameless stereotactic tubular retractor system for deep brain lesions can be assembled with equipment already available at many institutions. Use of this system can decrease incision and craniotomy size, decrease retractor-induced trauma to overlying cortex, and help prevent damage to underlying white matter tracts.

  4. Deep brain stimulation to reduce sexual drive.

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

    Beudel, M; Brown, P

    2016-01-01

    Although Deep Brain Stimulation (DBS) is an established treatment for Parkinson's disease (PD), there are still limitations in terms of effectivity, side-effects and battery consumption. One of the reasons for this may be that not only pathological but also physiological neural activity can be suppressed whilst stimulating. For this reason, adaptive DBS (aDBS), where stimulation is applied according to the level of pathological activity, might be advantageous. Initial studies of aDBS demonstrate effectiveness in PD, but there are still many questions to be answered before aDBS can be applied clinically. Here we discuss the feedback signals and stimulation algorithms involved in adaptive stimulation in PD and sketch a potential road-map towards clinical application. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Deep brain stimulation in obsessive-compulsive disorder

    NARCIS (Netherlands)

    Denys, Damiaan; Mantione, Mariska

    2009-01-01

    The use of deep brain stimulation in psychiatric disorders has received great interest owing to the small risk of the operation, the reversible nature of the technique, and the possibility of optimizing treatment postoperatively. Currently, deep brain stimulation in psychiatry is investigated for

  7. 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.

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

    Science.gov (United States)

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

    2015-06-01

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

  9. Brain, mind and internet a deep history and future

    CERN Document Server

    Staley, D

    2014-01-01

    This essay places the emerging brain-Internet interface within a broad historical context: that the Internet represents merely the next stage in a very long history of human cognition whereby the brain couples with symbolic technologies. Understanding this 'deep history' provides a way to imagine the future of brain-Internet cognition.

  10. Deep brain stimulation surgery for alcohol addiction.

    Science.gov (United States)

    Voges, Juergen; Müller, Ulf; Bogerts, Bernhard; Münte, Thomas; Heinze, Hans-Jochen

    2013-01-01

    The consequences of chronic alcohol dependence cause important health and economic burdens worldwide. Relapse rates after standard treatment (medication and psychotherapy) are high. There is evidence from in vivo investigations and from studies in patients that the brain's reward system is critically involved in the development and maintenance of addictive behavior, suggesting that modification of this system could significantly improve the prognosis of addictive patients. Motivated by an accidental observation, we used the nucleus accumbens (NAc), which has a central position in the dopaminergic reward system for deep brain stimulation (DBS) of alcohol addiction. We report our first experiences with NAc DBS for alcohol dependence and review the literature addressing the mechanisms leading to addiction. Five patients were treated off-label with bilateral NAc DBS for severe alcohol addiction (average follow-up 38 months). All patients experienced significant and ongoing improvement of craving. Two patients remained completely abstinent for more than 4 years. NAc stimulation was tolerated without permanent side effects. Simultaneous recording of local field potentials from the target area and surface electroencephalography while patients performed neuropsychological tasks gave a hint on the pivotal role of the NAc in processing alcohol-related cues. To our knowledge, the data presented here reflect the first attempt to treat alcohol-addicted patients with NAc DBS. Electrical NAc stimulation probably counterbalances the effect of drug-related stimuli triggering involuntarily drug-seeking behavior. Meanwhile, two prospective clinical studies using randomized, double-blind, and crossover stimulation protocols for DBS are underway to corroborate these preliminary results. Published by Elsevier Inc.

  11. Brain tumor segmentation with Deep Neural Networks.

    Science.gov (United States)

    Havaei, Mohammad; Davy, Axel; Warde-Farley, David; Biard, Antoine; Courville, Aaron; Bengio, Yoshua; Pal, Chris; Jodoin, Pierre-Marc; Larochelle, Hugo

    2017-01-01

    In this paper, we present a fully automatic brain tumor segmentation method based on Deep Neural Networks (DNNs). The proposed networks are tailored to glioblastomas (both low and high grade) pictured in MR images. By their very nature, these tumors can appear anywhere in the brain and have almost any kind of shape, size, and contrast. These reasons motivate our exploration of a machine learning solution that exploits a flexible, high capacity DNN while being extremely efficient. Here, we give a description of different model choices that we've found to be necessary for obtaining competitive performance. We explore in particular different architectures based on Convolutional Neural Networks (CNN), i.e. DNNs specifically adapted to image data. We present a novel CNN architecture which differs from those traditionally used in computer vision. Our CNN exploits both local features as well as more global contextual features simultaneously. Also, different from most traditional uses of CNNs, our networks use a final layer that is a convolutional implementation of a fully connected layer which allows a 40 fold speed up. We also describe a 2-phase training procedure that allows us to tackle difficulties related to the imbalance of tumor labels. Finally, we explore a cascade architecture in which the output of a basic CNN is treated as an additional source of information for a subsequent CNN. Results reported on the 2013 BRATS test data-set reveal that our architecture improves over the currently published state-of-the-art while being over 30 times faster. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Deep brain stimulation af behandlingsrefraktaer, invaliderende dystoni. Dansk Selskab for Bevaegeforstyrrelser (Danmodis)

    DEFF Research Database (Denmark)

    Hjermind, Lena E; Løkkegaard, Annemette; Werdelin, Lene M

    2005-01-01

    Deep brain stimulation af behandlingsrefraktaer, invaliderende dystoni. Dansk Selskab for Bevaegeforstyrrelser (Danmodis)......Deep brain stimulation af behandlingsrefraktaer, invaliderende dystoni. Dansk Selskab for Bevaegeforstyrrelser (Danmodis)...

  13. 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.

  14. 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.

  15. Deep brain stimulation: how does it work?

    Science.gov (United States)

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

    2013-01-01

    Chronic deep brain stimulation (DBS) has become a widely accepted surgical treatment for medication-refractory movement disorders and is under evaluation for a variety of neurological disorders. In order to create opportunities to improve treatment efficacy, streamline parameter selection, and foster new potential applications, it is important to have a clear and comprehensive understanding of how DBS works. Although early hypothesis proposed that high-frequency electrical stimulation inhibited neuronal activity proximal to the active electrode, recent studies have suggested that the output of the stimulated nuclei is paradoxically activated by DBS. Such regular, time-locked output is thought to override the transmission of pathological bursting and oscillatory activity through the stimulated nuclei, as well as inducing synaptic plasticity and network reorganization. This chapter reviews electrophysiological experiments, biochemical analyses, computer modeling and imaging studies positing that, although general principles exist, the therapeutic mechanism(s) of action depend both on the site of stimulation and on the disorder being treated. © 2013 Elsevier B.V. All rights reserved.

  16. 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...... risk. Twiddler's syndrome should be suspected whenever there is a failure of the DBS device to relieve symptoms previously responsive to stimulation. Surgical correction is usually required....

  17. Deep brain stimulation for bipolar disorder-review and outlook.

    Science.gov (United States)

    Gippert, Sabrina M; Switala, Christina; Bewernick, Bettina H; Kayser, Sarah; Bräuer, Alena; Coenen, Volker A; Schlaepfer, Thomas E

    2017-06-01

    Research on deep brain stimulation (DBS) for treatment-resistant psychiatric disorders has established preliminary efficacy signals for treatment-resistant depression. There are only few studies on DBS that included patients suffering from bipolar disorder. This article gives an overview of these studies concerning DBS targets, antidepressant efficacy, and the occurrence of manic/hypomanic symptoms under stimulation. First, promising results show that all patients experienced significant improvement in depressive symptomatology. In a single case, hypomanic symptoms occurred, but they could be resolved by adjusting stimulation parameters. Furthermore, this article highlights important clinical differences between unipolar and bipolar depression that have to be considered throughout the course of treatment.

  18. Deep brain stimulation for stroke: Current uses and future directions.

    Science.gov (United States)

    Elias, Gavin J B; Namasivayam, Andrew A; Lozano, Andres M

    Survivors of stroke often experience significant disability and impaired quality of life related to ongoing maladaptive responses and persistent neurologic deficits. Novel therapeutic options are urgently needed to augment current approaches. One way to promote recovery and ameliorate symptoms may be to electrically stimulate the surviving brain. Various forms of brain stimulation have been investigated for use in stroke, including deep brain stimulation (DBS). We conducted a comprehensive literature review in order to 1) review the use of DBS to treat post-stroke maladaptive responses including pain, dystonia, dyskinesias, and tremor and 2) assess the use and potential utility of DBS for enhancing plasticity and recovery from post-stroke neurologic deficits. A large variety of brain structures have been targeted in post-stroke patients, including motor thalamus, sensory thalamus, basal ganglia nuclei, internal capsule, and periventricular/periaqueductal grey. Overall, the reviewed clinical literature suggests a role for DBS in the management of several post-stroke maladaptive responses. More limited evidence was identified regarding DBS for post-stroke motor deficits, although existing work tentatively suggests DBS-particularly DBS targeting the posterior limb of the internal capsule-may improve paresis in certain circumstances. Substantial future work is required both to establish optimal targets and parameters for treatment of maladapative responses and to further investigate the effectiveness of DBS for post-stroke paresis. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Sharma, Mayur; Deogaonkar, Milind

    2015-05-01

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

  20. Deep brain stimulation for the treatment of uncommon tremor syndromes

    Science.gov (United States)

    Ramirez-Zamora, Adolfo; Okun, Michael S.

    2016-01-01

    ABSTRACT Introduction: Deep brain stimulation (DBS) has become a standard therapy for the treatment of select cases of medication refractory essential tremor and Parkinson’s disease however the effectiveness and long-term outcomes of DBS in other uncommon and complex tremor syndromes has not been well established. Traditionally, the ventralis intermedius nucleus (VIM) of the thalamus has been considered the main target for medically intractable tremors; however alternative brain regions and improvements in stereotactic techniques and hardware may soon change the horizon for treatment of complex tremors. Areas covered: In this article, we conducted a PubMed search using different combinations between the terms ‘Uncommon tremors’, ‘Dystonic tremor’, ‘Holmes tremor’ ‘Midbrain tremor’, ‘Rubral tremor’, ‘Cerebellar tremor’, ‘outflow tremor’, ‘Multiple Sclerosis tremor’, ‘Post-traumatic tremor’, ‘Neuropathic tremor’, and ‘Deep Brain Stimulation/DBS’. Additionally, we examined and summarized the current state of evolving interventions for treatment of complex tremor syndromes. Expert c ommentary: Recently reported interventions for rare tremors include stimulation of the posterior subthalamic area, globus pallidus internus, ventralis oralis anterior/posterior thalamic subnuclei, and the use of dual lead stimulation in one or more of these targets. Treatment should be individualized and dictated by tremor phenomenology and associated clinical features. PMID:27228280

  1. Beyond the Burke-Fahn-Marsden Dystonia Rating Scale: deep brain stimulation in childhood secondary dystonia.

    Science.gov (United States)

    Gimeno, Hortensia; Tustin, Kylee; Selway, Richard; Lin, Jean-Pierre

    2012-09-01

    Deep brain stimulation is now widely accepted as an effective treatment for children with primary generalized dystonia. More variable results are reported in secondary dystonias and its efficacy in this heterogeneous group has not been fully elucidated. Deep brain stimulation outcomes are typically reported using impairment-focused measures, such as the Burke-Fahn-Marsden Dystonia Rating Scale, which provide little information about function and participation outcomes or changes in non-motor areas. The aim is to demonstrate that in some cases of secondary dystonia, the sole use of impairment level measures, such as the Burke-Fahn-Marsden Dystonia Rating Scale, may be insufficient to fully evaluate outcome following deep brain stimulation. Six paediatric cases who underwent deep brain stimulation surgery with a minimum of one year follow up were selected on the basis of apparent non-response to deep brain stimulation, defined as a clinically insignificant change in the Burke-Fahn-Marsden Dystonia Movement Scale (<20%), but where other evaluation measures demonstrated clinical efficacy across several domains. Despite no significant change in Burke-Fahn-Marsden Dystonia Rating Scale scores following deep brain stimulation, parallel outcome measures demonstrated significant benefit in a range of child and family-centred goal areas including: pain and comfort, school attendance, seating tolerance, access to assistive technology and in some cases carer burden. Sole use of impairment-focused measures, are limited in scope to evaluate outcome following deep brain stimulation, particularly in secondary dystonias. Systematic study of effects across multiple dimensions of disability is needed to determine what deep brain stimulation offers patients in terms of function, participation, care, comfort and quality of life. Deep brain stimulation may offer meaningful change across multiple domains of functioning, disability and health even in the absence of significant change in

  2. Management of Elevated Therapeutic Impedances on Deep Brain Stimulation Leads

    OpenAIRE

    Wissam Deeb; Amar Patel; Michael S. Okun; Aysegul Gunduz

    2017-01-01

    Clinical Vignette: A 64-year-old male with a history of essential tremor with bilateral thalamic ventralis intermedius deep brain stimulation implants had elevated therapeutic impedance values despite normal lead integrity impedances and good response to stimulation.Clinical Dilemma: Do elevated therapeutic impedance values indicate a sign of hardware malfunction? What are the guidelines to approach deep brain stimulation hardware malfunction?Clinical Solution: Lead integrity i...

  3. The pedunculopontine nucleus as alternative target for deep brain stimulation

    NARCIS (Netherlands)

    Lourens, Marcel Antonius Johannes; Meijer, Hil Gaétan Ellart; Heida, Tjitske; van Gils, Stephanus A.

    2009-01-01

    Parkinson’s disease (PD) is a neurodegenerative disease associated with motor and nonmotor symptoms. Deep brain stimulation (DBS) is a surgical treatment where an electrode is implanted in a certain area in the brain. In PD this is mostly done in the subthalamic nucleus (STN) or the globus pallidus

  4. Deep Brain Stimulation: An Update Review Article. | Dawodu ...

    African Journals Online (AJOL)

    Deep brain stimulation [DBS] involves the stereo tactic placement of an electrode into the brain. This is done in advanced countries and then only at few centers. This practice is modifying the challenges imposed on the health sector, limiting the frustrations of health personnel and elevating affected patients distress. Though ...

  5. 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.

  6. 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

  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. 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.

  9. Red and NIR light dosimetry in the human deep brain.

    Science.gov (United States)

    Pitzschke, A; Lovisa, B; Seydoux, O; Zellweger, M; Pfleiderer, M; Tardy, Y; Wagnières, G

    2015-04-07

    Photobiomodulation (PBM) appears promising to treat the hallmarks of Parkinson's Disease (PD) in cellular or animal models. We measured light propagation in different areas of PD-relevant deep brain tissue during transcranial, transsphenoidal illumination (at 671 and 808 nm) of a cadaver head and modeled optical parameters of human brain tissue using Monte-Carlo simulations. Gray matter, white matter, cerebrospinal fluid, ventricles, thalamus, pons, cerebellum and skull bone were processed into a mesh of the skull (158 × 201 × 211 voxels; voxel side length: 1 mm). Optical parameters were optimized from simulated and measured fluence rate distributions. The estimated μeff for the different tissues was in all cases larger at 671 than at 808 nm, making latter a better choice for light delivery in the deep brain. Absolute values were comparable to those found in the literature or slightly smaller. The effective attenuation in the ventricles was considerably larger than literature values. Optimization yields a new set of optical parameters better reproducing the experimental data. A combination of PBM via the sphenoid sinus and oral cavity could be beneficial. A 20-fold higher efficiency of light delivery to the deep brain was achieved with ventricular instead of transcranial illumination. Our study demonstrates that it is possible to illuminate deep brain tissues transcranially, transsphenoidally and via different application routes. This opens therapeutic options for sufferers of PD or other cerebral diseases necessitating light therapy.

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

    Energy Technology Data Exchange (ETDEWEB)

    Li Gang; Yu Chao; Lin Ling; Lu, Stephen C-Y [Inspiring Technical Laboratory, College of Precision Instruments and Opto-Electronics Engineering, Tianjin University, Tianjin 300072 (China)

    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.

  11. 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

  12. In vivo mapping of current density distribution in brain tissues during deep brain stimulation (DBS

    Directory of Open Access Journals (Sweden)

    Saurav Z. K. Sajib

    2017-01-01

    Full Text Available New methods for in vivo mapping of brain responses during deep brain stimulation (DBS are indispensable to secure clinical applications. Assessment of current density distribution, induced by internally injected currents, may provide an alternative method for understanding the therapeutic effects of electrical stimulation. The current flow and pathway are affected by internal conductivity, and can be imaged using magnetic resonance-based conductivity imaging methods. Magnetic resonance electrical impedance tomography (MREIT is an imaging method that can enable highly resolved mapping of electromagnetic tissue properties such as current density and conductivity of living tissues. In the current study, we experimentally imaged current density distribution of in vivo canine brains by applying MREIT to electrical stimulation. The current density maps of three canine brains were calculated from the measured magnetic flux density data. The absolute current density values of brain tissues, including gray matter, white matter, and cerebrospinal fluid were compared to assess the active regions during DBS. The resulting current density in different tissue types may provide useful information about current pathways and volume activation for adjusting surgical planning and understanding the therapeutic effects of DBS.

  13. In vivo mapping of current density distribution in brain tissues during deep brain stimulation (DBS)

    Science.gov (United States)

    Sajib, Saurav Z. K.; Oh, Tong In; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

    2017-01-01

    New methods for in vivo mapping of brain responses during deep brain stimulation (DBS) are indispensable to secure clinical applications. Assessment of current density distribution, induced by internally injected currents, may provide an alternative method for understanding the therapeutic effects of electrical stimulation. The current flow and pathway are affected by internal conductivity, and can be imaged using magnetic resonance-based conductivity imaging methods. Magnetic resonance electrical impedance tomography (MREIT) is an imaging method that can enable highly resolved mapping of electromagnetic tissue properties such as current density and conductivity of living tissues. In the current study, we experimentally imaged current density distribution of in vivo canine brains by applying MREIT to electrical stimulation. The current density maps of three canine brains were calculated from the measured magnetic flux density data. The absolute current density values of brain tissues, including gray matter, white matter, and cerebrospinal fluid were compared to assess the active regions during DBS. The resulting current density in different tissue types may provide useful information about current pathways and volume activation for adjusting surgical planning and understanding the therapeutic effects of DBS.

  14. 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.

  15. Brain tumor classification of microscopy images using deep residual learning

    Science.gov (United States)

    Ishikawa, Yota; Washiya, Kiyotada; Aoki, Kota; Nagahashi, Hiroshi

    2016-12-01

    The crisis rate of brain tumor is about one point four in ten thousands. In general, cytotechnologists take charge of cytologic diagnosis. However, the number of cytotechnologists who can diagnose brain tumors is not sufficient, because of the necessity of highly specialized skill. Computer-Aided Diagnosis by computational image analysis may dissolve the shortage of experts and support objective pathological examinations. Our purpose is to support a diagnosis from a microscopy image of brain cortex and to identify brain tumor by medical image processing. In this study, we analyze Astrocytes that is a type of glia cell of central nerve system. It is not easy for an expert to discriminate brain tumor correctly since the difference between astrocytes and low grade astrocytoma (tumors formed from Astrocyte) is very slight. In this study, we present a novel method to segment cell regions robustly using BING objectness estimation and to classify brain tumors using deep convolutional neural networks (CNNs) constructed by deep residual learning. BING is a fast object detection method and we use pretrained BING model to detect brain cells. After that, we apply a sequence of post-processing like Voronoi diagram, binarization, watershed transform to obtain fine segmentation. For classification using CNNs, a usual way of data argumentation is applied to brain cells database. Experimental results showed 98.5% accuracy of classification and 98.2% accuracy of segmentation.

  16. Deep brain stimulation for treatment-refractory obsessive compulsive disorder: a systematic review.

    Science.gov (United States)

    Kohl, Sina; Schönherr, Deva M; Luigjes, Judy; Denys, Damiaan; Mueller, Ulf J; Lenartz, Doris; Visser-Vandewalle, Veerle; Kuhn, Jens

    2014-08-02

    Obsessive-compulsive disorder is one of the most disabling of all psychiatric illnesses. Despite available pharmacological and psychotherapeutic treatments about 10% of patients remain severely affected and are considered treatment-refractory. For some of these patients deep brain stimulation offers an appropriate treatment method. The scope of this article is to review the published data and to compare different target structures and their effectiveness. PubMed search, last update June 2013, was conducted using the terms "deep brain stimulation" and "obsessive compulsive disorder". In total 25 studies were found that reported five deep brain stimulation target structures to treat obsessive-compulsive disorder: the anterior limb of the internal capsule (five studies including 14 patients), nucleus accumbens (eight studies including 37 patients), ventral capsule/ventral striatum (four studies including 29 patients), subthalamic nucleus (five studies including 23 patients) and inferior thalamic peduncle (two studies including 6 patients). Despite the anatomical diversity, deep brain stimulation treatment results in similar response rates for the first four target structures. Inferior thalamic peduncle deep brain stimulation results in higher response rates but these results have to be interpreted with caution due to a very small number of cases. Procedure and device related adverse events are relatively low, as well as stimulation or therapy related side effects. Most stimulation related side effects are transient and decline after stimulation parameters have been changed. Deep brain stimulation in treatment-refractory obsessive-compulsive disorder seems to be a relatively safe and promising treatment option. However, based on these studies no superior target structure could be identified. More research is needed to better understand mechanisms of action and response predictors that may help to develop a more personalized approach for these severely affected

  17. 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

  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. Ultra High Field MRI-Guided Deep Brain Stimulation.

    Science.gov (United States)

    Forstmann, Birte U; Isaacs, Bethany R; Temel, Yasin

    2017-10-01

    Deep brain stimulation (DBS) is a neurosurgical treatment for neurological disorders often planned with 1.5-T or 3-T MRI. The clinical efficacy of DBS can be improved using ultrahigh-field (UHF) MRI for planning by increasing the level of precision required for an individualized approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Spasmodic dysphonia may respond to bilateral thalamic deep brain ...

    African Journals Online (AJOL)

    Background Spasmodic dysphonia is a primary focal dystonia manifested by loss of control of the vocal muscles during speech secondary to laryngeal muscle spasms. The pathophysiology is not well understood. Deep brain stimulation surgery (DBS) for other focal dystonias has been well reported. Methods We report the ...

  1. Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus.

    Science.gov (United States)

    Hescham, Sarah; Jahanshahi, Ali; Schweimer, Judith V; Mitchell, Stephen N; Carter, Guy; Blokland, Arjan; Sharp, Trevor; Temel, Yasin

    2016-11-01

    Deep brain stimulation (DBS) of the fornix has gained interest as a potential therapy for advanced treatment-resistant dementia, yet the mechanism of action remains widely unknown. Previously, we have reported beneficial memory effects of fornix DBS in a scopolamine-induced rat model of dementia, which is dependent on various brain structures including hippocampus. To elucidate mechanisms of action of fornix DBS with regard to memory restoration, we performed c-Fos immunohistochemistry in the hippocampus. We found that fornix DBS induced a selective activation of cells in the CA1 and CA3 subfields of the dorsal hippocampus. In addition, hippocampal neurotransmitter levels were measured using microdialysis before, during and after 60 min of fornix DBS in a next experiment. We observed a substantial increase in the levels of extracellular hippocampal acetylcholine, which peaked 20 min after stimulus onset. Interestingly, hippocampal glutamate levels did not change compared to baseline. Therefore, our findings provide first experimental evidence that fornix DBS activates the hippocampus and induces the release of acetylcholine in this region.

  2. Novel brain model for training of deep microvascular anastomosis.

    Science.gov (United States)

    Ishikawa, Tatsuya; Yasui, Nobuyuki; Ono, Hidenori

    2010-01-01

    Models of the brain and skull were developed using a selective laser sintering method for training in the procedures of deep microvascular anastomosis. Model A has an artificial skull with two craniotomies, providing fronto-temporal-subtemporal and suboccipital windows. The brain in Model A is soft and elastic, and consists of the brainstem and a hemispheric part with a detailed surface. Rehearsals or training for anastomosis to the insular part of the middle cerebral artery, superior cerebellar artery, posterior cerebral artery, and posterior inferior cerebellar artery can be performed through the craniotomies. Model B has an artificial skull with a bifrontal craniotomy and an artificial brain consisting of the bilateral frontal lobes with an interhemispheric fissure and corpus callosum. Rehearsals or training for anastomosis of the callosal segment of the anterior cerebral artery can be practiced through this craniotomy. These realistic models will help to develop skills for deep vascular anastomosis, which remains a challenging neurosurgical procedure, even for experienced neurosurgeons.

  3. Connectivity Predicts Deep Brain Stimulation Outcome in Parkinson Disease

    Science.gov (United States)

    Horn, Andreas; Reich, Martin; Vorwerk, Johannes; Li, Ningfei; Wenzel, Gregor; Fang, Qianqian; Schmitz-Hübsch, Tanja; Nickl, Robert; Kupsch, Andreas; Volkmann, Jens; Kühn, Andrea A.; Fox, Michael D.

    2018-01-01

    Objective The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. Methods A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. Results In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p<0.001). This same connectivity profile predicted response in an independent patient cohort (p<0.01). Structural and functional connectivity were independent predictors of clinical improvement (p<0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. Interpretation Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. PMID:28586141

  4. Deep brain stimulation in mental health: Review of evidence for clinical efficacy.

    Science.gov (United States)

    Fitzgerald, Paul B; Segrave, Rebecca A

    2015-11-01

    There is increasing interest in the use of deep brain stimulation as a treatment for psychiatric disorders. In this review, we consider the evidence for the effectiveness of deep brain stimulation for psychiatric indications, with a primary focus on obsessive compulsive disorder and major depressive disorder. Case reports, case series and clinical trials where deep brain stimulation was primarily utilised in the treatment of a psychiatric disorder, including obsessive compulsive disorder, major depressive disorder, anorexia nervosa or an addictive disorder were identified. The evidence for the effectiveness of deep brain stimulation in the treatment of obsessive compulsive disorder and major depressive disorder was reviewed with studies clustered by the site of implantation. The majority of identified manuscripts report small case series or single cases. A limited number of studies have reported some form of randomised or blinded stimulation comparison. All of these comparative reports have included small samples of subjects (less than 20 per study in total) compromising the feasibility of making statistical comparison between outcomes in the comparison phases. The two exceptions to this have been industry-sponsored studies conducted in the treatment of major depressive disorder. However, both were stopped prematurely due to concerns about poor efficacy. There is insufficient evidence at this point in time to support the use of deep brain stimulation as a clinical treatment for any psychiatric disorder outside of research and programmes where formal outcome data are being systematically collated. While some promising initial data exist to support its potential efficacy for a number of psychiatric conditions, further research is required to establish optimal implantation targets, patient characteristics associated with positive therapeutic outcomes and optimal deep brain stimulation parameters and parameter-programming methods. © The Royal Australian and New

  5. 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.

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

    Science.gov (United States)

    Chiken, Satomi; Nambu, Atsushi

    2016-06-01

    Deep brain stimulation (DBS), applying high-frequency electrical stimulation to deep brain structures, has now provided an effective therapeutic option for treatment of various neurological and psychiatric disorders. DBS targeting the internal segment of the globus pallidus, subthalamic nucleus, and thalamus is used to treat symptoms of movement disorders, such as Parkinson's disease, dystonia, and tremor. However, the mechanism underlying the beneficial effects of DBS remains poorly understood and is still under debate: Does DBS inhibit or excite local neuronal elements? In this short review, we would like to introduce our recent work on the physiological mechanism of DBS and propose an alternative explanation: DBS dissociates input and output signals, resulting in the disruption of abnormal information flow through the stimulation site. © The Author(s) 2015.

  7. Management of Elevated Therapeutic Impedances on Deep Brain Stimulation Leads

    Directory of Open Access Journals (Sweden)

    Wissam Deeb

    2017-09-01

    Full Text Available Clinical Vignette: A 64-year-old male with a history of essential tremor with bilateral thalamic ventralis intermedius deep brain stimulation implants had elevated therapeutic impedance values despite normal lead integrity impedances and good response to stimulation.Clinical Dilemma: Do elevated therapeutic impedance values indicate a sign of hardware malfunction? What are the guidelines to approach deep brain stimulation hardware malfunction?Clinical Solution: Lead integrity impedance values are a better evaluation of hardware integrity. The discrepancy between therapeutic and lead-integrity impedance values can arise when using low voltage settings.Gaps in Knowledge: There are no established guidelines for the management of possible hardware malfunction in deep brain stimulation. The recommended approach is to distinguish between open and short circuit problems followed by an “inching” evaluation, assessing the structures from the implantable and programmable generator to the intracranial leads. Constant-current devices will deliver a more stable stimulation but the effect of their adoption is still not clear.Expert Commentary: This case emphasizes the need for clinicians to understand fundamental differences in lead integrity and therapeutic impedance while utilizing a methodical approach in treating hardware malfunction. It highlights future avenues of investigation regarding the utility of constant current DBS technology.

  8. Management of Elevated Therapeutic Impedances on Deep Brain Stimulation Leads.

    Science.gov (United States)

    Deeb, Wissam; Patel, Amar; Okun, Michael S; Gunduz, Aysegul

    2017-01-01

    A 64-year-old male with a history of essential tremor with bilateral thalamic ventralis intermedius deep brain stimulation implants had elevated therapeutic impedance values despite normal lead integrity impedances and good response to stimulation. Do elevated therapeutic impedance values indicate a sign of hardware malfunction? What are the guidelines to approach deep brain stimulation hardware malfunction? Lead integrity impedance values are a better evaluation of hardware integrity. The discrepancy between therapeutic and lead-integrity impedance values can arise when using low voltage settings. There are no established guidelines for the management of possible hardware malfunction in deep brain stimulation. The recommended approach is to distinguish between open and short circuit problems followed by an "inching" evaluation, assessing the structures from the implantable and programmable generator to the intracranial leads. Constant-current devices will deliver a more stable stimulation but the effect of their adoption is still not clear. This case emphasizes the need for clinicians to understand fundamental differences in lead integrity and therapeutic impedance while utilizing a methodical approach in treating hardware malfunction. It highlights future avenues of investigation regarding the utility of constant current DBS technology.

  9. Deep brain stimulation for intractable tardive dystonia: Literature overview.

    Science.gov (United States)

    Sobstyl, Michał; Ząbek, Mirosław

    2016-01-01

    Tardive dystonia (TD) represents a side effect of prolonged intake of dopamine receptor blocking compounds. TD can be a disabling movement disorder persisting despite available medical treatment. Deep brain stimulation (DBS) has been reported successful in this condition although the number of treated patients with TD is still limited to small clinical studies or case reports. The aim of this study was to present the systematical overview of the existing literature regarding DBS for intractable TD. A literature search was carried out in PudMed. Clinical case series or case reports describing the patients with TD after DBS treatment were included in the present overview. Literature search revealed 19 articles reporting 59 individuals operated for TD. GPi was the target in 55 patients, while subthalamic nucleus (STN) was the target in the remaining 4. In most studies the motor part of Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was improved by more than 80% when compared to preoperative BFMDRS scores. The performed literature analysis indicates that bilateral GPi DBS is an effective treatment for disabling TD. The response of TD to bilateral GPi DBS may be very rapid and occurs within days/weeks after the procedure. The efficacy of bilateral GPi DBS in TD patients is comparable to results achieved in patients with primary generalized dystonia. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  10. Deep brain stimulation for psychiatric disorders: where we are now.

    Science.gov (United States)

    Cleary, Daniel R; Ozpinar, Alp; Raslan, Ahmed M; Ko, Andrew L

    2015-06-01

    Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

  11. Quantification of deep medullary veins at 7 T brain MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kuijf, Hugo J.; Viergever, Max A.; Vincken, Koen L. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Bouvy, Willem H.; Razoux Schultz, Tom B.; Biessels, Geert Jan [University Medical Center Utrecht, Department of Neurology, Brain Center Rudolf Magnus, Utrecht (Netherlands); Zwanenburg, Jaco J.M. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands)

    2016-10-15

    Deep medullary veins support the venous drainage of the brain and may display abnormalities in the context of different cerebrovascular diseases. We present and evaluate a method to automatically detect and quantify deep medullary veins at 7 T. Five participants were scanned twice, to assess the robustness and reproducibility of manual and automated vein detection. Additionally, the method was evaluated on 24 participants to demonstrate its application. Deep medullary veins were assessed within an automatically created region-of-interest around the lateral ventricles, defined such that all veins must intersect it. A combination of vesselness, tubular tracking, and hysteresis thresholding located individual veins, which were quantified by counting and computing (3-D) density maps. Visual assessment was time-consuming (2 h/scan), with an intra-/inter-observer agreement on absolute vein count of ICC = 0.76 and 0.60, respectively. The automated vein detection showed excellent inter-scan reproducibility before (ICC = 0.79) and after (ICC = 0.88) visually censoring false positives. It had a positive predictive value of 71.6 %. Imaging at 7 T allows visualization and quantification of deep medullary veins. The presented method offers fast and reliable automated assessment of deep medullary veins. (orig.)

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

    Science.gov (United States)

    Smith, Kara M.; Spindler, Meredith A.

    2015-01-01

    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. PMID:25713746

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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 stimulation-induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]). Deep brain stimulation was associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.

  15. Effects of Deep Brain Stimulation on Autonomic Function

    Directory of Open Access Journals (Sweden)

    Adam Basiago

    2016-08-01

    Full Text Available Over the course of the development of deep brain stimulation (DBS into a well-established therapy for Parkinson’s disease, essential tremor, and dystonia, its utility as a potential treatment for autonomic dysfunction has emerged. Dysfunction of autonomic processes is common in neurological diseases. Depending on the specific target in the brain, DBS has been shown to raise or lower blood pressure, normalize the baroreflex, to alter the caliber of bronchioles, and eliminate hyperhidrosis, all through modulation of the sympathetic nervous system. It has also been shown to improve cortical control of the bladder, directly induce or inhibit the micturition reflex, and to improve deglutition and gastric emptying. In this review, we will attempt to summarize the relevant available studies describing these effects of DBS on autonomic function, which vary greatly in character and magnitude with respect to stimulation target.

  16. VoxResNet: Deep voxelwise residual networks for brain segmentation from 3D MR images.

    Science.gov (United States)

    Chen, Hao; Dou, Qi; Yu, Lequan; Qin, Jing; Heng, Pheng-Ann

    2018-04-15

    Segmentation of key brain tissues from 3D medical images is of great significance for brain disease diagnosis, progression assessment and monitoring of neurologic conditions. While manual segmentation is time-consuming, laborious, and subjective, automated segmentation is quite challenging due to the complicated anatomical environment of brain and the large variations of brain tissues. We propose a novel voxelwise residual network (VoxResNet) with a set of effective training schemes to cope with this challenging problem. The main merit of residual learning is that it can alleviate the degradation problem when training a deep network so that the performance gains achieved by increasing the network depth can be fully leveraged. With this technique, our VoxResNet is built with 25 layers, and hence can generate more representative features to deal with the large variations of brain tissues than its rivals using hand-crafted features or shallower networks. In order to effectively train such a deep network with limited training data for brain segmentation, we seamlessly integrate multi-modality and multi-level contextual information into our network, so that the complementary information of different modalities can be harnessed and features of different scales can be exploited. Furthermore, an auto-context version of the VoxResNet is proposed by combining the low-level image appearance features, implicit shape information, and high-level context together for further improving the segmentation performance. Extensive experiments on the well-known benchmark (i.e., MRBrainS) of brain segmentation from 3D magnetic resonance (MR) images corroborated the efficacy of the proposed VoxResNet. Our method achieved the first place in the challenge out of 37 competitors including several state-of-the-art brain segmentation methods. Our method is inherently general and can be readily applied as a powerful tool to many brain-related studies, where accurate segmentation of brain

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

    2014-01-01

    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. PMID:24566670

  4. 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

  5. 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. 

  6. 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.

  7. Early application of deep brain stimulation: clinical and ethical aspects.

    Science.gov (United States)

    Woopen, Christiane; Pauls, K Amande M; Koy, Anne; Moro, Elena; Timmermann, Lars

    2013-11-01

    Deep brain stimulation (DBS) has proven to be a successful therapeutic approach in several patients with movement disorders such as Parkinson's disease and dystonia. Hitherto its application was mainly restricted to advanced disease patients resistant to medication or with severe treatment side effects. However, there is now growing interest in earlier application of DBS, aimed at improving clinical outcomes, quality of life, and avoiding psychosocial consequences of chronic disease-related impairments. We address the clinical and ethical aspects of two "early" uses of DBS, (1) DBS early in the course of the disease, and (2) DBS early in life (i.e. in children). Possible benefits, risks and burdens are discussed and thoroughly considered. Further research is needed to obtain a careful balance between exposing vulnerable patients to potential severe surgical risks and excluding them from a potentially good outcome. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

  10. Deep Brain Stimulation Target Selection for Parkinson's Disease.

    Science.gov (United States)

    Honey, Christopher R; Hamani, Clement; Kalia, Suneil K; Sankar, Tejas; Picillo, Marina; Munhoz, Renato P; Fasano, Alfonso; Panisset, Michel

    2017-01-01

    During the "DBS Canada Day" symposium held in Toronto July 4-5, 2014, the scientific committee invited experts to discuss three main questions on target selection for deep brain stimulation (DBS) of patients with Parkinson's disease (PD). First, is the subthalamic nucleus (STN) or the globus pallidus internus (GPi) the ideal target? In summary, both targets are equally effective in improving the motor symptoms of PD. STN allows a greater medications reduction, while GPi exerts a direct antidyskinetic effect. Second, are there further potential targets? Ventral intermediate nucleus DBS has significant long-term benefit for tremor control but insufficiently addresses other motor features of PD. DBS in the posterior subthalamic area also reduces tremor. The pedunculopontine nucleus remains an investigational target. Third, should DBS for PD be performed unilaterally, bilaterally or staged? Unilateral STN DBS can be proposed to asymmetric patients. There is no evidence that a staged bilateral approach reduces the incidence of DBS-related adverse events.

  11. Subthalamic Nucleus Deep Brain Stimulation: Basic Concepts and Novel Perspectives

    Science.gov (United States)

    Florence, Gerson; Heinsen, Helmut; Plantinga, Birgit R.; Uludag, Kamil; Alho, Eduardo; Teixeira, Manoel J.; Fonoff, Erich T.

    2017-01-01

    Abstract Over the last decades, extensive basic and clinical knowledge has been acquired on the use of subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson’s disease (PD). It is now clear that mechanisms involved in the effects of this therapy are far more complex than previously anticipated. At frequencies commonly used in clinical practice, neural elements may be excited or inhibited and novel dynamic states of equilibrium are reached. Electrode contacts used for chronic DBS in PD are placed near the dorsal border of the nucleus, a highly cellular region. DBS may thus exert its effects by modulating these cells, hyperdirect projections from motor cortical areas, afferent and efferent fibers to the motor STN. Advancements in neuroimaging techniques may allow us to identify these structures optimizing surgical targeting. In this review, we provide an update on mechanisms and the neural elements modulated by STN DBS. PMID:28966978

  12. Mood stability in Parkinson disease following deep brain stimulation: a 6-month prospective follow-up study.

    Science.gov (United States)

    Chopra, Amit; Abulseoud, Osama A; Sampson, Shirlene; Lee, Kendall H; Klassen, Bryan T; Fields, Julie A; Matsumoto, Joseph Y; Adams, Andrea C; Stoppel, Cynthia J; Geske, Jennifer R; Frye, Mark A

    2014-01-01

    Deep brain stimulation for Parkinson disease has been associated with psychiatric adverse effects including anxiety, depression, mania, psychosis, and suicide. The purpose of this study was to evaluate the safety of deep brain stimulation in a large Parkinson disease clinical practice. Patients approved for surgery by the Mayo Clinic deep brain stimulation clinical committee participated in a 6-month prospective naturalistic follow-up study. In addition to the Unified Parkinson's Disease Rating Scale, stability and psychiatric safety were measured using the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating scale. Outcomes were compared in patients with Parkinson disease who had a psychiatric history to those with no co-morbid psychiatric history. The study was completed by 49 of 54 patients. Statistically significant 6-month baseline to end-point improvement was found in motor and mood scales. No significant differences were found in psychiatric outcomes based on the presence or absence of psychiatric comorbidity. Our study suggests that patients with Parkinson disease who have a history of psychiatric co-morbidity can safely respond to deep brain stimulation with no greater risk of psychiatric adverse effect occurrence. A multidisciplinary team approach, including careful psychiatric screening ensuring mood stabilization and psychiatric follow-up, should be viewed as standard of care to optimize the psychiatric outcome in the course of deep brain stimulation treatment. © 2013 Published by The Academy of Psychosomatic Medicine on behalf of The Academy of Psychosomatic Medicine.

  13. 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.

  14. 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.

  15. In vivo impedance spectroscopy of deep brain stimulation electrodes

    Science.gov (United States)

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

    2009-08-01

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

  16. Deep Learning for Brain MRI Segmentation: State of the Art and Future Directions.

    Science.gov (United States)

    Akkus, Zeynettin; Galimzianova, Alfiia; Hoogi, Assaf; Rubin, Daniel L; Erickson, Bradley J

    2017-08-01

    Quantitative analysis of brain MRI is routine for many neurological diseases and conditions and relies on accurate segmentation of structures of interest. Deep learning-based segmentation approaches for brain MRI are gaining interest due to their self-learning and generalization ability over large amounts of data. As the deep learning architectures are becoming more mature, they gradually outperform previous state-of-the-art classical machine learning algorithms. This review aims to provide an overview of current deep learning-based segmentation approaches for quantitative brain MRI. First we review the current deep learning architectures used for segmentation of anatomical brain structures and brain lesions. Next, the performance, speed, and properties of deep learning approaches are summarized and discussed. Finally, we provide a critical assessment of the current state and identify likely future developments and trends.

  17. Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation.

    Science.gov (United States)

    Hadar, Ravit; Dong, Le; Del-Valle-Anton, Lucia; Guneykaya, Dilansu; Voget, Mareike; Edemann-Callesen, Henriette; Schweibold, Regina; Djodari-Irani, Anais; Goetz, Thomas; Ewing, Samuel; Kettenmann, Helmut; Wolf, Susanne A; Winter, Christine

    2017-07-01

    In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. 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

  19. 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

    2016-01-01

    Abstract 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

  20. Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation

    DEFF Research Database (Denmark)

    Thrane, Jens F; Sunde, Niels A; Bergholt, Bo

    2014-01-01

    Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation......Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation...

  1. Characterizing Deep Brain Stimulation effects in computationally efficient neural network models

    OpenAIRE

    Latteri, Alberta; Arena, Paolo; Mazzone, Paolo

    2011-01-01

    Background Recent studies on the medical treatment of Parkinson's disease (PD) led to the introduction of the so called Deep Brain Stimulation (DBS) technique. This particular therapy allows to contrast actively the pathological activity of various Deep Brain structures, responsible for the well known PD symptoms. This technique, frequently joined to dopaminergic drugs administration, replaces the surgical interventions implemented to contrast the activity of specific brain nuclei, called Bas...

  2. Falls related to accidental deactivation of deep brain stimulators in patients with Parkinson's disease living in long term care facilities.

    Science.gov (United States)

    Tousi, Babak; Wilson, Kathy

    2013-01-01

    This case series highlights three patients with Parkinson's disease residing at nursing home facilities whose deep brain stimulators were accidentally deactivated for varying lengths of time, which was associated with an increase in falls. In all three cases, neither the patients nor the caregivers were aware of the random deactivations/reactivations. We propose a specific care plan for these patients that includes further education of caregivers regarding deep brain stimulators and regular checks of the review device, especially when there is concern about a patient's mobility or balance that is out of character. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

  3. In vivo deep brain imaging of rats using oral-cavity illuminated photoacoustic computed tomography

    Science.gov (United States)

    Lin, Li; Xia, Jun; Wong, Terence T. W.; Zhang, Ruiying; Wang, Lihong V.

    2015-03-01

    We demonstrate, by means of internal light delivery, photoacoustic imaging of the deep brain of rats in vivo. With fiber illumination via the oral cavity, we delivered light directly into the bottom of the brain, much more than can be delivered by external illumination. The study was performed using a photoacoustic computed tomography (PACT) system equipped with a 512-element full-ring transducer array, providing a full two-dimensional view aperture. Using internal illumination, the PACT system provided clear cross sectional photoacoustic images from the palate to the middle brain of live rats, revealing deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.

  4. Parkinson's disease progression at 30 years: a study of subthalamic deep brain-stimulated patients.

    Science.gov (United States)

    Merola, Aristide; Zibetti, Maurizio; Angrisano, Serena; Rizzi, Laura; Ricchi, Valeria; Artusi, Carlo A; Lanotte, Michele; Rizzone, Mario G; Lopiano, Leonardo

    2011-07-01

    of language, reasoning and memory. Thirty years after the disease onset, most patients presented non-levodopa-responsive symptoms, although the effect of both subthalamic nucleus deep brain stimulation and dopaminergic therapies still showed significant efficacy on the main disease cardinal features. Nevertheless, compared with other subthalamic nucleus deep brain stimulation follow-up studies, which included patients with a shorter disease duration at the time of surgery, a higher prevalence of axial and non-levodopa-responsive symptoms was observed in the long-term evaluations, confirming that several complex aspects underlie the development of non-motor symptoms and other features of Parkinson's disease progression, even in patients with an early disease onset and a prior long-lasting response to dopaminergic therapies.

  5. Classification of CT brain images based on deep learning networks.

    Science.gov (United States)

    Gao, Xiaohong W; Hui, Rui; Tian, Zengmin

    2017-01-01

    While computerised tomography (CT) may have been the first imaging tool to study human brain, it has not yet been implemented into clinical decision making process for diagnosis of Alzheimer's disease (AD). On the other hand, with the nature of being prevalent, inexpensive and non-invasive, CT does present diagnostic features of AD to a great extent. This study explores the significance and impact on the application of the burgeoning deep learning techniques to the task of classification of CT brain images, in particular utilising convolutional neural network (CNN), aiming at providing supplementary information for the early diagnosis of Alzheimer's disease. Towards this end, three categories of CT images (N = 285) are clustered into three groups, which are AD, lesion (e.g. tumour) and normal ageing. In addition, considering the characteristics of this collection with larger thickness along the direction of depth (z) (~3-5 mm), an advanced CNN architecture is established integrating both 2D and 3D CNN networks. The fusion of the two CNN networks is subsequently coordinated based on the average of Softmax scores obtained from both networks consolidating 2D images along spatial axial directions and 3D segmented blocks respectively. As a result, the classification accuracy rates rendered by this elaborated CNN architecture are 85.2%, 80% and 95.3% for classes of AD, lesion and normal respectively with an average of 87.6%. Additionally, this improved CNN network appears to outperform the others when in comparison with 2D version only of CNN network as well as a number of state of the art hand-crafted approaches. As a result, these approaches deliver accuracy rates in percentage of 86.3, 85.6 ± 1.10, 86.3 ± 1.04, 85.2 ± 1.60, 83.1 ± 0.35 for 2D CNN, 2D SIFT, 2D KAZE, 3D SIFT and 3D KAZE respectively. The two major contributions of the paper constitute a new 3-D approach while applying deep learning technique to extract signature information

  6. The epistemology of Deep Brain Stimulation and neuronal pathophysiology

    Science.gov (United States)

    Montgomery, Erwin B.

    2012-01-01

    Deep Brain Stimulation (DBS) is a remarkable therapy succeeding where all manner of pharmacological manipulations and brain transplants fail. The success of DBS has resurrected the relevance of electrophysiology and dynamics on the order of milliseconds. Despite the remarkable effects of DBS, its mechanisms of action are largely unknown. There has been an expanding catalogue of various neuronal and neural responses to DBS or DBS-like stimulation but no clear conceptual encompassing explanatory scheme has emerged despite the technological prowess and intellectual sophistication of the scientists involved. Something is amiss. If the scientific observations are sound, then why has there not been more progress? The alternative is that it may be the hypotheses that frame the questions are at fault as well as the methods of inference (logic) used to validate the hypotheses. An analysis of the past and current notions of the DBS mechanisms of action is the subject in order to identify the presuppositions (premises) and logical fallacies that may be at fault. The hope is that these problems will be avoided in the future so the DBS can realize its full potential quickly. In this regard, the discussion of the methods of inference and presuppositions that underlie many current notions is no different then a critique of experimental methods common in scientific discussions and consequently, examinations of the epistemology and logic are appropriate. This analysis is in keeping with the growing appreciation among scientists and philosophers of science, the scientific observations (data) to not “speak for themselves” nor is the scientific method self-evidently true and that consideration of the underlying inferential methods is necessary. PMID:23024631

  7. 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.

  8. Movement Disorders and Deep Brain Stimulation in the Middle East.

    Science.gov (United States)

    Siddiqui, Junaid H; Bhatti, Danish; Alsubaie, Fahd; Bajwa, Jawad A

    2018-02-13

    Deep brain stimulation (DBS) is a well-established neuromodulation therapy for advanced Parkinson disease, essential tremor and dystonia. In as much as this therapy is being developed in the Middle East, a better understanding of the incidence and prevalence of movement disorders, health care, and social framework is required for the region. We reviewed current literature on the incidence and prevalence of various movement disorders in the Middle East amenable to DBS surgery. We also assessed recent efforts to develop DBS in the region. Available data on incidence and prevalence of movement disorders in the Middle East are old, inconclusive, and conflicting. We identify key areas such as cultural background, availability of accessible information, training, infrastructure, and public support groups in the region that may pose challenges. The Middle East is projected to be a growing market for neuromodulation. The available data on incidence and prevalence of movement disorders is from studies that were small, partial, and old, with inconsistent results, highlighting the need for newer, better-designed, and larger studies. DBS in the Middle East will need assessment of incidence and prevalence of movement disorders, existing challenges to its application, and focused efforts on key opportunities to foster development of DBS for this underserved region. This article is an attempt to identify and explore these challenges and propose solutions in anticipation. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-08-01

    The thalamus is thought to contribute to language-related processing, but specifications of this notion remain vague. An assessment of potential effects of thalamic deep brain stimulation (DBS) on spontaneous language may help to delineate respective functions. For this purpose, we analyzed spontaneous language samples from thirteen (six female / seven male) patients with essential tremor treated with DBS of the thalamic ventral intermediate nucleus (VIM) in their respective ON vs. OFF conditions. Samples were obtained from semi-structured interviews and examined on multidimensional linguistic levels. In the VIM-DBS ON condition, participants used a significantly higher proportion of paratactic as opposed to hypotactic sentence structures. This increase correlated negatively with the change in the more global cognitive score, which in itself did not change significantly. In conclusion, VIM-DBS appears to induce the use of a simplified syntactic structure. The findings are discussed in relation to concepts of thalamic roles in language-related cognitive behavior. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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. Bladder function in patients with dystonia undergoing deep brain stimulation.

    Science.gov (United States)

    Mordasini, Livio; Kessler, Thomas M; Kiss, Bernhard; Schüpbach, Michael; Pollo, Claudio; Kaelin-Lang, Alain

    2014-09-01

    Neurogenic bladder dysfunction is well described in Parkinson's disease and has a major impact on quality of live. In contrast, little is known about the extent of urinary symptoms in other movement disorders such as dystonia and about the role of the basal ganglia in bladder control.. A consecutive series of 11 patients with severe dystonia undergoing deep brain stimulation (DBS) of the globus pallidus internus was prospectively enrolled. Bladder function was assessed by the International Prostate Symptom Score and urodynamic investigation (UDI) before DBS surgery and afterwards in the conditions with and without DBS. In UDI before DBS surgery, detrusor overactivity was found in 36% (4/11) of dystonia patients. With pallidal DBS ON, maximum flow rate significantly decreased, post-void residual significantly increased and detrusor overactivity disappeared.. Pathological urodynamic changes can be found in a relevant percentage of dystonia patients. Pallidal DBS has a relaxing effect on detrusor function indicating a role of the basal ganglia in lower urinary tract control. Thus, a better understanding on how subcortical networks influence lower urinary tract function might open new therapeutic perspectives.. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Ventral tegmental area deep brain stimulation in refractory short-lasting unilateral neuralgiform headache attacks.

    Science.gov (United States)

    Miller, Sarah; Akram, Harith; Lagrata, Susie; Hariz, Marwan; Zrinzo, Ludvic; Matharu, Manjit

    2016-10-01

    SEE LEONE AND PROIETTI CECCHINI DOI101093/AWW233 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Short-lasting unilateral neuralgiform headache attacks are primary headache disorders characterized by short-lasting attacks of unilateral pain accompanied by autonomic features. A small minority are refractory to medical treatment. Neuroimaging studies have suggested a role of the posterior hypothalamic region in their pathogenesis. Previous case reports on deep brain stimulation of this region, now understood to be the ventral tegmental area, for this disorder are limited to a total of three patients. We present a case series of 11 new patients treated with ventral tegmental area deep brain stimulation in an uncontrolled, open-label prospective observational study. Eleven patients with refractory short-lasting unilateral neuralgiform headache attacks underwent ipsilateral ventral tegmental area deep brain stimulation in a specialist unit. All patients had failed, or been denied access to, occipital nerve stimulation within the UK's National Health Service. Primary endpoint was change in mean daily attack frequency at final follow-up. Secondary outcomes included attack severity, attack duration, headache load (a composite score of attack frequency, severity and duration), quality of life measures, disability and affective scores. Information was also collected on adverse events. Eleven patients (six male) with a median age of 50 years (range 26-67) were implanted between 2009 and 2014. Median follow-up was 29 months (range 7-63). At final follow-up the median improvement in daily attack frequency was 78% (interquartile range 33%). Response rate (defined as at least a 50% improvement in daily attack frequency) was 82% and four patients were rendered pain-free for prolonged periods of time. Headache load improved by 99% (interquartile range 52%). Improvements were observed in a number of quality of life, disability and affect measures. Adverse events included mild incision

  14. 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.

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

    DEFF Research Database (Denmark)

    van Hartevelt, Tim Johannes

    2014-01-01

    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...... function in PD patients with DBS. The first two studies in this dissertation are reviews of the olfactory system and one of its most vital roles in eating behaviour. These studies indicate the extent of the olfactory system in terms of anatomy and implication in certain behaviours. In the third study...

  16. Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline

    Science.gov (United States)

    Gunduz, Aysegul; Morita, Hokuto; Rossi, P. Justin; Allen, William L.; Alterman, Ron L.; Bronte-Stewart, Helen; Butson, Christopher R.; Charles, David; Deckers, Sjaak; de Hemptinne, Coralie; DeLong, Mahlon; Dougherty, Darin; Ellrich, Jens; Foote, Kelly D.; Giordano, James; Goodman, Wayne; Greenberg, Benjamin D.; Greene, David; Gross, Robert; Judy, Jack W.; Karst, Edward; Kent, Alexander; Kopell, Brian; Lang, Anthony; Lozano, Andres; Lungu, Codrin; Lyons, Kelly E.; Machado, Andre; Martens, Hubert; McIntyre, Cameron; Min, Hoon-Ki; Neimat, Joseph; Ostrem, Jill; Pannu, Sat; Ponce, Francisco; Pouratian, Nader; Reymers, Donnie; Schrock, Lauren; Sheth, Sameer; Shih, Ludy; Stanslaski, Scott; Steinke, G. Karl; Stypulkowski, Paul; Tröster, Alexander I.; Verhagen, Leo; Walker, Harrison; Okun, Michael S.

    2015-01-01

    The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of 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 advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies. PMID:25526555

  17. 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. 

  18. Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

    Directory of Open Access Journals (Sweden)

    Guangjun Zhao

    2016-01-01

    Full Text Available Cryosection brain images in Chinese Visible Human (CVH dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel. Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

  19. Deep Brain Stimulation Influences Brain Structure in Alzheimer’s Disease

    Science.gov (United States)

    Sankar, Tejas; Chakravarty, M. Mallar; Bescos, Agustin; Lara, Monica; Obuchi, Toshiki; Laxton, Adrian W.; McAndrews, Mary Pat; Tang-Wai, David F.; Workman, Clifford I.; Smith, Gwenn S.; Lozano, Andres M.

    2017-01-01

    Background Deep Brain Stimulation (DBS) is thought to improve the symptoms of selected neurological disorders by modulating activity within dysfunctional brain circuits. To date, there is no evidence that DBS counteracts progressive neurodegeneration in any particular disorder. Objective/Hypothesis We hypothesized that DBS applied to the fornix in patients with Alzheimer’s Disease (AD) could have an effect on brain structure. Methods In six AD patients receiving fornix DBS, we used structural MRI to assess one-year change in hippocampal, fornix, and mammillary body volume. We also used deformation-based morphometry to identify whole-brain structural changes. We correlated volumetric changes to hippocampal glucose metabolism. We also compared volumetric changes to those in an age-, sex-, and severity-matched group of AD patients (n = 25) not receiving DBS. Results We observed bilateral hippocampal volume increases in the two patients with the best clinical response to fornix DBS. In one patient, hippocampal volume was preserved three years after diagnosis. Overall, mean hippocampal atrophy was significantly slower in the DBS group compared to the matched AD group, and no matched AD patients demonstrated bilateral hippocampal enlargement. Across DBS patients, hippocampal volume change correlated strongly with hippocampal metabolism and with volume change in the fornix and mammillary bodies, suggesting a circuit-wide effect of stimulation. Deformation-based morphometry in DBS patients revealed local volume expansions in several regions typically atrophied in AD. Conclusion We present the first in-human evidence that, in addition to modulating neural circuit activity, DBS may influence the natural course of brain atrophy in a neurodegenerative disease. PMID:25814404

  20. 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

  1. 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.

  2. 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.

  3. 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

    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

  4. Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

    Science.gov (United States)

    Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

    2014-07-01

    Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Anatomic correlates of deep brain stimulation electrode impedance.

    Science.gov (United States)

    Satzer, David; Maurer, Eric W; Lanctin, David; Guan, Weihua; Abosch, Aviva

    2015-04-01

    The location of the optimal target for deep brain stimulation (DBS) of the subthalamic nucleus (STN) remains controversial. Electrode impedance affects tissue activation by DBS and has been found to vary by contact number, but no studies have examined association between impedance and anatomic location. To evaluate the relationship between electrode impedance and anatomic contact location, and to assess the clinical significance of impedance. We gathered retrospective impedance data from 101 electrodes in 73 patients with Parkinson's disease. We determined contact location using microelectrode recording (MER) and high-field 7T MRI, and assessed the relationship between impedance and contact location. For contact location as assessed via MER, impedance was significantly higher for contacts in STN, at baseline (111 Ω vs STN border, p=0.03; 169 Ω vs white matter, pimpedance was lowest in contacts situated at STN border (p=0.03). Impedance did not vary by contact location as assessed via imaging. Location determination was 75% consistent between MER and imaging. Impedance was inversely related to absolute symptom reduction during stimulation (-2.5 motor portion of the Unified Parkinson's Disease Rating Scale (mUPDRS) points per 1000 Ω, p=0.01). In the vicinity of DBS electrodes chronically implanted in STN, impedance is lower at the rostral STN border and in white matter, than in STN. This finding suggests that current reaches white matter fibres more readily than neuronal cell bodies in STN, which may help explain anatomic variation in stimulation efficacy. 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.

  6. Sources and effects of electrode impedance during deep brain stimulation.

    Science.gov (United States)

    Butson, Christopher R; Maks, Christopher B; McIntyre, Cameron C

    2006-02-01

    Clinical impedance measurements for deep brain stimulation (DBS) electrodes in human patients are normally in the range 500-1500 Omega. DBS devices utilize voltage-controlled stimulation; therefore, the current delivered to the tissue is inversely proportional to the impedance. The goals of this study were to evaluate the effects of various electrical properties of the tissue medium and electrode-tissue interface on the impedance and to determine the impact of clinically relevant impedance variability on the volume of tissue activated (VTA) during DBS. Axisymmetric finite-element models (FEM) of the DBS system were constructed with explicit representation of encapsulation layers around the electrode and implanted pulse generator. Impedance was calculated by dividing the stimulation voltage by the integrated current density along the active electrode contact. The models utilized a Fourier FEM solver that accounted for the capacitive components of the electrode-tissue interface during voltage-controlled stimulation. The resulting time- and space-dependent voltage waveforms generated in the tissue medium were superimposed onto cable model axons to calculate the VTA. The primary determinants of electrode impedance were the thickness and conductivity of the encapsulation layer around the electrode contact and the conductivity of the bulk tissue medium. The difference in the VTA between our low (790 Omega) and high (1244 Omega) impedance models with typical DBS settings (-3 V, 90 mus, 130 Hz pulse train) was 121 mm3, representing a 52% volume reduction. Electrode impedance has a substantial effect on the VTA and accurate representation of electrode impedance should be an explicit component of computational models of voltage-controlled DBS. Impedance is often used to identify broken leads (for values > 2000 Omega) or short circuits in the hardware (for values impedance values also represent an important parameter in defining the spread of stimulation during DBS.

  7. Subthalamic deep brain stimulation and trunk posture in Parkinson's disease.

    Science.gov (United States)

    Artusi, C A; Zibetti, M; Romagnolo, A; Rizzone, M G; Merola, A; Lopiano, L

    2017-12-29

    We sought to assess the efficacy of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD)-associated trunk posture abnormalities retrospectively analyzing data from 101 patients reporting mild-to-severe trunk posture abnormalities of a cohort of 216 PD patients treated with STN-DBS at our center. Abnormal trunk posture was rated on a scale of 0 (normal) to 4 (marked flexion with an extreme abnormality of posture) as per the grading score reported in the Unified Parkinson's Disease Rating Scale. The independent effect of STN-DBS on trunk posture was assessed comparing Medication-Off (presurgery) vs Stimulation-On/Medication-Off (post-surgery). The combined effect of STN-DBS plus levodopa was evaluated comparing Medication-On (presurgery) vs Stimulation-On/Medication-On (post-surgery). Analyses were conducted considering both the entire cohort of patients and the subgroup with camptocormia (CMC) and Pisa syndrome (PS). The independent effect of STN-DBS resulted in a 41.4% improvement in abnormal trunk posture severity (P < .001), with 78.2% of patients (n = 79) reporting an improvement of at least 1 point. The combined effect of STN-DBS and levodopa resulted in a 30.9% improvement (P = .061), with 54.5% of patients (n = 55) reporting an improvement of at least 1 point. The subanalysis of patients with CMC (n = 23) and PS (n = 5) showed a 42.7% improvement in abnormal posture severity when considering the independent effect of STN-DBS (P < .001) and 30.5% when considering the combined effect of STN-DBS and levodopa (P < .001). STN-DBS may have the potential for improving posture in patients with advanced PD. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Lars Wojtecki

    Full Text Available 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.

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

    Science.gov (United States)

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

    2011-07-01

    The objective of this study was to evaluate the efficiency and the effects of changes in parameters of chronic amygdala-hippocampal deep brain stimulation (AH-DBS) in mesial temporal lobe epilepsy (TLE). Eight pharmacoresistant patients, not candidates for ablative surgery, received chronic AH-DBS (130 Hz, follow-up 12-24 months): two patients with hippocampal sclerosis (HS) and six patients with non-lesional mesial TLE (NLES). The effects of stepwise increases in intensity (0-Off to 2 V) and stimulation configuration (quadripolar and bipolar), on seizure frequency and neuropsychological performance were studied. The two HS patients obtained a significant decrease (65-75%) in seizure frequency with high voltage bipolar DBS (≥1 V) or with quadripolar stimulation. Two out of six NLES patients became seizure-free, one of them without stimulation, suggesting a microlesional effect. Two NLES patients experienced reductions of seizure frequency (65-70%), whereas the remaining two showed no significant seizure reduction. Neuropsychological evaluations showed reversible memory impairments in two patients under strong stimulation only. AH-DBS showed long-term efficiency in most of the TLE patients. It is a valuable treatment option for patients who suffer from drug resistant epilepsy and who are not candidates for resective surgery. The effects of changes in the stimulation parameters suggest that a large zone of stimulation would be required in HS patients, while a limited zone of stimulation or even a microlesional effect could be sufficient in NLES patients, for whom the importance of the proximity of the electrode to the epileptogenic zone remains to be studied. Further studies are required to ascertain these latter observations. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  10. Modulation of hippocampal activity with fornix Deep Brain Stimulation.

    Science.gov (United States)

    Stypulkowski, Paul H; Stanslaski, Scott R; Giftakis, Jonathon E

    Deep Brain Stimulation (DBS) within the Papez circuit is under investigation as a treatment for epilepsy and Alzheimer's disease. We previously reported the effects of stimulation at nodes within this network (anterior thalamic nucleus and hippocampus) on hippocampal activity in a large animal model, using a chronic implantable, clinical-grade system that permits concurrent stimulation and recording. In this study we extended earlier work to compare the effects of fornix DBS on evoked potentials (EPs) and local field potential (LFP) activity within the hippocampus, and to assess closed-loop stimulation. Unilateral fornix and hippocampal DBS leads were implanted in three ovine subjects using image-guided, frameless stereotaxy. Chronic, awake recordings of EPs and LFPs in response to fornix and hippocampal stimulation were collected with the implanted device and analyzed off-line. Stimulation of the fornix produced robust, short latency hippocampal EPs. High frequency fornix stimulation generated parameter-dependent effects. At low amplitudes, short lasting inhibition of LFP activity occurred. Above a specific amplitude threshold, DBS elicited pronounced bursts of theta activity, followed by a marked state shift in hippocampal activity. These effects persisted for minutes post-DBS and were reflected as changes in LFP spectral content and phase-amplitude coupling. Real-time modulation of hippocampal activity via the implanted device was demonstrated using LFPs as the control signal for closed-loop stimulation. The current results expand earlier findings and demonstrate target-specific effects produced by DBS within this neural circuit. These changes in network activity may provide insights into stimulation targets and parameter selection for clinical investigations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Cognitive assessment instruments in Parkinson's disease patients undergoing deep brain stimulation

    OpenAIRE

    Romann, Aline Juliane; Dornelles, Silvia; Maineri, Nicole de Liz; Rieder, Carlos Roberto de Mello; Olchik, Maira Rozenfeld

    2012-01-01

    ABSTRACT Deep Brain Stimulation (DBS) is a widely used surgical technique in individuals with Parkinson's disease (PD) that can lead to significant reductions in motor symptoms. Objectives: To determine, from publications, the most commonly used instruments for cognitive evaluation of individuals with PD undergoing DBS. Methods: A systematic review of the databases: PubMed, Medline, EBECS, Scielo and LILACS was conducted, using the descriptors "Deep Brain Stimulation", "Verbal Fluency", "...

  12. 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.

  13. Current clinical application of deep-brain stimulation for essential tremor

    Directory of Open Access Journals (Sweden)

    Chopra A

    2013-12-01

    Full Text Available Amit Chopra, Bryan T Klassen, Matt Stead Department of Neurology, Mayo Clinic, Rochester, MN, USA Background: Deep-brain stimulation (DBS is an established treatment for medically refractory essential tremor (ET. This article reviews the current evidence supporting the efficacy and safety of DBS targets, including the ventral intermediate (VIM nucleus and posterior subthalamic area (PSA in treatment of ET. Methods: A structured PubMed search was performed through December 2012 with keywords "deep brain stimulation (DBS," "essential tremor (ET," "ventral intermediate (VIM nucleus," "posterior subthalamic area (PSA," "safety," and "efficacy." Results: Based on level IV evidence, both VIM and PSA DBS targets appear to be safe and efficacious in ET patients in tremor reduction and improving activities of daily living, though the literature on PSA DBS is limited in terms of bilateral stimulation and long-term follow-up. DBS-related adverse effects are typically mild and stimulation-related. Hardware-related complications after DBS may not be uncommon, and often require additional surgical procedures. Few studies assessed quality-of-life and cognition outcomes in ET patients undergoing DBS stimulation. Conclusion: DBS appears to be a safe and effective treatment for medically refractory ET. More systematic studies comparing VIM and PSA targets are needed to ascertain the most safe and effective DBS treatment for medically refractory ET. More research is warranted to assess quality-of-life and cognition outcomes in ET patients undergoing DBS. Keywords: deep-brain stimulation (DBS, essential tremor (ET, ventral intermediate (VIM nucleus, posterior subthalamic area (PSA, safety, efficacy

  14. 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.

  15. Temporal profile of improvement of tardive dystonia after globus pallidus deep brain stimulation.

    Science.gov (United States)

    Shaikh, Aasef G; Mewes, Klaus; DeLong, Mahlon R; Gross, Robert E; Triche, Shirley D; Jinnah, H A; Boulis, Nicholas; Willie, Jon T; Freeman, Alan; Alexander, Garrett E; Aia, Pratibha; Butefisch, Cathrine M; Esper, Christine D; Factor, Stewart A

    2015-02-01

    Several case reports and small series have indicated that tardive dystonia is responsive to globus pallidus deep brain stimulation. Whether different subtypes or distributions of tardive dystonia are associated with different outcomes remains unknown. We assessed the outcomes and temporal profile of improvement of eight tardive dystonia patients who underwent globus pallidus deep brain stimulation over the past six years through record review. Due to the retrospective nature of this study, it was not blinded or placebo controlled. Consistent with previous studies, deep brain stimulation improved the overall the Burke-Fahn-Marsden motor scores by 85.1 ± 13.5%. The distributions with best responses in descending order were upper face, lower face, larynx/pharynx, limbs, trunk, and neck. Patients with prominent cervical dystonia demonstrated improvement in the Toronto Western Spasmodic Torticollis Rating Scale but improvements took several months. In four patients the effects of deep brain stimulation on improvement in Burke Fahn Marsden score was rapid, while in four cases there was partial rapid response of neck and trunk dystonia followed by was gradual resolution of residual symptoms over 48 months. Our retrospective analysis shows excellent resolution of tardive dystonia after globus pallidus deep brain stimulation. We found instantaneous response, except with neck and trunk dystonia where partial recovery was followed by further resolution at slower rate. Such outcome is encouraging for using deep brain stimulation in treatment of tardive dystonia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Noninvasive deep brain stimulation using focused energy sources

    NARCIS (Netherlands)

    Sierra, C. V. Rizzo

    2010-01-01

    A non-invasive methodological possibility for brain stimulation through the simultaneous use of an external energy beam and an existing brain imaging system such as functional magnetic resonance imaging (fMRI) is herein proposed; the main advantage is to confine the stimulation into a single brain

  17. Successful management of super-refractory status epilepticus with thalamic deep brain stimulation.

    Science.gov (United States)

    Lehtimäki, Kai; Långsjö, Jaakko W; Ollikainen, Jyrki; Heinonen, Hanna; Möttönen, Timo; Tähtinen, Timo; Haapasalo, Joonas; Tenhunen, Jyrki; Katisko, Jani; Öhman, Juha; Peltola, Jukka

    2017-01-01

    Super-refractory status epilepticus is a condition characterized by recurrence of status epilepticus despite use of deep general anesthesia, and it has high morbidity and mortality rates. We report a case of a 17-year-old boy with a prolonged super-refractory status epilepticus that eventually resolved after commencing deep brain stimulation of the centromedian nucleus of the thalamus. Later attempt to reduce stimulation parameters resulted in immediate relapse of status epilepticus, suggesting a pivotal role of deep brain stimulation in the treatment response. Deep brain stimulation may be a treatment option in super-refractory status epilepticus when other treatment options have failed. ANN NEUROL 2017;81:142-146. © 2016 American Neurological Association.

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

    DEFF Research Database (Denmark)

    Gjedde, Albert; Geday, Jacob

    2009-01-01

    -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......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...

  19. 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.

  20. Deep sequencing analysis of the developing mouse brain reveals a novel microRNA

    OpenAIRE

    Ling, King-Hwa; Brautigan, Peter J; Hahn, Christopher N; Daish, Tasman; Rayner, John R; Cheah, Pike-See; Raison, Joy M; Piltz, Sandra; Mann, Jeffrey R; Mattiske, Deidre M; Thomas, Paul Q; Adelson, David L; Scott, Hamish S

    2011-01-01

    Abstract Background MicroRNAs (miRNAs) are small non-coding RNAs that can exert multilevel inhibition/repression at a post-transcriptional or protein synthesis level during disease or development. Characterisation of miRNAs in adult mammalian brains by deep sequencing has been reported previously. However, to date, no small RNA profiling of the developing brain has been undertaken using this method. We have performed deep sequencing and small RNA analysis of a developing (E15.5) mouse brain. ...

  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 for people with Alzheimer's disease: Anticipating potential effects on the tripartite self.

    Science.gov (United States)

    Viaña, John Noel M; Gilbert, Frederic

    2018-01-01

    Memory dysfunction and cognitive impairments due to Alzheimer's disease can affect the selfhood and identity of afflicted individuals, causing distress to both people with Alzheimer's disease and their caregivers. Recently, a number of case studies and clinical trials have been conducted to determine the potential of deep brain stimulation as a therapeutic modality for people with Alzheimer's disease. Some of these studies have shown that deep brain stimulation could induce flashbacks and stabilize or even improve memory. However, deep brain stimulation itself has also been attributed as a potential threat to identity and selfhood, especially when procedure-related adverse events arise. We anticipate potential effects of deep brain stimulation for people with Alzheimer's disease on selfhood, reconciling information from medical reports, psychological, and sociological investigations on the impacts of deep brain stimulation or Alzheimer's disease on selfhood. A tripartite model of the self that extends the scope of Rom Harré's and Steve Sabat's social constructionist framework was used. In this model, potential effects of deep brain stimulation for Alzheimer's disease on Self 1 or singularity through use of first-person indexicals, and gestures of self-reference, attribution, and recognition; Self 2 or past and present attributes, knowledge of these characteristics, and continuity of narrative identity; and Self 3 or the relational and social self are explored. The ethical implications of potential effects of deep brain stimulation for Alzheimer's disease on the tripartite self are then highlighted, focusing on adapting informed consent procedures and care provided throughout the trial to account for both positive and negative plausible effects on Self 1, Self 2, and Self 3.

  3. Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

    Science.gov (United States)

    Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

    2012-01-01

    Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

  4. Constructing fine-granularity functional brain network atlases via deep convolutional autoencoder.

    Science.gov (United States)

    Zhao, Yu; Dong, Qinglin; Chen, Hanbo; Iraji, Armin; Li, Yujie; Makkie, Milad; Kou, Zhifeng; Liu, Tianming

    2017-12-01

    State-of-the-art functional brain network reconstruction methods such as independent component analysis (ICA) or sparse coding of whole-brain fMRI data can effectively infer many thousands of volumetric brain network maps from a large number of human brains. However, due to the variability of individual brain networks and the large scale of such networks needed for statistically meaningful group-level analysis, it is still a challenging and open problem to derive group-wise common networks as network atlases. Inspired by the superior spatial pattern description ability of the deep convolutional neural networks (CNNs), a novel deep 3D convolutional autoencoder (CAE) network is designed here to extract spatial brain network features effectively, based on which an Apache Spark enabled computational framework is developed for fast clustering of larger number of network maps into fine-granularity atlases. To evaluate this framework, 10 resting state networks (RSNs) were manually labeled from the sparsely decomposed networks of Human Connectome Project (HCP) fMRI data and 5275 network training samples were obtained, in total. Then the deep CAE models are trained by these functional networks' spatial maps, and the learned features are used to refine the original 10 RSNs into 17 network atlases that possess fine-granularity functional network patterns. Interestingly, it turned out that some manually mislabeled outliers in training networks can be corrected by the deep CAE derived features. More importantly, fine granularities of networks can be identified and they reveal unique network patterns specific to different brain task states. By further applying this method to a dataset of mild traumatic brain injury study, it shows that the technique can effectively identify abnormal small networks in brain injury patients in comparison with controls. In general, our work presents a promising deep learning and big data analysis solution for modeling functional connectomes, with

  5. Neural plasticity in human brain connectivity: the effects of long term deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

    Science.gov (United States)

    van Hartevelt, Tim J; Cabral, Joana; Deco, Gustavo; Møller, Arne; Green, Alexander L; Aziz, Tipu Z; Kringelbach, Morten L

    2014-01-01

    Positive clinical outcomes are now well established for deep brain stimulation, but little is known about the effects of long-term deep brain stimulation on brain structural and functional connectivity. Here, we used the rare opportunity to acquire pre- and postoperative diffusion tensor imaging in a patient undergoing deep brain stimulation in bilateral subthalamic nuclei for Parkinson's Disease. This allowed us to analyse the differences in structural connectivity before and after deep brain stimulation. Further, a computational model of spontaneous brain activity was used to estimate the changes in functional connectivity arising from the specific changes in structural connectivity. We found significant localised structural changes as a result of long-term deep brain stimulation. These changes were found in sensory-motor, prefrontal/limbic, and olfactory brain regions which are known to be affected in Parkinson's Disease. The nature of these changes was an increase of nodal efficiency in most areas and a decrease of nodal efficiency in the precentral sensory-motor area. Importantly, the computational model clearly shows the impact of deep brain stimulation-induced structural alterations on functional brain changes, which is to shift the neural dynamics back towards a healthy regime. The results demonstrate that deep brain stimulation in Parkinson's Disease leads to a topological reorganisation towards healthy bifurcation of the functional networks measured in controls, which suggests a potential neural mechanism for the alleviation of symptoms. The findings suggest that long-term deep brain stimulation has not only restorative effects on the structural connectivity, but also affects the functional connectivity at a global level. Overall, our results support causal changes in human neural plasticity after long-term deep brain stimulation and may help to identify the underlying mechanisms of deep brain stimulation.

  6. Ethical Considerations for Deep Brain Stimulation Trials in Patients with Early-Onset Alzheimer's Disease.

    Science.gov (United States)

    Viaña, John Noel M; Bittlinger, Merlin; Gilbert, Frederic

    2017-01-01

    Several studies of deep brain stimulation (DBS) of the fornix or the nucleus basalis of Meynert have been recently conducted in people with Alzheimer's disease, with several recruiting participants early-onset Alzheimer's disease (EOAD). Although EOAD accounts for less than 5.5% of AD cases, ethical considerations must still be made when performing DBS trials including these participants since a portion of people with EOAD, especially those possessing autosomal-dominant mutations, have an atypical and more aggressive disease progression. These considerations include appropriate patient selection and signing of an informed consent for genetic testing; appropriate study design; potential outcomes that people with EOAD could expect; and accurate interpretation and balanced discussion of trial results. Finally, recommendations for future DBS for AD trials will be made to ensure that EOAD patients will not experience avoidable harms should they be enrolled in these experimental studies.

  7. Subthalamic deep brain stimulation can improve gastric emptying in Parkinson's disease.

    Science.gov (United States)

    Arai, Eiji; Arai, Makoto; Uchiyama, Tomoyuki; Higuchi, Yoshinori; Aoyagi, Kyoko; Yamanaka, Yoshitaka; Yamamoto, Tatsuya; Nagano, Osamu; Shiina, Akihiro; Maruoka, Daisuke; Matsumura, Tomoaki; Nakagawa, Tomoo; Katsuno, Tatsuro; Imazeki, Fumio; Saeki, Naokatsu; Kuwabara, Satoshi; Yokosuka, Osamu

    2012-05-01

    It is established that deep brain stimulation of the subthalamic nucleus improves motor function in advanced Parkinson's disease, but its effects on autonomic function remain to be elucidated. The present study was undertaken to investigate the effects of subthalamic deep brain stimulation on gastric emptying. A total of 16 patients with Parkinson's disease who underwent bilateral subthalamic deep brain stimulation were enrolled. Gastric emptying was expressed as the peak time of (13)CO(2) excretion (T(max)) in the (13)C-acetate breath test and was assessed in patients with and without administration of 100-150 mg levodopa/decarboxylase inhibitor before surgery, and with and without subthalamic deep brain stimulation at 3 months post-surgery. The pattern of (13)CO(2) excretion curve was analysed. To evaluate potential factors related to the effect of subthalamic deep brain stimulation on gastric emptying, we also examined the association between gastric emptying, clinical characteristics, the equivalent dose of levodopa and serum ghrelin levels. The peak time of (13)CO(2) excretion (T(max)) values for gastric emptying in patients without and with levodopa/decarboxylase inhibitor treatment were 45.6 ± 22.7 min and 42.5 ± 13.6 min, respectively (P = not significant), thus demonstrating levodopa resistance. The peak time of (13)CO(2) excretion (T(max)) values without and with subthalamic deep brain stimulation after surgery were 44.0 ± 17.5 min and 30.0 ± 12.5 min (P deep brain stimulation was effective. Simultaneously, the pattern of the (13)CO(2) excretion curve was also significantly improved relative to surgery with no stimulation (P = 0.002), although the difference with and without levodopa/decarboxylase inhibitor was not significant. The difference in peak time of (13)CO(2) excretion (T(max)) values without levodopa/decarboxylase inhibitor before surgery and without levodopa/decarboxylase inhibitor and subthalamic deep

  8. 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

  9. 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

  10. Deep Brain Stimulation for the Treatment of Dejerine-Roussy Syndrome.

    Science.gov (United States)

    Ward, Max; Mammis, Antonios

    2017-01-01

    Patients who suffer from Dejerine-Roussy syndrome commonly experience severe poststroke hemibody pain which has historically been attributed to thalamic lesions. Despite pharmacological treatment, a significant proportion of the population is resistant to traditional therapy. Deep brain stimulation is often appropriate for the treatment of resistant populations. In this review we aim to summarize the targets that are used to treat Dejerine-Roussy syndrome and provide insight into their clinical efficacy. In reviewing the literature, we defined stimulation success as achievement of a minimum of 50% pain relief. Contemporary targets for deep brain stimulation are the ventral posterior medial/ventral posterior lateral thalamic nuclei, periaqueductal/periventricular gray matter, the ventral striatum/anterior limb of the internal capsule, left centromedian thalamic nuclei, the nucleus ventrocaudalis parvocellularis internis, and the posterior limb of the internal capsule. Due to technological advancements in deep brain stimulation, its therapeutic effects must be reevaluated. Despite a lack of controlled evidence, deep brain stimulation has been effectively used as a therapeutic in clinical pain management. Further clinical investigation is needed to definitively evaluate the therapeutic efficacy of deep brain stimulation in treating the drug-resistant patient population. © 2017 S. Karger AG, Basel.

  11. A suggested minimum standard deep brain stimulation evaluation for essential tremor.

    Science.gov (United States)

    Shah, Neha; Leventhal, Daniel; Persad, Carol; Patil, Parag G; Chou, Kelvin L

    2016-03-15

    A comprehensive, multidisciplinary screening process for deep brain stimulation (DBS) candidates is recommended, but is often time-consuming. To determine the number of essential tremor (ET) referrals excluded from surgery and why, in order to develop recommendations for a minimum standard DBS evaluation process. We reviewed the referrals of 100 consecutive potential DBS candidates with presumed ET at our center, identified reasons for excluding patients from DBS, and the point at which they dropped out of our evaluation process. Of the 100 tremor patients referred for DBS, 36 patients were approved for surgery. Patients were mainly excluded because of the movement disorders neurologist and neuropsychologist evaluations. Reasons included an inadequate medication trial (n=20), incorrect diagnosis (n=3), dementia (n=3), and antagonistic interactions with the team (n=1). 37 patients did not present, were uninterested or lost to follow-up. Neither neurosurgical evaluation nor brain imaging excluded candidates in this study, but are needed to proceed with DBS. Our suggested minimum standard DBS screening process begins with a movement disorders neurologist and neuropsychologist evaluation in order to determine eligibility. Neurosurgical evaluation and brain imaging can then be performed if candidates are deemed eligible. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. 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.

  13. Evolving Applications, Technological Challenges and Future Opportunities in Neuromodulation: Proceedings of the Fifth Annual Deep Brain Stimulation Think Tank

    OpenAIRE

    Adolfo Ramirez-Zamora; James J. Giordano; Aysegul Gunduz; Peter Brown; Justin C. Sanchez; Kelly D. Foote; Leonardo Almeida; Philip A. Starr; Helen M. Bronte-Stewart; Wei Hu; Cameron McIntyre; Wayne Goodman; Wayne Goodman; Doe Kumsa; Warren M. Grill

    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 c...

  14. Evolving applications, technological challenges and future opportunities in neuromodulation: Proceedings of the fifth annual deep brain stimulation think tank

    OpenAIRE

    Ramirez-Zamora, A; Giordano, JJ; Gunduz, A; Brown, P; Sanchez, JC; Foote, KD; Almeida, L; Starr, PA; Bronte-Stewart, HM; Hu, W; McIntyre, C; Goodman, W; Kumsa, D; Grill, WM; Walker, HC

    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 c...

  15. 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.

  16. Dyspnea as a side effect of subthalamic nucleus deep brain stimulation for Parkinson's disease.

    Science.gov (United States)

    Chalif, Joshua I; Sitsapesan, Holly A; Pattinson, Kyle T S; Herigstad, Mari; Aziz, Tipu Z; Green, Alexander L

    2014-02-01

    Bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease improves limb function. Unpublished observations from our clinic noted that some subthalamic nucleus deep brain stimulation patients complain of post-operative dyspnea. Therefore, we designed a prospective, longitudinal study to characterize this in greater depth. We used specific questionnaires to assess dyspnea in patients with electrodes in the subthalamic nucleus (n=13) or ventral intermediate thalamus (n=7). St. George's Hospital Respiratory Questionnaire symptom subscale scores were greater in subthalamic nucleus patients (median=18.60, interquartile range=40.80) than ventral intermediate thalamus patients (median = 0.00, interquartile range=15.38) at greater than 6 months post-operatively (pdyspnea severity. We have shown, for the first time, that dyspnea can be a side effect of subthalamic nucleus deep brain stimulation, and that this dyspnea may be highly disabling. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Parasomnia overlap disorder, Parkinson's disease and subthalamic deep brain stimulation: three case reports.

    Science.gov (United States)

    Bargiotas, Panagiotis; Muellner, Julia; Schuepbach, W M Michael; Bassetti, Claudio L

    2017-07-18

    Parasomnia overlap disorder (POD) is a distinct parasomnia and characterized by concomitant manifestation of rapid-eye-movement (REM)- and non-REM (NREM)-parasomnias. Although not uncommon among patients with Parkinson's disease, POD is often under-investigated. This is the first report of patients with PD and features of POD that underwent deep brain stimulation. Our patients exhibited different outcomes of POD features after subthalamic deep brain stimulation. We expect that the reporting of these first patients will open the discussion about the need for more detailed and broad-spectrum assessments regarding parasomnias in PD patients that undergo deep brain stimulation. The implications of our observations are both clinical and neurobiological.

  18. 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.

  19. 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.

  20. Management of impulse control disorders with deep brain stimulation: A double-edged sword.

    Science.gov (United States)

    Kasemsuk, Chayut; Oyama, Genko; Hattori, Nobutaka

    2017-03-15

    Deep brain stimulation (DBS) is a surgical option for advanced Parkinson's disease. Although DBS is used to treat motor fluctuation, DBS may affect non-motor symptoms including mood disorders, cognitive dysfunction, and behavior problems. Impulse control disorders (ICDs) are abnormal behaviors with various manifestations such as pathological gambling, hypersexuality, compulsive shopping, and binge eating, which can affect the quality of life in patients with Parkinson's disease. The effect of DBS on ICD is controversial. Reducing medication by DBS may improve ICDs, however, worsening or even developing new ICDs after DBS can occur. We will review the impact of DBS on ICDs and reveal factors associated with a good response to DBS as well as risk factors for developing ICDs after DBS. We also propose a strategy to manage preexisting ICD and prevent postoperative de novo ICDs. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2016-08-01

    High-frequency deep brain stimulation (DBS) is an effective treatment for some movement disorders. Though mechanisms underlying DBS are still unclear, commonly accepted theories include a "functional inhibition" of neuronal cell bodies and the excitation of axonal projections near the electrodes. It is becoming clear, however, that the paradoxical dissociation "local inhibition" and "distant excitation" is far more complex than initially thought. Despite an initial increase in neuronal activity following stimulation, cells are often unable to maintain normal ionic concentrations, particularly those of sodium and potassium. Based on currently available evidence, we proposed an alternative hypothesis. Increased extracellular concentrations of potassium during DBS may change the dynamics of both cells and axons, contributing not only to the intermittent excitation and inhibition of these elements but also to interrupt abnormal pathological activity. In this article, we review mechanisms through which high extracellular potassium may mediate some of the effects of DBS. © The Author(s) 2015.

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

    Science.gov (United States)

    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.

  3. Superficial and deep blood vessel distribution in the frog telencephalon. Reference to morphological brain asymmetries.

    Science.gov (United States)

    Kemali, M; Sada, E; Fiorino, L

    1990-01-01

    Nine frogs of the species "Rana esculenta" were heart perfused with Microfile Silicone Rubber. The frogs were examined both after dissection (cut with a razor blade) to study the superficial blood vessel pattern, and histologically (the Nissl staining method) to study the distribution of the deep blood capillaries. While the superficial blood vary in pattern, the deep capillaries are distributed symmetrically. This finding does not support a correlation between blood vessel pattern and morphological brain asymmetry, at least in the frog, and thus other explanations must be sought to explain brain asymmetry.

  4. 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.

  5. Longitudinal Follow-up of Impedance Drift in Deep Brain Stimulation Cases.

    Science.gov (United States)

    Wong, Joshua; Gunduz, Aysegul; Shute, Jonathan; Eisinger, Robert; Cernera, Stephanie; Ho, Kwo Wei David; Martinez-Ramirez, Daniel; Almeida, Leonardo; Wilson, Christina A; Okun, Michael S; Hess, Christopher W

    2018-01-01

    Impedance is an integral property of neuromodulation devices that determines the current delivered to brain tissue. Long-term variability in therapeutic impedance following deep brain stimulation (DBS) has not been extensively investigated across different brain targets. The aim was to evaluate DBS impedance drift and variability over an extended postoperative period across common DBS targets. Retrospective data from 1,764 electrode leads were included and drawn from 866 DBS patients enrolled in the University of Florida Institutional Review Board-approved INFORM database and analyzed up to 84 months post implantation. An exploratory analysis was conducted to identify trends in impedances using a Mann-Kendall test of trend. There were 866 patients and 1,764 leads available for analysis. The majority of subjects had Parkinson's disease (60.7%). The mean age at implantation was 58.7 years old and the mean follow-up time was 36.8 months. There were significant fluctuations in the mean impedance of all electrodes analyzed that largely stabilized by 6 months except for the subthalamic nucleus (STN) target, in which fluctuations persisted throughout the duration of follow-up with a continued downward trend (p < 0.001). The drift in impedance observed primarily within the first 6 months is in keeping with prior studies and is likely due to surgical micro-lesioning effects and brain parenchyma remodeling at the electrode-tissue interface, typically at values approximating 1,000 Ω . The differences in impedance trends over time in the various DBS targets may be due to underlying differences in structure and tissue composition.

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

    Science.gov (United States)

    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.

  7. 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, ...

  8. Gemella morbillorum deep brain abscess successfully treated with combined stereotactic, medical, and imaging approach

    Energy Technology Data Exchange (ETDEWEB)

    Messori, Anna; Bartolucci, Francesca; Dini, Marco; Paggi, Alessandra Mataloni; Ricciuti, Riccardo A.; Rychlicki, Franco; Salvolini, Ugo E-mail: u.salvolini@popcsi.unian.it

    2002-11-01

    A rare case of brain abscess due to Gemella morbillorum, a normal inhabitant of the oral cavity, is presented. The aim of this report is to draw the attention of radiology literature readers to this little known pathogen, which caused a potentially life-threatening condition in an immunocompetent young man, and to emphasise the usefulness of a combined stereotactic, medical, and imaging approach to deep-located brain abscesses.

  9. Gemella morbillorum deep brain abscess successfully treated with combined stereotactic, medical, and imaging approach

    International Nuclear Information System (INIS)

    Messori, Anna; Bartolucci, Francesca; Dini, Marco; Paggi, Alessandra Mataloni; Ricciuti, Riccardo A.; Rychlicki, Franco; Salvolini, Ugo

    2002-01-01

    A rare case of brain abscess due to Gemella morbillorum, a normal inhabitant of the oral cavity, is presented. The aim of this report is to draw the attention of radiology literature readers to this little known pathogen, which caused a potentially life-threatening condition in an immunocompetent young man, and to emphasise the usefulness of a combined stereotactic, medical, and imaging approach to deep-located brain abscesses

  10. Deep brain stimulation of the posteromedial hypothalamus: indications, long-term results, and neurophysiological considerations.

    Science.gov (United States)

    Franzini, Angelo; Messina, Giuseppe; Cordella, Roberto; Marras, Carlo; Broggi, Giovanni

    2010-08-01

    The aim of this study was to review the indications for and results of deep brain stimulation (DBS) of the posterior hypothalamus (pHyp) in the treatment of drug-refractory and severe painful syndromes of the face, disruptive and aggressive behavior associated with epilepsy, and below-average intelligence. The preoperative clinical picture, functional imaging studies, and overall clinical results in the literature are discussed. All patients underwent stereotactic implantation of deep-brain electrodes within the pHyp. Data from several authors have been collected and reported for each clinical entity, as have clinical results, adverse events, and neurophysiological characteristics of the pHyp. The percentage of patients with chronic cluster headache who responded to DBS was 50% in the overall reported series. The response rate was 100% for short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing and for chronic paroxysmal hemicrania, although only 2 patients and 1 patient, respectively, have been described as having these conditions. None of the 4 patients suffering from refractory neuropathic trigeminal pain benefited from the procedure (0% response rate), whereas all 5 patients (100%) affected with refractory trigeminal neuralgia (TN) due to multiple sclerosis (MS) and undergoing pHyp DBS experienced a significant decrease in pain attacks within the first branch of cranial nerve V. Six (75%) of 8 patients presenting with aggressive behavior and mental retardation benefited from pHyp stimulation; 6 patients were part of the authors' series and 2 were reported in the literature. In carefully selected patients, DBS of the pHyp can be considered an effective procedure for the treatment of refractory trigeminal autonomic cephalalgias, aggressive behavior, and MS-related TN in the first trigeminal branch. Only larger and prospective studies along with multidisciplinary approaches (including, by necessity, neuroimaging studies) can

  11. 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.

  12. Traumatic Brain Injury and NADPH Oxidase: A Deep Relationship

    Directory of Open Access Journals (Sweden)

    Cristina Angeloni

    2015-01-01

    Full Text Available Traumatic brain injury (TBI represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox, ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS, have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI.

  13. Developments in deep brain stimulation using time dependent magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Crowther, L.J.; Nlebedim, I.C.; Jiles, D.C.

    2012-03-07

    The effect of head model complexity upon the strength of field in different brain regions for transcranial magnetic stimulation (TMS) has been investigated. Experimental measurements were used to verify the validity of magnetic field calculations and induced electric field calculations for three 3D human head models of varying complexity. Results show the inability for simplified head models to accurately determine the site of high fields that lead to neuronal stimulation and highlight the necessity for realistic head modeling for TMS applications.

  14. Observation and modeling of deep brain stimulation electrode depth in the pallidal target of the developing brain.

    Science.gov (United States)

    Lumsden, Daniel E; Ashmore, Jonathan; Charles-Edwards, Geoffrey; Selway, Richard; Lin, Jean-Pierre; Ashkan, Keyoumars

    2015-04-01

    It is unclear how brain growth with age affects electrode position in relation to target for children undergoing deep brain stimulation surgery. We aimed to model projected change in the distance between the entry point of the electrode into the brain and target during growth to adulthood. Modeling was performed using a neurodevelopmental magnetic resonance imaging database of age-specific templates in 6-month increments from 4 to 18 years of age. Coordinates were chosen for a set of entry points into both cerebral hemispheres and target positions within the globus pallidus internus on the youngest magnetic resonance imaging template. The youngest template was nonlinearly registered to the older templates, and the transformations generated by these registrations were applied to the original coordinates of entry and target positions, mapping these positions with increasing age. Euclidean geometry was used to calculate the distance between projected electrode entry and target with increasing age. A projected increase in distance between entry point and target of 5-10 mm was found from age 4 to 18 years. Most change appeared to occur before 7 years of age, after which minimal change in distance was found. Electrodes inserted during deep brain stimulation surgery are tethered at the point of entry to the skull. Brain growth, which could result in a relative retraction with respect to the original target position, appears to occur before 7 years of age, suggesting careful monitoring is needed for children undergoing implantation before this age. Reengineering of electrode design could avoid reimplantation surgery in young children undergoing deep brain stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Potential subjects' responses to an ethics questionnaire in a phase I study of deep brain stimulation in early Parkinson's disease.

    Science.gov (United States)

    Finder, Stuart G; Bliton, Mark J; Gill, Chandler E; Davis, Thomas L; Konrad, Peter E; Charles, P David

    2012-01-01

    Central to ethically justified clinical trial design is the need for an informed consent process responsive to how potential subjects actually comprehend study participation, especially study goals, risks, and potential benefits. This will be particularly challenging when studying deep brain stimulation and whether it impedes symptom progression in Parkinson's disease, since potential subjects will be Parkinson's patients for whom deep brain stimulation will likely have therapeutic value in the future as their disease progresses. As part of an expanded informed consent process for a pilot Phase I study of deep brain stimulation in early stage Parkinson's disease, an ethics questionnaire composed of 13 open-ended questions was distributed to potential subjects. The questionnaire was designed to guide potential subjects in thinking about their potential participation. While the purpose of the study (safety and tolerability) was extensively presented during the informed consent process, in returned responses 70 percent focused on effectiveness and 91 percent included personal benefit as poten- tial benefit from enrolling. However, 91 percent also indicated helping other Parkinson's patients as motivation when considering whether or not to enroll. This combination of responses highlights two issues to which investigators need to pay close attention in future trial designs: (1) how, and in what ways, informed consent processes reinforce potential subjects' preconceived understandings of benefit, and (2) that potential subjects see themselves as part of a community of Parkinson's sufferers with responsibilities extending beyond self-interest. More importantly, it invites speculation that a different paradigm for informed consent may be needed.

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

    Directory of Open Access Journals (Sweden)

    Vinata Vedam-Mai

    2016-04-01

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

  17. 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

  18. Conflicts of interest in deep brain stimulation research and the ethics of transparency.

    Science.gov (United States)

    Fins, Joseph J; Schiff, Nicholas D

    2010-01-01

    In this article we will draw on experiences from our own research on deep brain stimulation of the central thalamus in the minimally conscious state. We describe ethical challenges faced in clinical research involving medical devices and offer several cautionary notes about its funding and the interplay of market forces and scientific inquiry and suggest some reforms.

  19. 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

  20. Deep brain stimulation for obsessive-compulsive disorder is associated with cortisol changes

    NARCIS (Netherlands)

    de Koning, Pelle P.; Figee, Martijn; Endert, Erik; Storosum, Jitschak G.; Fliers, Eric; Denys, Damiaan

    2013-01-01

    Deep brain stimulation (DBS) is an effective treatment for obsessive-compulsive disorder (OCD), but its mechanism of action is largely unknown. Since DBS may induce rapid symptomatic changes and the pathophysiology of OCD has been linked to the hypothalamic-pituitary-adrenal (HPA) axis, we set out

  1. 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

  2. Deep brain stimulation of the accumbens increases dopamine, serotonin, and noradrenaline in the prefrontal cortex

    NARCIS (Netherlands)

    van Dijk, Addy; Klompmakers, Andre A.; Feenstra, Matthijs G. P.; Denys, Damiaan

    2012-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is effective in treatment-refractory obsessive-compulsive disorder and major depressive disorder. However, little is known about the neurobiological mechanisms underlying the rapid and effective changes of DBS. One of the hypotheses is that

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

    NARCIS (Netherlands)

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

    2014-01-01

    Deep brain stimulation (DBS) of the ventral internal capsule is effective in treating therapy refractory obsessive-compulsive disorder (OCD). Given the close proximity of the stimulation site to the stria terminalis (BNST), we hypothesized that the striking decrease in anxiety symptoms following DBS

  4. 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

  5. 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

  6. Accuracy of Intraoperative Computed Tomography during Deep Brain Stimulation Procedures: Comparison with Postoperative Magnetic Resonance Imaging

    NARCIS (Netherlands)

    Bot, Maarten; van den Munckhof, Pepijn; Bakay, Roy; Stebbins, Glenn; Verhagen Metman, Leo

    2017-01-01

    To determine the accuracy of intraoperative computed tomography (iCT) in localizing deep brain stimulation (DBS) electrodes by comparing this modality with postoperative magnetic resonance imaging (MRI). Optimal lead placement is a critical factor for the outcome of DBS procedures and preferably

  7. 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.

  8. Cognitive effects of deep brain stimulation in patients with obsessive-compulsive disorder

    NARCIS (Netherlands)

    Mantione, Mariska; Nieman, Dorien; Figee, Martijn; van den Munckhof, Pepijn; Schuurman, Rick; Denys, Damiaan

    2015-01-01

    Deep brain stimulation (DBS) is a promising treatment for treatment-refractory obsessive-compulsive disorder (OCD). However, the effects of DBS on cognitive functioning remain unclear. Therefore, we aimed to assess cognitive safety of DBS for treatment-refractory OCD and the association between

  9. Cognitive effects of deep brain stimulation in patients with obsessive-compulsive disorder

    NARCIS (Netherlands)

    Mantione, Mariska; Nieman, Dorien; Figee, Martijn; van den Munckhof, Pepijn; Schuurman, Rick; Denys, D.

    2015-01-01

    BACKGROUND: Deep brain stimulation (DBS) is a promising treatment for treatment-refractory obsessive-compulsive disorder (OCD). However, the effects of DBS on cognitive functioning remain unclear. Therefore, we aimed to assess cognitive safety of DBS for treatment-refractory OCD and the association

  10. Clinical Outcome and Mechanisms of Deep Brain Stimulation for Obsessive-Compulsive Disorder

    NARCIS (Netherlands)

    van Westen, Maarten; Rietveld, Erik; Figee, Martijn; Denys, Damiaan

    2015-01-01

    Clinical outcome of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) shows robust effects in terms of a mean Yale-Brown Obsessive-Compulsive Scale (YBOCS) reduction of 47.7 % and a mean response percentage (minimum 35 % YBOCS reduction) of 58.2 %. It appears that most patients

  11. Clinical outcome and mechanisms of deep brain stimulation for obsessive-compulsive disorder

    NARCIS (Netherlands)

    van Westen, M.; Rietveld, E.; Figee, M.; Denys, D.

    Clinical outcome of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) shows robust effects in terms of a mean Yale-Brown Obsessive-Compulsive Scale (YBOCS) reduction of 47.7 % and a mean response percentage (minimum 35 % YBOCS reduction) of 58.2 %. It appears that most patients

  12. Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder

    NARCIS (Netherlands)

    Figee, Martijn; Luigjes, Judy; Smolders, Ruud; Valencia-Alfonso, Carlos-Eduardo; van Wingen, Guido; de Kwaasteniet, Bart; Mantione, Mariska; Ooms, Pieter; de Koning, Pelle; Vulink, Nienke; Levar, Nina; Droge, Lukas; van den Munckhof, Pepijn; Schuurman, P. Richard; Nederveen, Aart; van den Brink, Wim; Mazaheri, Ali; Vink, Matthijs; Denys, Damiaan

    2013-01-01

    Little is known about the underlying neural mechanism of deep brain stimulation (DBS). We found that DBS targeted at the nucleus accumbens (NAc) normalized NAc activity, reduced excessive connectivity between the NAc and prefrontal cortex, and decreased frontal low-frequency oscillations during

  13. Parkinsonian gait improves with bilateral subthalamic nucleus deep brain stimulation during cognitive multi-tasking.

    Science.gov (United States)

    Chenji, Gaurav; Wright, Melissa L; Chou, Kelvin L; Seidler, Rachael D; Patil, Parag G

    2017-05-01

    Gait impairment in Parkinson's disease reduces mobility and increases fall risk, particularly during cognitive multi-tasking. Studies suggest that bilateral subthalamic deep brain stimulation, a common surgical therapy, degrades motor performance under cognitive dual-task conditions, compared to unilateral stimulation. To measure the impact of bilateral versus unilateral subthalamic deep brain stimulation on walking kinematics with and without cognitive dual-tasking. Gait kinematics of seventeen patients with advanced Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation were examined off medication under three stimulation states (bilateral, unilateral left, unilateral right) with and without a cognitive challenge, using an instrumented walkway system. Consistent with earlier studies, gait performance declined for all six measured parameters under cognitive dual-task conditions, independent of stimulation state. However, bilateral stimulation produced greater improvements in step length and double-limb support time than unilateral stimulation, and achieved similar performance for other gait parameters. Contrary to expectations from earlier studies of dual-task motor performance, bilateral subthalamic deep brain stimulation may assist in maintaining temporal and spatial gait performance under cognitive dual-task conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Cognitive Functioning in Children with Pantothenate-Kinase-Associated Neurodegeneration Undergoing Deep Brain Stimulation

    Science.gov (United States)

    Mahoney, Rachel; Selway, Richard; Lin, Jean-Pierre

    2011-01-01

    Aim: To examine the cognitive functioning of young people with pantothenate-kinase-associated neurodegeneration (PKAN) after pallidal deep brain stimulation (DBS). PKAN is characterized by progressive generalized dystonia and has historically been associated with cognitive decline. With growing evidence that DBS can improve motor function in…

  15. 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

    2014-01-01

    Purpose: 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…

  16. Effects of deep brain stimulation in dyskinetic cerebral palsy: a meta-analysis.

    Science.gov (United States)

    Koy, Anne; Hellmich, Martin; Pauls, K Amande M; Marks, Warren; Lin, Jean-Pierre; Fricke, Oliver; Timmermann, Lars

    2013-05-01

    Secondary dystonia encompasses a heterogeneous group with different etiologies. Cerebral palsy is the most common cause. Pharmacological treatment is often unsatisfactory. There are only limited data on the therapeutic outcomes of deep brain stimulation in dyskinetic cerebral palsy. The published literature regarding deep brain stimulation and secondary dystonia was reviewed in a meta-analysis to reevaluate the effect on cerebral palsy. The Burke-Fahn-Marsden Dystonia Rating Scale movement score was chosen as the primary outcome measure. Outcome over time was evaluated and summarized by mixed-model repeated-measures analysis, paired Student t test, and Pearson's correlation coefficient. Twenty articles comprising 68 patients with cerebral palsy undergoing deep brain stimulation assessed by the Burke-Fahn-Marsden Dystonia Rating Scale were identified. Most articles were case reports reflecting great variability in the score and duration of follow-up. The mean Burke-Fahn-Marsden Dystonia Rating Scale movement score was 64.94 ± 25.40 preoperatively and dropped to 50.5 ± 26.77 postoperatively, with a mean improvement of 23.6% (P cerebral palsy. In view of the heterogeneous data, a prospective study with a large cohort of patients in a standardized setting with a multidisciplinary approach would be helpful in further evaluating the role of deep brain stimulation in cerebral palsy. © 2013 Movement Disorder Society. Copyright © 2013 Movement Disorder Society.

  17. 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…

  18. 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

  19. Transmission in near-infrared optical windows for deep brain imaging.

    Science.gov (United States)

    Shi, Lingyan; Sordillo, Laura A; Rodríguez-Contreras, Adrián; Alfano, Robert

    2016-01-01

    Near-infrared (NIR) radiation has been employed using one- and two-photon excitation of fluorescence imaging at wavelengths 650-950 nm (optical window I) for deep brain imaging; however, longer wavelengths in NIR have been overlooked due to a lack of suitable NIR-low band gap semiconductor imaging detectors and/or femtosecond laser sources. This research introduces three new optical windows in NIR and demonstrates their potential for deep brain tissue imaging. The transmittances are measured in rat brain tissue in the second (II, 1,100-1,350 nm), third (III, 1,600-1,870 nm), and fourth (IV, centered at 2,200 nm) NIR optical tissue windows. The relationship between transmission and tissue thickness is measured and compared with the theory. Due to a reduction in scattering and minimal absorption, window III is shown to be the best for deep brain imaging, and windows II and IV show similar but better potential for deep imaging than window I. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. 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

  1. 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

  2. Treatment of neurological and psychiatric disorders with deep brain stimulation; raising hopes and future challenges.

    Science.gov (United States)

    Sharifi, Mohammad Sharif

    2013-01-01

    The technology of Neural Stimulation in recent years has become the focus of the research and treatment, although it has been around for many years. The potential use of stimulating the brain and nerves ranges from the spinal cord stimulation to the implantations of cochlear and bionic eyes with a large discrepancy between the clinical readiness for these various uses. Electrical high-frequency Deep Brain Stimulation (DBS) was developed as an alternative option to treat a few neurological disorders. However, with advancing in surgical procedures, technologies and safeties, the applications of DBS are expanding not only for therapeutic purposes but also for research. Although the exact mechanisms of action/s are not fully understood, the outcome of the ongoing research and clinical trials are promising. DBS has been used to treat the essential tremor since 1997, Parkinson's disease (PD) since 2002 and dystonia since 2003. It has also been used to treat various disorders, including major depression. The therapeutic effect of DBS in PD is well established but for other diseases such as epilepsy the outcomes are unclear and ambiguous. This article is a succinct review of the literature, focusing on PD, epilepsy and Obsessive Compulsive Disorder (OCD).

  3. Treatment of Neurological and Psychiatric Disorders with Deep Brain Stimulation Raising Hopes and Future Challenges

    Directory of Open Access Journals (Sweden)

    Mohammad Sharif Sharifi

    2013-08-01

    Full Text Available The technology of Neural Stimulation in recent years has become the focus of the research and treatment, although it has been around for many years. The potential use of stimulating the brain and nerves ranges from the spinal cord stimulation to the implantations of cochlear and bionic eyes with a large discrepancy between the clinical readiness for these various uses. Electrical high-frequency Deep Brain Stimulation (DBS was developed as an alternative option to treat a few neurological disorders. However, with advancing in surgical procedures, technologies and safeties, the applications of DBS are expanding not only for therapeutic purposes but also for research. Although the exact mechanisms of action/s are not fully understood, the outcome of the ongoing research and clinical trials are promising. DBS has been used to treat the essential tremor since 1997, Parkinson’s disease (PD since 2002 and dystonia since 2003. It has also been used to treat various disorders, including major depression.  The therapeutic effect of DBS in PD is well established but for other diseases such as epilepsy the outcomes are unclear and ambiguous. This article is a succinct review of the literature, focusing on PD, epilepsy and Obsessive Compulsive Disorder (OCD.

  4. Impedance characteristics of deep brain stimulation electrodes in vitro and in vivo

    Science.gov (United States)

    Wei, Xuefeng F.; Grill, Warren M.

    2009-08-01

    The objective of this study was to quantify the electrode-tissue interface impedance of electrodes used for deep brain stimulation (DBS). We measured the impedance of DBS electrodes using electrochemical impedance spectroscopy in vitro in a carbonate- and phosphate-buffered saline solution and in vivo following acute implantation in the brain. The components of the impedance, including the series resistance (Rs), the Faradaic resistance (Rf) and the double layer capacitance (Cdl), were estimated using an equivalent electrical circuit. Both Rf and Cdl decreased as the sinusoidal frequency was increased, but the ratio of the capacitive charge transfer to the Faradaic charge transfer was relatively insensitive to the change of frequency. Rf decreased and Cdl increased as the current density was increased, and above a critical current density the interface impedance became nonlinear. Thus, the magnitude of the interface impedance was strongly dependent on the intensity (pulse amplitude and duration) of stimulation. The temporal dependence and spatial non-uniformity of Rf and Cdl suggested that a distributed network, with each element of the network having dynamics tailored to a specific stimulus waveform, is required to describe adequately the impedance of the DBS electrode-tissue interface. Voltage transients to biphasic square current pulses were measured and suggested that the electrode-tissue interface did not operate in a linear range at clinically relevant current amplitudes, and that the assumption of the DBS electrode being ideally polarizable was not valid under clinical stimulating conditions.

  5. 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 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.

  6. 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.

  7. Electrophysiologic Validation of Diffusion Tensor Imaging Tractography during Deep Brain Stimulation Surgery.

    Science.gov (United States)

    Coenen, V A; Jenkner, C; Honey, C R; Mädler, B

    2016-08-01

    Diffusion tensor imaging fiber tractography-assisted planning of deep brain stimulation is an emerging technology. We investigated its accuracy by using electrophysiology under clinical conditions. We hypothesized that a level of concordance between electrophysiology and DTI fiber tractography can be reached, comparable with published modeling approaches for deep brain stimulation surgery. Eleven patients underwent subthalamic nucleus deep brain stimulation. DTI scans and high-resolution T1- and T2-weighted MR imaging was performed at 3T. Corticospinal tracts were traced. We studied electrode positions and current amplitudes that elicited corticospinal tract effects during the operation to determine relative corticospinal tract distance. Postoperatively, 3D deep brain stimulation electrode contact locations and stimulation patterns were applied for the same corticospinal tract distance estimation. Intraoperative electrophysiologic (n = 40) clinical effects in 11 patients were detected. The mean intraoperative electrophysiologic corticospinal tract distance was 3.0 ± 0.6 mm; the mean image-derived corticospinal tract distance (DTI fiber tractography) was 3.0 ± 1.3 mm. The 95% limits of agreement were ±2.4 mm. Postoperative electrophysiology (n = 44) corticospinal tract activation effects were encountered in 9 patients; 39 were further evaluated. Mean electrophysiologic corticospinal tract distance was 3.7 ± 0.7 mm; for DTI fiber tractography, it was 3.2 ± 1.9 mm. The 95% limits of agreement were ±2.5 mm. DTI fiber tractography depicted the medial corticospinal tract border with proved concordance. Although the overall range of measurements was relatively small and variance was high, we believe that further use of DTI fiber tractography to assist deep brain stimulation procedures is advisable if inherent limitations are respected. These results confirm our previously published electric field simulation studies. © 2016 by American Journal of Neuroradiology.

  8. 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.

  9. Deep convolutional neural networks for annotating gene expression patterns in the mouse brain.

    Science.gov (United States)

    Zeng, Tao; Li, Rongjian; Mukkamala, Ravi; Ye, Jieping; Ji, Shuiwang

    2015-05-07

    Profiling gene expression in brain structures at various spatial and temporal scales is essential to understanding how genes regulate the development of brain structures. The Allen Developing Mouse Brain Atlas provides high-resolution 3-D in situ hybridization (ISH) gene expression patterns in multiple developing stages of the mouse brain. Currently, the ISH images are annotated with anatomical terms manually. In this paper, we propose a computational approach to annotate gene expression pattern images in the mouse brain at various structural levels over the course of development. We applied deep convolutional neural network that was trained on a large set of natural images to extract features from the ISH images of developing mouse brain. As a baseline representation, we applied invariant image feature descriptors to capture local statistics from ISH images and used the bag-of-words approach to build image-level representations. Both types of features from multiple ISH image sections of the entire brain were then combined to build 3-D, brain-wide gene expression representations. We employed regularized learning methods for discriminating gene expression patterns in different brain structures. Results show that our approach of using convolutional model as feature extractors achieved superior performance in annotating gene expression patterns at multiple levels of brain structures throughout four developing ages. Overall, we achieved average AUC of 0.894 ± 0.014, as compared with 0.820 ± 0.046 yielded by the bag-of-words approach. Deep convolutional neural network model trained on natural image sets and applied to gene expression pattern annotation tasks yielded superior performance, demonstrating its transfer learning property is applicable to such biological image sets.

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

    Science.gov (United States)

    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

  11. Tau, Amyloid Beta and Deep Brain Stimulation: Aiming to Restore Cognitive Deficit in Alzheimer's Disease.

    Science.gov (United States)

    Mondragón-Rodríguez, Siddhartha; Perry, George; Pena-Ortega, Fernando; Williams, Sylvain

    2017-01-01

    The last two decades have seen a great advance in the data that supports the two current hypotheses in Alzheimer`s disease field, the amyloid beta hypothesis and the tau hypothesis. Not surprisingly, Aβ and tau proteins are currently the major therapeutic research targets for AD treatment. Unfortunately, nothing but moderate success has emerged from such therapeutic approaches. With this in mind, we will discuss deep brain stimulation as a promising therapeutic strategy that aims to restore brain activity. Lastly, in the scope of cognitive deficit restoration, we will discuss the relevance of the limbic formation as a promising neuroanatomical target for deep brain stimulation. Immunohistochemistry for modified tau (phosphorylated at Ser199-202-Thr205 labelled by the antibody AT8) was performed on paraffin-embedded human brain sections providing a detailed characterization of NFT pathology. Abnormally phosphorylated tau protein is the key common marker in several brain diseases such as Alzheimer's disease, Parkinson`s disease, Pick Disease, Down syndrome and frontotemporal dementia and is capable of affecting synaptic events that are critical for memory formation. With this in mind, therapeutic strategies aiming to restore synaptic events could offer better outcomes. The humble success of current therapeutic strategies along with the lack of basic knowledge of the brain disease mechanisms calls for alternatives that benefit patients in the present moment. One of particular interest is the neurostimulation strategy that is already a well-established treatment for several movement disorders and when compared to current Alzheimer`s therapeutic strategies, deep brain stimulation does not directly interfere with the normal protein function, therefore increasing the probability of success.

  12. Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic dystonic movements.

    Science.gov (United States)

    Barow, Ewgenia; Neumann, Wolf-Julian; Brücke, Christof; Huebl, Julius; Horn, Andreas; Brown, Peter; Krauss, Joachim K; Schneider, Gerd-Helge; Kühn, Andrea A

    2014-11-01

    Deep brain stimulation of the globus pallidus internus alleviates involuntary movements in patients with dystonia. However, the mechanism is still not entirely understood. One hypothesis is that deep brain stimulation suppresses abnormally enhanced synchronized oscillatory activity within the motor cortico-basal ganglia network. Here, we explore deep brain stimulation-induced modulation of pathological low frequency (4-12 Hz) pallidal activity that has been described in local field potential recordings in patients with dystonia. Therefore, local field potentials were recorded from 16 hemispheres in 12 patients undergoing deep brain stimulation for severe dystonia using a specially designed amplifier allowing simultaneous high frequency stimulation at therapeutic parameter settings and local field potential recordings. For coherence analysis electroencephalographic activity (EEG) over motor areas and electromyographic activity (EMG) from affected neck muscles were recorded before and immediately after cessation of high frequency stimulation. High frequency stimulation led to a significant reduction of mean power in the 4-12 Hz band by 24.8 ± 7.0% in patients with predominantly phasic dystonia. A significant decrease of coherence between cortical EEG and pallidal local field potential activity in the 4-12 Hz range was revealed for the time period of 30 s after switching off high frequency stimulation. Coherence between EMG activity and pallidal activity was mainly found in patients with phasic dystonic movements where it was suppressed after high frequency stimulation. Our findings suggest that high frequency stimulation may suppress pathologically enhanced low frequency activity in patients with phasic dystonia. These dystonic features are the quickest to respond to high frequency stimulation and may thus directly relate to modulation of pathological basal ganglia activity, whereas improvement in tonic features may depend on long-term plastic changes within the

  13. 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 

  14. 3D printed optical phantoms and deep tissue imaging for in vivo applications including oral surgery

    Science.gov (United States)

    Bentz, Brian Z.; Costas, Alfonso; Gaind, Vaibhav; Garcia, Jose M.; Webb, Kevin J.

    2017-03-01

    Progress in developing optical imaging for biomedical applications requires customizable and often complex objects known as "phantoms" for testing, evaluation, and calibration. This work demonstrates that 3D printing is an ideal method for fabricating such objects, allowing intricate inhomogeneities to be placed at exact locations in complex or anatomically realistic geometries, a process that is difficult or impossible using molds. We show printed mouse phantoms we have fabricated for developing deep tissue fluorescence imaging methods, and measurements of both their optical and mechanical properties. Additionally, we present a printed phantom of the human mouth that we use to develop an artery localization method to assist in oral surgery.

  15. Rapid Modulation of Protein Expression in the Rat Hippocampus Following Deep Brain Stimulation of the Fornix.

    Science.gov (United States)

    Gondard, Elise; Chau, Hien N; Mann, Amandeep; Tierney, Travis S; Hamani, Clement; Kalia, Suneil K; Lozano, Andres M

    2015-01-01

    The forniceal area is currently being evaluated as a target for deep brain stimulation (DBS) to improve cognitive function in patients with Alzheimer's disease. The molecular changes at downstream targets within the stimulated circuit are unknown. To analyze the modulation of hippocampal protein expression following 1 h of fornix DBS in the rat. Animals underwent bilateral forniceal DBS for 1 h and sacrificed at different time-points after the initiation of the stimulation (1 h, 2.5 h, 5 h, 25 h). Bilateral hippocampi were isolated for western blot analyses. Forniceal DBS led to a dramatic elevation of cFos post-stimulation, suggesting that forniceal DBS activates the hippocampus. There was also a significant increase in candidate proteins including several trophic factors, such as brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) but not glial cell-derived neurotrophic factor (GDNF). There was in addition, increased expression of the synaptic markers growth associated protein 43 (GAP-43), synaptophysin and α-synuclein. No changes were observed at the studied time-points in Alzheimer's-related proteins including amyloid precursor protein (APP), tau, phosphorylated tau (ptau), or selected chaperone proteins (HSP40, HSP70 and CHIP). Forniceal DBS triggers hippocampal activity and rapidly modulate the expression of neurotrophic factors and markers of synaptic plasticity known to play key roles in memory processing. The clinical effects of DBS of the fornix may, in part, be mediated by producing changes in the expression of these proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Preserving cortico-striatal function: Deep brain stimulation in Huntington's disease

    Directory of Open Access Journals (Sweden)

    Sean J Nagel

    2015-03-01

    Full Text Available Huntington’s disease (HD is an incurable neurodegenerative disease characterized by the triad of chorea, cognitive dysfunction and psychiatric disturbances. Since the discovery of the HD gene, the pathogenesis has been outlined, but to date a cure has not been found. Disease modifying therapies are needed desperately to improve function, alleviate suffering, and provide hope for symptomatic patients. Deep brain stimulation (DBS, a proven therapy for managing the symptoms of some neurodegenerative movement disorders, including Parkinson’s disease, has been reported as a palliative treatment in select cases of HD with debilitating chorea with variable success. New insights into the mechanism of action of DBS suggest it may have the potential to circumvent other manifestations of HD including cognitive deterioration. Furthermore, because DBS is already widely used, reversible, and has a risk profile that is relatively low, new studies can be initiated. In this article we contend that new clinical trials be considered to test the effects of DBS for HD

  17. Deep brain stimulation for obsessive-compulsive disorder: Knowledge and concerns among psychiatrists, psychotherapists and patients

    Science.gov (United States)

    Naesström, Matilda; Blomstedt, Patric; Hariz, Marwan; Bodlund, Owe

    2017-01-01

    Background: Deep brain stimulation (DBS) is under investigation for severe obsessive-compulsive disorder (OCD) resistant to other therapies. The number of implants worldwide is slowly increasing. Therefore, it is of importance to explore knowledge and concerns of this novel treatment among patients and their psychiatric healthcare contacts. This information is relevant for scientific professionals working with clinical studies for DBS for this indication. Especially, for future study designs and the creation of information targeting healthcare professionals and patients. The aim of this study was to explore the knowledge and concerns toward DBS among patients with OCD, psychiatrists, and cognitive behavioral therapists. Methods: The study was conducted through web-based surveys for the aimed target groups –psychiatrist, patients, and cognitive behavioral therapists. The surveys contained questions regarding previous knowledge of DBS, source of knowledge, attitudes, and concerns towards the therapy. Results: The main source of information was from scientific sources among psychiatrists and psychotherapists. The patient's main source of information was the media. Common concerns among the groups included complications from surgery, anesthesia, stimulation side effects, and the novelty of the treatment. Specific concerns for the groups included; personality changes mentioned by patients and psychotherapists, and ethical concerns among psychiatrists. Conclusion: There are challenges for DBS in OCD as identified by the participants of this study; source and quality of information, efficacy, potential adverse effects, and eligibility. In all of which the current evidence base still is limited. A broad research agenda is needed for studies going forward. PMID:29285414

  18. Posttraumatic Stress Disorder: Perspectives for the Use of Deep Brain Stimulation.

    Science.gov (United States)

    Reznikov, Roman; Hamani, Clement

    2017-01-01

    Deep Brain Stimulation (DBS) has been either approved or is currently under investigation for a number of psychiatric disorders. We review clinical and preclinical concepts as well as the neurocircuitry that may be of relevance for the implementation of DBS in posttraumatic stress disorder (PTSD). PTSD is a chronic and debilitating illness associated with dysfunction in well-established neural circuits, including the amygdala and prefrontal cortex. Although most patients often improve with medications and/or psychotherapy, approximately 20-30% are considered to be refractory to conventional treatments. In other psychiatric disorders, DBS has been investigated in treatment-refractory patients. To date, preclinical work suggests that stimulation at high frequency delivered at particular timeframes to different targets, including the amygdala, ventral striatum, hippocampus, and prefrontal cortex may improve fear extinction and anxiety-like behavior in rodents. In the only clinical report published so far, a patient implanted with electrodes in the amygdala has shown striking improvements in PTSD symptoms. Neuroimaging, preclinical, and preliminary clinical data suggest that the use of DBS for the treatment of PTSD may be practical but the field requires further investigation. © 2016 International Neuromodulation Society.

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

    Science.gov (United States)

    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

  20. Swallowing and deep brain stimulation in Parkinson's disease: a systematic review.

    Science.gov (United States)

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

    2013-09-01

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Ethical Considerations in Deep Brain Stimulation for the Treatment of Addiction and Overeating Associated With Obesity.

    Science.gov (United States)

    Pisapia, Jared M; Halpern, Casey H; Muller, Ulf J; Vinai, Piergiuseppe; Wolf, John A; Whiting, Donald M; Wadden, Thomas A; Baltuch, Gordon H; Caplan, Arthur L

    2013-05-01

    The success of deep brain stimulation (DBS) for movement disorders and the improved understanding of the neurobiologic and neuroanatomic bases of psychiatric diseases have led to proposals to expand current DBS applications. Recent preclinical and clinical work with Alzheimer's disease and obsessive-compulsive disorder, for example, supports the safety of stimulating regions in the hypothalamus and nucleus accumbens in humans. These regions are known to be involved in addiction and overeating associated with obesity. However, the use of DBS targeting these areas as a treatment modality raises common ethical considerations, which include informed consent, coercion, enhancement, threat to personhood, and manipulation of the reward center. Pilot studies for both of these conditions are currently investigational. If these studies show promise, then there is a need to address the ethical concerns related to the initiation of clinical trials including the reliability of preclinical evidence, patient selection, study design, compensation for participation and injury, cost-effectiveness, and the need for long-term follow-up. Multidisciplinary teams are necessary for the ethical execution of such studies. In addition to establishing safety and efficacy, the consideration of these ethical issues is vital to the adoption of DBS as a treatment for these conditions. We offer suggestions about the pursuit of future clinical trials of DBS for the treatment of addiction and overeating associated with obesity and provide a framework for addressing ethical concerns related to treatment.

  2. The study on a real-time remote monitoring system for Parkinson's disease patients with deep brain stimulators.

    Science.gov (United States)

    Chen, Yue; Hao, Hongwei; Chen, Hao; Tian, Ye; Li, Luming

    2014-01-01

    The Deep Brain Stimulation (DBS) has become a well-accepted treatment for Parkinson's disease patients around the world. However, postoperative care of the stimulators usually puts a heavy burden on the patients' families, especially in China. To solve the problem, this study developed a real-time remote monitoring system for deep brain stimulators. Based on Internet technologies, the system offers remote adjustment service so that in vivo stimulators could be programmed at patients' home by clinic caregivers. We tested the system on an experimental condition and the results have proved that this early exploration of remote monitoring deep brain stimulators was successful.

  3. A deep learning model integrating FCNNs and CRFs for brain tumor segmentation.

    Science.gov (United States)

    Zhao, Xiaomei; Wu, Yihong; Song, Guidong; Li, Zhenye; Zhang, Yazhuo; Fan, Yong

    2018-01-01

    Accurate and reliable brain tumor segmentation is a critical component in cancer diagnosis, treatment planning, and treatment outcome evaluation. Build upon successful deep learning techniques, a novel brain tumor segmentation method is developed by integrating fully convolutional neural networks (FCNNs) and Conditional Random Fields (CRFs) in a unified framework to obtain segmentation results with appearance and spatial consistency. We train a deep learning based segmentation model using 2D image patches and image slices in following steps: 1) training FCNNs using image patches; 2) training CRFs as Recurrent Neural Networks (CRF-RNN) using image slices with parameters of FCNNs fixed; and 3) fine-tuning the FCNNs and the CRF-RNN using image slices. Particularly, we train 3 segmentation models using 2D image patches and slices obtained in axial, coronal and sagittal views respectively, and combine them to segment brain tumors using a voting based fusion strategy. Our method could segment brain images slice-by-slice, much faster than those based on image patches. We have evaluated our method based on imaging data provided by the Multimodal Brain Tumor Image Segmentation Challenge (BRATS) 2013, BRATS 2015 and BRATS 2016. The experimental results have demonstrated that our method could build a segmentation model with Flair, T1c, and T2 scans and achieve competitive performance as those built with Flair, T1, T1c, and T2 scans. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Anatomy-preserving nonlinear registration of deep brain ROIs using confidence-based block-matching.

    Science.gov (United States)

    Bhattacharjee, Manik; Pitiot, Alain; Roche, Alexis; Dormont, Didier; Bardinet, Eric

    2008-01-01

    Brain atlases are commonly used in a number of applications such as MRI segmentation and surgery targetting. Our goal is to register a basal ganglia atlas to a subject using MR image registration. Existing registration methods are for the most part either too constrained (linear registration) or can deform deep brain ROIs into implausible anatomical shapes. We developed a block-matching registration method suitable for atlas registration, using a new confidence-based regularization of the vector field. The method was used to register a set of 17 manually segmented MRI onto one subject. Results show that basal ganglia structures were better registered than when using an affine registration method.

  5. 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.)

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Aging and technology in medical care: using the example of patient controllers in deep brain stimulation.

    Science.gov (United States)

    Kaiser, Iris; Oppenauer-Meerskraut, Claudia; Kryspin-Exner, Ilse; Czech, Thomas; Alesch, François

    2010-11-01

    Deep brain stimulation is a neurosurgical therapy for patients with advanced movement disorders (e.g., Parkinson's disease). This therapy involves the use of a patient controller for home-use. So far, there are four different patient controllers available on the European market. However, use and acceptance of the patient controller is relatively low. The main end-user group is patients above the age of 60 years. This article compares the design of the different interfaces, with a special focus on gerotechnological aspects (display, acoustic signals, coloring, lettering, cognitive load and haptics). We suggest strategies to optimize the use and acceptance of these devices, which have already entered the market. Moreover, future directions of deep brain stimulation and the usability of patient controllers are discussed.

  9. 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.

  10. Patterned photostimulation via visible-wavelength photonic probes for deep brain optogenetics.

    Science.gov (United States)

    Segev, Eran; Reimer, Jacob; Moreaux, Laurent C; Fowler, Trevor M; Chi, Derrick; Sacher, Wesley D; Lo, Maisie; Deisseroth, Karl; Tolias, Andreas S; Faraon, Andrei; Roukes, Michael L

    2017-01-01

    Optogenetic methods developed over the past decade enable unprecedented optical activation and silencing of specific neuronal cell types. However, light scattering in neural tissue precludes illuminating areas deep within the brain via free-space optics; this has impeded employing optogenetics universally. Here, we report an approach surmounting this significant limitation. We realize implantable, ultranarrow, silicon-based photonic probes enabling the delivery of complex illumination patterns deep within brain tissue. Our approach combines methods from integrated nanophotonics and microelectromechanical systems, to yield photonic probes that are robust, scalable, and readily producible en masse . Their minute cross sections minimize tissue displacement upon probe implantation. We functionally validate one probe design in vivo with mice expressing channelrhodopsin-2. Highly local optogenetic neural activation is demonstrated by recording the induced response-both by extracellular electrical recordings in the hippocampus and by two-photon functional imaging in the cortex of mice coexpressing GCaMP6.

  11. Cognitive assessment instruments in Parkinson's disease patients undergoing deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Aline Juliane Romann

    Full Text Available ABSTRACT Deep Brain Stimulation (DBS is a widely used surgical technique in individuals with Parkinson's disease (PD that can lead to significant reductions in motor symptoms. Objectives: To determine, from publications, the most commonly used instruments for cognitive evaluation of individuals with PD undergoing DBS. Methods: A systematic review of the databases: PubMed, Medline, EBECS, Scielo and LILACS was conducted, using the descriptors "Deep Brain Stimulation", "Verbal Fluency", "Parkinson Disease", "Executive Function", "Cognition" and "Cognitive Assessment" in combination. Results: The Verbal Fluency test was found to be the most used instrument for this investigation in the studies, followed by the Boston Naming Test. References to the Stroop Test, Trail Making Test, and Rey's Auditory Verbal Learning Test were also found. Conclusions: The validation of instruments for this population is needed as is the use of batteries offering greater specificity and sensitivity for the detection of cognitive impairment.

  12. A case of musical preference for Johnny Cash following deep brain stimulation of the nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Mariska eMantione

    2014-05-01

    Full Text Available Music is among all cultures an important part of the live of most people. Music has psychological benefits and may generate strong emotional and physiological responses. Recently, neuroscientists have discovered that music influences the reward circuit of the nucleus accumbens, even when no explicit reward is present. In this clinical case study, we describe a 60-year old patient who developed a sudden and distinct musical preference for Johnny Cash following deep brain stimulation targeted at the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. This case report substantiates the assumption that the nucleus accumbens is involved in musical preference, based on the observation of direct stimulation of the accumbens with deep brain stimulation. It also shows that accumbens DBS can change musical preference without habituation of its rewarding properties.

  13. Deep brain stimulation: BCI at large, where are we going to?

    Science.gov (United States)

    Benabid, Alim Louis; Costecalde, Thomas; Torres, Napoleon; Moro, Cecile; Aksenova, Tetiana; Eliseyev, Andrey; Charvet, Guillaume; Sauter, Fabien; Ratel, David; Mestais, Corinne; Pollak, Pierre; Chabardes, Stephan

    2011-01-01

    Brain-computer interfaces (BCIs) include stimulators, infusion devices, and neuroprostheses. They all belong to functional neurosurgery. Deep brain stimulators (DBS) are widely used for therapy and are in need of innovative evolutions. Robotized exoskeletons require BCIs able to drive up to 26 degrees of freedom (DoF). We report the nanomicrotechnology development of prototypes for new 3D DBS and for motor neuroprostheses. For this complex project, all compounds have been designed and are being tested. Experiments were performed in rats and primates for proof of concepts and development of the electroencephalogram (EEG) recognition algorithm. Various devices have been designed. (A) In human, a programmable multiplexer connecting five tetrapolar (20 contacts) electrodes to one DBS channel has been designed and implanted bilaterally into STN in two Parkinsonian patients. (B) A 50-mm diameter titanium implant, telepowered, including a radioset, emitting ECoG data recorded by a 64-electrode array using an application-specific integrated circuit, is being designed to be implanted in a 50-mm trephine opening. Data received by the radioreceiver are processed through an original wavelet-based Iterative N-way Partial Least Square algorithm (INPLS, CEA patent). Animals, implanted with ECoG recording electrodes, had to press a lever to obtain a reward. The brain signature associated to the lever press (LP) was detected online by ECoG processing using INPLS. This detection allowed triggering the food dispenser. (A) The 3D multiplexer allowed tailoring the electrical field to the STN. The multiplication of the contacts affected the battery life and suggested different implantation schemes. (B) The components of the human implantable cortical BCI are being tested for reliability and toxicology to meet criteria for chronicle implantation in 2012. (C) In rats, the algorithm INPLS could detect the cortical signature with an accuracy of about 80% of LPs on the electrodes with the

  14. 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

  15. Effects of deep brain stimulation amplitude on motor performance in Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Conovaloff A

    2012-12-01

    Full Text Available Alison Conovaloff,1 Narayanan Krishnamurthi,1 Padma Mahant,2 Johan Samanta,2 James Abbas11Center for Adaptive Neural Systems, School of Biological and Health Systems Engineering, Ira A Fulton School of Engineering, Arizona State University, Tempe, AZ, USA, 2Movement Disorders Clinic, Banner Good Samaritan Medical Center, Phoenix, AZ, USABackground: The efficacy of deep brain stimulation (DBS in Parkinson’s disease has been convincingly demonstrated in studies comparing motor performance with and without stimulation, but characterization of the stimulation dose-response curves has been limited.Methods: In a series of case studies, eight subjects with Parkinson’s disease and bilateral DBS systems were evaluated at their clinically determined stimulation (CDS and at three reduced amplitudes, ie, approximately 70%, 30%, and 0% of the CDS (MOD, LOW, and OFF, respectively. Performance was assessed using the motor section of the Unified Parkinson’s Disease Rating Scale (UPDRS-III, which includes subscores for tremor, bradykinesia, gait, posture, and tapping. Data at the reduced settings were analyzed to determine if individual subjects demonstrated a threshold-like response, which was defined as a dose-response curve in which one decrement in stimulation accounted for ≥70% of the maximum change observed. Day-to-day variability was assessed using the CDS data from the three different days.Results: In the dose-response curves, two subjects exhibited a threshold-like response, four exhibited a graded change, and two did not exhibit substantial changes. For some subjects, variability in CDS performance across the three days exceeded the change observed when reducing amplitude to the MOD setting. Comparisons across this set of eight subjects demonstrated that the mean UPDRS-III and all but one subscore significantly increased (performance degraded when amplitude was reduced from CDS to the LOW and OFF conditions, but there were no significant

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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...

  18. 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...

  19. Patterned photostimulation via visible-wavelength photonic probes for deep brain optogenetics

    OpenAIRE

    Segev, Eran; Reimer, Jacob; Moreaux, Laurent C.; Fowler, Trevor M.; Chi, Derrick; Sacher, Wesley D.; Lo, Maisie; Deisseroth, Karl; Tolias, Andreas S.; Faraon, Andrei; Roukes, Michael L.

    2016-01-01

    Optogenetic methods developed over the past decade enable unprecedented optical activation and silencing of specific neuronal cell types. However, light scattering in neural tissue precludes illuminating areas deep within the brain via free-space optics; this has impeded employing optogenetics universally. Here, we report an approach surmounting this significant limitation. We realize implantable, ultranarrow, silicon-based photonic probes enabling the delivery of complex illumination pattern...

  20. Combined diffuse light reflectance and electric impedance measurements for navigation aid in deep brain surgery

    OpenAIRE

    Johansson, Johannes D.; Blomstedt, Patric; Haj-Hosseini, Neda; Bergenheim, Tommy; Eriksson, Ola; Wårdell, Karin

    2009-01-01

    Aim: The aim of this study is to investigate reflected light intensity combined with impedance for navigation aid during stereotactic neurosurgery. Methods: During creation of 21 trajectories for stereotactic implantation of deep brain stimulation electrodes in the globus pallidus internus or subthalamus (zona incerta or subthalamic nucleus), impedance at 512 kHz and reflected light intensity at 780 nm were measured continuously and simultaneously with a radio frequency electrode containing o...

  1. Electric field distribution in a finite-volume head model of deep brain stimulation

    OpenAIRE

    Grant, Peadar F.; Lowery, Madeleine M.

    2009-01-01

    This study presents a whole-head finite element model of deep brain stimulation to examine the effect of electrical grounding, the finite conducting volume of the head, and scalp, skull and cerebrospinal fluid layers. The impedance between the stimulating and reference electrodes in the whole-head model was found to lie within clinically reported values when the reference electrode was incorporated on a localized surface in the model. Incorporation of the finite volume of the head and inclusi...

  2. 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.

  3. 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...

  4. Barriers to investigator-initiated deep brain stimulation and device research

    OpenAIRE

    Kelly, Michael L.; Malone, Donald; Okun, Michael S.; Booth, Joan; Machado, Andre G.

    2014-01-01

    The success of device-based research in the clinical neurosciences has overshadowed a critical and emerging problem in the biomedical research environment in the United States. Neuroprosthetic devices, such as deep brain stimulation (DBS), have been shown in humans to be promising technologies for scientific exploration of neural pathways and as powerful treatments. Large device companies have, over the past several decades, funded and developed major research programs. However, both the stru...

  5. Ethical Considerations in Deep Brain Stimulation for the Treatment of Addiction and Overeating Associated With Obesity

    OpenAIRE

    Pisapia, Jared M.; Halpern, Casey H.; Muller, Ulf J.; Vinai, Piergiuseppe; Wolf, John A.; Whiting, Donald M.; Wadden, Thomas A.; Baltuch, Gordon H.; Caplan, Arthur L.

    2013-01-01

    The success of deep brain stimulation (DBS) for movement disorders and the improved understanding of the neurobiologic and neuroanatomic bases of psychiatric diseases have led to proposals to expand current DBS applications. Recent preclinical and clinical work with Alzheimer’s disease and obsessive-compulsive disorder, for example, supports the safety of stimulating regions in the hypothalamus and nucleus accumbens in humans. These regions are known to be involved in addiction and overeating...

  6. Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens.

    Science.gov (United States)

    Ross, Erika K; Kim, Joo Pyung; Settell, Megan L; Han, Seong Rok; Blaha, Charles D; Min, Hoon-Ki; Lee, Kendall H

    2016-03-01

    Deep brain stimulation (DBS) is a circuit-based treatment shown to relieve symptoms from multiple neurologic and neuropsychiatric disorders. In order to treat the memory deficit associated with Alzheimer's disease (AD), several clinical trials have tested the efficacy of DBS near the fornix. Early results from these studies indicated that patients who received fornix DBS experienced an improvement in memory and quality of life, yet the mechanisms behind this effect remain controversial. It is known that transmission between the medial limbic and corticolimbic circuits plays an integral role in declarative memory, and dysfunction at the circuit level results in various forms of dementia, including AD. Here, we aimed to determine the potential underlying mechanism of fornix DBS by examining the functional circuitry and brain structures engaged by fornix DBS. A multimodal approach was employed to examine global and local temporal changes that occur in an anesthetized swine model of fornix DBS. Changes in global functional activity were measured by functional MRI (fMRI), and local neurochemical changes were monitored by fast scan cyclic voltammetry (FSCV) during electrical stimulation of the fornix. Additionally, intracranial microinfusions into the nucleus accumbens (NAc) were performed to investigate the global activity changes that occur with dopamine and glutamate receptor-specific antagonism. Hemodynamic responses in both medial limbic and corticolimbic circuits measured by fMRI were induced by fornix DBS. Additionally, fornix DBS resulted in increases in dopamine oxidation current (corresponding to dopamine efflux) monitored by FSCV in the NAc. Finally, fornix DBS-evoked hemodynamic responses in the amygdala and hippocampus decreased following dopamine and glutamate receptor antagonism in the NAc. The present findings suggest that fornix DBS modulates dopamine release on presynaptic dopaminergic terminals in the NAc, involving excitatory glutamatergic input, and

  7. A clinical pathway including psychotherapy approaches for managing emotional difficulties after acquired brain injury.

    Science.gov (United States)

    Coetzer, Rudi

    2009-11-01

    Emotional difficulties, such as anxiety and depression, are common after acquired brain injury in adults and can influence long-term outcome. Diagnosis in a brain injury context can be difficult. Ideally, rehabilitation approaches should consider the specific treatment of anxiety and depression as well and may include pharmacotherapy, individual psychotherapy, and family interventions. Psychotherapy, especially in regards to longer-term adjustment to brain injury, may have an important adjunctive role in treatment approaches, but adaptations of techniques may be needed. A clinical pathway is described which can help to raise clinicians awareness, as well as increase detection rates and consideration of the specific role of individual psychotherapy in this clinical population. However, an important caveat is that clinical pathways should not serve as a substitute, but rather a facilitator, for the process of reasoning about individual patients in everyday clinical practice.

  8. Unilateral neuromodulation of the ventromedial hypothalamus of the rat through deep brain stimulation

    Science.gov (United States)

    Lehmkuhle, M. J.; Mayes, S. M.; Kipke, D. R.

    2010-06-01

    This study offers evidence that long-term deep brain stimulation of the ventromedial hypothalamus (VMH) can alter weight gain in mammals without affecting feeding behavior. Animals stimulated unilaterally at high frequencies of 150 or 500 Hz demonstrated increased CO2 production that decreased from prestimulation levels after the stimulation was removed. Animals stimulated for up to 6 weeks gained weight at a lower rate than normal animals or animals implanted with an electrode but not stimulated. Stimulated animals exhibited normal food and water consumption. A significant decrease in efficiency was observed during stimulation that coincided with an increase in the amount of feces produced. Whereas the weight of control animals was significantly different from week to week, the weight of stimulated animals did not change accordingly. These data suggest that the VMH may be a viable target for long-term deep brain stimulation for modulation of the neural mechanisms of metabolism. The potential therapeutic effects of deep brain stimulation of the hypothalamus are discussed.

  9. 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.

  10. Primary experimental study on safety of deep brain stimulation in RF electromagnetic field.

    Science.gov (United States)

    Jun, Xu; Luming, Li; Hongwei, Hao

    2009-01-01

    With the rapid growth of clinical application of Deep Brain Stimulation, its safety and functional concern in the electromagnetic field, another pollution becoming much more serious, has become more and more significant. Meanwhile, the measuring standards on Electromagnetic Compatibility (EMC) for DBS are still incomplete. Particularly, the knowledge of the electromagnetic field induced signals on the implanted lead is ignorant while some informal reports some side effects. This paper briefly surmised the status of EMC standards on implantable medical devices. Based on the EMC experiments of DBS device we developed, two experiments for measuring the induced voltage of the deep brain stimulator in RF electromagnetic field were reported. The measured data showed that the induced voltage in some frequency was prominent, for example over 2V. As a primary research, we think these results would be significant to cause researcher to pay more attention to the EMC safety problem and biological effects of the induced voltage in deep brain stimulation and other implantable devices.

  11. Computational Field Shaping for Deep Brain Stimulation With Thousands of Contacts in a Novel Electrode Geometry.

    Science.gov (United States)

    Willsie, Andrew C; Dorval, Alan D

    2015-10-01

    Deep brain stimulation (DBS) alleviates symptoms associated with some neurological disorders by stimulating specific deep brain targets. However, incomplete stimulation of the target region can provide suboptimal therapy, and spread of stimulation to tissue outside the target can generate side-effects. Existing DBS electrodes generate stimulation profiles that are roughly spherical, neither matching nor enabling the mapping of therapeutic targets. We present a novel electrode design and will perform computational modeling of the new design to investigate its use as a next generation DBS electrode. Computational simulations of a finite element model are performed for both the novel electrode and for a commercially available DBS electrode. Computational modeling results show that this new electrode design is able to steer stimulation radially around the device, creating voltage distributions that may more closely match deep brain targets. The ability to better match the anatomy and compensate for targeting errors during implantation will enable strict localization of the generated stimulation fields to within target tissues, potentially providing more complete symptom alleviation while reducing the occurrence of side-effects. © 2015 International Neuromodulation Society.

  12. Low-frequency deep brain stimulation for Parkinson's disease: Great expectation or false hope?

    Science.gov (United States)

    di Biase, Lazzaro; Fasano, Alfonso

    2016-07-01

    The long-term efficacy of subthalamic deep brain stimulation for Parkinson's disease is not always retained, and many patients lose the improvement achieved during the "second honeymoon" following surgery. Deep brain stimulation is a versatile tool, as stimulation parameters may undergo a fine-tuning depending on clinical needs. Among them, frequency is the parameter that leads to more complex scenarios because there is no generalizable relationship between its modulation and the overall clinical response, which also depends on the specific considered sign. High-frequency stimulation (>100 Hz) has shown to be effective in improving most parkinsonian signs, particularly the levodopa-responsive ones. However, its effect on axial signs (such as balance, gait, speech, or swallowing) may not be sustained, minimal, or even detrimental. For these reasons, several studies have explored the effectiveness of low-frequency stimulation (generally 60 or 80 Hz). Methods, results, and especially interpretations of these studies are quite variable. Although the use of low-frequency stimulation certainly opens new avenues in the field of deep brain stimulation, after having gathered all the available evidence in patients with subthalamic implants, our conclusion is that it might be clinically useful mainly when it lessens the detrimental effects of high-frequency stimulation. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  13. Flexible deep brain neural probes based on a parylene tube structure

    Science.gov (United States)

    Zhao, Zhiguo; Kim, Eric; Luo, Hao; Zhang, Jinsheng; Xu, Yong

    2018-01-01

    Most microfabricated neural probes have limited shank length, which prevents them from reaching many deep brain structures. This paper reports deep brain neural probes with ultra-long penetrating shanks based on a simple but novel parylene tube structure. The mechanical strength of the parylene tube shank is temporarily enhanced during implantation by inserting a metal wire. The metal wire can be removed after implantation, making the implanted probe very flexible and thus minimizing the stress caused by micromotions of brain tissues. Optogenetic stimulation and chemical delivery capabilities can be potentially integrated by taking advantage of the tube structure. Single-shank prototypes with a shank length of 18.2 mm have been developed. The microfabrication process comprises of deep reactive ion etching (DRIE) of silicon, parylene conformal coating/refilling, and XeF2 isotropic silicon etching. In addition to bench-top insertion characterization, the functionality of developed probes has been preliminarily demonstrated by implanting into the amygdala of a rat and recording neural signals.

  14. Bimanual force coordination in Parkinson's disease patients with bilateral subthalamic deep brain stimulation.

    Directory of Open Access Journals (Sweden)

    Stacey L Gorniak

    Full Text Available Studies of bimanual actions similar to activities of daily living (ADLs are currently lacking in evaluating fine motor control in Parkinson's disease patients implanted with bilateral subthalamic deep brain stimulators. We investigated basic time and force characteristics of a bimanual task that resembles performance of ADLs in a group of bilateral subthalamic deep brain stimulation (DBS patients.Patients were evaluated in three different DBS parameter conditions off stimulation, on clinically derived stimulation parameters, and on settings derived from a patient-specific computational model. Model-based parameters were computed as a means to minimize spread of current to non-motor regions of the subthalamic nucleus via Cicerone Deep Brain Stimulation software. Patients were evaluated off parkinsonian medications in each stimulation condition.The data indicate that DBS parameter state does not affect most aspects of fine motor control in ADL-like tasks; however, features such as increased grip force and grip symmetry varied with the stimulation state. In the absence of DBS parameters, patients exhibited significant grip force asymmetry. Overall UPDRS-III and UPDRS-III scores associated with hand function were lower while patients were experiencing clinically-derived or model-based parameters, as compared to the off-stimulation condition.While bilateral subthalamic DBS has been shown to alleviate gross motor dysfunction, our results indicate that DBS may not provide the same magnitude of benefit to fine motor coordination.

  15. Nucleus accumbens deep brain stimulation results in insula and prefrontal activation: a large animal FMRI study.

    Directory of Open Access Journals (Sweden)

    Emily J Knight

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

  16. 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.

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

    Science.gov (United States)

    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.

  18. Ethical concerns regarding commercialization of deep brain stimulation for obsessive compulsive disorder.

    Science.gov (United States)

    Erickson-Davis, Cordelia

    2012-10-01

    The United States Food and Drug Administration's recent approval of the commercial use of Deep Brain Stimulation (DBS) as a treatment for Obsessive Compulsive Disorder (OCD) will be discussed within the context of the existing USA regulatory framework. The purpose will be to illustrate the current lack of regulation and oversight of the DBS market, which has resulted in the violation of basic ethical norms. The discussion will focus on: 1) the lack of available evidence on procedural safety and efficacy, 2) the numerous conflicts of interest held by research investigators, and 3) the ambiguity of both aforementioned categories due to an inherent lack of transparency in the research. It is argued that in order to address these issues, ethical analyses of DBS for psychiatric disorders must include the role of the industry forces that have become the primary impetus for this research. As such, DBS for OCD serves as an important case example in studies of neurotechnology and innovative surgery. © 2011 Blackwell Publishing Ltd.

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

    Science.gov (United States)

    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.

  20. Challenges to deep brain stimulation: a pragmatic response to ethical, fiscal, and regulatory concerns.

    Science.gov (United States)

    Fins, Joseph J; Dorfman, Gary S; Pancrazio, Joseph J

    2012-08-01

    In response to the early success of deep brain stimulation, we offer some common-sense strategies to sustain the work, addressing the need to do so in a fiscally workable, ethically transparent, and scientifically informed manner. After delineating major threats, we will suggest reforms in both the legislative and regulatory spheres that might remediate these challenges. We will recommend (1) revisions to the Bayh-Dole Act of 1980, which governs intellectual property exchange resulting from federally funded research; (2) revisions to the Association of American Medical Colleges recommendations concerning the management of conflicts of interest when scientists with an intellectual property interest participate in clinical research in tandem; (3) revisions to the Food and Drug Administration's pre-market approval process for new devices, including a proposal for a mini-investigational device exemption; and (4) the establishment of a public-private partnership to build ethical and sustainable synergies between the scientific community, industry, and government that would foster discovery and innovation. © 2012 New York Academy of Sciences.

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

    Directory of Open Access Journals (Sweden)

    A. Etiévant

    2015-08-01

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

  2. 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.

  3. Fine-tuning convolutional deep features for MRI based brain tumor classification

    Science.gov (United States)

    Ahmed, Kaoutar B.; Hall, Lawrence O.; Goldgof, Dmitry B.; Liu, Renhao; Gatenby, Robert A.

    2017-03-01

    Prediction of survival time from brain tumor magnetic resonance images (MRI) is not commonly performed and would ordinarily be a time consuming process. However, current cross-sectional imaging techniques, particularly MRI, can be used to generate many features that may provide information on the patient's prognosis, including survival. This information can potentially be used to identify individuals who would benefit from more aggressive therapy. Rather than using pre-defined and hand-engineered features as with current radiomics methods, we investigated the use of deep features extracted from pre-trained convolutional neural networks (CNNs) in predicting survival time. We also provide evidence for the power of domain specific fine-tuning in improving the performance of a pre-trained CNN's, even though our data set is small. We fine-tuned a CNN initially trained on a large natural image recognition dataset (Imagenet ILSVRC) and transferred the learned feature representations to the survival time prediction task, obtaining over 81% accuracy in a leave one out cross validation.

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

    Directory of Open Access Journals (Sweden)

    Han-Joon Kim

    2015-05-01

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

  5. 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.

  6. 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.

  7. Potential indications for deep brain stimulation in neurological disorders: an evolving field.

    Science.gov (United States)

    Budman, E; Deeb, W; Martinez-Ramirez, D; Pilitsis, J G; Peng-Chen, Z; Okun, M S; Ramirez-Zamora, A

    2018-03-01

    Deep brain stimulation (DBS) is an established therapy for appropriately selected patients with movement disorders and neuropsychiatric conditions. Although the exact mechanisms and biology of DBS are not fully understood, it is a safe and well-tolerated therapy for many refractory cases of neuropsychiatric disease. Increasingly, DBS has been explored in other conditions with encouraging results. In this paper, available data is reviewed and new DBS targets, challenges and future directions in neurological disorders are explored. A detailed search of the medical literature discussing the potential use of DBS for neurological disorders excluding accepted indications was conducted. All reports were analyzed individually for content and redundant articles were excluded by examining individual abstracts. The level of evidence for each indication was summarized. Multiple studies report promising preliminary data regarding the safety and efficacy of DBS for a variety of neurological indications including chronic pain, tinnitus, epilepsy, Tourette syndrome, Huntington's disease, tardive dyskinesia and Alzheimer's disease. The initial results of DBS studies for diverse neurological disorders are encouraging but larger, controlled, prospective, homogeneous clinical trials are necessary to establish long-term safety and effectiveness. The field of neuromodulation continues to evolve and advances in DBS technology, stereotactic techniques, neuroimaging and DBS programming capabilities are shaping the present and future of DBS research and use in practice. © 2017 EAN.

  8. 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

  9. 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

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

    Science.gov (United States)

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

    2017-02-01

    The substantia nigra pars reticulata (SNr) and external globus pallidus (GPe) constitute the two major output targets of the rodent striatum. Both the SNr and GPe converge upon thalamic relay nuclei (directly or indirectly, respectively), and are traditionally modeled as functionally antagonistic relay inputs. However, recent anatomical and functional studies have identified unanticipated circuit connectivity in both the SNr and GPe, demonstrating their potential as far more than relay nuclei. In the present study, we employed simultaneous deep brain stimulation and functional magnetic resonance imaging (DBS-fMRI) with cerebral blood volume (CBV) measurements to functionally and unbiasedly map the circuit- and network level connectivity of the SNr and GPe. Sprague-Dawley rats were implanted with a custom-made MR-compatible stimulating electrode in the right SNr (n=6) or GPe (n=7). SNr- and GPe-DBS, conducted across a wide range of stimulation frequencies, revealed a number of surprising evoked responses, including unexpected CBV decreases within the striatum during DBS at either target, as well as GPe-DBS-evoked positive modulation of frontal cortex. Functional connectivity MRI revealed global modulation of neural networks during DBS at either target, sensitive to stimulation frequency and readily reversed following cessation of stimulation. This work thus contributes to a growing literature demonstrating extensive and unanticipated functional connectivity among basal ganglia nuclei. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Clinical analysis and treatment of symptomatic intracranial hemorrhage after deep brain stimulation surgery.

    Science.gov (United States)

    Wang, Xin; Wang, Jing; Zhao, Haikang; Li, Nan; Ge, Shunnan; Chen, Lei; Li, Jiaming; Jing, Jiangpeng; Su, Mingming; Zheng, Zhaohui; Zhang, Jinan; Gao, Guodong; Wang, Xuelian

    2017-04-01

    Symptomatic intracranial hemorrhage (ICH) may lead to permanent neurological disability of patients and has impeded the extensive clinical application of deep brain stimulation (DBS). The present study was conducted to discuss the incidence, prevention, and treatment of symptomatic ICH after DBS surgery. From January 2009 to December 2014, 396 patients underwent DBS with a total of 691 implanted leads. In all, 10 patients had symptomatic ICH. We analyzed these cases' clinical characteristics, including comorbid diagnoses and coagulation profile. We described the onset of ICH, imaging features, clinical manifestations, treatment, neurological impairment, and outcome of DBS. Of the 10 patients with symptomatic ICH, 2 had hypertension. Three cases of ICH occurred within 12 h of the procedure; four cases within 24 h. Five experienced grand mal seizures concurrently with hemorrhage. Unilateral frontal lobe hemorrhage occurred in all cases. In seven cases, hematomas occurred around the electrodes. Some hematomas were not well-circumscribed and had perihematomal edema. Conservative therapy was administered to 8 patients, and 2 patients underwent craniotomy and hematoma evacuation. All electrodes were successfully preserved. Neurological dysfunction in all patients gradually improved. Nine patients ultimately experienced effective symptom relief of Parkinson's disease with DBS. Symptomatic ICH should be identified as soon as possible after implantation surgery and treated effectively to limit neurological deficit and preserve DBS leads.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

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

    Science.gov (United States)

    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.

  15. Deep into the Brain: Artificial Intelligence in Stroke Imaging.

    Science.gov (United States)

    Lee, Eun-Jae; Kim, Yong-Hwan; Kim, Namkug; Kang, Dong-Wha

    2017-09-01

    Artificial intelligence (AI), a computer system aiming to mimic human intelligence, is gaining increasing interest and is being incorporated into many fields, including medicine. Stroke medicine is one such area of application of AI, for improving the accuracy of diagnosis and the quality of patient care. For stroke management, adequate analysis of stroke imaging is crucial. Recently, AI techniques have been applied to decipher the data from stroke imaging and have demonstrated some promising results. In the very near future, such AI techniques may play a pivotal role in determining the therapeutic methods and predicting the prognosis for stroke patients in an individualized manner. In this review, we offer a glimpse at the use of AI in stroke imaging, specifically focusing on its technical principles, clinical application, and future perspectives.

  16. Deep Brain Stimulation for Pantothenate Kinase-Associated Neurodegeneration

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    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.

  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 Learning and Texture-Based Semantic Label Fusion for Brain Tumor Segmentation.

    Science.gov (United States)

    Vidyaratne, L; Alam, M; Shboul, Z; Iftekharuddin, K M

    2018-01-01

    Brain tumor segmentation is a fundamental step in surgical treatment and therapy. Many hand-crafted and learning based methods have been proposed for automatic brain tumor segmentation from MRI. Studies have shown that these approaches have their inherent advantages and limitations. This work proposes a semantic label fusion algorithm by combining two representative state-of-the-art segmentation algorithms: texture based hand-crafted, and deep learning based methods to obtain robust tumor segmentation. We evaluate the proposed method using publicly available BRATS 2017 brain tumor segmentation challenge dataset. The results show that the proposed method offers improved segmentation by alleviating inherent weaknesses: extensive false positives in texture based method, and the false tumor tissue classification problem in deep learning method, respectively. Furthermore, we investigate the effect of patient's gender on the segmentation performance using a subset of validation dataset. Note the substantial improvement in brain tumor segmentation performance proposed in this work has recently enabled us to secure the first place by our group in overall patient survival prediction task at the BRATS 2017 challenge.

  19. 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.

  20. Deep sequencing analysis of the developing mouse brain reveals a novel microRNA

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    Piltz Sandra

    2011-04-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are small non-coding RNAs that can exert multilevel inhibition/repression at a post-transcriptional or protein synthesis level during disease or development. Characterisation of miRNAs in adult mammalian brains by deep sequencing has been reported previously. However, to date, no small RNA profiling of the developing brain has been undertaken using this method. We have performed deep sequencing and small RNA analysis of a developing (E15.5 mouse brain. Results We identified the expression of 294 known miRNAs in the E15.5 developing mouse brain, which were mostly represented by let-7 family and other brain-specific miRNAs such as miR-9 and miR-124. We also discovered 4 putative 22-23 nt miRNAs: mm_br_e15_1181, mm_br_e15_279920, mm_br_e15_96719 and mm_br_e15_294354 each with a 70-76 nt predicted pre-miRNA. We validated the 4 putative miRNAs and further characterised one of them, mm_br_e15_1181, throughout embryogenesis. Mm_br_e15_1181 biogenesis was Dicer1-dependent and was expressed in E3.5 blastocysts and E7 whole embryos. Embryo-wide expression patterns were observed at E9.5 and E11.5 followed by a near complete loss of expression by E13.5, with expression restricted to a specialised layer of cells within the developing and early postnatal brain. Mm_br_e15_1181 was upregulated during neurodifferentiation of P19 teratocarcinoma cells. This novel miRNA has been identified as miR-3099. Conclusions We have generated and analysed the first deep sequencing dataset of small RNA sequences of the developing mouse brain. The analysis revealed a novel miRNA, miR-3099, with potential regulatory effects on early embryogenesis, and involvement in neuronal cell differentiation/function in the brain during late embryonic and early neonatal development.

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

    OpenAIRE

    Wissam Deeb; James J Giordano; James J Giordano; Peter Justin Rossi; Alon Mogilner; Aysegul Gunduz; Aysegul Gunduz; Jack William Judy; Jack William Judy; Bryan T. Klassen; Christopher R. Butson; Craig van Horne; Damiaan Denys; Darin D Dougherty; David Rowell

    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 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 r...

  2. Delayed Onset Eye Opening Apraxia due to Progression of Brain Atrophy following Subthalamic Nucleus Deep Brain Stimulation: A Case Report.

    Science.gov (United States)

    Morishita, Takashi; Higuchi, Masa-Aki; Tsuboi, Yoshio; Samura, Kazuhiro; Inoue, Tooru

    2017-01-01

    Eye opening apraxia (EOA) has been described in literature as a complication of deep brain stimulation (DBS), especially after electrode implantation in the subthalamic nucleus (STN). EOA can be either worsened or alleviated by DBS depending on the etiology. Herein, we report a rare case where the progression of brain atrophy may have contributed to the delayed onset of EOA. The patient, a 73-year-old woman, had previously undergone bilateral STN-DBS for advanced Parkinson's disease (PD), which was performed by another DBS team, at the age of 68 years. She initially experienced a dramatic improvement in her motor symptoms, with no adverse events. However, she had difficulty in opening her right eye 3 years after the DBS surgery. Imaging studies showed that the brain atrophy had progressed over the past 5 years, and that the DBS electrodes were implanted through the far anterior entry points. We considered that the relative movement of the DBS might have been caused by the progression of the brain atrophy to the posterior limb of the internal capsule (IC) where the corticobulbar tract exists, and this was enhanced by the lower implantation angle. The present case illustrates the importance of the DBS insertion angle considering the a+ trophic effect and the follow-up imaging studies after DBS.

  3. Detection of Alzheimer’s disease amyloid-beta plaque deposition by deep brain impedance profiling

    Science.gov (United States)

    Béduer, Amélie; Joris, Pierre; Mosser, Sébastien; Fraering, Patrick C.; Renaud, Philippe

    2015-04-01

    Objective. Alzheimer disease (AD) is the most common form of neurodegenerative disease in elderly people. Toxic brain amyloid-beta (Aß) aggregates and ensuing cell death are believed to play a central role in the pathogenesis of the disease. In this study, we investigated if we could monitor the presence of these aggregates by performing in situ electrical impedance spectroscopy measurements in AD model mice brains. Approach. In this study, electrical impedance spectroscopy measurements were performed post-mortem in APPPS1 transgenic mice brains. This transgenic model is commonly used to study amyloidogenesis, a pathological hallmark of AD. We used flexible probes with embedded micrometric electrodes array to demonstrate the feasibility of detecting senile plaques composed of Aß peptides by localized impedance measurements. Main results. We particularly focused on deep brain structures, such as the hippocampus. Ex vivo experiments using brains from young and old APPPS1 mice lead us to show that impedance measurements clearly correlate with the percentage of Aβ plaque load in the brain tissues. We could monitor the effects of aging in the AD APPPS1 mice model. Significance. We demonstrated that a localized electrical impedance measurement constitutes a valuable technique to monitor the presence of Aβ-plaques, which is complementary with existing imaging techniques. This method does not require prior Aβ staining, precluding the risk of variations in tissue uptake of dyes or tracers, and consequently ensuring reproducible data collection.

  4. STN vs. GPi Deep Brain Stimulation: Translating the Rematch into Clinical Practice

    Science.gov (United States)

    Williams, Nolan R.; Foote, Kelly D.; Okun, Michael S.

    2014-01-01

    When formulating a deep brain stimulation (DBS) treatment plan for a patient with Parkinson’s disease (PD), two critical questions should be addressed: 1- Which brain target should be chosen to optimize this patient’s outcome? and 2- Should this patient’s DBS operation be unilateral or bilateral? Over the past two decades, two targets have emerged as leading contenders for PD DBS; the subthalamic nucleus (STN) and the globus pallidus internus (GPi). While the GPi target does have a following, most centers have uniformly employed bilateral STN DBS for all Parkinson’s disease cases (Figure 1). This bilateral STN “one-size-fits-all” approach was challenged by an editorial entitled “STN vs. GPi: The Rematch,” which appeared in the Archives of Neurology in 2005. Since 2005, a series of well designed clinical trials and follow-up studies have addressed the question as to whether a more tailored approach to DBS therapy might improve overall outcomes. Such a tailored approach would include the options of targeting the GPi, or choosing a unilateral operation. The results of the STN vs. GPi ‘rematch’ studies support the conclusion that bilateral STN DBS may not be the best option for every Parkinson’s disease surgical patient. Off period motor symptoms and tremor improve in both targets, and with either unilateral or bilateral stimulation. Advantages of the STN target include more medication reduction, less frequent battery changes, and a more favorable economic profile. Advantages of GPi include more robust dyskinesia suppression, easier programming, and greater flexibility in adjusting medications. In cases where unilateral stimulation is anticipated, the data favor GPi DBS. This review summarizes the accumulated evidence regarding the use of bilateral vs. unilateral DBS and the selection of STN vs. GPi DBS, including definite and possible advantages of different targets and approaches. Based on this evidence, a more patient-tailored, symptom specific

  5. Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits

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    Sarah Kathleen Bourne

    2012-06-01

    Full Text Available Deep brain stimulation (DBS has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive-compulsive disorder (OCD, which is characterized by recurrent unwanted thoughts or ideas (obsessions and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions. Abnormal activity in cortico-striato-thalamo-cortical (CSTC circuits including the orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mediodorsal thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule, ventral capsule/ventral striatum, ventral caudate nucleus, subthalamic nucleus, nucleus accumbens, and the inferior thalamic peduncle have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level.

  6. 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.

  7. Deep ensemble learning of sparse regression models for brain disease diagnosis.

    Science.gov (United States)

    Suk, Heung-Il; Lee, Seong-Whan; Shen, Dinggang

    2017-04-01

    Recent studies on brain imaging analysis witnessed the core roles of machine learning techniques in computer-assisted intervention for brain disease diagnosis. Of various machine-learning techniques, sparse regression models have proved their effectiveness in handling high-dimensional data but with a small number of training samples, especially in medical problems. In the meantime, deep learning methods have been making great successes by outperforming the state-of-the-art performances in various applications. In this paper, we propose a novel framework that combines the two conceptually different methods of sparse regression and deep learning for Alzheimer's disease/mild cognitive impairment diagnosis and prognosis. Specifically, we first train multiple sparse regression models, each of which is trained with different values of a regularization control parameter. Thus, our multiple sparse regression models potentially select different feature subsets from the original feature set; thereby they have different powers to predict the response values, i.e., clinical label and clinical scores in our work. By regarding the response values from our sparse regression models as target-level representations, we then build a deep convolutional neural network for clinical decision making, which thus we call 'Deep Ensemble Sparse Regression Network.' To our best knowledge, this is the first work that combines sparse regression models with deep neural network. In our experiments with the ADNI cohort, we validated the effectiveness of the proposed method by achieving the highest diagnostic accuracies in three classification tasks. We also rigorously analyzed our results and compared with the previous studies on the ADNI cohort in the literature. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Differentiated baroreflex modulation of sympathetic nerve activity during deep brain stimulation in humans.

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    Sverrisdóttir, Yrsa B; Green, Alexander L; Aziz, Tipu Z; Bahuri, Nor Faizal A; Hyam, Jonathan; Basnayake, Shanika D; Paterson, David J

    2014-05-01

    Targeted electric deep brain stimulation in midbrain nuclei in humans alters cardiovascular parameters, presumably by modulating autonomic and baroreflex function. Baroreflex modulation of sympathetic outflow is crucial for cardiovascular regulation and is hypothesized to occur at 2 distinct brain locations. The aim of this study was to evaluate sympathetic outflow in humans with deep brain stimulating electrodes during ON and OFF stimulation of specific midbrain nuclei known to regulate cardiovascular function. Multiunit muscle sympathetic nerve activity was recorded in 17 patients undergoing deep brain stimulation for treatment of chronic neuropathic pain (n=7) and Parkinson disease (n=10). Sympathetic outflow was recorded during ON and OFF stimulation. Arterial blood pressure, heart rate, and respiratory frequency were monitored during the recording session, and spontaneous vasomotor and cardiac baroreflex sensitivity were assessed. Head-up tilt testing was performed separately in the patients with Parkinson disease postoperatively. Stimulation of the dorsal most part of the subthalamic nucleus and ventrolateral periaqueductal gray resulted in improved vasomotor baroreflex sensitivity, decreased burst frequency and blood pressure, unchanged burst amplitude distribution, and a reduced fall in blood pressure after tilt. Stimulation of the dorsolateral periaqueductal gray resulted in a shift in burst amplitude distribution toward larger amplitudes, decreased spontaneous beat-to-beat blood pressure variability, and unchanged burst frequency, baroreflex sensitivity, and blood pressure. Our results indicate that a differentiated regulation of sympathetic outflow occurs in the subthalamic nucleus and periaqueductal gray. These results may have implications in our understanding of abnormal sympathetic discharge in cardiovascular disease and provide an opportunity for therapeutic targeting.

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

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    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.

  10. Increased precursor cell proliferation after deep brain stimulation for Parkinson's disease: a human study.

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    Vinata Vedam-Mai

    Full Text Available Deep brain stimulation (DBS has been used for more than a decade to treat Parkinson's disease (PD; however, its mechanism of action remains unknown. Given the close proximity of the electrode trajectory to areas of the brain known as the "germinal niches," we sought to explore the possibility that DBS influences neural stem cell proliferation locally, as well as more distantly.We studied the brains of a total of 12 idiopathic Parkinson's disease patients that were treated with DBS (the electrode placement occurred 0.5-6 years before death, and who subsequently died of unrelated illnesses. These were compared to the brains of 10 control individuals without CNS disease, and those of 5 PD patients with no DBS.Immunohistochemical analyses of the subventricular zone (SVZ of the lateral ventricles, the third ventricle lining, and the tissue surrounding the DBS lead revealed significantly greater numbers of proliferating cells expressing markers of the cell cycle, plasticity, and neural precursor cells in PD-DBS tissue compared with both normal brain tissue and tissue from PD patients not treated with DBS. The level of cell proliferation in the SVZ in PD-DBS brains was 2-6 fold greater than that in normal and untreated PD brains.Our data suggest that DBS is capable of increasing cellular plasticity in the brain, and we hypothesize that it may have more widespread effects beyond the electrode location. It is unclear whether these effects of DBS have any symptomatic or other beneficial influences on PD.

  11. Human brain activity patterns beyond the isoelectric line of extreme deep coma.

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    Daniel Kroeger

    Full Text Available The electroencephalogram (EEG reflects brain electrical activity. A flat (isoelectric EEG, which is usually recorded during very deep coma, is considered to be a turning point between a living brain and a deceased brain. Therefore the isoelectric EEG constitutes, together with evidence of irreversible structural brain damage, one of the criteria for the assessment of brain death. In this study we use EEG recordings for humans on the one hand, and on the other hand double simultaneous intracellular recordings in the cortex and hippocampus, combined with EEG, in cats. They serve to demonstrate that a novel brain phenomenon is observable in both humans and animals during coma that is deeper than the one reflected by the isoelectric EEG, and that this state is characterized by brain activity generated within the hippocampal formation. This new state was induced either by medication applied to postanoxic coma (in human or by application of high doses of anesthesia (isoflurane in animals leading to an EEG activity of quasi-rhythmic sharp waves which henceforth we propose to call ν-complexes (Nu-complexes. Using simultaneous intracellular recordings in vivo in the cortex and hippocampus (especially in the CA3 region we demonstrate that ν-complexes arise in the hippocampus and are subsequently transmitted to the cortex. The genesis of a hippocampal ν-complex depends upon another hippocampal activity, known as ripple activity, which is not overtly detectable at the cortical level. Based on our observations, we propose a scenario of how self-oscillations in hippocampal neurons can lead to a whole brain phenomenon during coma.

  12. Deep brain stimulation of the antero-medial globus pallidus interna for Tourette syndrome.

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    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.

  13. Deep convolutional neural networks for multi-modality isointense infant brain image segmentation.

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    Zhang, Wenlu; Li, Rongjian; Deng, Houtao; Wang, Li; Lin, Weili; Ji, Shuiwang; Shen, Dinggang

    2015-03-01

    The segmentation of infant brain tissue images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) plays an important role in studying early brain development in health and disease. In the isointense stage (approximately 6-8 months of age), WM and GM exhibit similar levels of intensity in both T1 and T2 MR images, making the tissue segmentation very challenging. Only a small number of existing methods have been designed for tissue segmentation in this isointense stage; however, they only used a single T1 or T2 images, or the combination of T1 and T2 images. In this paper, we propose to use deep convolutional neural networks (CNNs) for segmenting isointense stage brain tissues using multi-modality MR images. CNNs are a type of deep models in which trainable filters and local neighborhood pooling operations are applied alternatingly on the raw input images, resulting in a hierarchy of increasingly complex features. Specifically, we used multi-modality information from T1, T2, and fractional anisotropy (FA) images as inputs and then generated the segmentation maps as outputs. The multiple intermediate layers applied convolution, pooling, normalization, and other operations to capture the highly nonlinear mappings between inputs and outputs. We compared the performance of our approach with that of the commonly used segmentation methods on a set of manually segmented isointense stage brain images. Results showed that our proposed model significantly outperformed prior methods on infant brain tissue segmentation. In addition, our results indicated that integration of multi-modality images led to significant performance improvement. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Comparison of neuropathology in Parkinson's disease subjects with and without deep brain stimulation.

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    Pal, Gian D; Ouyang, Bichun; Serrano, Geidy; Shill, Holly A; Goetz, Christopher; Stebbins, Glenn; Metman, Leo Verhagen; Driver-Dunckley, Erika; Mehta, Shyamal H; Caviness, John N; Sabbagh, Marwan N; Adler, Charles H; Beach, Thomas G

    2017-02-01

    The aim of this postmortem study was to compare, in Parkinson's disease subjects with and without bilateral subthalamic nucleus deep brain stimulation (STN-DBS), the loss of pigmented neurons within the substantia nigra and pathological alpha-synuclein density within the SN and other brain regions. PD subjects were identified from the Arizona Study of Aging and Neurodegenerative Disorders database (STN-DBS = 11, non-DBS = 156). Pigmented neuron loss scores within the substantia nigra as well as alpha-synuclein density scores within the substantia nigra and 9 other brain regions were compared, the latter individually and in summary as the Lewy body brain load score. DBS subjects had higher alpha-synuclein density scores within the substantia nigra, olfactory bulb, and locus ceruleus, as well as higher total Lewy body brain load scores when compared with non-DBS subjects. No differences in substantia nigra pigmented neuron loss scores were found. STN-DBS subjects tend to have higher alpha-synuclein density scores, but do not have a differential loss of substantia nigra pigmented neurons. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  15. A deep convolutional neural network-based automatic delineation strategy for multiple brain metastases stereotactic radiosurgery.

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    Yan Liu

    Full Text Available Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS treatment planning. In this work, we developed a deep learning convolutional neural network (CNN algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases.

  16. A deep convolutional neural network-based automatic delineation strategy for multiple brain metastases stereotactic radiosurgery.

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    Liu, Yan; Stojadinovic, Strahinja; Hrycushko, Brian; Wardak, Zabi; Lau, Steven; Lu, Weiguo; Yan, Yulong; Jiang, Steve B; Zhen, Xin; Timmerman, Robert; Nedzi, Lucien; Gu, Xuejun

    2017-01-01

    Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS) treatment planning. In this work, we developed a deep learning convolutional neural network (CNN) algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI) datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS) data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs) of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases.

  17. Decoding of Human Movements Based on Deep Brain Local Field Potentials Using Ensemble Neural Networks

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    Mohammad S. Islam

    2017-01-01

    Full Text Available Decoding neural activities related to voluntary and involuntary movements is fundamental to understanding human brain motor circuits and neuromotor disorders and can lead to the development of neuromotor prosthetic devices for neurorehabilitation. This study explores using recorded deep brain local field potentials (LFPs for robust movement decoding of Parkinson’s disease (PD and Dystonia patients. The LFP data from voluntary movement activities such as left and right hand index finger clicking were recorded from patients who underwent surgeries for implantation of deep brain stimulation electrodes. Movement-related LFP signal features were extracted by computing instantaneous power related to motor response in different neural frequency bands. An innovative neural network ensemble classifier has been proposed and developed for accurate prediction of finger movement and its forthcoming laterality. The ensemble classifier contains three base neural network classifiers, namely, feedforward, radial basis, and probabilistic neural networks. The majority voting rule is used to fuse the decisions of the three base classifiers to generate the final decision of the ensemble classifier. The overall decoding performance reaches a level of agreement (kappa value at about 0.729±0.16 for decoding movement from the resting state and about 0.671±0.14 for decoding left and right visually cued movements.

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

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    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.

  19. Deep brain stimulation of the subthalamic nucleus modulates sensitivity to decision outcome value in Parkinson’s disease

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    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.

  20. Validation of a Portable Low-Power Deep Brain Stimulation Device Through Anxiolytic Effects in a Laboratory Rat Model.

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    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.

  1. Modification of electrophysiological activity pattern after anterior thalamic deep brain stimulation for intractable epilepsy: report of 3 cases.

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    Kim, Hae Yu; Hur, Yun Jung; Kim, Heung-Dong; Park, Kang Min; Kim, Sung Eun; Hwang, Tae Gyu

    2017-06-01

    OBJECTIVE Thalamic stimulation can provoke electroencephalography (EEG) synchronization or desynchronization, which can help to reduce the occurrence of seizures in intractable epilepsy, though the underlying mechanism is not fully understood. Therefore, the authors investigated changes in EEG electrical activity to better understand the seizure-reducing effects of deep brain stimulation (DBS) in patients with intractable epilepsy. METHODS Electrical activation patterns in the epileptogenic brains of 3 patients were analyzed using classical low-resolution electromagnetic tomography analysis recursively applied (CLARA). Electrical activity recorded during thalamic stimulation was compared with that recorded during the preoperative and postoperative off-stimulation states in patients who underwent anterior thalamic nucleus DBS for intractable epilepsy. RESULTS Interictal EEG was fully synchronized to the β frequency in the postoperative on-stimulation period. The CLARA showed that electrical activity during preoperative and postoperative off-stimulation states was localized in cortical and subcortical areas, including the insular, middle frontal, mesial temporal, and precentral areas. No electrical activity was localized in deep nucleus structures. However, with CLARA, electrical activity in the postoperative on-stimulation period was localized in the anterior cingulate area, basal ganglia, and midbrain. CONCLUSIONS Anterior thalamic stimulation could spread electrical current to the underlying neuronal networks that connect with the thalamus, which functions as a cortical pacemaker. Consequently, the thalamus could modify electrical activity within these neuronal networks and influence cortical EEG activity by inducing neuronal synchronization between the thalamus and cortical structures.

  2. Effect of electrical vs. chemical deep brain stimulation at midbrain sites on micturition in anaesthetized rats.

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    Stone, E; Coote, J H; Lovick, T A

    2015-05-01

    To understand how deep brain stimulation of the midbrain influences control of the urinary bladder. In urethane-anaesthetized male rats, saline was infused continuously into the bladder to evoke cycles of filling and voiding. The effect of electrical (0.1-2.0 ms pulses, 5-180 Hz, 0.5-2.5 V) compared to chemical stimulation (microinjection of D,L-homocysteic acid, 50 nL 0.1 M solution) at the same midbrain sites was tested. Electrical stimulation of the periaqueductal grey matter and surrounding midbrain disrupted normal coordinated voiding activity in detrusor and sphincters muscles and suppressed urine output. The effect occurred within seconds was reversible and not secondary to cardiorespiratory changes. Bladder compliance remained unchanged. Chemical stimulation over the same area using microinjection of D,L-homocysteic acid (DLH) to preferentially activate somatodendritic receptors decreased the frequency of micturition but did not disrupt the coordinated pattern of voiding. In contrast, chemical stimulation within the caudal ventrolateral periaqueductal grey, in the area where critical synapses in the micturition reflex pathway are located, increased the frequency of micturition. Electrical deep brain stimulation within the midbrain can inhibit reflex micturition. We suggest that the applied stimulus entrained activity in the neural circuitry locally, thereby imposing an unphysiological pattern of activity. In a way similar to the use of electrical signals to 'jam' radio transmission, this may prevent a synchronized pattern of efferent activity being transmitted to the spinal outflows to orchestrate a coordinated voiding response. Further experiments to record neuronal firing in the midbrain during the deep brain stimulation will be necessary to test this hypothesis. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  3. 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.

  4. Subthalamic nucleus deep brain stimulation impacts language in early Parkinson's disease.

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    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.

  5. The relationship between clinical phenotype and early staged bilateral deep brain stimulation in Parkinson disease.

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    Sung, Victor W; Watts, Ray L; Schrandt, Christian J; Guthrie, Stephanie; Wang, Deli; Amara, Amy W; Guthrie, Barton L; Walker, Harrison C

    2013-12-01

    While many centers place bilateral deep brain stimulation (DBS) systems simultaneously, unilateral subthalamic nucleus (STN) DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However, little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite STN will be required. The authors aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second STN DBS electrode in patients who undergo unilateral STN DBS for Parkinson disease (PD). Eighty-two consecutive patients with advanced PD underwent unilateral STN DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression analysis determined preoperative characteristics that predicted staged placement of a second electrode in the opposite STN. Preoperative measurements included aspects of the Unified Parkinson's Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. At 2-year follow-up, 28 (34%) of the 82 patients had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and Part 3 scores were retained at the end of the 2-year follow-up period in both subsets of patients. Multivariate logistic regression analysis showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (OR 13.4, 95% CI 2.8-64.9), high tremor subscore (OR 7.2, CI 1.5-35.0), and low body weight (OR 5.5, 95% CI 1.4-22.3). This single-center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral STN DBS. These data may aid in the management of patients with advanced PD who undergo STN DBS.

  6. Deep brain stimulation of the subcallosal cingulate gyrus: further evidence in treatment-resistant major depression.

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    Puigdemont, Dolors; Pérez-Egea, Rosario; Portella, Maria J; Molet, Joan; de Diego-Adeliño, Javier; Gironell, Alexandre; Radua, Joaquim; Gómez-Anson, Beatriz; Rodríguez, Rodrigo; Serra, Maria; de Quintana, Cristian; Artigas, Francesc; Álvarez, Enric; Pérez, Víctor

    2012-02-01

    Deep brain stimulation (DBS) is currently tested as an experimental therapy for patients with treatment-resistant depression (TRD). Here we report on the short- and long-term (1 yr) clinical outcomes and tolerance of DBS in eight TRD patients. Electrodes were implanted bilaterally in the subgenual cingulate gyrus (SCG; Broadman areas 24-25), and stimulated at 135 Hz (90-μs pulsewidth). Voltage and active electrode contacts were adjusted to maximize short-term responses. Clinical assessments included the 17-item Hamilton Depression Rating Scale (HAMD17; primary measure), the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI) Scale. In the first week after surgery, response and remission (HAMD ⩽7) rates were, respectively 87.5% and 50%. These early responses were followed by an overall worsening, with a response and remission rates of 37.5% (3/8) at 1 month. From then onwards, patients showed a progressive improvement, with response and remission rates of 87.5% and 37.5%, respectively, at 6 months. The corresponding figures at 1 yr were 62.5% and 50%, respectively. Clinical effects were seen in all HAMD subscales without a significant incidence of side-effects. Surgical procedure and post-operative period were well-tolerated for all patients. This is the second independent study on the use of DBS of the SCG to treat chronic depression resistant to current therapeutic strategies. DBS fully remitted 50% of the patients at 1 yr, supporting its validity as a new therapeutic strategy for TRD.

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

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    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.

  8. Short-Term Adverse Outcomes After Deep Brain Stimulation Treatment in Patients with Parkinson Disease.

    Science.gov (United States)

    Hu, Kejia; Moses, Ziev B; Hutter, Matthew M; Williams, Ziv

    2017-02-01

    Despite ongoing progress in our understanding of long-term outcomes after neuromodulation procedures, acute adverse outcomes shortly after deep brain stimulation (DBS) treatment have remained remarkably limited. To identify risk factors associated with acute 30-day outcomes after DBS treatment in patients with Parkinson disease (PD). We evaluated patients who underwent DBS treatment for PD from 2005 to 2014 through the American College of Surgeons National Surgical Quality Improvement Program database. We used bivariate analysis and multivariate logistic regression to identify short-term postoperative outcomes, including 30-day complication, discharge destination, and unplanned readmission. Overall, 650 patients with PD underwent DBS procedures and complications were identified in 32 patients (4.9%). Of 481 patients who had complete discharge data, 18 patients (3.7%) were discharged to a facility and 16 patients (3.3%) experienced an unplanned readmission. Patients with PD who were obese (P = 0.045), who had preoperative anemia (P = 0.008), and who experienced longer operative durations (P = 0.01) had increased odds of postoperative complications. Inpatient status (P = 0.001), dependent functional status (P anemia (P = 0.043) were all associated with discharge to a facility other than home. Longer operative duration (P = 0.013), anemia (P = 0.036), and dependent functional status (P = 0.03) were significantly associated with unplanned readmission. As expected, complications increased the likelihood of unplanned readmission (P < 0.001). This study provides individualized estimates of the risks associated with short-term adverse outcomes based on patient demographics and comorbidities. These data can be used as an adjunct for short-term risk stratification of patients with PD being considered for DBS treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. 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.

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

    Science.gov (United States)

    Vedam-Mai, Vinata; Baradaran-Shoraka, Massoud; Reynolds, Brent A; Okun, Michael S

    2016-07-01

    Deep brain stimulation (DBS) is used for a variety of movement disorders, including Parkinson's disease. There are several theories regarding the biology and mechanisms of action of DBS. Previously, we observed an up-regulation of neural progenitor cell proliferation in post-mortem tissue suggesting that DBS can influence cellular plasticity in regions beyond the site of stimulation. We wanted to support these observations and investigate the relationship if any, between DBS, neural progenitor cells, and microglia. We used naïve rats in this study for DBS electrode implantation, stimulation, and microlesions. We used immunohistochemistry techniques for labeling microglial and progenitor cells, and fluorescence microscopy for viewing and quantification of labeled cells. We present data that demonstrates a reciprocal relationship of microglia and neural precursor cells in the presence of acute high frequency stimulation. In our hands, stimulated animals demonstrate significantly lower numbers of activated microglia (p = 0.026) when compared to microlesion and sham animals. The subthalamic region surrounding the DBS stimulating electrode reveals a significant increase in the number of neural precursor cells expressing cell cycle markers, plasticity and precursor cell markers (Ki67; p = 0.0013, MCM2; p = 0.0002). We conclude that in this animal model, acute DBS results in modest local progenitor cell proliferation and influenced the total number of activated microglia. This could be of clinical significance in patients with PD, as it is thought to progress via neuroinflammatory processes involving microglia, cytokines, and the complement system. Further studies are required to comprehend the behavior of microglia in different activation states and their ability to regulate adult neurogenesis under physiologic and pathologic conditions. © 2016 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of

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

    Science.gov (United States)

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

    2016-02-01

    Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms, such as tremor, rigidity, and bradykinesia, but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. This study proposes an animal model of DBS-exacerbated dysarthria. We use the unilateral, 6-hydroxydopamine (6-OHDA) rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually experienced male rats under healthy and parkinsonian conditions and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. The individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism-associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism-associated changes in each of these metrics, the subthalamic stimulated 6-OHDA rat is a good model of DBS-induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life. © 2015 Wiley Periodicals, Inc.

  13. 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...

  14. 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

    The clinical picture in Parkinson's disease (PD) is characterized by bradykinesia, rigidity, resting tremor and postural instability. In advanced stages of the disease, many patients will experience reduced efficacy of medication with fluctuations in symptoms and dyskinesias. Surgical treatment...... 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...

  15. Patient Perspectives on Deep Brain Stimulation Clinical Research in Early Stage Parkinson's Disease.

    Science.gov (United States)

    Heusinkveld, Lauren; Hacker, Mallory; Turchan, Maxim; Bollig, Madelyn; Tamargo, Christina; Fisher, William; McLaughlin, Lauren; Martig, Adria; Charles, David

    2017-01-01

    The FDA has approved a multicenter, double-blind, Phase III, pivotal trial testing deep brain stimulation (DBS) in 280 people with very early stage Parkinson's disease (PD; IDE#G050016). In partnership with The Michael J. Fox Foundation for Parkinson's Research, we conducted a survey to investigate motivating factors, barriers, and gender differences among potentially eligible patients for participation in a trial testing DBS in early PD compared to standard medical treatment. The majority of survey respondents (72%) indicated they would consider learning more about participating. Early PD patients are therefore likely to consider enrolling in trials of invasive therapies that may slow symptom progression and help future patients.

  16. Controlling mechanism of absence seizures by deep brain stimulus applied on subthalamic nucleus.

    Science.gov (United States)

    Hu, Bing; Guo, Yu; Zou, Xiaoqiang; Dong, Jing; Pan, Long; Yu, Min; Yang, Zhejia; Zhou, Chaowei; Cheng, Zhang; Tang, Wanyue; Sun, Haochen

    2018-02-01

    Based on a classical model of the basal ganglia thalamocortical network, in this paper, we employed a type of the deep brain stimulus voltage on the subthalamic nucleus to study the control mechanism of absence epilepsy seizures. We found that the seizure can be well controlled by turning the period and the duration of current stimulation into suitable ranges. It is the very interesting bidirectional periodic adjustment phenomenon. These parameters are easily regulated in clinical practice, therefore, the results obtained in this paper may further help us to understand the treatment mechanism of the epilepsy seizure.

  17. 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 the STN and GPi of 12 patients with focal, multifocal, or generalized dystonia. Each patient was randomly selected to undergo initial bilateral stimulation of either the STN or the GPi for 6 months, followed by bilateral stimulation of the other nucleus for another 6 months. Preoperative and postoperative...

  18. 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.

  19. Combined thalamic and subthalamic deep brain stimulation for tremor-dominant Parkinson's disease.

    Science.gov (United States)

    Oertel, Markus F; Schüpbach, W Michael M; Ghika, Joseph-André; Stieglitz, Lennart H; Fiechter, Michael; Kaelin-Lang, Alain; Raabe, Andreas; Pollo, Claudio

    2017-02-01

    Deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) or the subthalamic nucleus (STN) reportedly improves medication-refractory Parkinson's disease (PD) tremor. However, little is known about the potential synergic effects of combined Vim and STN DBS. We describe a 79-year-old man with medication-refractory tremor-dominant PD. Bilateral Vim DBS electrode implantation produced insufficient improvement. Therefore, the patient underwent additional unilateral left-sided STN DBS. Whereas Vim or STN stimulation alone led to partial improvement, persisting tremor resolution occurred after simultaneous stimulation. The combination of both targets may have a synergic effect and is an alternative option in suitable cases.

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

    Science.gov (United States)

    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

  1. 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.

  2. 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.

  3. Four cases of small, traumatic hemorrhage in the deep midline portion of the brain

    International Nuclear Information System (INIS)

    Kim, Suho; Tsukahara, Tetsuya; Iwama, Mitsuru; Nishikawa, Michio

    1981-01-01

    Four cases recently encountered are presented in which computerized tomography (CT) demonstrated a small, traumatic hemorrhage in the deep midline portion of the brain. The lesions of hemorrhage revealed by CT were: Case 1, in the septum pellucidum and left lateral ventricle; Case 2, in the Monro's foramen and right lateral ventricle and Case 3, midbrain. These three cases had no other abnormal findings. In addition, a hemorrhage of the corpus callosum and diffuse brain damage were seen in Case 4. These small hemorrhages might be caused not only by the direct damage, but also by a local tendency to bleed due to hystoiogical fragility or the existence of a vascular anomaly, such as AVM or cryptic angioma. The prognoses quod vitam of our cases were relatively better than the previous reports of these hemorrhages, but the prognoses quod functionem were poor. The patients have shown prolonged psychoneurological disorder; these symptoms might be caused by damage to the limbic system. (author)

  4. Research progress of deep brain stimulation for the treatment of drug addiction

    Directory of Open Access Journals (Sweden)

    Lei CHEN

    2015-10-01

    Full Text Available Drug addiction is a serious problem all over the world involving both medical and social issues. The treatment strategy lies in two aspects, promoting detoxification and preventing relapse. The latter is the key for successful treatment. Although surgical measures, like stereotactic ablation of nucleusaccumbens (NAc, had already been proven to be effective for relapse prevention clinically, the application was restricted because of the damage to brain tissues. Deep brain stimulation (DBS, which had been successfully applied in movement disorders, was recently performed in addiction studies on both animals and humankind. Among numbers of brain areas related to addiction, NAc is the hottest target studied and may bring better clinical effect. In addition, combining stimulation of multiple brain targets is currently performed for relapse prevention. The mechanism of DBS for treatment of addiction remains unclear right now, however, DBS may be an experimental method to treat refractory addictive patients. Certainly, lots of problems need to be solved in large sample study before the wide application of DBS for addiction treatment, such as the setting of stimulation parameters, recognition of objective treatment feedback and ethical issues. DOI: 10.3969/j.issn.1672-6731.2015.10.004

  5. 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.

  6. Long-term outcome of deep brain stimulation in fragile X-associated tremor/ataxia syndrome.

    Science.gov (United States)

    Weiss, Daniel; Mielke, Carina; Wächter, Tobias; Bender, Benjamin; Liscic, Rajka M; Scholten, Marlieke; Naros, Georgios; Plewnia, Christian; Gharabaghi, Alireza; Krüger, Rejko

    2015-03-01

    Fragile X-associated tremor/ataxia syndrome (FXTAS) presents as complex movement disorder including tremor and cerebellar ataxia. The efficacy and safety of deep brain stimulation of the nucleus ventralis intermedius of the thalamus in atypical tremor syndromes like FXTAS remains to be determined. Here, we report the long-term outcome of three male genetically confirmed FXTAS patients treated with bilateral neurostimulation of the nucleus ventralis intermedius for up to four years. All patients demonstrated sustained improvement of both tremor and ataxia - the latter included improvement of intention tremor and axial tremor. Kinematic gait analyses further demonstrated a regularization of the gait cycle. Initial improvements of hand functional disability were not sustained and reached the preoperative level of impairment within one to two years from surgery. Our data on patients with a genetic cause of tremor show favorable outcome and may contribute to improved patient stratification for neurostimulation therapy in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Traumatic Brain Injury and Delayed Sequelae: A Review - Traumatic Brain Injury and Mild Traumatic Brain Injury (Concussion are Precursors to Later-Onset Brain Disorders, Including Early-Onset Dementia

    Directory of Open Access Journals (Sweden)

    Michael A. Kiraly

    2007-01-01

    Full Text Available Brain injuries are too common. Most people are unaware of the incidence of and horrendous consequences of traumatic brain injury (TBI and mild traumatic brain injury (MTBI. Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Seminal evidence from animal and human experiments demonstrate links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzheimer's disease (AD and Parkinson's disease (PD. Objectives of this summary are, therefore, to instill appreciation regarding the importance of brain injury prevention, diagnosis, and treatment, and to increase awareness regarding the long-term delayed consequences following TBI.

  8. [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.

  9. 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.

  10. Electric field distribution in a finite-volume head model of deep brain stimulation.

    Science.gov (United States)

    Grant, Peadar F; Lowery, Madeleine M

    2009-11-01

    This study presents a whole-head finite element model of deep brain stimulation to examine the effect of electrical grounding, the finite conducting volume of the head, and scalp, skull and cerebrospinal fluid layers. The impedance between the stimulating and reference electrodes in the whole-head model was found to lie within clinically reported values when the reference electrode was incorporated on a localized surface in the model. Incorporation of the finite volume of the head and inclusion of surrounding outer tissue layers reduced the magnitude of the electric field and activating function by approximately 20% in the region surrounding the electrode. Localized distortions of the electric field were also observed when the electrode was placed close to the skull. Under bipolar conditions the effect of the finite conducting volume was shown to be negligible. The results indicate that, for monopolar stimulation, incorporation of the finite volume and outer tissue layers can alter the magnitude of the electric field and activating function when the electrode is deep within the brain, and may further affect the shape if the electrode is close to the skull.

  11. Deep learning enables reduced gadolinium dose for contrast-enhanced brain MRI.

    Science.gov (United States)

    Gong, Enhao; Pauly, John M; Wintermark, Max; Zaharchuk, Greg

    2018-02-13

    There are concerns over gadolinium deposition from gadolinium-based contrast agents (GBCA) administration. To reduce gadolinium dose in contrast-enhanced brain MRI using a deep learning method. Retrospective, crossover. Sixty patients receiving clinically indicated contrast-enhanced brain MRI. 3D T 1 -weighted inversion-recovery prepped fast-spoiled-gradient-echo (IR-FSPGR) imaging was acquired at both 1.5T and 3T. In 60 brain MRI exams, the IR-FSPGR sequence was obtained under three conditions: precontrast, postcontrast images with 10% low-dose (0.01mmol/kg) and 100% full-dose (0.1 mmol/kg) of gadobenate dimeglumine. We trained a deep learning model using the first 10 cases (with mixed indications) to approximate full-dose images from the precontrast and low-dose images. Synthesized full-dose images were created using the trained model in two test sets: 20 patients with mixed indications and 30 patients with glioma. For both test sets, low-dose, true full-dose, and the synthesized full-dose postcontrast image sets were compared quantitatively using peak-signal-to-noise-ratios (PSNR) and structural-similarity-index (SSIM). For the test set comprised of 20 patients with mixed indications, two neuroradiologists scored blindly and independently for the three postcontrast image sets, evaluating image quality, motion-artifact suppression, and contrast enhancement compared with precontrast images. Results were assessed using paired t-tests and noninferiority tests. The proposed deep learning method yielded significant (n = 50, P 5 dB PSNR gains and >11.0% SSIM). Ratings on image quality (n = 20, P = 0.003) and contrast enhancement (n = 20, P < 0.001) were significantly increased. Compared to true full-dose images, the synthesized full-dose images have a slight but not significant reduction in image quality (n = 20, P = 0.083) and contrast enhancement (n = 20, P = 0.068). Slightly better (n = 20, P = 0.039) motion

  12. Immediate cerebral metabolic changes induced by discontinuation of deep brain stimulation of subcallosal cingulate gyrus in treatment-resistant depression.

    Science.gov (United States)

    Martín-Blanco, Ana; Serra-Blasco, Maria; Pérez-Egea, Rosario; de Diego-Adeliño, Javier; Carceller-Sindreu, Mar; Puigdemont, Dolors; Molet, Joan; Álvarez, Enric; Pérez, Víctor; Portella, Maria J

    2015-03-01

    Positron emission tomography (PET) studies have shown that the antidepressant effect of chronic deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) may be consequence of modifications of brain metabolism at key structures involved in depression. Like clinical benefits, these metabolic changes may reverse when the stimulation is discontinued, even preceding clinical worsening. However no data on immediate effects of DBS discontinuation are available. The aim of this study was to determine immediate cerebral metabolism changes during a short switch-off of electrical stimulation in implanted patients with treatment-resistant depression (TRD) who had achieved clinical improvement after a period of chronic DBS. Seven patients with TRD who had been previously implanted for DBS in SCG were included. After a period of clinical stabilization two consecutive FDG-PET were acquired, the first with active stimulation and the second after 48 h of inactive stimulation. A HAMD-17 to assess depressive symptoms was performed before both scans. Analyses were performed with SnPM8. Inactive stimulation was characterized by metabolism decreases in dorsal anterior cingulate (Broadmann Area, BA24), premotor region (BA6) and putamen with respect to active stimulation. No clinical changes according to HAMD-17 were detected. The main limitation of this study is the small sample size. Our results point to immediate effects of DBS discontinuation on metabolism of brain depressive network which precede clinical changes, helping to disentangle the rationale behind DBS efficacy in TRD. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Subthalamic nucleus deep brain stimulation for Parkinson's disease: evidence for effectiveness and limitations from 12 years' experience.

    Science.gov (United States)

    Chan, Anne Y Y; Yeung, Jonas H M; Mok, Vincent C T; Ip, Vincent H L; Wong, Adrian; Kuo, S H; Chan, Danny T M; Zhu, X L; Wong, Edith; Lau, Claire K Y; Wong, Rosanna K M; Tang, Venus; Lau, Christine; Poon, W S

    2014-12-01

    To present the result and experience of subthalamic nucleus deep brain stimulation for Parkinson's disease. Case series. Prince of Wales Hospital, Hong Kong. A cohort of patients with Parkinson's disease received subthalamic nucleus deep brain stimulation from September 1998 to January 2010. Patient assessment data before and after the operation were collected prospectively. Forty-one patients (21 male and 20 female) with Parkinson's disease underwent bilateral subthalamic nucleus deep brain stimulation and were followed up for a median interval of 12 months. For the whole group, the mean improvements of Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III were 32.5% and 31.5%, respectively (Pdeep brain stimulation protocol evolved and was substantiated by updated patient selection criteria and outcome assessment, integrated imaging and neurophysiological targeting, refinement of surgical technique as well as the accumulation of experience in deep brain stimulation programming. Most of the structural improvement occurred before mid-2005. Patients receiving the operation before June 2005 (19 cases) and after (22 cases) were compared; the improvements in UPDRS part III were 13.2% and 55.2%, respectively (Pdeep brain stimulation. A dedicated multidisciplinary team building, refined protocol for patient selection and assessment, improvement of targeting methods, meticulous surgical technique, and experience in programming are the key factors contributing to the improved outcome.

  14. Directional deep brain stimulation: an intraoperative double-blind pilot study.

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    Pollo, Claudio; Kaelin-Lang, Alain; Oertel, Markus F; Stieglitz, Lennart; Taub, Ethan; Fuhr, Peter; Lozano, Andres M; Raabe, Andreas; Schüpbach, Michael

    2014-07-01

    Deep brain stimulation of different targets has been shown to drastically improve symptoms of a variety of neurological conditions. However, the occurrence of disabling side effects may limit the ability to deliver adequate amounts of current necessary to reach the maximal benefit. Computed models have suggested that reduction in electrode size and the ability to provide directional stimulation could increase the efficacy of such therapies. This has never been demonstrated in humans. In the present study, we assess the effect of directional stimulation compared to omnidirectional stimulation. Three different directions of stimulation as well as omnidirectional stimulation were tested intraoperatively in the subthalamic nucleus of 11 patients with Parkinson's disease and in the nucleus ventralis intermedius of two other subjects with essential tremor. At the trajectory chosen for implantation of the definitive electrode, we assessed the current threshold window between positive and side effects, defined as the therapeutic window. A computed finite element model was used to compare the volume of tissue activated when one directional electrode was stimulated, or in case of omnidirectional stimulation. All but one patient showed a benefit of directional stimulation compared to omnidirectional. A best direction of stimulation was observed in all the patients. The therapeutic window in the best direction was wider than the second best direction (P = 0.003) and wider than the third best direction (P = 0.002). Compared to omnidirectional direction, the therapeutic window in the best direction was 41.3% wider (P = 0.037). The current threshold producing meaningful therapeutic effect in the best direction was 0.67 mA (0.3-1.0 mA) and was 43% lower than in omnidirectional stimulation (P = 0.002). No complication as a result of insertion of the directional electrode or during testing was encountered. The computed model revealed a volume of tissue activated of 10.5 mm(3) in

  15. Optimum design and sequential treatment allocation in an experiment in deep brain stimulation with sets of treatment combinations.

    Science.gov (United States)

    Atkinson, Anthony; Pedrosa, David

    2017-12-30

    In an experiment including patients who underwent surgery for deep brain stimulation electrode placement, each patient responds to a set of 9 treatment combinations. There are 16 such sets, and the design problem is to choose which sets should be administered and in what proportions. Extensions to the methods of nonsequential optimum experimental design lead to identification of an unequally weighted optimum design involving 4 sets of treatment combinations. In the actual experiment, patients arrive sequentially and present with sets of prognostic factors. The idea of loss due to Burman is extended and used to assess designs with varying randomization structures. It is found that a simple sequential design using only 2 sets of treatments has surprisingly good properties for trials with the proposed number of patients. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Deep Brain Stimulation Target Selection in an Advanced Parkinson's Disease Patient with Significant Tremor and Comorbid Depression

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    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.

  17. Deep Brain Stimulation in Parkinson’s Disease: New and Emerging Targets for Refractory Motor and Nonmotor Symptoms

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    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.

  18. Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation.

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    Oleksandr V Popovych

    Full Text Available High-frequency (HF deep brain stimulation (DBS is the gold standard for the treatment of medically refractory movement disorders like Parkinson's disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup. We here combine the notion of the adaptive high-frequency stimulation approach, that aims at delivering stimulation adapted to the extent of appropriately detected biomarkers, with specifically desynchronizing stimulation protocols. To this end, we extend the delayed feedback stimulation methods, which are intrinsically closed-loop techniques and specifically designed to desynchronize abnormal neuronal synchronization, to pulsatile electrical brain stimulation. We show that permanent pulsatile high-frequency stimulation subjected to an amplitude modulation by linear or nonlinear delayed feedback methods can effectively and robustly desynchronize a STN-GPe network of model neurons and suggest this approach for desynchronizing closed-loop DBS.

  19. Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation.

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    Popovych, Oleksandr V; Lysyansky, Borys; Rosenblum, Michael; Pikovsky, Arkady; Tass, Peter A

    2017-01-01

    High-frequency (HF) deep brain stimulation (DBS) is the gold standard for the treatment of medically refractory movement disorders like Parkinson's disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup. We here combine the notion of the adaptive high-frequency stimulation approach, that aims at delivering stimulation adapted to the extent of appropriately detected biomarkers, with specifically desynchronizing stimulation protocols. To this end, we extend the delayed feedback stimulation methods, which are intrinsically closed-loop techniques and specifically designed to desynchronize abnormal neuronal synchronization, to pulsatile electrical brain stimulation. We show that permanent pulsatile high-frequency stimulation subjected to an amplitude modulation by linear or nonlinear delayed feedback methods can effectively and robustly desynchronize a STN-GPe network of model neurons and suggest this approach for desynchronizing closed-loop DBS.

  20. Landmark-based deep multi-instance learning for brain disease diagnosis.

    Science.gov (United States)

    Liu, Mingxia; Zhang, Jun; Adeli, Ehsan; Shen, Dinggang

    2018-01-01

    In conventional Magnetic Resonance (MR) image based methods, two stages are often involved to capture brain structural information for disease diagnosis, i.e., 1) manually partitioning each MR image into a number of regions-of-interest (ROIs), and 2) extracting pre-defined features from each ROI for diagnosis with a certain classifier. However, these pre-defined features often limit the performance of the diagnosis, due to challenges in 1) defining the ROIs and 2) extracting effective disease-related features. In this paper, we propose a landmark-based deep multi-instance learning (LDMIL) framework for brain disease diagnosis. Specifically, we first adopt a data-driven learning approach to discover disease-related anatomical landmarks in the brain MR images, along with their nearby image patches. Then, our LDMIL framework learns an end-to-end MR image classifier for capturing both the local structural information conveyed by image patches located by landmarks and the global structural information derived from all detected landmarks. We have evaluated our proposed framework on 1526 subjects from three public datasets (i.e., ADNI-1, ADNI-2, and MIRIAD), and the experimental results show that our framework can achieve superior performance over state-of-the-art approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Multimodal Imaging in a Patient with Hemidystonia Responsive to GPi Deep Brain Stimulation

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    Christos Sidiropoulos

    2017-01-01

    Full Text Available Background. Dystonia is a syndrome with varied phenomenology but our understanding of its mechanisms is deficient. With neuroimaging techniques, such as fiber tractography (FT and magnetoencephalography (MEG, pathway connectivity can be studied to that end. We present a hemidystonia patient treated with deep brain stimulation (DBS. Methods. After 10 years of left axial hemidystonia, a 45-year-old male underwent unilateral right globus pallidus internus (GPi DBS. Whole brain MEG before and after anticholinergic medication was performed prior to surgery. 26-direction diffusion tensor imaging (DTI was obtained in a 3 T MRI machine along with FT. The patient was assessed before and one year after surgery by using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS. Results. In the eyes-closed MEG study there was an increase in brain coherence in the gamma band after medication in the middle and inferior frontal region. FT demonstrated over 50% more intense ipsilateral connectivity in the right hemisphere compared to the left. After DBS, BFMDRS motor and disability scores both dropped by 71%. Conclusion. Multimodal neuroimaging techniques can offer insights into the pathophysiology of dystonia and can direct choices for developing therapeutics. Unilateral pallidal DBS can provide significant symptom control in axial hemidystonia poorly responsive to medication.

  2. Rejecting deep brain stimulation artefacts from MEG data using ICA and mutual information.

    Science.gov (United States)

    Abbasi, Omid; Hirschmann, Jan; Schmitz, Georg; Schnitzler, Alfons; Butz, Markus

    2016-08-01

    Recording brain activity during deep brain stimulation (DBS) using magnetoencephalography (MEG) can potentially help clarifying the neurophysiological mechanism of DBS. The DBS artefact, however, distorts MEG data significantly. We present an artefact rejection approach to remove the DBS artefact from MEG data. We developed an approach consisting of four consecutive steps: (i) independent component analysis was used to decompose MEG data to independent components (ICs); (ii) mutual information (MI) between stimulation signal and all ICs was calculated; (iii) artefactual ICs were identified by means of an MI threshold; and (iv) the MEG signal was reconstructed using only non-artefactual ICs. This approach was applied to MEG data from five Parkinson's disease patients with implanted DBS stimulators. MEG was recorded with DBS ON (unilateral stimulation of the subthalamic nucleus) and DBS OFF during two experimental conditions: a visual attention task and alternating right and left median nerve stimulation. With the presented approach most of the artefact could be removed. The signal of interest could be retrieved in both conditions. In contrast to existing artefact rejection methods for MEG-DBS data (tSSS and S(3)P), the proposed method uses the actual artefact source, i.e. the stimulation signal, as reference signal. Using the presented method, the DBS artefact can be significantly rejected and the physiological data can be restored. This will facilitate research addressing the impact of DBS on brain activity during rest and various tasks. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. The rationale driving the evolution of deep brain stimulation to constant-current devices.

    Science.gov (United States)

    Bronstein, Jeff M; Tagliati, Michele; McIntyre, Cameron; Chen, Robert; Cheung, Tyler; Hargreaves, Eric L; Israel, Zvi; Moffitt, Michael; Montgomery, Erwin B; Stypulkowski, Paul; Shils, Jay; Denison, Timothy; Vitek, Jerrold; Volkman, Jens; Wertheimer, Jeffrey; Okun, Michael S

    2015-02-01

    Deep brain stimulation (DBS) is an effective therapy for the treatment of a number of movement and neuropsychiatric disorders. The effectiveness of DBS is dependent on the density and location of stimulation in a given brain area. Adjustments are made to optimize clinical benefits and minimize side effects. Until recently, clinicians would adjust DBS settings using a voltage mode, where the delivered voltage remained constant. More recently, a constant-current mode has become available where the programmer sets the current and the stimulator automatically adjusts the voltage as impedance changes. We held an expert consensus meeting to evaluate the current state of the literature and field on constant-current mode versus voltage mode in clinical brain-related applications. There has been little reporting of the use of constant-current DBS devices in movement and neuropsychiatric disorders. However, as impedance varies considerably between patients and over time, it makes sense that all new devices will likely use constant current. © 2014 International Neuromodulation Society.

  4. Role of Soft-Tissue Heterogeneity in Computational Models of Deep Brain Stimulation.

    Science.gov (United States)

    Howell, Bryan; McIntyre, Cameron C

    Bioelectric field models of deep brain stimulation (DBS) are commonly utilized in research and industrial applications. However, the wide range of different representations used for the human head in these models may be responsible for substantial variance in the stimulation predictions. Determine the relative error of ignoring cerebral vasculature and soft-tissue heterogeneity outside of the brain in computational models of DBS. We used a detailed atlas of the human head, coupled to magnetic resonance imaging data, to construct a range of subthalamic DBS volume conductor models. We incrementally simplified the most detailed base model and quantified changes in the stimulation thresholds for direct activation of corticofugal axons. Ignoring cerebral vasculature altered predictions of stimulation thresholds by brain altered predictions between -44 % and 174%. Heterogeneity in the soft tissues of the head, if unaccounted for, introduces a degree of uncertainty in predicting electrical stimulation of neural elements that is not negligible and thereby warrants consideration in future modeling studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Pulsatile desynchronizing delayed feedback for closed-loop deep brain stimulation

    Science.gov (United States)

    Lysyansky, Borys; Rosenblum, Michael; Pikovsky, Arkady; Tass, Peter A.

    2017-01-01

    High-frequency (HF) deep brain stimulation (DBS) is the gold standard for the treatment of medically refractory movement disorders like Parkinson’s disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup. We here combine the notion of the adaptive high-frequency stimulation approach, that aims at delivering stimulation adapted to the extent of appropriately detected biomarkers, with specifically desynchronizing stimulation protocols. To this end, we extend the delayed feedback stimulation methods, which are intrinsically closed-loop techniques and specifically designed to desynchronize abnormal neuronal synchronization, to pulsatile electrical brain stimulation. We show that permanent pulsatile high-frequency stimulation subjected to an amplitude modulation by linear or nonlinear delayed feedback methods can effectively and robustly desynchronize a STN-GPe network of model neurons and suggest this approach for desynchronizing closed-loop DBS. PMID:28273176

  6. Deep Brain Stimulation—Possible Treatment Strategy for Pathologically Altered Body Weight?

    Directory of Open Access Journals (Sweden)

    Philip Prinz

    2018-01-01

    Full Text Available The treatment of obesity and eating disorders such as binge-eating disorder or anorexia nervosa is challenging. Besides lifestyle changes and pharmacological options, bariatric surgery represents a well-established and effective-albeit invasive-treatment of obesity, whereas for binge-eating disorder and anorexia nervosa mostly psychotherapy options exist. Deep brain stimulation (DBS, a method that influences the neuronal network, is by now known for its safe and effective applicability in patients with Parkinson’s disease. However, the use does not seem to be restricted to these patients. Recent preclinical and first clinical evidence points towards the use of DBS in patients with obesity and eating disorders as well. Depending on the targeted area in the brain, DBS can either inhibit food intake and body weight or stimulate energy intake and subsequently body weight. The current review focuses on preclinical and clinical evidence of DBS to modulate food intake and body weight and highlight the different brain areas targeted, stimulation protocols applied and downstream signaling modulated. Lastly, this review will also critically discuss potential safety issues and gaps in knowledge to promote further studies.

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

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    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.

  8. Deep Neural Networks: A New Framework for Modeling Biological Vision and Brain Information Processing.

    Science.gov (United States)

    Kriegeskorte, Nikolaus

    2015-11-24

    Recent advances in neural network modeling have enabled major strides in computer vision and other artificial intelligence applications. Human-level visual recognition abilities are coming within reach of artificial systems. Artificial neural networks are inspired by the brain, and their computations could be implemented in biological neurons. Convolutional feedforward networks, which now dominate computer vision, take further inspiration from the architecture of the primate visual hierarchy. However, the current models are designed with engineering goals, not to model brain computations. Nevertheless, initial studies comparing internal representations between these models and primate brains find surprisingly similar representational spaces. With human-level performance no longer out of reach, we are entering an exciting new era, in which we will be able to build biologically faithful feedforward and recurrent computational models of how biological brains perform high-level feats of intelligence, including vision.

  9. Ablative surgery for Parkinson's disease: Is there still a role for pallidotomy in the deep brain stimulation era?

    Science.gov (United States)

    Spindola, Bruno; Leite, Marco Antônio; Orsini, Marco; Fonoff, Erich; Landeiro, José Alberto; Pessoa, Bruno Lima

    2017-07-01

    Posteroventral pallidotomy has already been considered the surgical procedure of choice for Parkinson's disease patients with motor complications. Recently, however, several factors led to its replacement by deep brain stimulation. Nevertheless, pallidotomy has a well-documented efficacy and safety evidence regarding the reduction of parkinsonian motor symptoms. Yet, there may be manysituations where it may be considered as a better option than neuromodulation. Herein we review those possible conditions, giving emphasis to the costs, which we found to be the most limiting factor. Importantly, a cost comparison between deep brain stimulation and pallidotomy was also provided. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Acute symptomatic peri-lead edema 33 hours after deep brain stimulation surgery: a case report.

    Science.gov (United States)

    Schoen, Nathan B; Jermakowicz, Walter J; Luca, Corneliu C; Jagid, Jonathan R

    2017-04-14

    Symptomatic peri-lead edema is a rare complication of deep brain stimulation that has been reported to develop 4 to 120 days postoperatively. Here we report the case of a 63-year-old Hispanic man with an 8-year history of Parkinson's disease who underwent bilateral placement of subthalamic nucleus deep brain stimulation leads and presented with acute, symptomatic, unilateral, peri-lead edema just 33 hours after surgery. We document a thorough radiographic time course showing the evolution of these peri-lead changes and their regression with steroid therapy, and discuss the therapeutic implications of these findings. We propose that the unilateral peri-lead edema after bilateral deep brain stimulation is the result of severe microtrauma with blood-brain barrier disruption. Knowledge of such early manifestation of peri-lead edema after deep brain stimulation is critical for ruling out stroke and infection and preventing unnecessary diagnostic testing or hardware removal in this rare patient population.

  11. Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

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    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

  12. Management of deep brain stimulator battery failure: battery estimators, charge density, and importance of clinical symptoms.

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    Kaihan Fakhar

    Full Text Available OBJECTIVE: We aimed in this investigation to study deep brain stimulation (DBS battery drain with special attention directed toward patient symptoms prior to and following battery replacement. BACKGROUND: Previously our group developed web-based calculators and smart phone applications to estimate DBS battery life (http://mdc.mbi.ufl.edu/surgery/dbs-battery-estimator. METHODS: A cohort of 320 patients undergoing DBS battery replacement from 2002-2012 were included in an IRB approved study. Statistical analysis was performed using SPSS 20.0 (IBM, Armonk, NY. RESULTS: The mean charge density for treatment of Parkinson's disease was 7.2 µC/cm(2/phase (SD = 3.82, for dystonia was 17.5 µC/cm(2/phase (SD = 8.53, for essential tremor was 8.3 µC/cm(2/phase (SD = 4.85, and for OCD was 18.0 µC/cm(2/phase (SD = 4.35. There was a significant relationship between charge density and battery life (r = -.59, p<.001, as well as total power and battery life (r = -.64, p<.001. The UF estimator (r = .67, p<.001 and the Medtronic helpline (r = .74, p<.001 predictions of battery life were significantly positively associated with actual battery life. Battery status indicators on Soletra and Kinetra were poor predictors of battery life. In 38 cases, the symptoms improved following a battery change, suggesting that the neurostimulator was likely responsible for symptom worsening. For these cases, both the UF estimator and the Medtronic helpline were significantly correlated with battery life (r = .65 and r = .70, respectively, both p<.001. CONCLUSIONS: Battery estimations, charge density, total power and clinical symptoms were important factors. The observation of clinical worsening that was rescued following neurostimulator replacement reinforces the notion that changes in clinical symptoms can be associated with battery drain.

  13. Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

    Science.gov (United States)

    Fundament, Tomasz; Eldridge, Paul R; Green, Alexander L; Whone, Alan L; Taylor, Rod S; Williams, Adrian C; Schuepbach, W M Michael

    2016-01-01

    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 cost

  14. Metal Artifact Reduction in Computed Tomography After Deep Brain Stimulation Electrode Placement Using Iterative Reconstructions.

    Science.gov (United States)

    Aissa, Joel; Boos, Johannes; Schleich, Christoph; Sedlmair, Martin; Krzymyk, Karl; Kröpil, Patric; Antoch, Gerald; Thomas, Christoph

    2017-01-01

    Diagnostic accuracy of intraoperative computed tomography (CT) after deep brain stimulation (DBS) electrode placement is limited due to artifacts induced by the metallic hardware, which can potentially mask intracranial postoperative complications. Different metal artifact reduction (MAR) techniques have been introduced to reduce artifacts from metal hardware in CT. The purpose of this study was to assess the impact of a novel iterative MAR technique on image quality and diagnostic performance in the follow-up of patients with DBS electrode implementation surgery. Seventeen patients who had received routine intraoperative CT of the head after implantation of DBS electrodes between March 2015 and June 2015 were retrospectively included. Raw data of all patients were reconstructed with standard weighted filtered back projection (WFBP) and additionally with a novel iterative MAR algorithm. We quantified frequencies of density changes to assess quantitative artifact reduction. For evaluation of qualitative image quality, the visibility of numerous cerebral anatomic landmarks and the detectability of intracranial electrodes were scored according to a 4-point scale. Furthermore, artifact strength overall and adjacent to the electrodes was rated. Our results of quantitative artifact reduction showed that images reconstructed with iterative MAR (iMAR) contained significantly lower metal artifacts (overall low frequency values, 1608.6 ± 545.5; range, 375.5-3417.2) compared with the WFBP (overall low frequency values, 4487.3 ± 875.4; range, 2218.3-5783.5) reconstructed images (P < 0.004). Qualitative image analysis showed a significantly improved image quality for iMAR (overall anatomical landmarks, 2.49 ± 0.15; median, 3; range, 0-3; overall electrode characteristics, 2.35 ± 0.16; median, 2; range, 0-3; artifact characteristics, 2.16 ± 0.08; median, 2.5; range, 0-3) compared with WFBP (overall anatomical landmarks, 1.21 ± 0.64; median, 1; range, 0-3; overall electrode

  15. 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

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

    Science.gov (United States)

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

    2012-02-01

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

  17. Brain function and glucocorticoids in obesity and type 2 diabetes including effects of lifestyle interventions

    OpenAIRE

    Stomby, Andreas

    2015-01-01

    Background Obesity and associated metabolic dysregulation are linked to impaired cognitive function and alterations in brain structure, which increases the risk of age-related dementia. Increased glucocorticoid (GC) exposure may be a potential mediator of these negative effects on the brain. Methods and results In paper 1, we tested the relationship between cortisol levels, brain morphology and cognitive function in 200 women and men. Salivary cortisol levels were negatively related to cortic...

  18. 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 ...

  19. Effect of subthalamic deep brain stimulation on non-motor fluctuations in Parkinson's disease.

    Science.gov (United States)

    Azulay, Jean-Philippe; Witjas, Tatiana; Eusebio, Alexandre

    2013-04-01

    The non-motor consequences of subthalamic stimulation are largely questioned. Cognition, motivation, anxiety, depression and even occurrence of suicides have been considered as a potential consequence of the surgical intervention. Non-motor fluctuations are present in all the patients with motor fluctuations and may sometimes be even more invalidating. Interestingly, subthalamic deep brain stimulation alleviates non-motor fluctuations allowing strikingly successful effects on sensory, dysautonomic and cognitive fluctuations while psychic fluctuations respond less consistently to this treatment. Nevertheless, severe mood fluctuations, oscillating from Off dysphoria to ON hypomania, are frequently associated with addictive behaviors and improve dramatically after subthalamic stimulation. This may be a further argument to support the indication of surgery for these patients.

  20. 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.

  1. Deep brain stimulation for aggressive behavior and obsessive-compulsive disorder.

    Science.gov (United States)

    Messina, Giuseppe; Islam, Lucrezia; Cordella, Roberto; Gambini, Orsola; Franzini, Angelo

    2016-06-01

    Drug-resistant obsessive-compulsive disorder and aggressive behavior are two severely disabling psychiatric conditions which may carry a certain burden on the patients themselves and on their families. In the last decade, the fields of interests of deep brain stimulation (DBS) also encompass psychiatric disorders, supported by imaging and neurophysiological techniques. We here report our institutional experience with the two above-mentioned disorders, describing the procedure commonly employed and the results obtained. Refinement of such techniques, possibly relying on advanced magnetic resonance imaging (MRI), together with probabilistic pictures of field of activation models, could shed more light into this complex field of investigation; further studies are necessary to confirm and make actual results a starting point to new and more precise methodologies in this stimulating research field.

  2. Apathy in patients with Parkinson's disease following deep brain stimulation of the subthalamic nucleus.

    Science.gov (United States)

    Hindle Fisher, Isabel; Pall, Hardev S; Mitchell, Rosalind D; Kausar, Jamilla; Cavanna, Andrea E

    2016-06-01

    Apathy has been reported as a possible adverse effect of deep brain stimulation of the subthalamic nucleus (STN-DBS). We investigated the prevalence and severity of apathy in 22 patients with Parkinson's disease (PD) who underwent STN-DBS, as well as the effects of apathy on quality of life (QOL). All patients were assessed with the Lille Apathy Rating Scale (LARS), the Apathy Scale (AS), and the Parkinson's Disease Questionnaire and were compared to a control group of 38 patients on pharmacotherapy alone. There were no significant differences in the prevalence or severity of apathy between patients who had undergone STN-DBS and those on pharmacotherapy alone. Significant correlations were observed between poorer QOL and degree of apathy, as measured by the LARS (papathy ratings (papathy in the PD population; however, more severe apathy appears to be associated with a higher level of disability due to PD and worse QOL, but no other clinico-demographic characteristics.

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

    Science.gov (United States)

    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 (DBS) at the interface of neurology and psychiatry

    Science.gov (United States)

    Williams, Nolan R.; Okun, Michael S.

    2013-01-01

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

  5. Role of Tc-Sulesomab Immunoscintigraphy in the Management of Infection following Deep Brain Stimulation Surgery

    Directory of Open Access Journals (Sweden)

    Raquel Real

    2011-01-01

    Full Text Available Infection constitutes a serious adverse event in patients submitted to deep brain stimulation, often leading to removal of the device. We set to evaluate the potential role of immunoscintigraphy with Tc-labelled antigranulocyte antibody fragments (Tc-sulesomab in the management of infection following DBS. Tc-sulesomab immunoscintigraphy seems to correlate well with the presence and extent of infection, thus contributing to differentiate between patients who should remove the hardware entirely at presentation and those who could undergo a more conservative approach. Also, Tc-sulesomab immunoscintigraphy has a role in determining the most appropriate timing for reimplantation. Finally, we propose an algorithm for the management of infection following DBS surgery, based on the results of the Tc-sulesomab immunoscintigraphy.

  6. 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. 

  7. [Influence of subthalamic deep brain stimulation on dysautonomia observed in Parkinson's disease].

    Science.gov (United States)

    Tykocki, Tomasz; Mandat, Tomasz; Nauman, Paweł

    2010-01-01

    Dysfunctions of the autonomic nervous system (DA) are common in Parkinson's disease (PD). DA appear in the premotor phase of PD and may antedate cardinal motor symptoms by years or decades. DA significantly impair quality of life in the majority of PD patients. DA are related to accumulation of Lewy bodies in the central and peripheral nervous system. Progression of neurodegeneration and chronic dopaminergic therapy may increase DA as well. It is accepted that bilateral deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in PD. The effect of STN DBS on DA, such as cardio-vascular symptoms and urinary, gastrointestinal and sexual dysfunction in PD, is not clear. STN DBS ameliorates some DA, but others might deteriorate at the same time.

  8. 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.

  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...... 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...... 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....

  10. Treatment of dysarthria following subthalamic nucleus deep brain stimulation for Parkinson’s disease

    Science.gov (United States)

    Tripoliti, Elina; Strong, Laura; Hickey, Freya; Foltynie, Tom; Zrinzo, Ludvic; Candelario, Joseph; Hariz, Marwan; Limousin, Patricia

    2011-01-01

    Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment for patients with Parkinson’s disease (PD). Speech impairment is a frequent side effect of the surgery. This study examined the efficacy of an intensive speech treatment (the Lee Silverman Voice Treatment, LSVT) on dysarthria after STN-DBS. The LSVT was administered in ten patients with STN-DBS (surgical group) and ten patients without (medical group). Patients were assessed before, immediately after and six months following the speech treatment using sustained phonation, a speech intelligibility scale and monologue. Vocal loudness, speech intelligibility and perceptual ratings were the primary outcome measures. Vocal loudness and perceptual scores improved significantly across tasks for the medical group only. Speech intelligibility did not significantly change for either group. Results in the surgical group were variable with some patients deteriorating. Treatment of dysarthria following STN-DBS needs further investigation due to the variable response to LSVT. PMID:21953693

  11. Tailored deep brain stimulation optimization for improved airway protective outcomes in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Michelle S. Troche

    2016-09-01

    Full Text Available There is no consensus regarding the effects of deep brain stimulation (DBS surgery on swallowing outcomes in Parkinson's disease (PD. No prospective studies have compared airway protective outcomes following DBS to the subthalamic nucleus (STN versus globus pallidus interna (GPi. A recent retrospective study described swallowing outcomes pre- and post-STN vs. GPi DBS in a cohort of 34 patients with PD. The results revealed that the patients who received GPi DBS maintained their swallowing function post-DBS, while those in the STN group significantly worsened in swallowing safety. As DBS surgery becomes a common management option in PD it is important to understand the impact of DBS on airway protective outcomes; especially given that aspiration pneumonia is the leading cause of death in this population. We present a case report in which optimizing DBS settings with the goal of improving laryngeal function resulted in immediate improvements to swallowing safety.

  12. Postoperative lead migration in deep brain stimulation surgery: Incidence, risk factors, and clinical impact.

    Directory of Open Access Journals (Sweden)

    Takashi Morishita

    Full Text Available Deep brain stimulation (DBS is an effective treatment for multiple movement disorders and shows substantial promise for the treatment of some neuropsychiatric and other disorders of brain neurocircuitry. Optimal neuroanatomical lead position is a critical determinant of clinical outcomes in DBS surgery. Lead migration, defined as an unintended post-operative displacement of the DBS lead, has been previously reported. Despite several reports, however, there have been no systematic investigations of this issue. This study aimed to: 1 quantify the incidence of lead migration in a large series of DBS patients, 2 identify potential risk factors contributing to DBS lead migration, and 3 investigate the practical importance of this complication by correlating its occurrence with clinical outcomes.A database of all DBS procedures performed at UF was queried for patients who had undergone multiple post-operative DBS lead localization imaging studies separated by at least two months. Bilateral DBS implantation has commonly been performed as a staged procedure at UF, with an interval of six or more months between sides. To localize the position of each DBS lead, a head CT is acquired ~4 weeks after lead implantation and fused to the pre-operative targeting MRI. The fused targeting images (MR + stereotactic CT acquired in preparation for the delayed second side lead implantation provide an opportunity to repeat the localization of the first implanted lead. This paradigm offers an ideal patient population for the study of delayed DBS lead migration because it provides a large cohort of patients with localization of the same implanted DBS lead at two time points. The position of the tip of each implanted DBS lead was measured on both the initial post-operative lead localization CT and the delayed CT. Lead tip displacement, intracranial lead length, and ventricular indices were collected and analyzed. Clinical outcomes were characterized with validated rating

  13. Postoperative lead migration in deep brain stimulation surgery: Incidence, risk factors, and clinical impact.

    Science.gov (United States)

    Morishita, Takashi; Hilliard, Justin D; Okun, Michael S; Neal, Dan; Nestor, Kelsey A; Peace, David; Hozouri, Alden A; Davidson, Mark R; Bova, Francis J; Sporrer, Justin M; Oyama, Genko; Foote, Kelly D

    2017-01-01

    Deep brain stimulation (DBS) is an effective treatment for multiple movement disorders and shows substantial promise for the treatment of some neuropsychiatric and other disorders of brain neurocircuitry. Optimal neuroanatomical lead position is a critical determinant of clinical outcomes in DBS surgery. Lead migration, defined as an unintended post-operative displacement of the DBS lead, has been previously reported. Despite several reports, however, there have been no systematic investigations of this issue. This study aimed to: 1) quantify the incidence of lead migration in a large series of DBS patients, 2) identify potential risk factors contributing to DBS lead migration, and 3) investigate the practical importance of this complication by correlating its occurrence with clinical outcomes. A database of all DBS procedures performed at UF was queried for patients who had undergone multiple post-operative DBS lead localization imaging studies separated by at least two months. Bilateral DBS implantation has commonly been performed as a staged procedure at UF, with an interval of six or more months between sides. To localize the position of each DBS lead, a head CT is acquired ~4 weeks after lead implantation and fused to the pre-operative targeting MRI. The fused targeting images (MR + stereotactic CT) acquired in preparation for the delayed second side lead implantation provide an opportunity to repeat the localization of the first implanted lead. This paradigm offers an ideal patient population for the study of delayed DBS lead migration because it provides a large cohort of patients with localization of the same implanted DBS lead at two time points. The position of the tip of each implanted DBS lead was measured on both the initial post-operative lead localization CT and the delayed CT. Lead tip displacement, intracranial lead length, and ventricular indices were collected and analyzed. Clinical outcomes were characterized with validated rating scales for all

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

    Science.gov (United States)

    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.

  15. Post-operative assessment in Deep Brain Stimulation based on multimodal images: registration workflow and validation

    Science.gov (United States)

    Lalys, Florent; Haegelen, Claire; Abadie, Alexandre; Jannin, Pierre

    2009-02-01

    Object Movement disorders in Parkinson disease patients may require functional surgery, when medical therapy isn't effective. In Deep Brain Stimulation (DBS) electrodes are implanted within the brain to stimulate deep structures such as SubThalamic Nucleus (STN). This paper describes successive steps for constructing a digital Atlas gathering patient's location of electrodes and contacts for post operative assessment. Materials and Method 12 patients who had undergone bilateral STN DBS have participated to the study. Contacts on post-operative CT scans were automatically localized, based on black artefacts. For each patient, post operative CT images were rigidly registered to pre operative MR images. Then, pre operative MR images were registered to a MR template (super-resolution Collin27 average MRI template). This last registration was the combination of global affine, local affine and local non linear registrations, respectively. Four different studies were performed in order to validate the MR patient to template registration process, based on anatomical landmarks and clinical scores (i.e., Unified Parkinson's disease rating Scale). Visualisation software was developed for displaying into the template images the stimulated contacts represented as cylinders with a colour code related to the improvement of the UPDRS. Results The automatic contact localization algorithm was successful for all the patients. Validation studies for the registration process gave a placement error of 1.4 +/- 0.2 mm and coherence with UPDRS scores. Conclusion The developed visualization tool allows post-operative assessment for previous interventions. Correlation with additional clinical scores will certainly permit to learn more about DBS and to better understand clinical side-effects.

  16. A prospective pilot trial for pallidal deep brain stimulation in Huntington´s disease

    Directory of Open Access Journals (Sweden)

    Lars eWojtecki

    2015-08-01

    Full Text Available Background: Movement disorders in Huntington´s disease are often medically refractive. The aim of the trial was assessment of procedure safety of deep brain stimulation, equality of internal- and external-pallidal stimulation and efficacy followed-up for 6 months in a prospective pilot trial.Methods: In a conrolled double-blind phase 6 patients (4 chorea-dominant, 2 Westphal-variant with predominant movement disorder were randomly assigned to either the sequence of 6 week internal-/6 week external-pallidal stimulation, or vice versa, followed by further 3 months chronic pallidal stimulation at the target with best effect-side-effect ratio. Primary endpoints were changes in the Unified Huntington´s Disease Rating Scale motor-score, chorea subscore and total motor-score 4 (blinded video ratings, comparing internal- versus external-pallidal stimulation, and 6 month versus baseline. Secondary endpoints assessed scores on dystonia, hypokinesia, cognition, mood, functionality/disability and quality-of-life. Results: Intention-to-treat analysis of all patients (n=3 in each treatment sequence: Both targets were equal in terms of efficacy. Chorea subscores decreased significantly over 6 months (-5.3 (60.2%, p=0.037. Effects on dystonia were not significant over the group due to it consisting of three responders (>50% improvement and three non-responders. Westphal patients did not improve. Cognition was stable. Mood and some functionality/disability and quality-of-life scores improved significantly. 8 adverse events and 2 additional serious adverse events - mostly internal-pallidal stimulation-related - resolved without sequalae. No procedure-related complications occurred.Conclusion: Pallidal deep brain stimulation was demonstrated to be a safe treatment option for the reduction of chorea in Huntington´s disease. Their effects on chorea and dystonia and on quality-of-life, should be examined in larger controlled trials.

  17. Accurate CT-MR image registration for deep brain stimulation: a multi-observer evaluation study

    Science.gov (United States)

    Rühaak, Jan; Derksen, Alexander; Heldmann, Stefan; Hallmann, Marc; Meine, Hans

    2015-03-01

    Since the first clinical interventions in the late 1980s, Deep Brain Stimulation (DBS) of the subthalamic nucleus has evolved into a very effective treatment option for patients with severe Parkinson's disease. DBS entails the implantation of an electrode that performs high frequency stimulations to a target area deep inside the brain. A very accurate placement of the electrode is a prerequisite for positive therapy outcome. The assessment of the intervention result is of central importance in DBS treatment and involves the registration of pre- and postinterventional scans. In this paper, we present an image processing pipeline for highly accurate registration of postoperative CT to preoperative MR. Our method consists of two steps: a fully automatic pre-alignment using a detection of the skull tip in the CT based on fuzzy connectedness, and an intensity-based rigid registration. The registration uses the Normalized Gradient Fields distance measure in a multilevel Gauss-Newton optimization framework and focuses on a region around the subthalamic nucleus in the MR. The accuracy of our method was extensively evaluated on 20 DBS datasets from clinical routine and compared with manual expert registrations. For each dataset, three independent registrations were available, thus allowing to relate algorithmic with expert performance. Our method achieved an average registration error of 0.95mm in the target region around the subthalamic nucleus as compared to an inter-observer variability of 1.12 mm. Together with the short registration time of about five seconds on average, our method forms a very attractive package that can be considered ready for clinical use.

  18. Bilateral deep brain stimulation of the subthalamic nucleus in primary Meige syndrome.

    Science.gov (United States)

    Zhan, Shikun; Sun, Fafa; Pan, Yixin; Liu, Wei; Huang, Peng; Cao, Chunyan; Zhang, Jing; Li, Dianyou; Sun, Bomin

    2018-03-01

    OBJECTIVE Subthalamic nucleus deep brain stimulation has been shown to be effective in reducing symptoms of primary Meige syndrome. However, assessments of its efficacy and safety have been limited to several case reports and small studies. METHODS The authors performed a retrospective study to assess the efficacy and safety of bilateral subthalamic nucleus stimulation in 15 patients with primary Meige syndrome who responded poorly to medical treatments or botulinum toxin injections. Using the movement and disability subscores of the Burke-Fahn-Marsden Dystonia Rating Scale, the authors evaluated the severity of patients' dystonia and related before surgery and at final follow-up during neurostimulation. The movement scale was assessed based on preoperative and postoperative video documentation by an independent rater who was unaware of each patient's neurostimulation status. Quality of life was assessed with the Medical Outcomes Study 36-Item Short-Form General Health Survey. RESULTS The dystonia movement subscores in 14 consecutive patients improved from 19.3 ± 7.6 (mean ± standard deviation) before surgery to 5.5 ± 4.5 at final follow-up (28.5 ± 16.5 months), with a mean improvement of 74% (p stimulation of the subthalamic nucleus immediately improved patient symptoms after stimulation and required lower stimulation parameters than those needed for pallidal deep brain stimulation for primary Meige syndrome. Four adverse events occurred in 3 patients; all of these events resolved without permanent sequelae. CONCLUSIONS These findings provide further evidence to support the long-term efficacy and safety of subthalamic nucleus stimulation as an alternative treatment for patients with medically intractable Meige syndrome.

  19. Outcome based definition of the anterior thalamic deep brain stimulation target in refractory epilepsy.

    Science.gov (United States)

    Lehtimäki, K; Möttönen, T; Järventausta, K; Katisko, J; Tähtinen, T; Haapasalo, J; Niskakangas, T; Kiekara, T; Öhman, J; Peltola, J

    2016-01-01

    Deep brain stimulation of the anterior nucleus of the thalamus (ANT) is an emerging therapy for refractory focal epilepsy. However, the most optimal target for stimulation has not been unambiguously described. In the present study, we investigated the correlation between the stimulation site and outcome in order to define the optimal target for deep brain stimulation in refractory epilepsy. The locations of 62 contacts used in 30 treatment attempts in 15 prospectively followed patients during a 5 year period were assessed. Treatment attempts were classified into responding and non-responding trials using seizure reduction and side effect profile as criteria. The locations of active contacts were calculated with respect to mid-commissural point and visible borders of ANT in 3T MRI (ANT-normalized coordinate system) aiming to minimize the confounding effect of individual variation in the location and size of the ANT. Contacts in successful treatment trials were located significantly more anterior and superior both in AC-PC and ANT-normalized coordinate systems. Favourable outcome was observed at 3T MRI based location of ANT but not at location predicted by Schaltenbrandt atlas sagittal data. Contacts used in successful trials were at anterior aspect of the ANT complex evidenced by the ANT-normalized coordinate system. The anti-epileptic effect of anterior thalamic DBS may be dependent on stimulation site especially in the anterior to posterior axis. Extensive anatomical variation confounds severely the targeting of ANT. Therefore, direct visualization of the desired target for stimulation is essential for favourable outcome in refractory epilepsy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Effect of subthalamic nucleus deep brain stimulation on balance in Parkinson's disease: A static posturographic analysis.

    Science.gov (United States)

    De la Casa-Fages, Beatriz; Alonso-Frech, Fernando; Grandas, Francisco

    2017-02-01

    The effect of subthalamic deep brain stimulation on balance in Parkinson's disease remains unclear. To evaluate the effect of subthalamic nucleus stimulation on balance in Parkinson's disease using posturography. 16 patients (9 women) who underwent subthalamic deep brain stimulation [mean age 59.6 years (46-70); mean disease duration 15.6 years (7-25); mean duration of subthalamic stimulation 32.1 months (3.0-69.6)] and 13 healthy age-matched controls were evaluated using a static posturography analysis. Patients were assessed under four conditions: 1) off medication/off stimulation; 2) off medication/on stimulation; 3) on medication/off stimulation and 4) on medication/on stimulation in ten experimental paradigms, some reproducing common situations of daily living. The displacement of the centre of pressure was analyzed using 14 posturographic parameters. The Mann-Whitney test was used to compare patients with controls. The Wilcoxon signed rank test was used to compare patients under different clinical conditions. Patients off medication/off stimulation showed larger and more rapid displacements of the centre of pressure than controls in most paradigms (pstimulation alone reduced the lateral excursion and anterior-posterior velocity of the centre of pressure in quite stance paradigms (pstimulation combined with antiparkinsonian medication did not induce statistically significant changes in posturagraphic measures in any experimental paradigm. Although subthalamic stimulation alone may induce some positive effect on balance, subthalamic stimulation in addition to antiparkinsonian medication, which is the usual treatment in clinical practice, did not modify balance as assessed by static posturography in patients with Parkinson's disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. A Prospective Pilot Trial for Pallidal Deep Brain Stimulation in Huntington's Disease.

    Science.gov (United States)

    Wojtecki, Lars; Groiss, Stefan J; Ferrea, Stefano; Elben, Saskia; Hartmann, Christian J; Dunnett, Stephen B; Rosser, Anne; Saft, Carsten; Südmeyer, Martin; Ohmann, Christian; Schnitzler, Alfons; Vesper, Jan

    2015-01-01

    Movement disorders in Huntington's disease are often medically refractive. The aim of the trial was assessment of procedure safety of deep brain stimulation, equality of internal- and external-pallidal stimulation and efficacy followed-up for 6 months in a prospective pilot trial. In a controlled double-blind phase six patients (four chorea-dominant, two Westphal-variant) with predominant movement disorder were randomly assigned to either the sequence of 6-week internal- or 6-week external-pallidal stimulation, or vice versa, followed by further 3 months chronic pallidal stimulation at the target with best effect-side-effect ratio. Primary endpoints were changes in the Unified Huntington's Disease Rating Scale motor-score, chorea subscore, and total motor-score 4 (blinded-video ratings), comparing internal- versus external-pallidal stimulation, and 6 months versus baseline. Secondary endpoints assessed scores on dystonia, hypokinesia, cognition, mood, functionality/disability, and quality-of-life. Intention-to-treat analysis of all patients (n = 3 in each treatment sequence): Both targets were equal in terms of efficacy. Chorea subscores decreased significantly over 6 months (-5.3 (60.2%), p = 0.037). Effects on dystonia were not significant over the group due to it consisting of three responders (>50% improvement) and three non-responders. Westphal patients did not improve. Cognition was stable. Mood and some functionality/disability and quality-of-life scores improved significantly. Eight adverse events and two additional serious adverse events - mostly internal-pallidal stimulation-related - resolved without sequalae. No procedure-related complications occurred. Pallidal deep brain stimulation was demonstrated to be a safe treatment option for the reduction of chorea in Huntington's disease. Their effects on chorea and dystonia and on quality-of-life should be examined in larger controlled trials.

  2. Deep brain stimulation compared with bariatric surgery for the treatment of morbid obesity: a decision analysis study.

    Science.gov (United States)

    Pisapia, Jared M; Halpern, Casey H; Williams, Noel N; Wadden, Thomas A; Baltuch, Gordon H; Stein, Sherman C

    2010-08-01

    Roux-en-Y gastric bypass is the gold standard treatment for morbid obesity, although failure rates may be high, particularly in patients with a BMI > 50 kg/m(2). With improved understanding of the neuropsychiatric basis of obesity, deep brain stimulation (DBS) offers a less invasive and reversible alternative to available surgical treatments. In this decision analysis, the authors determined the success rate at which DBS would be equivalent to the two most common bariatric surgeries. Medline searches were performed for studies of laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux-en-Y gastric bypass (LRYGB), and DBS for movement disorders. Bariatric surgery was considered successful if postoperative excess weight loss exceeded 45% at 1-year follow-up. Using complication and success rates from the literature, the authors constructed a decision analysis model for treatment by LAGB, LRYGB, DBS, or no surgical treatment. A sensitivity analysis in which major parameters were systematically varied within their 95% CIs was used. Fifteen studies involving 3489 and 3306 cases of LAGB and LRYGB, respectively, and 45 studies involving 2937 cases treated with DBS were included. The operative successes were 0.30 (95% CI 0.247-0.358) for LAGB and 0.968 (95% CI 0.967-0.969) for LRYGB. Sensitivity analysis revealed utility of surgical complications in LRYGB, probability of surgical complications in DBS, and success rate of DBS as having the greatest influence on outcomes. At no values did LAGB result in superior outcomes compared with other treatments. Deep brain stimulation must achieve a success rate of 83% to be equivalent to bariatric surgery. This high-threshold success rate is probably due to the reported success rate of LRYGB, despite its higher complication rate (33.4%) compared with DBS (19.4%). The results support further research into the role of DBS for the treatment of obesity.

  3. Parkinson's disease outcomes after intraoperative CT-guided "asleep" deep brain stimulation in the globus pallidus internus.

    Science.gov (United States)

    Mirzadeh, Zaman; Chapple, Kristina; Lambert, Margaret; Evidente, Virgilio G; Mahant, Padma; Ospina, Maria C; Samanta, Johan; Moguel-Cobos, Guillermo; Salins, Naomi; Lieberman, Abraham; Tröster, Alexander I; Dhall, Rohit; Ponce, Francisco A

    2016-04-01

    Recent studies show that deep brain stimulation can be performed safely and accurately without microelectrode recording ortest stimulation but with the patient under general anesthesia. The procedure couples techniques for direct anatomical targeting on MRI with intraoperative imaging to verify stereotactic accuracy. However, few authors have examined the clinical outcomes of Parkinson's disease (PD) patients after this procedure. The purpose of this study was to evaluate PD outcomes following "asleep" deep brain stimulation in the globus pallidus internus (GPi). The authors prospectively examined all consecutive patients with advanced PD who underwent bilateral GPi electrode placement while under general anesthesia. Intraoperative CT was used to assess lead placement accuracy. The primary outcome measure was the change in the off-medication Unified Parkinson's Disease Rating Scale motor score 6 months after surgery. Secondary outcomes included effects on the 39-Item Parkinson's Disease Questionnaire (PDQ-39) scores, on-medication motor scores, and levodopa equivalent daily dose. Lead locations, active contact sites, stimulation parameters, and adverse events were documented. Thirty-five patients (24 males, 11 females) had a mean age of 61 years at lead implantation. The mean radial error off plan was 0.8 mm. Mean coordinates for the active contact were 21.4 mm lateral, 4.7 mm anterior, and 0.4 mm superior to the midcommissural point. The mean off-medication motor score improved from 48.4 at baseline to 28.9 (40.3% improvement) at 6 months (p < 0.001). The PDQ-39 scores improved (50.3 vs 42.0; p = 0.03), and the levodopa equivalent daily dose was reduced (1207 vs 1035 mg; p = 0.004). There were no significant adverse events. Globus pallidus internus leads placed with the patient under general anesthesia by using direct anatomical targeting resulted in significantly improved outcomes as measured by the improvement in the off-medication motor score at 6 months after

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

    Science.gov (United States)

    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.

  5. 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

  6. 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).

  7. 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).

  8. A three-photon microscope with adaptive optics for deep-tissue in vivo structural and functional brain imaging

    Science.gov (United States)

    Tao, Xiaodong; Lu, Ju; Lam, Tuwin; Rodriguez, Ramiro; Zuo, Yi; Kubby, Joel

    2017-02-01

    We developed a three-photon adaptive optics add-on to a commercial two-photon laser scanning microscope. We demonstrated its capability for structural and functional imaging of neurons labeled with genetically encoded red fluorescent proteins or calcium indicators deep in the living mouse brain with cellular and subcellular resolution.

  9. 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

  10. 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

  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. 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

  13. 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.

  14. 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…

  15. 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…

  16. 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

  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. 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

    2017-01-01

    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.

  19. 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.

  20. Influence of the implanted pulse generator as reference electrode in finite element model of monopolar deep brain stimulation.

    Science.gov (United States)

    Walckiers, Grégoire; Fuchs, Benjamin; Thiran, Jean-Philippe; Mosig, Juan R; Pollo, Claudio

    2010-01-30

    Electrical deep brain stimulation (DBS) is an efficient method to treat movement disorders. Many models of DBS, based mostly on finite elements, have recently been proposed to better understand the interaction between the electrical stimulation and the brain tissues. In monopolar DBS, clinically widely used, the implanted pulse generator (IPG) is used as reference electrode (RE). In this paper, the influence of the RE model of monopolar DBS is investigated. For that purpose, a finite element model of the full electric loop including the head, the neck and the superior chest is used. Head, neck and superior chest are made of simple structures such as parallelepipeds and cylinders. The tissues surrounding the electrode are accurately modelled from data provided by the diffusion tensor magnetic resonance imaging (DT-MRI). Three different configurations of RE are compared with a commonly used model of reduced size. The electrical impedance seen by the DBS system and the potential distribution are computed for each model. Moreover, axons are modelled to compute the area of tissue activated by stimulation. Results show that these indicators are influenced by the surface and position of the RE. The use of a RE model corresponding to the implanted device rather than the usually simplified model leads to an increase of the system impedance (+48%) and a reduction of the area of activated tissue (-15%). (c) 2009 Elsevier B.V. All rights reserved.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Woong-Woo Lee

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

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

    Directory of Open Access Journals (Sweden)

    Johanna M.P. Baas

    2014-09-01

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

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

    Science.gov (United States)

    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.

  5. Deep brain stimulation or thalamotomy in fragile X-associated tremor/ataxia syndrome? Case report.

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    Tamás, Gertrúd; Kovács, Norbert; Varga, Noémi Ágnes; Barsi, Péter; Erőss, Loránd; Molnár, Mária Judit; Balás, István

    2016-01-01

    We present the case of a 66-year-old man who has been treated for essential tremor since the age of 58. He developed mild cerebellar gait ataxia seven years after tremor onset. Moderate, global brain atrophy was identified on MRI scans. At the age of 68, only temporary tremor relief could be achieved by bilateral deep brain stimulation of the ventral intermedius nucleus of the thalamus. Bilateral stimulation of the subthalamic nucleus also resulted only in transient improvement. In the meantime, progressive gait ataxia and tetraataxia developed accompanied by other cerebellar symptoms, such as nystagmus and scanning speech. These correlated with progressive development of bilateral symmetric hyperintensity of the middle cerebellar peduncles on T2 weighted MRI scans. Genetic testing revealed premutation of the FMR1 gene, establishing the diagnosis of fragile X-associated tremor/ataxia syndrome. Although this is a rare disorder, it should be taken into consideration during preoperative evaluation of essential tremor. Postural tremor ceased two years later after thalamotomy on the left side, while kinetic tremor of the right hand also improved. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    Hickey, Patrick; Stacy, Mark

    2016-01-01

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

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

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

    2016-01-01

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

  9. Deep brain stimulation for childhood dystonia: Is 'where' as important as in 'whom'?

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    Lumsden, Daniel E; Kaminska, Margaret; Ashkan, Keyoumars; Selway, Richard; Lin, Jean-Pierre

    2017-01-01

    Deep brain stimulation (DBS) has become a mainstay of dystonia management in adulthood. Typically targeting electrode placement in the GPi, sustained improvement in dystonic symptoms are anticipated in adults with isolated genetic dystonias. Dystonia in childhood is more commonly a symptomatic condition, with dystonia frequently expressed on the background of a structurally abnormal brain. Outcomes following DBS in this setting are much more variable, the reasons for which have yet to be elucidated. Much of the focus on improving outcomes following DBS in dystonia management has been on the importance of patient selection, with, until recently, little discussion of the choice of target. In this review, we advance the argument that patient selection for DBS in childhood cannot be made separate from the choice of target nuclei. The anatomy of common DBS targets is considered, and factors influencing their choice for electrode insertion are discussed. We propose an "ABC" for DBS in childhood dystonia is proposed: Appropriate Child selected; Best nuclei chosen for electrode insertion; Correct position within that nucleus. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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. Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis.

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    Hescham, Sarah; Temel, Yasin; Schipper, Sandra; Lagiere, Mélanie; Schönfeld, Lisa-Maria; Blokland, Arjan; Jahanshahi, Ali

    2017-03-01

    Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity-dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release.

  12. Parallel Radiofrequency Transmission for the Reduction of Heating in Deep Brain Stimulation Leads at 3T

    Science.gov (United States)

    McElcheran, Clare

    Deep Brain Stimulation (DBS) is increasingly used to treat a variety of brain diseases by sending electrical impulses to deep brain nuclei through long, electrically conductive leads. Magnetic resonance imaging (MRI) of patients pre- and post-implantation is desirable to target and position the implant, to evaluate possible side-effects and to examine DBS patients who have other health conditions. Although MRI is the preferred modality for pre-operative planning, MRI post-implantation is limited due to the risk of high local power deposition, and therefore tissue heating, at the tip of the lead. The localized power deposition arises from currents induced in the leads caused by coupling with the radiofrequency (RF) transmission field during imaging. In this thesis, parallel RF transmission (pTx) is used to tailor the RF electric field to suppress coupling effects. Three pTx coil configurations with 2-elements, 4-elements, and 8-elements, respectively, were investigated. Optimal input voltages to minimize coupling, while maintaining RF magnetic field homogeneity, were determined using a Nelder-Mead optimization algorithm. Resulting electric and magnetic fields were compared to that of a 16-rung birdcage coil. Experimental validation was performed with a custom-built 4-element pTx coil. Three cases were investigated to develop and evaluate this technique. First, a Proof-of-Concept study was performed to investigate the case of a simple, uniform cylindrical phantom with a straight, perfectly conducting wire. Second, a heterogeneous subject with bilateral, curved implanted wires was investigated. Finally, the third case investigated realistic patient lead-trajectories obtained from intra-operative CT scans. In all three cases, specific absorption rate (SAR), a metric used to quantify power deposition which results in heating, was reduced by over 90%. Maximal reduction in SAR was obtained with the 8-element pTx coil. Magnetic field homogeneity was comparable to the

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2014-05-01

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

  15. 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.

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

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

    2017-02-01

    Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [ 11 C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or Anaesthesia Dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [ 11 C]DPN and [ 15 O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation. The regional cerebral tracer distribution and kinetics were quantified for the whole brain and brainstem. Analysis was performed on a voxel-wise basis using statistical parametric mapping (SPM) and also within brainstem regions of interest and correlated to the DBS-induced improvement in pain score and mood. Brain-wide analysis identified a single cluster of reduced [ 11 C]DPN binding (15.5% reduction) in the caudal, dorsal PAG following DBS from effective electrodes located in rostral dorsal/lateral PAG. There was no evidence for an accompanying focal change in blood flow within the PAG. No correlation was found between the change in PAG [ 11 C]DPN binding and the analgesic effect or the effect on mood (POMS SV ) of DBS. The analgesic effect of DBS in these subjects was not altered by systemic administration of the opioid antagonist naloxone (400ug). These findings indicate that DBS of the PAG does indeed release endogenous opioid peptides focally within the midbrain of these neuropathic pain patients but we are unable to further resolve the question of whether this release is responsible for the observed analgesic benefit. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

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

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    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.

  18. A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer's Disease.

    Science.gov (United States)

    Lozano, Andres M; Fosdick, Lisa; Chakravarty, M Mallar; Leoutsakos, Jeannie-Marie; Munro, Cynthia; Oh, Esther; Drake, Kristen E; Lyman, Christopher H; Rosenberg, Paul B; Anderson, William S; Tang-Wai, David F; Pendergrass, Jo Cara; Salloway, Stephen; Asaad, Wael F; Ponce, Francisco A; Burke, Anna; Sabbagh, Marwan; Wolk, David A; Baltuch, Gordon; Okun, Michael S; Foote, Kelly D; McAndrews, Mary Pat; Giacobbe, Peter; Targum, Steven D; Lyketsos, Constantine G; Smith, Gwenn S

    2016-09-06

    Deep brain stimulation (DBS) is used to modulate the activity of dysfunctional brain circuits. The safety and efficacy of DBS in dementia is unknown. To assess DBS of memory circuits as a treatment for patients with mild Alzheimer's disease (AD). We evaluated active "on" versus sham "off" bilateral DBS directed at the fornix-a major fiber bundle in the brain's memory circuit-in a randomized, double-blind trial (ClinicalTrials.gov NCT01608061) in 42 patients with mild AD. We measured cognitive function and cerebral glucose metabolism up to 12 months post-implantation. Surgery and electrical stimulation were safe and well tolerated. There were no significant differences in the primary cognitive outcomes (ADAS-Cog 13, CDR-SB) in the "on" versus "off" stimulation group at 12 months for the whole cohort. Patients receiving stimulation showed increased metabolism at 6 months but this was not significant at 12 months. On post-hoc analysis, there was a significant interaction between age and treatment outcome: in contrast to patients <65 years old (n = 12) whose results trended toward being worse with DBS ON versus OFF, in patients≥65 (n = 30) DBS-f ON treatment was associated with a trend toward both benefit on clinical outcomes and a greater increase in cerebral glucose metabolism. DBS for AD was safe and associated with increased cerebral glucose metabolism. There were no differences in cognitive outcomes for participants as a whole, but participants aged≥65 years may have derived benefit while there was possible worsening in patients below age 65 years with stimulation.

  19. Deep Independence Network Analysis of Structural Brain Imaging: Application to Schizophrenia.

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    Castro, Eduardo; Hjelm, R Devon; Plis, Sergey M; Dinh, Laurent; Turner, Jessica A; Calhoun, Vince D

    2016-07-01

    Linear independent component analysis (ICA) is a standard signal processing technique that has been extensively used on neuroimaging data to detect brain networks with coherent brain activity (functional MRI) or covarying structural patterns (structural MRI). However, its formulation assumes that the measured brain signals are generated by a linear mixture of the underlying brain networks and this assumption limits its ability to detect the inherent nonlinear nature of brain interactions. In this paper, we introduce nonlinear independent component estimation (NICE) to structural MRI data to detect abnormal patterns of gray matter concentration in schizophrenia patients. For this biomedical application, we further addressed the issue of model regularization of nonlinear ICA by performing dimensionality reduction prior to NICE, together with an appropriate control of the complexity of the model and the usage of a proper approximation of the probability distribution functions of the estimated components. We show that our results are consistent with previous findings in the literature, but we also demonstrate that the incorporation of nonlinear associations in the data enables the detection of spatial patterns that are not identified by linear ICA. Specifically, we show networks including basal ganglia, cerebellum and thalamus that show significant differences in patients versus controls, some of which show distinct nonlinear patterns.

  20. Impact of an Interdisciplinary Deep Brain Stimulation Screening Model on Post-Surgical Complications in Essential Tremor Patients.

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    Masa-aki Higuchi

    Full Text Available To investigate the relationship of our interdisciplinary screening process on post-operative unintended hospitalizations and quality of life.There are currently no standardized criteria for selection of appropriate Deep Brain Stimulation candidates and little hard data exists to support the use of any singular method.An Essential Tremor cohort was selected from our institutional Deep Brain Stimulation database. The interdisciplinary model utilized seven specialties who pre-operatively screened all potential Deep Brain Stimulation candidates. Concerns for surgery raised by each specialty were documented and classified as none, minor, or major. Charts were reviewed to identify unintended hospitalizations and quality of life measurements at 1 year post-surgery.Eighty-six percent (44/51 of the potential screened candidates were approved for Deep Brain Stimulation. Eight (18% patients had an unintended hospitalization during the follow-up period. Patients with minor or major concerns raised by any specialty service had significantly more unintended hospitalizations when compared to patients without concerns (75% vs. 25%, p < 0.005. The rate of hospitalization revealed a direct relationship to the "level of concern"; ranging from 100% if major concerns, 42% if minor concerns, and 7% if no concerns raised, p = 0.001. Quality of life scores significantly worsened in patients with unintended hospitalizations at 6 (p = 0.046 and 12 months (p = 0.027 when compared to baseline scores. No significant differences in tremor scores between unintended and non-unintended hospitalizations were observed.The number and level of concerns raised during interdisciplinary Deep Brain Stimulation screenings were significantly related to unintended hospitalizations and to a reduced quality of life. The interdisciplinary evaluation may help to stratify risk for these complications. However, data should be interpreted with caution due to the limitations of our study. Further

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

    Science.gov (United States)

    Howell, Bryan; McIntyre, Cameron C.

    2016-06-01

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

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

    Science.gov (United States)

    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

  3. Report of whole-brain radiation therapy in a patient with an implanted deep brain stimulator: important neurosurgical considerations and radiotherapy practice principles.

    Science.gov (United States)

    Kotecha, Rupesh; Berriochoa, Camille A; Murphy, Erin S; Machado, Andre G; Chao, Samuel T; Suh, John H; Stephans, Kevin L

    2016-04-01

    Patients with implanted neuromodulation devices present potential challenges for radiation therapy treatment planning and delivery. Although guidelines exist regarding the irradiation of cardiac pacemakers and defibrillators, fewer data and less clinical experience exist regarding the effects of radiation therapy on less frequently used devices, such as deep brain stimulators. A 79-year-old woman with a history of coarse tremors effectively managed with deep brain stimulation presented with multiple intracranial metastases from a newly diagnosed lung cancer and was referred for whole-brain radiation therapy. She was treated with a German helmet technique to a total dose of 30 Gy in 10 fractions using 6 MV photons via opposed lateral fields with the neurostimulator turned off prior to delivery of each fraction. The patient tolerated the treatment well with no acute complications and no apparent change in the functionality of her neurostimulator device or effect on her underlying neuromuscular disorder. This represents the first reported case of the safe delivery of whole-brain radiation therapy in a patient with an implanted neurostimulator device. In cases such as this, neurosurgeons and radiation oncologists should have discussions with patients about the risks of brain injury, device malfunction or failure of the device, and plans for rigorous testing of the device before and after radiation therapy.

  4. A multi-modal approach to computer-assisted deep brain stimulation trajectory planning.

    Science.gov (United States)

    Bériault, Silvain; Subaie, Fahd Al; Collins, D Louis; Sadikot, Abbas F; Pike, G Bruce

    2012-09-01

    Both frame-based and frameless approaches to deep brain stimulation (DBS) require planning of insertion trajectories that mitigate hemorrhagic risk and loss of neurological function. Currently, this is done by manual inspection of multiple potential electrode trajectories on MR-imaging data. We propose and validate a method for computer-assisted DBS trajectory planning. Our framework integrates multi-modal MRI analysis (T1w, SWI, TOF-MRA) to compute suitable DBS trajectories that optimize the avoidance of specific critical brain structures. A cylinder model is used to process each trajectory and to evaluate complex surgical constraints described via a combination of binary and fuzzy segmented datasets. The framework automatically aggregates the multiple constraints into a unique ranking of recommended low-risk trajectories. Candidate trajectories are represented as a few well-defined cortical entry patches of best-ranked trajectories and presented to the neurosurgeon for final trajectory selection. The proposed algorithm permits a search space containing over 8,000 possible trajectories to be processed in less than 20 s. A retrospective analysis on 14 DBS cases of patients with severe Parkinson's disease reveals that our framework can improve the simultaneous optimization of many pre-formulated surgical constraints. Furthermore, all automatically computed trajectories were evaluated by two neurosurgeons, were judged suitable for surgery and, in many cases, were judged preferable or equivalent to the manually planned trajectories used during the operation. This work provides neurosurgeons with an intuitive and flexible decision-support system that allows objective and patient-specific optimization of DBS lead trajectories, which should improve insertion safety and reduce surgical time.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. 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.

  7. 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

  8. 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.

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

    Science.gov (United States)

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

    2016-09-01

    Deep brain stimulation (DBS) is a treatment that has shown some efficacy in treatment-resistant depression. In particular, DBS of the subcallosal cingulate gyrus (Brodmann's area 25, Cg25) has been successfully applied to treat refractory depression. In the rat, we have demonstrated that DBS applied to infralimbic (IL) cortex elevates the levels of glutamate and monoamines in the prefrontal cortex, and requires the stimulation of cortical α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors for its antidepressant-like effects. However, the molecular targets of IL DBS are not fully known. To gain insight into these pathways, we have investigated whether IL DBS is able to reverse the behavioral, biochemical and molecular changes exhibited by the olfactory bulbectomized (OBX) rat. Our results revealed that 1 h IL DBS diminished hyperlocomotion, hyperemotionality and anhedonia, and increased social interaction shown by the OBX rats. Further, IL DBS increased prefrontal efflux of glutamate and serotonin in both sham-operated and OBX rats. With regard to molecular targets, IL DBS increases the synthesis of brain-derived neurotrophic factor (BDNF) and the GluA1 AMPA receptor subunit, and stimulates the Akt/mammalian target of rapamycin (mTOR) as well as the AMPA receptor/c-AMP response element binding (CREB) pathways. Temsirolimus, a known in vivo mTOR blocker, suppressed the antidepressant-like effect of IL DBS in naïve rats in the forced swim test, thus demonstrating for the first time that mTOR signaling is required for the antidepressant-like effects of IL DBS, which is in line with the antidepressant response of other rapid-acting antidepressant drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-09-01

    Schizophrenia is a debilitating psychiatric disorder with a significant number of patients not adequately responding to treatment. Deep brain stimulation (DBS) is a surgical technique currently investigated for medically-refractory psychiatric disorders. Here, we use the poly I:C rat model of schizophrenia to study the effects of medial prefrontal cortex (mPFC) and nucleus accumbens (Nacc) DBS on two behavioral schizophrenia-like deficits, i.e. sensorimotor gating, as reflected by disrupted prepulse inhibition (PPI), and attentional selectivity, as reflected by disrupted latent inhibition (LI). In addition, the neurocircuitry influenced by DBS was studied using FDG PET. We found that mPFC- and Nacc-DBS alleviated PPI and LI abnormalities in poly I:C offspring, whereas Nacc- but not mPFC-DBS disrupted PPI and LI in saline offspring. In saline offspring, mPFC-DBS increased metabolism in the parietal cortex, striatum, ventral hippocampus and Nacc, while reducing it in the brainstem, cerebellum, hypothalamus and periaqueductal gray. Nacc-DBS, on the other hand, increased activity in the ventral hippocampus and olfactory bulb and reduced it in the septal area, brainstem, periaqueductal gray and hypothalamus. In poly I:C offspring changes in metabolism following mPFC-DBS were similar to those recorded in saline offspring, except for a reduced activity in the brainstem and hypothalamus. In contrast, Nacc-DBS did not induce any statistical changes in brain metabolism in poly I:C offspring. Our study shows that mPFC- or Nacc-DBS delivered to the adult progeny of poly I:C treated dams improves deficits in PPI and LI. Despite common behavioral responses, stimulation in the two targets induced different metabolic effects. Copyright © 2016. Published by Elsevier Inc.

  11. 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.

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

    Science.gov (United States)

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

    2015-02-15

    Epilepsy is a debilitating condition affecting 1% of the population worldwide. Medications fail to control seizures in at least 30% of patients, and deep brain stimulation (DBS) is a promising alternative treatment. A modified clinical DBS hardware platform was recently described (PC+S) allowing long-term recording of electrical brain activity such that effects of DBS on neural networks can be examined. This study reports the first use of this device to characterize idiopathic epilepsy and assess the effects of stimulation in a nonhuman primate (NHP). Clinical DBS electrodes were implanted in the hippocampus of an epileptic NHP bilaterally, and baseline local field potential (LFP) recordings were collected for seizure characterization with the PC+S. Real-time automatic detection of ictal events was demonstrated and validated by concurrent visual observation of seizure behavior. Seizures consisted of large-amplitude 8- to 25-Hz oscillations originating from the right hemisphere and quickly generalizing, with an average occurrence of 0.71 ± 0.15 seizures/day. Various stimulation parameters resulted in suppression of LFP activity or in seizure induction during stimulation under ketamine anesthesia. Chronic stimulation in the awake animal was studied to evaluate how seizure activity was affected by stimulation configurations that suppressed broadband LFPs in acute experiments. This is the first electrophysiological characterization of epilepsy using a next-generation clinical DBS system that offers the ability to record and analyze neural signals from a chronically implanted stimulating electrode. These results will direct further development of this technology and ultimately provide insight into therapeutic mechanisms of DBS for epilepsy. Copyright © 2015 the American Physiological Society.

  13. Targeting of deep-brain structures in nonhuman primates using MR and CT Images

    Science.gov (United States)

    Chen, Antong; Hines, Catherine; Dogdas, Belma; Bone, Ashleigh; Lodge, Kenneth; O'Malley, Stacey; Connolly, Brett; Winkelmann, Christopher T.; Bagchi, Ansuman; Lubbers, Laura S.; Uslaner, Jason M.; Johnson, Colena; Renger, John; Zariwala, Hatim A.

    2015-03-01

    In vivo gene delivery in central nervous systems of nonhuman primates (NHP) is an important approach for gene therapy and animal model development of human disease. To achieve a more accurate delivery of genetic probes, precise stereotactic targeting of brain structures is required. However, even with assistance from multi-modality 3D imaging techniques (e.g. MR and CT), the precision of targeting is often challenging due to difficulties in identification of deep brain structures, e.g. the striatum which consists of multiple substructures, and the nucleus basalis of meynert (NBM), which often lack clear boundaries to supporting anatomical landmarks. Here we demonstrate a 3D-image-based intracranial stereotactic approach applied toward reproducible intracranial targeting of bilateral NBM and striatum of rhesus. For the targeting we discuss the feasibility of an atlas-based automatic approach. Delineated originally on a high resolution 3D histology-MR atlas set, the NBM and the striatum could be located on the MR image of a rhesus subject through affine and nonrigid registrations. The atlas-based targeting of NBM was compared with the targeting conducted manually by an experienced neuroscientist. Based on the targeting, the trajectories and entry points for delivering the genetic probes to the targets could be established on the CT images of the subject after rigid registration. The accuracy of the targeting was assessed quantitatively by comparison between NBM locations obtained automatically and manually, and finally demonstrated qualitatively via post mortem analysis of slices that had been labelled via Evan Blue infusion and immunohistochemistry.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. Development of intraoperative electrochemical detection: wireless instantaneous neurochemical concentration sensor for deep brain stimulation feedback.

    Science.gov (United States)

    Van Gompel, Jamie J; Chang, Su-Youne; Goerss, Stephan J; Kim, In Yong; Kimble, Christopher; Bennet, Kevin E; Lee, Kendall H

    2010-08-01

    Deep brain stimulation (DBS) is effective when there appears to be a distortion in the complex neurochemical circuitry of the brain. Currently, the mechanism of DBS is incompletely understood; however, it has been hypothesized that DBS evokes release of neurochemicals. Well-established chemical detection systems such as microdialysis and mass spectrometry are impractical if one is assessing changes that are happening on a second-to-second time scale or for chronically used implanted recordings, as would be required for DBS feedback. Electrochemical detection techniques such as fast-scan cyclic voltammetry (FSCV) and amperometry have until recently remained in the realm of basic science; however, it is enticing to apply these powerful recording technologies to clinical and translational applications. The Wireless Instantaneous Neurochemical Concentration Sensor (WINCS) currently is a research device designed for human use capable of in vivo FSCV and amperometry, sampling at subsecond time resolution. In this paper, the authors review recent advances in this electrochemical application to DBS technologies. The WINCS can detect dopamine, adenosine, and serotonin by FSCV. For example, FSCV is capable of detecting dopamine in the caudate evoked by stimulation of the subthalamic nucleus/substantia nigra in pig and rat models of DBS. It is further capable of detecting dopamine by amperometry and, when used with enzyme linked sensors, both glutamate and adenosine. In conclusion, WINCS is a highly versatile instrument that allows near real-time (millisecond) detection of neurochemicals important to DBS research. In the future, the neurochemical changes detected using WINCS may be important as surrogate markers for proper DBS placement as well as the sensor component for a "smart" DBS system with electrochemical feedback that allows automatic modulation of stimulation parameters. Current work is under way to establish WINCS use in humans.

  17. Deep Conservation of Genes Required for Both Drosophila melanogaster and Caenorhabditis elegans Sleep Includes a Role for Dopaminergic Signaling

    Science.gov (United States)

    Singh, Komudi; Ju, Jennifer Y.; Walsh, Melissa B.; DiIorio, Michael A.; Hart, Anne C.

    2014-01-01

    Objectives: Cross-species conservation of sleep-like behaviors predicts the presence of conserved molecular mechanisms underlying sleep. However, limited experimental evidence of conservation exists. Here, this prediction is tested directly. Measurements and Results: During lethargus, Caenorhabditis elegans spontaneously sleep in short bouts that are interspersed with bouts of spontaneous locomotion. We identified 26 genes required for Drosophila melanogaster sleep. Twenty orthologous C. elegans genes were selected based on similarity. Their effect on C. elegans sleep and arousal during the last larval lethargus was assessed. The 20 most similar genes altered both the quantity of sleep and arousal thresholds. In 18 cases, the direction of change was concordant with Drosophila studies published previously. Additionally, we delineated a conserved genetic pathway by which dopamine regulates sleep and arousal. In C. elegans neurons, G-alpha S, adenylyl cyclase, and protein kinase A act downstream of D1 dopamine receptors to regulate these behaviors. Finally, a quantitative analysis of genes examined herein revealed that C. elegans arousal thresholds were directly correlated with amount of sleep during lethargus. However, bout duration varies little and was not correlated with arousal thresholds. Conclusions: The comprehensive analysis presented here suggests that conserved genes and pathways are required for sleep in invertebrates and, likely, across the entire animal kingdom. The genetic pathway delineated in this study implicates G-alpha S and previously known genes downstream of dopamine signaling in sleep. Quantitative analysis of various components of quiescence suggests that interdependent or identical cellular and molecular mechanisms are likely to regulate both arousal and sleep entry. Citation: Singh K, Ju JY, Walsh MB, Dilorio MA, Hart AC. Deep conservation of genes required for both Drosophila melanogaster and Caenorhabditis elegans sleep includes a role for

  18. Perioperative brain damage after cardiovascular surgery; Clinical evaluation including CT scans

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    Maruyama, Michiyuki; Kuriyama, Yoshihiro; Sawada, Toru; Fujita, Tsuyoshi; Omae, T. (National Cardiovascular Center, Suita, Osaka (Japan))

    1989-08-01

    We examined 39 cases (1.6%) of post-operative brain damages out of 2,445 sequential cases of cardiovascular surgery in NCVC during past three years. In this study, we investigated clinical course and CT findings of each patient in details and analyzed the causes of the post operative brain damages. Of 39 cases, 23 (59%) were complicated with cerebral ischemia, 8 (21%) with subdural hematoma (SDH), 2 (5%) with intracranial hemorrhage (ICH) and 1 (2%) with subarachnoid hemorrhage (SAH), respectively. 5 cases (13%) had unclassified brain damages. In 23 cases of cerebral ischemia there were 5 cases of hypotension-induced ischemia, 4 cases of hypoxic encephalopathy, 3 cases of ischemia induced by intra-operative maneuvers, 3 cases of embolism after operation and a single case of 'microembolism'. Seven cases could not be classified into any of these categories. Duration of ECC was 169.9 {plus minus} 48.5 min on the average in patients with such brain damages as SDH, ICH, SAH and cardiogenic embolism, which were thought not to be related with ECC. On the other hand, that of the patients hypotensive ischemia or 'microembolism' gave an average value of 254.5 {plus minus} 96.8 min. And these patients were thought to have occurred during ECC. There was a statistically significant difference between these two mean values. (J.P.N.).

  19. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    International Nuclear Information System (INIS)

    Green, Daniel M.; Merchant, Thomas E.; Billups, Catherine A.; Stokes, Dennis C.; Broniscer, Alberto; Bartels, Ute; Chintagumpala, Murali; Hassall, Timothy E.; Gururangan, Sridharan; McCowage, Geoffrey B.; Heath, John A.; Cohn, Richard J.; Fisher, Michael J.; Srinivasan, Ashok; Robinson, Giles W.; Gajjar, Amar

    2015-01-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV 1 ] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO corr ]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m 2 (IQR, 15.7-16.0 g/m 2 ). At 24 and 60 months ACT, DLCO corr was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV 1 was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO corr was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO corr were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI. Continued monitoring of this cohort

  20. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Green, Daniel M., E-mail: daniel.green@stjude.org [Department of Epidemiology and Cancer Control, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Merchant, Thomas E. [Department of Radiological Sciences, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Billups, Catherine A. [Department of Biostatistics, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Stokes, Dennis C. [Department of Pediatrics, University of Tennessee School of Medicine, Memphis, Tennessee (United States); Broniscer, Alberto [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Bartels, Ute [Department of Haematology and Oncology, The Hospital for Sick Children, Toronto, Ontario (Canada); Chintagumpala, Murali [Department of Pediatric Medicine, Texas Children' s Cancer and Hematology Centers, Baylor College of Medicine, Houston, Texas (United States); Hassall, Timothy E. [Department of Haematology and Oncology, Royal Children' s Hospital, Brisbane (Australia); Gururangan, Sridharan [Department of Pediatrics, Duke University Medical Center, Durham, North Carolina (United States); McCowage, Geoffrey B. [Department of Pediatrics, Children' s Hospital at Westmead, Sydney (Australia); Heath, John A. [Children' s Cancer Center, Royal Children' s Hospital Melbourne, Melbourne (Australia); Cohn, Richard J. [Department of Clinical Oncology, Sydney Children' s Hospital, Sydney (Australia); Fisher, Michael J. [Department of Pediatrics, Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States); Srinivasan, Ashok [Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Robinson, Giles W.; Gajjar, Amar [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States)

    2015-09-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV{sub 1}] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO{sub corr}]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m{sup 2} (IQR, 15.7-16.0 g/m{sup 2}). At 24 and 60 months ACT, DLCO{sub corr} was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV{sub 1} was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO{sub corr} was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO{sub corr} were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI

  1. The differences of brain cortical activation between superficial pain and deep pain

    International Nuclear Information System (INIS)

    Ikemoto, Tatsunori; Ushida, Takahiro; Taniguchi, Shinichirou; Tani, Toshikazu; Morio, Kazuo; Sasaki, Toshikazu; Tanaka, Shigeki

    2006-01-01

    Using functional magnetic resonance imaging (FMRI) technology, we investigated the difference of pain related brain cortical activation derived from noxious stimulation to the skin and muscular tissue. Ten healthy volunteers who have no history of brain vascular disease were enrolled in this study. A cutaneous pain was provoked by isotonic (0.9%) saline injection into intra-dermal space on right lower leg through 24G plastic catheter, and a muscle pain was provoked by hypertonic (3%) saline injection into right tibialis anterior muscle. We used event-related FMRI to measure brain activity during each injection. Visual analogue scale (VAS) was used to quantify pain intensity and unpleasantness, and pain quality was assessed with several verbal descriptions. Pain unpleasantness rating was higher in the muscle pain compared to the cutaneous pain, despite the same pain intensity rating. The cutaneous pain had more acute pain onset than the muscle pain. Pain duration after stimulation was short in the cutaneous pain, but long in the muscle pain. The extent of the painful region tended to be larger with the muscle pain, but there was no statistical significance. Evoked FMRI response from the cutaneous pain showed distinct brain activation in the inferior and superior parietal cortex (BA: Brodmann area 5/7/40), primary and secondary somatosensory cortex (S1 and S2), insula, supplementary motor area (SMA, BA6), posterior cingulate cortex and cerebellum. On the other hand, FMRI response from muscle pain showed distinct brain activation mainly in the contralateral insula. These results suggest that the parietal lobe including the S1 is the essential area for cognition of sharp and well-localized pain conditions such as cutaneous pain, and may not be essential for cognition of diffuse pain derived from muscular tissue. (author)

  2. A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes

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    Björn eNitzsche

    2015-06-01

    Full Text Available Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams were acquired on a 1.5T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight, age and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM and white (WM matter as well as cerebrospinal fluid (CSF classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM. Overall, a positive correlation of GM volume and body weight explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species.

  3. 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

  4. 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.

  5. 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.

  6. Systematic Optimization of Long Gradient Chromatography Mass Spectrometry for Deep Analysis of Brain Proteome

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    Wang, Hong; Yang, Yanling; Li, Yuxin; Bai, Bing; Wang, Xusheng; Tan, Haiyan; Liu, Tao; Beach, Thomas G.; Peng, Junmun; Wu, Zhiping

    2015-02-06

    Development of high resolution liquid chromatography (LC) is essential for improving the sensitivity and throughput of mass spectrometry (MS)-based proteomics. Here we present systematic optimization of a long gradient LC-MS/MS platform to enhance protein identification from a complex mixture. The platform employed an in-house fabricated, reverse phase column (100 μm x 150 cm) coupled with Q Exactive MS. The column was capable of achieving a peak capacity of approximately 700 in a 720 min gradient of 10-45% acetonitrile. The optimal loading level was about 6 micrograms of peptides, although the column allowed loading as many as 20 micrograms. Gas phase fractionation of peptide ions further increased the number of peptide identification by ~10%. Moreover, the combination of basic pH LC pre-fractionation with the long gradient LC-MS/MS platform enabled the identification of 96,127 peptides and 10,544 proteins at 1% protein false discovery rate in a postmortem brain sample of Alzheimer’s disease. As deep RNA sequencing of the same specimen suggested that ~16,000 genes were expressed, current analysis covered more than 60% of the expressed proteome. Further improvement strategies of the LC/LC-MS/MS platform were also discussed.

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

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    Jean-Philippe Langevin

    2016-08-01

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

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

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    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.

  9. 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.)

  10. Automated assessment of symptom severity changes during deep brain stimulation (DBS) therapy for Parkinson's disease.

    Science.gov (United States)

    Angeles, Paolo; Tai, Yen; Pavese, Nicola; Wilson, Samuel; Vaidyanathan, Ravi

    2017-07-01

    Deep brain stimulation (DBS) is currently being used as a treatment for symptoms of Parkinson's disease (PD). Tracking symptom severity progression and deciding the optimal stimulation parameters for people with PD is extremely difficult. This study presents a sensor system that can quantify the three cardinal motor symptoms of PD - rigidity, bradykinesia and tremor. The first phase of this study assesses whether data recorded from the system during physical examinations can be used to correlate to clinician's severity score using supervised machine learning (ML) models. The second phase concludes whether the sensor system can distinguish differences before and after DBS optimisation by a clinician when Unified Parkinson's Disease Rating Scale (UPDRS) scores did not change. An average accuracy of 90.9 % was achieved by the best ML models in the first phase, when correlating sensor data to clinician's scores. Adding on to this, in the second phase of the study, the sensor system was able to pick up discernible differences before and after DBS optimisation sessions in instances where UPDRS scores did not change.

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

    Science.gov (United States)

    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.

  12. Hypokinesia upon pallidal deep brain stimulation of dystonia: support of a GABAergic mechanism

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    Florian eAmtage

    2013-12-01

    Full Text Available In the past, many studies have documented the beneficial effects of deep brain stimulation (DBS in the globus pallidus internus for treatment of primary segmental or generalized dystonia. Recently however, several reports focused on DBS-induced hypokinesia or freezing of gait as a side effect in these patients. Here we report on two patients suffering from freezing of gait after successful treatment of their dystonic movement disorder with pallidal high frequency stimulation (HFS. Several attempts to reduce the freezing of gait resulted in worsening of the control of dystonia. In one patient levodopa treatment was initialized which was somewhat successful to relieve freezing of gait. We discuss the possible mechanisms of hypokinetic side effects of pallidal DBS which can be explained by the hypothesis of selective GABA release as the mode of action of HFS. Pallidal HFS is also effective in treating idiopathic Parkinson’s disease as a hypokinetic disorder which at first sight seems to be a paradox. In our view, however, the GABAergic hypothesis can explain this and other clinical observations.

  13. Deep brain stimulation of the accumbens increases dopamine, serotonin, and noradrenaline in the prefrontal cortex.

    Science.gov (United States)

    van Dijk, Addy; Klompmakers, Andre A; Feenstra, Matthijs G P; Denys, Damiaan

    2012-12-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is effective in treatment-refractory obsessive-compulsive disorder and major depressive disorder. However, little is known about the neurobiological mechanisms underlying the rapid and effective changes of DBS. One of the hypotheses is that DBS modulates activity of monoamine neurotransmitters. In this study, we evaluated the effects of DBS in the NAc core on the extracellular concentration of monoaminergic neurotransmitters in the medial (mPFC) and orbital prefrontal cortex (OFC). Freely moving rats were bilaterally stimulated in the NAc core for 2 h while dopamine, serotonin, and noradrenaline were measured using in vivo microdialysis in the mPFC and the OFC. We report rapid increases in the release of dopamine and serotonin to a maximum of 177% and 127% in the mPFC and an increase up to 171% and 166% for dopamine and noradrenaline in the OFC after onset of stimulation in the NAc core. These results provide further evidence for the distal effects of DBS and corroborate previous clinical and pre-clinical findings of altered neuronal activity in prefrontal areas. © 2012 International Society for Neurochemistry.

  14. 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.

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

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    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.

  16. Controlling absence seizures by deep brain stimulus applied on substantia nigra pars reticulata and cortex

    International Nuclear Information System (INIS)

    Hu, Bing; Wang, Qingyun

    2015-01-01

    Epilepsy is a typical neural disease in nervous system, and the control of seizures is very important for treating the epilepsy. It is well known that the drug treatment is the main strategy for controlling the epilepsy. However, there are about 10–15 percent of patients, whose seizures cannot be effectively controlled by means of the drug. Alternatively, the deep brain stimulus (DBS) technology is a feasible method to control the serious seizures. However, theoretical explorations of DBS are still absent, and need to be further made. Presently, we will explore to control the absence seizures by introducing the DBS to a basal ganglia thalamocortical network model. In particular, we apply DBS onto substantia nigra pars reticulata (SNr) and the cortex to explore its effects on controlling absence seizures, respectively. We can find that the absence seizure can be well controlled within suitable parameter ranges by tuning the period and duration of current stimulation as DBS is implemented in the SNr. And also, as the DBS is applied onto the cortex, it is shown that for the ranges of present parameters, only adjusting the duration of current stimulation is an effective control method for the absence seizures. The obtained results can have better understanding for the mechanism of DBS in the medical treatment.

  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. 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.

  19. Bilateral thalamic deep brain stimulation for the treatment of head tremor. Report of two cases.

    Science.gov (United States)

    Berk, Caglar; Honey, Christopher R

    2002-03-01

    Isolated head tremor is rare, but can be disabling. The authors' experience with the treatment of limb tremor due to essential tremor led them to consider using bilateral thalamic deep brain stimulation (DBS) in two patients presenting only with disabling head tremor. One patient exhibited no peripheral tremor and the other displayed only a slight upper-limb tremor. Both patients underwent placement of units that apply simultaneous bilateral thalamic DBS. Surgical targets were verified by using intraoperative macrostimulation, and the stimulators were implanted during the same surgery. Patients were videotaped preoperatively and at 2, 4, 6, and 9 months postoperatively during periods in which the stimulators were turned on and off. Videotapes were randomized and rated for resting, postural, and action tremors according to the Fahn clinical rating scale for tremor. Because this scale is not designed for head tremor, the patients were also evaluated on the basis of a functional scale that reflected their quality of life and the amount of disability caused by head tremor. Both patients experienced no tremor after their stimulators were turned on and properly adjusted at the 6th postoperative week. The patients were followed for a total of 9 months and results remained stable throughout this period. No complications were encountered. Bilateral thalamic DBS appears to be an effective and safe treatment for isolated head tremor in patients with essential tremor. The authors present a scale for the functional assessment of head tremor.

  20. 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.

  1. Does deep brain stimulation improve lower urinary tract symptoms in Parkinson's disease?

    Science.gov (United States)

    Witte, Lambertus P; Odekerken, Vincent J J; Boel, Judith A; Schuurman, P Richard; Gerbrandy-Schreuders, Lara C; de Bie, Rob M A

    2018-01-01

    To investigate whether deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) or the subthalamic nucleus (STN) improve lower urinary tract symptoms (LUTS) in advanced Parkinson's disease (PD). An exploratory post-hoc analysis was performed of specific LUTS items of questionnaires used in a randomized clinical trial with 128 patients (NSTAPS study). First, we compared scores on LUTS items at baseline and 12 months for the GPi DBS and STN DBS group separately. Second, we divided the group by sex, instead of DBS location; to assess a possible gender associated influence of anatomical and pathophysiological differences, again comparing scores at baseline and 12 months. Third, we reported on Foley-catheter use at baseline and after 12 months. Urinary incontinence and frequency improved after both GPi DBS and STN DBS at 12 months, postoperatively, but this was only statistically significant for the STN DBS group (P = 0.004). The improvements after DBS were present in both men (P = 0.01) and women (P = 0.05). Nocturia and urinary incontinence did not improve significantly after any type of DBS, irrespective of sex. At 12 months, none of the patients had a Foley-catheter. Urinary incontinence and frequency significantly improved after STN DBS treatment in male and female patients with PD. Nocturia and nighttime incontinence due to parkinsonism did not improve after DBS, irrespective of gender. © 2017 Wiley Periodicals, Inc.

  2. Hyperhidrosis associated with subthalamic deep brain stimulation in Parkinson's disease: Insights into central autonomic functional anatomy.

    Science.gov (United States)

    Ramirez-Zamora, Adolfo; Smith, Heather; Youn, Youngwon; Durphy, Jennifer; Shin, Damian S; Pilitsis, Julie G

    2016-07-15

    There is limited evidence regarding the precise location and connections of thermoregulatory centers in humans. We present two patients managed with subthalamic nucleus (STN) Deep Brain Stimulation (DBS) for motor fluctuations in PD that developed reproducible hyperhidrosis with high frequency DBS. To describe the clinical features and analyze the location of the electrodes leading to autonomic activation in both patients. We retrospectively assessed the anatomical localization, electrode programming settings and effects of unilateral STN DBS leading to hyperhidrosis. Unilateral stimulation of anterior and medially located contacts within the STN and zona incerta (Zi) caused bilateral, consistent, reproducible, and reversible sweating in our patients. Adequate control of motor symptoms without autonomic side effects was accomplished with alternative programming settings. Stimulation of the medial Zi and medial and anterior STN causes hyperhidrosis in a pattern similar to that described in primates and rats. We speculate that central autonomic fibers originating in the lateral hypothalamic area project laterally to the ventral/medial Zi and then to brainstem nuclei following an medial and posterior trajectory in relationship to STN. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. 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.

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

    Science.gov (United States)

    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

    2016-03-01

    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 DBS (n = 63). Standardized psychiatric and social questionnaires were assessed at baseline and after 12 months. No differences were found between GPi DBS and STN DBS on psychiatric evaluation. Within-group comparisons showed small but statistically significant changes on several measures in both groups. Descriptive statistics indicated slight changes in social functioning. Marital satisfaction of patients and partners remained relatively stable after GPi and STN DBS. We found neither differences in psychiatric and social outcome between GPi DBS and STN DBS nor any relevant within-group differences. The decision for GPi DBS or STN DBS cannot be based on expected psychiatric or social effects. © 2015 International Parkinson and Movement Disorder Society.

  5. Accuracy of Intraoperative Computed Tomography during Deep Brain Stimulation Procedures: Comparison with Postoperative Magnetic Resonance Imaging.

    Science.gov (United States)

    Bot, Maarten; van den Munckhof, Pepijn; Bakay, Roy; Stebbins, Glenn; Verhagen Metman, Leo

    2017-01-01

    To determine the accuracy of intraoperative computed tomography (iCT) in localizing deep brain stimulation (DBS) electrodes by comparing this modality with postoperative magnetic resonance imaging (MRI). Optimal lead placement is a critical factor for the outcome of DBS procedures and preferably confirmed during surgery. iCT offers 3-dimensional verification of both microelectrode and lead location during DBS surgery. However, accurate electrode representation on iCT has not been extensively studied. DBS surgery was performed using the Leksell stereotactic G frame. Stereotactic coordinates of 52 DBS leads were determined on both iCT and postoperative MRI and compared with intended final target coordinates. The resulting absolute differences in X (medial-lateral), Y (anterior-posterior), and Z (dorsal-ventral) coordinates (ΔX, ΔY, and ΔZ) for both modalities were then used to calculate the euclidean distance. Euclidean distances were 2.7 ± 1.1 and 2.5 ± 1.2 mm for MRI and iCT, respectively (p = 0.2). Postoperative MRI and iCT show equivalent DBS lead representation. Intraoperative localization of both microelectrode and DBS lead in stereotactic space enables direct adjustments. Verification of lead placement with postoperative MRI, considered to be the gold standard, is unnecessary. © 2017 The Author(s) Published by S. Karger AG, Basel.

  6. Combined diffuse light reflectance and electrical impedance measurements as a navigation aid in deep brain surgery.

    Science.gov (United States)

    Johansson, Johannes D; Blomstedt, Patric; Haj-Hosseini, Neda; Bergenheim, A Tommy; Eriksson, Ola; Wårdell, Karin

    2009-01-01

    The aim of this study is to assess reflected light intensity combined with impedance as a navigation aid during stereotactic neurosurgery. During creation of 21 trajectories for stereotactic implantation of deep brain stimulation electrodes in the globus pallidus internus or subthalamus (zona incerta or subthalamic nucleus), impedance at 512 kHz and reflected light intensity at 780 nm were measured continuously and simultaneously with a radio frequency electrode containing optical fibres. The signals were compared with the anatomy, determined from pre- and post-operative MRI and CT. The measurements were performed within minutes, and signal analysis was done post-operatively. Reflected light intensity was low from the cortex, lateral ventricle, caudate nucleus and putamen; intermediate from the globus pallidus and thalamus; while it was high from the subcortical white matter, internal capsule and subthalamus. The electrical impedance was less consistent, but generally low in the cortex, intermediate in the subcortical white matter, putamen, globus pallidus and thalamus, and high in the internal capsule and subthalamus. Reflected light intensity and electrical impedance give complementary information about passed tissue, and the combination seems promising as a navigation aid during stereotactic neurosurgery. (c) 2009 S. Karger AG, Basel.

  7. Variation in Deep Brain Stimulation Electrode Impedance over Years Following Electrode Implantation

    Science.gov (United States)

    Satzer, David; Lanctin, David; Eberly, Lynn E.; Abosch, Aviva

    2014-01-01

    Background Deep brain stimulation (DBS) electrode impedance is a major determinant of current delivery to target tissues, but long-term variation in impedance has received little attention. Objectives To assess the relationship between electrode impedance and time in a large DBS patient population and characterize the relationship between contact activity and impedance. Methods We collected retrospective impedance and programming data from 128 electrodes in 84 patients with Parkinson's disease, essential tremor, or dystonia. Effects of time, contact activity, stimulation voltage, and other parameters on impedance were assessed. We also examined impedance changes following contact activation and deactivation. Results Impedance decreased by 73 Ω/year (P Impedance was on average 163 Ω lower in active contacts (P impedance, respectively. Higher stimulation voltages were associated with lower impedance values (P impedance. Conclusions Impedance decreases gradually in a stimulation-dependent manner. These trends have implications for long-term programming, the development of a closed-loop DBS device, and current understanding of the electrode-tissue interface. PMID:24503709

  8. 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.

  9. Acute and Subacute Presentations of Cerebral Edema following Deep Brain Stimulation Lead Implantation.

    Science.gov (United States)

    Fenoy, Albert J; Villarreal, Sebastian J; Schiess, Mya C

    2017-01-01

    Postoperative cerebral edema around a deep brain stimulation (DBS) electrode is an uncommon reported complication. The goal of this study was to identify instances of postoperative edema based on clinical presentation, and to remark on their management. A retrospective chart review was performed on all patients who underwent DBS electrode implantation over a 3-year period. Routine CT imaging on postoperative day (POD) 1 was negative. Patients were identified based on clinical neurological changes, leading to imaging and subsequent diagnosis. Five of 145 patients (3.4%) presented with new neurological symptoms from POD 1 to 14, which were confirmed by CT imaging to show perilead and/or subcortical edema around 6 of 281 electrodes (2.1%). Four of 5 patients had unilateral edema despite bilateral implantation. Clinical presentations varied widely. Two patients presenting on POD 1 with deteriorating conditions required longer inpatient stays with supportive measures than those presenting later (p = 0.0002). All patients were treated with corticosteroids and returned to baseline by 3 months after surgery. Acute instances of DBS lead edema may occur as early as POD 1 and can rapidly progress into profound deficits. Treatment with supportive care and corticosteroids is otherwise identical to those cases presenting later. © 2017 S. Karger AG, Basel.

  10. The role of modern imaging modalities on deep brain stimulation targeting for mental illness.

    Science.gov (United States)

    Sedrak, M; Gorgulho, A; De Salles, A F; Frew, A; Behnke, E; Ishida, W; Klochkov, T; Malkasian, D

    2008-01-01

    The reversible nature of deep brain stimulation (DBS) brought renewed interest on surgery to medically intractable mental illnesses. The explosion of anatomical and functional imaging has allowed the development of new potential targets and the understanding of historical targets. Fifteen patients undergoing stereotactic surgery for movement disorders, at UCLAs interventional MRI operating-room, were studied with fiber tracking. Stereotactic targets and fiber tracking were determined on MRIs using the Schaltenbrand-Wahren atlas for definition in the iPlan software. Cingulate, subcaudate, BA25/CgWM, amygdala, posterior hypothalamus, orbitofrontal cortex, nucleus accumbens, anterior limb of the internal capsule and dorsomedial thalamus were studied. DTI parameters used ranged from 10 to 20mm for voxel size in the x/y/z planes, fiber length was kept constant at 36 mm, and fractional anisotropy (FA) threshold varied from 0.20 to 0.25. Reliable interconnectivity of targets were determined with DTI and related to PET imaging. Mental illness targets were observed with functional and fiber tract maps. This confirmation yields reliability to DTI imaging in order to determine novel targets and enhance the understanding of areas not well understood. Currently available imaging techniques, the reversibility of DBS to modulate targets promises to bring a brighter future for surgery of mental illness.

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