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Sample records for deep brain areas

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

    PubMed

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

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive-compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of principal interest to understand which brain area is responsible for the anxiolytic effect and whether high-frequency stimulation of different areas differentially affect unconditioned (innate) and conditioned (learned) anxiety. In this study, we examined the effect of stimulation in five brain areas in rats (NAc core and shell, bed nucleus of the stria terminalis (BNST), internal capsule (IC) and the ventral medial caudate nucleus (CAU)). The elevated plus maze was used to test the effect of stimulation on unconditioned anxiety, the Vogel conflict test for conditioned anxiety, and an activity test for general locomotor behaviour. We found different anxiolytic effects of stimulation in the five target areas. Stimulation of the CAU decreased both conditioned and unconditioned anxiety, while stimulation of the IC uniquely reduced conditioned anxiety. Remarkably, neither the accumbens nor the BNST stimulation affected conditioned or unconditioned anxiety. Locomotor activity increased with NAc core stimulation but decreased with the BNST. These findings suggest that (1) DBS may have a differential effect on unconditioned and conditioned anxiety depending on the stimulation area, and that (2) stimulation of the IC exclusively reduces conditioned anxiety. This suggests that the anxiolytic effects of DBS seen in OCD patients may not be induced by stimulation of the NAc, but rather by the IC. PMID:23900312

  2. An acute method for multielectrode recording from the interior of sulci and other deep brain areas.

    PubMed

    Purushothaman, Gopathy; Scott, Benjamin B; Bradley, David C

    2006-05-15

    Most current techniques for multielectrode recording involve chronically implanting planar or staggered arrays of electrodes. Such chronic implants are suited for studying a stable population of neurons over long periods of time but exploratory studies of the physiological properties of cortical subdivisions require the ability to sample multiple neural populations. This makes it necessary to penetrate frequently with small multielectrode assemblies. Some commercial systems allow daily penetrations with multiple electrodes, but they tend to be bulky, complex and expensive, and some make no provision for piercing the barrier of fibrous tissue that often covers the brain surface. We describe an apparatus for inserting bundles of 3-16 electrodes on a daily basis, thus allowing different neural populations to be sampled. The system is designed to allow penetration through a thick dura mater into deep brain structures. We discuss a simple method for performing multielectrode recording from cortical areas buried inside sulci using acute implantations of a bundle of electrodes. Our results show that it is possible to obtain stable recordings for at least 4h and that repeated implantations yield an average of two neurons per electrode with every electrode in the bundle picking up at least one single neuron in 70% of the implantations. PMID:16316688

  3. Cortical Potentials Evoked by Deep Brain Stimulation in the Subthalamic Area

    PubMed Central

    Devergnas, Annaelle; Wichmann, Thomas

    2011-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been used since the mid-1990s as a treatment for patients with Parkinson's disease, and more recently also in other conditions, such as dystonia or obsessive compulsive disorder. Non-invasive studies of cortical evoked potentials (EPs) that follow individual STN–DBS stimuli has provided us with insights about the conduction of the DBS pulses to the cortex. Such EPs have multiple components of different latencies, making it possible to distinguish short-latency and long-latency responses (3–8 ms and 18–25 ms latency, respectively). The available evidence indicates that these short- and long-latency EPs correspond to conduction from the STN stimulation site to the cortical recording location via anti- and orthodromic pathways, respectively. In this review we survey the literature from recording studies in human patients treated with STN–DBS for Parkinson's disease and other conditions, as well as recent animal studies (including our own) that have begun to elucidate details of the pathways, frequency dependencies, and other features of EPs. In addition, we comment on the possible clinical utility of this knowledge. PMID:21625611

  4. Wireless magnetothermal deep brain stimulation.

    PubMed

    Chen, Ritchie; Romero, Gabriela; Christiansen, Michael G; Mohr, Alan; Anikeeva, Polina

    2015-03-27

    Wireless deep brain stimulation of well-defined neuronal populations could facilitate the study of intact brain circuits and the treatment of neurological disorders. Here, we demonstrate minimally invasive and remote neural excitation through the activation of the heat-sensitive capsaicin receptor TRPV1 by magnetic nanoparticles. When exposed to alternating magnetic fields, the nanoparticles dissipate heat generated by hysteresis, triggering widespread and reversible firing of TRPV1(+) neurons. Wireless magnetothermal stimulation in the ventral tegmental area of mice evoked excitation in subpopulations of neurons in the targeted brain region and in structures receiving excitatory projections. The nanoparticles persisted in the brain for over a month, allowing for chronic stimulation without the need for implants and connectors. PMID:25765068

  5. Deep Brain Stimulation

    PubMed Central

    Perlmutter, Joel S.; Mink, Jonathan W.

    2015-01-01

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

  6. Deep brain stimulation

    MedlinePlus

    ... the brain The neurostimulator, which puts out the electric current. The stimulator is similar to a heart pacemaker . It is usually placed under the skin near the collarbone, but may be ... pulses travel from the neurostimulator, along the extension ...

  7. Deep Brain Stimulation Tested for Early Alzheimer's

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_160137.html Deep Brain Stimulation Tested for Early Alzheimer's Although treatment seems ... 2016 THURSDAY, July 28, 2016 (HealthDay News) -- Deep brain stimulation appears safe for people with early Alzheimer's ...

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

    PubMed

    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. PMID

  9. Deep Brain Stimulation: Expanding Applications

    PubMed Central

    TEKRIWAL, Anand; BALTUCH, Gordon

    2015-01-01

    For over two decades, deep brain stimulation (DBS) has shown significant efficacy in treatment for refractory cases of dyskinesia, specifically in cases of Parkinson's disease and dystonia. DBS offers potential alleviation from symptoms through a well-tolerated procedure that allows personalized modulation of targeted neuroanatomical regions and related circuitries. For clinicians contending with how to provide patients with meaningful alleviation from often debilitating intractable disorders, DBSs titratability and reversibility make it an attractive treatment option for indications ranging from traumatic brain injury to progressive epileptic supra-synchrony. The expansion of our collective knowledge of pathologic brain circuitries, as well as advances in imaging capabilities, electrophysiology techniques, and material sciences have contributed to the expanding application of DBS. This review will examine the potential efficacy of DBS for neurologic and psychiatric disorders currently under clinical investigation and will summarize findings from recent animal models. PMID:26466888

  10. Deep brain stimulation: new techniques.

    PubMed

    Hariz, Marwan

    2014-01-01

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

  11. Increased number of TH-immunoreactive cells in the ventral tegmental area after deep brain stimulation of the anterior nucleus of the thalamus.

    PubMed

    Dela Cruz, J A D; Hescham, S; Adriaanse, B; Campos, F L; Steinbusch, H W M; Rutten, B P F; Temel, Y; Jahanshahi, A

    2015-09-01

    Dopamine (DA) has been long implicated with the processes of memory. In long-term memory, the hippocampus and ventral tegmental area (VTA) use DA to enhance long-term potentiation, while prefrontal DA D1 receptors are involved in working memory. Deep brain stimulation (DBS) of specific brain areas have been shown to affect memory impairments in animal models. Here, we tested the hypothesis that DBS could reverse memory impairments by increasing the number of dopaminergic cells in the VTA. Rats received DBS at the level of the mammillothalamic tract, the anterior nucleus of the thalamus, and entorhinal cortex before euthanasia. These regions are part of the so-called memory circuit. Brain sections were processed for c-Fos and tyrosine hydroxylase (TH) immunocytochemistry in the VTA and the substantia nigra pars compacta (SNc). c-Fos, TH and c-Fos/TH immunoreactive cells were analyzed by means of stereology and confocal microscopy. Our results showed that DBS of the anterior nucleus of the thalamus induced substantial higher numbers of TH-immunoreactive cells in the VTA, while there were no significant differences between the experimental groups in the number of TH immunoreactive cells in the SNc, c-Fos immunoreactive cells and c-Fos/TH double-labeled cells in both the SNc and VTA. Our findings suggest a phenotypic switch, or neurotransmitter respecification, of DAergic cells specifically in the VTA which may be induced by DBS in the anterior nucleus of the thalamus. PMID:25074751

  12. Deep Brain Stimulation for Obesity

    PubMed Central

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

    2015-01-01

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

  13. Tractography patterns of subthalamic nucleus deep brain stimulation.

    PubMed

    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

  14. [MRI compatibility of deep brain stimulator].

    PubMed

    Zhang, Yujing

    2013-07-01

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

  15. Deep brain stimulation, ethics, and society.

    PubMed

    Bell, Emily; Racine, Eric

    2010-01-01

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

  16. Deep brain stimulation: new directions.

    PubMed

    Ostergard, T; Miller, J P

    2014-12-01

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

  17. Deep Brain Electrical Stimulation in Epilepsy

    NASA Astrophysics Data System (ADS)

    Rocha, Luisa L.

    2008-11-01

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

  18. Deep brain stimulation for chronic pain.

    PubMed

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

    2015-10-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

    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.

  20. Neuropsychiatric deep brain stimulation for translational neuroimaging.

    PubMed

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

    2013-10-01

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

  1. Deep Brain Stimulation for Parkinson Disease

    PubMed Central

    Bronstein, Jeff M.; Tagliati, Michele; Alterman, Ron L.; Lozano, Andres M.; Volkmann, Jens; Stefani, Alessandro; Horak, Fay B.; Okun, Michael S.; Foote, Kelly D.; Krack, Paul; Pahwa, Rajesh; Henderson, Jaimie M.; Hariz, Marwan I.; Bakay, Roy A.; Rezai, Ali; Marks, William J.; Moro, Elena; Vitek, Jerrold L.; Weaver, Frances M.; Gross, Robert E.; DeLong, Mahlon R.

    2015-01-01

    Objective To provide recommendations to patients, physicians, and other health care providers on several issues involving deep brain stimulation (DBS) for Parkinson disease (PD). Data Sources and Study Selection An international consortium of experts organized, reviewed the literature, and attended the workshop. Topics were introduced at the workshop, followed by group discussion. Data Extraction and Synthesis A draft of a consensus statement was presented and further edited after plenary debate. The final statements were agreed on by all members. Conclusions (1) Patients with PD without significant active cognitive or psychiatric problems who have medically intractable motor fluctuations, intractable tremor, or intolerance of medication adverse effects are good candidates for DBS. (2) Deep brain stimulation surgery is best performed by an experienced neurosurgeon with expertise in stereotactic neurosurgery who is working as part of a interprofessional team. (3) Surgical complication rates are extremely variable, with infection being the most commonly reported complication of DBS. (4) Deep brain stimulation programming is best accomplished by a highly trained clinician and can take 3 to 6 months to obtain optimal results. (5) Deep brain stimulation improves levodopa-responsive symptoms, dyskinesia, and tremor; benefits seem to be long-lasting in many motor domains. (6) Subthalamic nuclei DBS may be complicated by increased depression, apathy, impulsivity, worsened verbal fluency, and executive dysfunction in a subset of patients. (7) Both globus pallidus pars interna and subthalamic nuclei DBS have been shown to be effective in addressing the motor symptoms of PD. (8) Ablative therapy is still an effective alternative and should be considered in a select group of appropriate patients. PMID:20937936

  2. Pathways of Translation: Deep Brain Stimulation

    PubMed Central

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

    2014-01-01

    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 electric 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 17th century and was fostered by technological advances of the 20th. In this article we review that journey and discuss how the quest to expand its applications and continue to improve outcomes is taking DBS from the bedside back to the bench. PMID:24330698

  3. Network effects of deep brain stimulation.

    PubMed

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

    2015-10-01

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

  4. Deep brain stimulation for movement disorders.

    PubMed

    Larson, Paul S

    2014-07-01

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

  5. Novel applications of deep brain stimulation

    PubMed Central

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

    2012-01-01

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

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

    PubMed

    Unterrainer, Marcus; Oduncu, Fuat S

    2015-11-01

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

  7. Origin and Evolution of Deep Brain Stimulation

    PubMed Central

    Sironi, Vittorio A.

    2011-01-01

    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 eighteenth century and was subsequently used by the early twentieth century, even for therapeutic purposes. In mid-twentieth 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, deep brain stimulation (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. PMID:21887135

  8. Deep brain stimulation to reduce sexual drive

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Beudel, M; Brown, P

    2016-01-01

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

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

    PubMed Central

    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

  11. Deep brain stimulation for major depression.

    PubMed

    Schlaepfer, T E; Bewernick, B H

    2013-01-01

    A third of patients suffering from major depression cannot be helped by conventional treatment methods. These patients face reduced quality of life, high risk of suicide, and little hope of recovery. Deep brain stimulation (DBS) is under scientific evaluation as a new treatment option for these treatment-resistant patients. First clinical studies with small samples have been stimulated at the subgenual cingulate gyrus (Cg25/24), the anterior limb of the capsula interna (ALIC), and the nucleus accumbens (NAcc). Long-term antidepressant effects, augmentation of social functioning, and normalization of brain metabolism have been shown in about 50% of patients. Cognitive safety regarding attention, learning, and memory has been reported. Adverse events were wound infection, suicide, and hypomania, amongst others. Larger studies are under way to confirm these preliminary encouraging results. New hypothesis-guided targets (e.g., medial forebrain bundle, habenula) are about to be assessed in clinical trials. The application of DBS for other psychiatric diseases (e.g., bipolar disorder, alcohol dependency, opioid addiction, schizophrenia) is debated and single case studies are under way. Standards are needed for study registration, target selection, patient inclusion and monitoring, and publication of results to guarantee safety for the patients and scientific exchange. PMID:24112897

  12. Emerging applications of deep brain stimulation.

    PubMed

    Sharma, Mayur; Naik, Vikas; Deogaonkar, Milind

    2016-06-01

    Deep brain stimulation (DBS) implantation surgery is an established treatment modality for a variety of medical refractory movement disorders such as Parkinson's disease, essential tremors and dystonia. Following the success of DBS in these movement disorders with a high rate of safety and efficacy, there is a resurgence of interest in the utility of this modality in other medical refractory disorders. Consequently, neuromodulation has been explored for a variety of refractory conditions such as neuropsychiatric disorders (major depressive disorders, obsessive-compulsive disorders, addictions), eating disorders including obesity, traumatic brain injury, post-traumatic stress disorders (PTSD), dementias and chronic pain. This review provides an overview of the emerging applications of DBS in these disorders, including summary of the published literature. We have highlighted the pathophysiology and likely aberrant neural circuits involved in these refractory disorders. Current and possible surgical targets for neurosurgical intervention related to these disorders have also been discussed. Furthermore, recent advances such as closed loop systems; responsive neurostimulation systems and optogenetics techniques have been addressed. PMID:26788743

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

    PubMed

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

    2015-06-01

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

  14. Closing the loop of deep brain stimulation.

    PubMed

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

    2013-01-01

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

  15. The adaptive deep brain stimulation challenge.

    PubMed

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

    2016-07-01

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

  16. Ethical Issues in Deep Brain Stimulation

    PubMed Central

    Schermer, Maartje

    2011-01-01

    Deep 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 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. PMID:21625629

  17. Technological Advances in Deep Brain Stimulation.

    PubMed

    Ughratdar, Ismail; Samuel, Michael; Ashkan, Keyoumars

    2015-01-01

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

  18. Deep Brain Stimulation for Chronic Pain.

    PubMed

    Falowski, Steven M

    2015-07-01

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

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

    PubMed

    Sauleau, Paul; Drapier, Sophie; Duprez, Joan; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Drapier, Dominique; Jannin, Pierre; Robert, Gabriel; Le Jeune, Florence; Vérin, Marc

    2016-01-01

    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. PMID:27070317

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

    PubMed Central

    Sauleau, Paul; Drapier, Sophie; Duprez, Joan; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Drapier, Dominique; Jannin, Pierre; Robert, Gabriel; Le Jeune, Florence; Vérin, Marc

    2016-01-01

    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. PMID:27070317

  1. Stochastic Phase Resetting: a Theory for Deep Brain Stimulation

    NASA Astrophysics Data System (ADS)

    Tass, Peter A.

    2000-03-01

    A stochastic approach to phase resetting in clusters of interacting oscillators is presented. This theory explains how a stimulus, especially a single pulse, induces synchronization and desynchronization processes. The theory is used to design a new technique for deep brain stimulation in patients suffering from Parkinson's disease or essential tremor that do no longer respond to drug therapy. This stimulation mode is a feedback controlled single pulse stimulation. The feedback signal is registered with the deep brain electrode, and the desynchronizing pulses are administered via the same electrode. The stochastic phase resetting theory is used as a starting point of a model based design of intelligent and gentle deep brain stimulation techniques.

  2. Using Saccadometry with Deep Brain Stimulation to Study Normal and Pathological Brain Function.

    PubMed

    Antoniades, Chrystalina A; FitzGerald, James J

    2016-01-01

    The oculomotor system involves a large number of brain areas including parts of the basal ganglia, and various neurodegenerative diseases including Parkinson's and Huntington's can disrupt it. People with Parkinson's disease, for example, tend to have increased saccadic latencies. Consequently, the quantitative measurement of saccadic eye movements has received considerable attention as a potential biomarker for neurodegenerative conditions. A lot more can be learned about the brain in both health and disease by observing what happens to eye movements when the function of specific brain areas is perturbed. Deep brain stimulation is a surgical intervention used for the management of a range of neurological conditions including Parkinson's disease, in which stimulating electrodes are placed in specific brain areas including several sites in the basal ganglia. Eye movement measurements can then be made with the stimulator systems both off and on and the results compared. With suitable experimental design, this approach can be used to study the pathophysiology of the disease being treated, the mechanism by which DBS exerts it beneficial effects, and even aspects of normal neurophysiology. PMID:27501123

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

    NASA Astrophysics Data System (ADS)

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

    2008-09-01

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

  4. Brain areas in abyssal demersal fishes.

    PubMed

    Wagner, H J

    2001-06-01

    Four areas of the brain which receive primary projections from chemical senses ([1] olfactory bulb, [2] gustatory area including facial and vagal lobes), the eye ([3] optic tectum), and mechanosensory, and-hair-cell based systems i.e. the lateral line, vestibular and auditory systems ([4] trigeminal and octavolateral regions) have been studied and relative size differences used to make deductions on the sensory preferences of 35 fish species living on or near the bottom of the deep sea. Furthermore the relative volumes of the telencephalon and the corpus cerebelli were determined. Two evaluation modes were applied: (1) the relative mean of each system was calculated and species with above-average areas identified; (2) a cluster analysis established multivariate correlations among the sensory systems. The diversity of sensory brain areas in this population of fish suggests that the benthic and epibenthic environment of the abyss presents a rich sensory environment. Vision seems to be the single most important sense suggesting the presence of relevant bioluminescent stimuli. However, in combination the chemical senses, smell and taste, surpass the visual system; most prominent among them is olfaction. The trigeminal/octavolateral area indicating the role of lateral line input and possibly audition is also well represented, but only in association with other sensory modalities. A large volume telencephalon was often observed in combination with a prominent olfactory system, whereas cerebella of unusually large sizes occurred in species with above-average visual, hair-cell based, but also olfactory systems, confirming their role as multimodal sensorimotor coordination centers. In several species the predictions derived from the volumetric brain analyses were confirmed by earlier observations of stomach content and data obtained by baited cameras. PMID:11713385

  5. "Asleep" deep brain stimulation for essential tremor.

    PubMed

    Chen, Tsinsue; Mirzadeh, Zaman; Chapple, Kristina; Lambert, Margaret; Dhall, Rohit; Ponce, Francisco A

    2016-06-01

    OBJECT Deep brain stimulation (DBS) performed under general anesthesia ("asleep" DBS) has not been previously reported for essential tremor. This is in part due to the inability to visualize the target (the ventral intermediate nucleus [VIM]) on MRI. The authors evaluate the efficacy of this asleep technique in treating essential tremor by indirect VIM targeting. METHODS The authors retrospectively reviewed consecutive cases of initial DBS for essential tremor performed by a single surgeon. DBS was performed with patients awake (n = 40, intraoperative test stimulation without microelectrode recording) or asleep (n = 17, under general anesthesia). Targeting proceeded with standardized anatomical coordinates on preoperative MRI. Intraoperative CT was used for stereotactic registration and lead position confirmation. Functional outcomes were evaluated with pre- and postoperative Bain and Findley Tremor Activities of Daily Living scores. RESULTS A total of 29 leads were placed in asleep patients, and 60 were placed in awake patients. Bain and Findley Tremor Activities of Daily Living Questionnaire scores were not significantly different preoperatively for awake versus asleep cohorts (p = 0.2). The percentage of postoperative improvement was not significantly different between asleep (48.6%) and awake (45.5%) cohorts (p = 0.35). Euclidean error (mm) was higher for awake versus asleep patients (1.7 ± 0.8 vs 1.2 ± 0.4, p = 0.01), and radial error (mm) trended higherfor awake versus asleep patients (1.3 ± 0.8 vs 0.9 ± 0.5, p = 0.06). There were no perioperative complications. CONCLUSIONS In the authors' initial experience, asleep VIM DBS for essential tremor without intraoperative test stimulation can be performed safely and effectively. PMID:26613177

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

    PubMed Central

    Chakrabarti, Rajkalyan; Ghazanwy, Mahmood; Tewari, Anurag

    2014-01-01

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

  7. Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease

    PubMed Central

    Weaver, Frances M.; Follett, Kenneth; Stern, Matthew; Hur, Kwan; Harris, Crystal; Marks, William J.; Rothlind, Johannes; Sagher, Oren; Reda, Domenic; Moy, Claudia S.; Pahwa, Rajesh; Burchiel, Kim; Hogarth, Penelope; Lai, Eugene C.; Duda, John E.; Holloway, Kathryn; Samii, Ali; Horn, Stacy; Bronstein, Jeff; Stoner, Gatana; Heemskerk, Jill; Huang, Grant D.

    2010-01-01

    quality-of-life scores (P<.001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients (P<.001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage. Conclusion In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events. Trial Registration clinicaltrials.gov Identifier: NCT00056563 PMID:19126811

  8. Correlation of the CT Compatible Stereotaxic Craniotomy with MRI Scans of the Patients for Removing Cranial Lesions Located Eloquent Areas and Deep Sites of Brain

    PubMed Central

    Gulsen, Salih

    2015-01-01

    The first goal in neurosurgery is to protect neural function as long as it is possible. Moreover, while protecting the neural function, a neurosurgeon should extract the maximum amount of tumoral tissue from the tumour region of the brain. So neurosurgery and technological advancement go hand in hand to realize this goal. Using of CT compatible stereotaxy for removing a cranial tumour is to be commended as a cornerstone of these technological advancements. Following CT compatible stereotaxic system applications in neurosurgery, different techniques have taken place in neurosurgical practice. These techniques are magnetic resonance imaging (MRI), MRI compatible stereotaxis, frameless stereotaxy, volumetric stereotaxy, functional MRI, diffusion tensor (DT) imaging techniques (tractography of the white matter), intraoperative MRI and neuronavigation systems. However, to use all of this equipment having these technologies would be impossible because of economic reasons. However, when we correlated this technique with MRI scans of the patients with CT compatible stereotaxy scans, it is possible to provide gross total resection and protect and improve patients’ neural functions.

  9. A linearized current stimulator for deep brain stimulation.

    PubMed

    Shen, Ding-Lan; Chu, Yu-Jung

    2010-01-01

    This paper develops the front end of the stimulator which is applied in the implantable deep brain stimulation (DBS) for the therapy of Parkinson's disease. This stimulator adopts the low power switched-capacitor DAC accompanying with voltage-to-current transconductance amplifiers to obtain the adjustable output currents. The proposed distortion cancellation technique improves the linearity of the current stimulator. Multiple transconductance amplifiers sharing a single DAC save the circuit area. The biphasic stimulation waveform is generated from the bridge switching technique and the programmable pulse. This stimulation circuit provides the 0 approximately 165 microA current for a typical loading of 10 kΩ, 8 approximately 120 micros pulse width, and 126 approximately 244 Hz frequencies with a 0.35 microm CMOS technology at 3.3 V supply voltage. PMID:21096724

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

    PubMed

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

    2016-05-01

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

  11. Memory enhancement induced by hypothalamic/fornix deep brain stimulation.

    PubMed

    Hamani, Clement; McAndrews, Mary Pat; Cohn, Melanie; Oh, Michael; Zumsteg, Dominik; Shapiro, Colin M; Wennberg, Richard A; Lozano, Andres M

    2008-01-01

    Bilateral hypothalamic deep brain stimulation was performed to treat a patient with morbid obesity. We observed, quite unexpectedly, that stimulation evoked detailed autobiographical memories. Associative memory tasks conducted in a double-blinded "on" versus "off" manner demonstrated that stimulation increased recollection but not familiarity-based recognition, indicating a functional engagement of the hippocampus. Electroencephalographic source localization showed that hypothalamic deep brain stimulation drove activity in mesial temporal lobe structures. This shows that hypothalamic stimulation in this patient modulates limbic activity and improves certain memory functions. PMID:18232017

  12. Stochastic Phase Resetting: A Theory for Deep Brain Stimulation

    NASA Astrophysics Data System (ADS)

    Tass, P. A.

    The basic principles of a stochastic approach to phase resetting in populations of interacting phase oscillators are presented in this article. This theory explains how synchronization and desynchronization processes are caused by a pulsatile stimulus. It is a central goal of this approach to establish a theoretical basis for the design of efficient and intelligent new deep brain stimulation techniques. Accordingly, the theory is used to design a new deep brain stimulation technique with feedback control in patients suffering from Parkinson's disease or essential tremor.

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

    PubMed Central

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

    2015-01-01

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

  14. Deep Brain Stimulation for Essential Vocal Tremor: A Technical Report.

    PubMed

    Ho, Allen L; Choudhri, Omar; Sung, C Kwang; DiRenzo, Elizabeth E; Halpern, Casey H

    2015-03-01

    Essential vocal tremor (EVT) is the presence of a tremulous voice that is commonly associated with essential tremor. Patients with EVT often report a necessary increase in vocal effort that significantly worsens with stress and anxiety and can significantly impact quality of life despite optimal medical and behavioral treatment options. Deep brain stimulation (DBS) has been proposed as an effective therapy for vocal tremor, but very few studies exist in the literature that comprehensively evaluate the efficacy of DBS for specifically addressing EVT. We present a technical report on our multidisciplinary, comprehensive operative methodology for treatment of EVT with frameless, awake deep brain stimulation (DBS). PMID:26180680

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

    NASA Astrophysics Data System (ADS)

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

    2005-01-01

    Deep brain stimulators, often called `pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

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

    PubMed

    Oshima, Hideki; Katayama, Yoichi

    2010-01-01

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

  17. Optogenetic Tools for Confined Stimulation in Deep Brain Structures.

    PubMed

    Castonguay, Alexandre; Thomas, Sébastien; Lesage, Frédéric; Casanova, Christian

    2016-01-01

    Optogenetics has emerged in the past decade as a technique to modulate brain activity with cell-type specificity and with high temporal resolution. Among the challenges associated with this technique is the difficulty to target a spatially restricted neuron population. Indeed, light absorption and scattering in biological tissues make it difficult to illuminate a minute volume, especially in the deep brain, without the use of optical fibers to guide light. This work describes the design and the in vivo application of a side-firing optical fiber adequate for delivering light to specific regions within a brain subcortical structure. PMID:26965129

  18. Laser treatments of deep-seated brain lesions

    NASA Astrophysics Data System (ADS)

    Ward, Helen A.

    1997-06-01

    The five year survival rate of deep-seated malignant brain tumors after surgery/radiotherapy is virtually 100 percent mortality. Special problems include: (1) Lesions often present late. (2) Position: lesion overlies vital structures, so complete surgical/radiotherapy lesion destruction can damage vital brain-stem functions. (3) Difficulty in differentiating normal brain form malignant lesions. This study aimed to use the unique properties of the laser: (a) to minimize damage during surgical removal of deep-seated brain lesions by operating via fine optic fibers; and (b) to employ the propensity of certain lasers for absorption of dyes and absorption and induction of fluorescence in some brain substances, to differentiate borders of malignant and normal brain, for more complete tumor removal. In the method a fine laser endoscopic technique was devised for removal of brain lesions. The results of this technique, were found to minimize and accurately predict the extent of thermal damage and shock waves to within 1-2mm of the surgical laser beam. Thereby it eliminated the 'popcorn' effect.

  19. A history of deep brain stimulation: Technological innovation and the role of clinical assessment tools

    PubMed Central

    2013-01-01

    Deep brain stimulation involves using a pacemaker-like device to deliver constant electrical stimulation to problematic areas within the brain. It has been used to treat over 40,000 people with Parkinson’s disease and essential tremor worldwide and is currently undergoing clinical trials as a treatment for depression and obsessive–compulsive disorder. This article will provide an historical account of deep brain stimulation in order to illustrate the plurality of interests involved in the development and stabilization of deep brain stimulation technology. Using Latour’s notion of immutable mobiles, this article will illustrate the importance of clinical assessment tools in shaping technological development in the era of medical device regulation. Given that such tools can serve commercial and professional interests, this article suggests that it is necessary to scrutinise their application in research contexts to ensure that they capture clinical changes that are meaningful for patients and their families. This is particularly important in relation to potentially ethically problematic therapies such as deep brain stimulation for psychiatric disorders.

  20. [Some peculiarities of brain phospholipids in deep sea fishes].

    PubMed

    Pomazanskaia, L F; Pravdina, N I; Chirkovskaia, E V

    1975-01-01

    Total phospholipids (PL) as well as the content of various phospholipid classes and their fatty acid composition have been investigated in the brain of mesopelagic and abyssal marine teleosts. These species were compared to shallow water ones. The brain of deep sea fishes was found to be very poor in PL as compared to the brain of mesopelagic ans surface water species. No differences concerning the brain PL content were revealed between the two last mentioned groups. The relative content of separate PL classes was very similar in all the species studied irrespectively of the depth of their habitat. Peculiarities were found in fatty acid composition of individual PL from deep sea species as compared to surface ones. The deeper the habitat, the lower the content of saturated fatty acids, especially of the stearic acid. The lowest content of saturated fatty acids, maximum level of polyenoic fatty acids as well as some peculiarities in the relative content of particular fatty acids were found in the brain of ultraabyssal (6, 000 m) Leucicorus sp. PMID:1217333

  1. [Shining light on translational research in deep brain stimulation].

    PubMed

    Lüscher, Christian; Davoine, Elise; Bellone, Carmilla

    2015-04-29

    For the last decade, optogenetics has revolutionised the neurosciences by enabling an unprecedented characterisation of the circuits involved in brain diseases, in particular addiction, depression, and obsessive compulsive disorders (OCD) and other anxiety disorders. Recently, the technique has also been used to propose blueprints for novel treatments of these diseases. For many reasons, optogenetics cannot be applied to humans applications anytime soon; we therefore argue that an intermediate step would be novel deep brain stimulation (DBS) protocols that emulate successful optogenetic "treatments" in animal models. Here we provide a roadmap of a translational path to rational, optogenetically inspired DBS protocols to refine existing approaches and expand it to novel indications. PMID:26062226

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

    PubMed

    Chiken, Satomi; Nambu, Atsushi

    2016-06-01

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

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

    PubMed

    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. PMID:26030702

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

    PubMed

    Lee, Hweeling; Fell, Jürgen; Axmacher, Nikolai

    2013-11-01

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

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

    PubMed

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

    2014-01-01

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

  6. Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens

    PubMed Central

    Hadar, R; Vengeliene, V; Barroeta Hlusicke, E; Canals, S; Noori, H R; Wieske, F; Rummel, J; Harnack, D; Heinz, A; Spanagel, R; Winter, C

    2016-01-01

    Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse. PMID:27327255

  7. Paradoxical augmented relapse in alcohol-dependent rats during deep-brain stimulation in the nucleus accumbens.

    PubMed

    Hadar, R; Vengeliene, V; Barroeta Hlusicke, E; Canals, S; Noori, H R; Wieske, F; Rummel, J; Harnack, D; Heinz, A; Spanagel, R; Winter, C

    2016-01-01

    Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse. PMID:27327255

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

    PubMed Central

    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

  9. Is deep brain stimulation a treatment option for anorexia nervosa?

    PubMed

    Oudijn, Marloes S; Storosum, Jitschak G; Nelis, Elise; Denys, Damiaan

    2013-01-01

    Anorexia nervosa (AN) is a severe psychiatric disorder with high rates of morbidity, comorbidity and mortality, which in a subset of patients (21%) takes on a chronic course. Since an evidence based treatment for AN is scarce, it is crucial to investigate new treatment options, preferably focused on influencing the underlying neurobiological mechanisms of AN. The objective of the present paper was to review the evidence for possible neurobiological correlates of AN, and to hypothesize about potential targets for Deep brain stimulation (DBS) as a treatment for chronic, therapy-refractory AN. One avenue for exploring new treatment options based on the neurobiological correlates of AN, is the search for symptomatologic and neurobiologic parallels between AN and other compulsivity- or reward-related disorders. As in other compulsive disorders, the fronto-striatal circuitry, in particular the insula, the ventral striatum (VS) and the prefrontal, orbitofrontal, temporal, parietal and anterior cingulate cortices, are likely to be implicated in the neuropathogenesis of AN. In this paper we will review the few available cases in which DBS has been performed in patients with AN (either as primary diagnosis or as comorbid condition). Given the overlap in symptomatology and neurocircuitry between reward-related disorders such as obsessive compulsive disorder (OCD) and AN, and the established efficacy of accumbal DBS in OCD, we hypothesize that DBS of the nucleus accumbens (NAc) and other areas associated with reward, e.g. the anterior cingulated cortex (ACC), might be an effective treatment for patients with chronic, treatment refractory AN, providing not only weight restoration, but also significant and sustained improvement in AN core symptoms and associated comorbidities and complications. Possible targets for DBS in AN are the ACC, the ventral anterior limb of the capsula interna (vALIC) and the VS. We suggest conducting larger efficacy studies that also explore the

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

    NASA Astrophysics Data System (ADS)

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

    2009-12-01

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

  11. Mapping of language brain areas in patients with brain tumors.

    PubMed

    Hyder, Rasha; Kamel, Nidal; Boon, Tang Tong; Reza, Faruque

    2015-08-01

    Language cortex in the human brain shows high variability among normal individuals and may exhibit a considerable shift from its original position due to tumor growth. Mapping the precise location of language areas is important before surgery to avoid postoperative language deficits. In this paper, the Magnetoencephalography (MEG) recording and the MRI scanning of six brain tumorous subjects are used to localize the language specific areas. MEG recordings were performed during two silent reading tasks; silent word reading and silent picture naming. MEG source imaging is performed using distributed source modeling technique called CLARA ("Classical LORETA Analysis Recursively Applied"). Estimated MEG sources are overlaid on individual MRI of each patient to improve interpretation of MEG source imaging results. The results show successful identification of the essential language areas and clear definition of the time course of neural activation connecting them. PMID:26736340

  12. Deep brain stimulation in tinnitus: current and future perspectives.

    PubMed

    Smit, J V; Janssen, M L F; Schulze, H; Jahanshahi, A; Van Overbeeke, J J; Temel, Y; Stokroos, R J

    2015-05-22

    Chronic tinnitus, also known as ringing in the ears, affects up to 15% of the adults and causes a serious socio-economic burden. At present, there is no treatment available which substantially reduces the perception of this phantom sound. In the past few years, preclinical and clinical studies have unraveled central mechanisms involved in the pathophysiology of tinnitus, replacing the classical periphery-based hypothesis. In subcortical auditory and non-auditory regions, increased spontaneous activity, neuronal bursting and synchrony were found. When reaching the auditory cortex, these neuronal alterations become perceptually relevant and consequently are perceived as phantom sound. A therapy with a potential to counteract deeply located pathological activity is deep brain stimulation, which has already been demonstrated to be effective in neurological diseases such as Parkinson's disease. In this review, several brain targets are discussed as possible targets for deep brain stimulation in tinnitus. The potential applicability of this treatment in tinnitus is discussed with examples from the preclinical field and clinical case studies. PMID:25758066

  13. A mammalian neural tissue opsin (Opsin 5) is a deep brain photoreceptor in birds

    PubMed Central

    Nakane, Yusuke; Ikegami, Keisuke; Ono, Hiroko; Yamamoto, Naoyuki; Yoshida, Shosei; Hirunagi, Kanjun; Ebihara, Shizufumi; Kubo, Yoshihiro; Yoshimura, Takashi

    2010-01-01

    It has been known for many decades that nonmammalian vertebrates detect light by deep brain photoreceptors that lie outside the retina and pineal organ to regulate seasonal cycle of reproduction. However, the identity of these photoreceptors has so far remained unclear. Here we report that Opsin 5 is a deep brain photoreceptive molecule in the quail brain. Expression analysis of members of the opsin superfamily identified as Opsin 5 (OPN5; also known as Gpr136, Neuropsin, PGR12, and TMEM13) mRNA in the paraventricular organ (PVO), an area long believed to be capable of phototransduction. Immunohistochemistry identified Opsin 5 in neurons that contact the cerebrospinal fluid in the PVO, as well as fibers extending to the external zone of the median eminence adjacent to the pars tuberalis of the pituitary gland, which translates photoperiodic information into neuroendocrine responses. Heterologous expression of Opsin 5 in Xenopus oocytes resulted in light-dependent activation of membrane currents, the action spectrum of which showed peak sensitivity (λmax) at ∼420 nm. We also found that short-wavelength light, i.e., between UV-B and blue light, induced photoperiodic responses in eye-patched, pinealectomized quail. Thus, Opsin 5 appears to be one of the deep brain photoreceptive molecules that regulates seasonal reproduction in birds. PMID:20679218

  14. Intraoperative neurophysiology in deep brain surgery for psychogenic dystonia

    PubMed Central

    Ramos, Vesper Fe Marie L; Pillai, Ajay S; Lungu, Codrin; Ostrem, Jill; Starr, Philip; Hallett, Mark

    2015-01-01

    Psychogenic dystonia is a challenging entity to diagnose and treat because little is known about its pathophysiology. We describe two cases of psychogenic dystonia who underwent deep brain stimulation when thought to have organic dystonia. The intraoperative microelectrode recordings in globus pallidus internus were retrospectively compared with those of five patients with known DYT1 dystonia using spontaneous discharge parameters of rate and bursting, as well as movement-related discharges. Our data suggest that simple intraoperative neurophysiology measures in single subjects do not differentiate psychogenic dystonia from DYT1 dystonia. PMID:26125045

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

    PubMed

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

    2016-01-01

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

  16. Deep-Brain Stimulation for Basal Ganglia Disorders

    PubMed Central

    Wichmann, Thomas; DeLong, Mahlon R.

    2011-01-01

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

  17. Effects of Deep Brain Stimulation on Autonomic Function.

    PubMed

    Basiago, Adam; Binder, Devin K

    2016-01-01

    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. PMID:27537920

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

    NASA Astrophysics Data System (ADS)

    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. Diffusion Tractography in Deep Brain Stimulation Surgery: A Review

    PubMed Central

    Calabrese, Evan

    2016-01-01

    Deep brain stimulation (DBS) is believed to exert its therapeutic effects through modulation of brain circuitry, yet conventional preoperative planning does not allow direct targeting or visualization of white matter pathways. Diffusion MRI tractography (DT) is virtually the only non-invasive method of visualizing structural connectivity in the brain, leading many to suggest its use to guide DBS targeting. DT-guided DBS not only has the potential to allow direct white matter targeting for established applications [e.g., Parkinson’s disease (PD), essential tremor (ET), dystonia], but may also aid in the discovery of new therapeutic targets for a variety of other neurologic and psychiatric diseases. Despite these exciting opportunities, DT lacks standardization and rigorous anatomic validation, raising significant concern for the use of such data in stereotactic brain surgery. This review covers the technical details, proposed methods, and initial clinical data for the use of DT in DBS surgery. Rather than focusing on specific disease applications, this review focuses on methods that can be applied to virtually any DBS target. PMID:27199677

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  1. Manifold learning of brain MRIs by deep learning.

    PubMed

    Brosch, Tom; Tam, Roger

    2013-01-01

    Manifold learning of medical images plays a potentially important role for modeling anatomical variability within a population with pplications that include segmentation, registration, and prediction of clinical parameters. This paper describes a novel method for learning the manifold of 3D brain images that, unlike most existing manifold learning methods, does not require the manifold space to be locally linear, and does not require a predefined similarity measure or a prebuilt proximity graph. Our manifold learning method is based on deep learning, a machine learning approach that uses layered networks (called deep belief networks, or DBNs) and has received much attention recently in the computer vision field due to their success in object recognition tasks. DBNs have traditionally been too computationally expensive for application to 3D images due to the large number of trainable parameters. Our primary contributions are (1) a much more computationally efficient training method for DBNs that makes training on 3D medical images with a resolution of up to 128 x 128 x 128 practical, and (2) the demonstration that DBNs can learn a low-dimensional manifold of brain volumes that detects modes of variations that correlate to demographic and disease parameters. PMID:24579194

  2. Pallidal deep brain stimulation relieves camptocormia in primary dystonia.

    PubMed

    Hagenacker, Tim; Gerwig, Marcus; Gasser, Thomas; Miller, Dorothea; Kastrup, Oliver; Jokisch, Daniel; Sure, Ulrich; Frings, Markus

    2013-07-01

    Camptocormia, characterised by a forward flexion of the thoracolumbar spine may occur in various movement disorders, mainly in Parkinson's disease or in primary dystonia. In severe cases, patients with camptocormia are unable to walk. While treatment options are limited, deep brain stimulation (DBS) with bilateral stimulation of the subthalamic nucleus or globus pallidus internus (GPi) has been proposed as a therapeutic option in refractory cases of Parkinson's disease. Here we present two patients with severe camptocormia as an isolated form of dystonia and as part of generalised dystonia, respectively, which were both treated with bilateral stimulation of the GPi. Symptoms of dystonia were assessed using the Burke-Fahn-Marsden dystonia rating scale (BFM) before and during deep brain stimulation. In both patients there was a significant functional improvement following long-term bilateral GPi stimulation and both patients gained ability to walk. In the first patient with an isolated dystonic camptocormia the BFM motor subscore for the truncal flexion improved by 75 %. The total BFM motor score in the second patient with a camptocormia in generalised dystonia improved by 45 %, while the BFM score for truncal flexion improved by 87 %. In both patients the effect of the bilateral GPi stimulation on camptocormia was substantial, independent of generalisation of dystonia. Therefore, GPi DBS is a possible treatment option for this rare disease. PMID:23483215

  3. Dynamics of Parkinsonian tremor during deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Titcombe, Michèle S.; Glass, Leon; Guehl, Dominique; Beuter, Anne

    2001-12-01

    The mechanism by which chronic, high frequency, electrical deep brain stimulation (HF-DBS) suppresses tremor in Parkinson's disease is unknown. Rest tremor in subjects with Parkinson's disease receiving HF-DBS was recorded continuously throughout switching the deep brain stimulator on (at an effective frequency) and off. These data suggest that the stimulation induces a qualitative change in the dynamics, called a Hopf bifurcation, so that the stable oscillations are destabilized. We hypothesize that the periodic stimulation modifies a parameter affecting the oscillation in a time dependent way and thereby induces a Hopf bifurcation. We explore this hypothesis using a schematic network model of an oscillator interacting with periodic stimulation. The mechanism of time-dependent change of a control parameter in the model captures two aspects of the dynamics observed in the data: (1) a gradual increase in tremor amplitude when the stimulation is switched off and a gradual decrease in tremor amplitude when the stimulation is switched on and (2) a time delay in the onset and offset of the oscillations. This mechanism is consistent with these rest tremor transition data and with the idea that HF-DBS acts via the gradual change of a network property.

  4. Nonvisual photoreceptors of the deep brain, pineal organs and retina.

    PubMed

    Vigh, B; Manzano, M J; Zádori, A; Frank, C L; Lukáts, A; Röhlich, P; Szél, A; Dávid, C

    2002-04-01

    The role of the nonvisual photoreception is to synchronise periodic functions of living organisms to the environmental light periods in order to help survival of various species in different biotopes. In vertebrates, the so-called deep brain (septal and hypothalamic) photoreceptors, the pineal organs (pineal- and parapineal organs, frontal- and parietal eye) and the retina (of the "lateral" eye) are involved in the light-based entrain of endogenous circadian clocks present in various organs. In humans, photoperiodicity was studied in connection with sleep disturbances in shift work, seasonal depression, and in jet-lag of transmeridional travellers. In the present review, experimental and molecular aspects are discussed, focusing on the histological and histochemical basis of the function of nonvisual photoreceptors. We also offer a view about functional changes of these photoreceptors during pre- and postnatal development as well as about its possible evolution. Our scope in some points is different from the generally accepted views on the nonvisual photoreceptive systems. The deep brain photoreceptors are hypothalamic and septal nuclei of the periventricular cerebrospinal fluid (CSF)-contacting neuronal system. Already present in the lancelet and representing the most ancient type of vertebrate nerve cells ("protoneurons"), CSF-contacting neurons are sensory-type cells sitting in the wall of the brain ventricles that send a ciliated dendritic process into the CSF. Various opsins and other members of the phototransduction cascade have been demonstrated in telencephalic and hypothalamic groups of these neurons. In all species examined so far, deep brain photoreceptors play a role in the circadian and circannual regulation of periodic functions. Mainly called pineal "glands" in the last decades, the pineal organs actually represent a differentiated form of encephalic photoreceptors. Supposed to be intra- and extracranially outgrown groups of deep brain photoreceptors

  5. Reversing cognitive-motor impairments in Parkinson's disease patients using a computational modelling approach to deep brain stimulation programming.

    PubMed

    Frankemolle, Anneke M M; Wu, Jennifer; Noecker, Angela M; Voelcker-Rehage, Claudia; Ho, Jason C; Vitek, Jerrold L; McIntyre, Cameron C; Alberts, Jay L

    2010-03-01

    Deep brain stimulation in the subthalamic nucleus is an effective and safe surgical procedure that has been shown to reduce the motor dysfunction of patients with advanced Parkinson's disease. Bilateral subthalamic nucleus deep brain stimulation, however, has been associated with declines in cognitive and cognitive-motor functioning. It has been hypothesized that spread of current to nonmotor areas of the subthalamic nucleus may be responsible for declines in cognitive and cognitive-motor functioning. The aim of this study was to assess the cognitive-motor performance in advanced Parkinson's disease patients with subthalamic nucleus deep brain stimulation parameters determined clinically (Clinical) to settings derived from a patient-specific computational model (Model). Data were collected from 10 patients with advanced Parkinson's disease bilaterally implanted with subthalamic nucleus deep brain stimulation systems. These patients were assessed off medication and under three deep brain stimulation conditions: Off, Clinical or Model based stimulation. Clinical stimulation parameters had been determined based on clinical evaluations and were stable for at least 6 months prior to study participation. Model-based parameters were selected to minimize the spread of current to nonmotor portions of the subthalamic nucleus using Cicerone Deep Brain Stimulation software. For each stimulation condition, participants performed a working memory (n-back task) and motor task (force tracking) under single- and dual-task settings. During the dual-task, participants performed the n-back and force-tracking tasks simultaneously. Clinical and Model parameters were equally effective in improving the Unified Parkinson's disease Rating Scale III scores relative to Off deep brain stimulation scores. Single-task working memory declines, in the 2-back condition, were significantly less under Model compared with Clinical deep brain stimulation settings. Under dual-task conditions, force

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

    PubMed

    Yousif, Nada; Liu, Xuguang

    2007-09-01

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

  7. Network Perspectives on the Mechanisms of Deep Brain Stimulation

    PubMed Central

    McIntyre, Cameron C.; Hahn, Philip J.

    2009-01-01

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

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

    PubMed Central

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

    2016-01-01

    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

  9. Penfield’s Prediction: A Mechanism for Deep Brain Stimulation

    PubMed Central

    Murrow, Richard W.

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  11. Neuronal Organization of Deep Brain Opsin Photoreceptors in Adult Teleosts

    PubMed Central

    Hang, Chong Yee; Kitahashi, Takashi; Parhar, Ishwar S.

    2016-01-01

    Biological impacts of light beyond vision, i.e., non-visual functions of light, signify the need to better understand light detection (or photoreception) systems in vertebrates. Photopigments, which comprise light-absorbing chromophores bound to a variety of G-protein coupled receptor opsins, are responsible for visual and non-visual photoreception. Non-visual opsin photopigments in the retina of mammals and extra-retinal tissues of non-mammals play an important role in non-image-forming functions of light, e.g., biological rhythms and seasonal reproduction. This review highlights the role of opsin photoreceptors in the deep brain, which could involve conserved neurochemical systems that control different time- and light-dependent physiologies in in non-mammalian vertebrates including teleost fish. PMID:27199680

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

    PubMed

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

    2014-06-01

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

  13. Clustered Desynchronization from High-Frequency Deep Brain Stimulation

    PubMed Central

    Wilson, Dan; Moehlis, Jeff

    2015-01-01

    While high-frequency deep brain stimulation is a well established treatment for Parkinson’s disease, its underlying mechanisms remain elusive. Here, we show that two competing hypotheses, desynchronization and entrainment in a population of model neurons, may not be mutually exclusive. We find that in a noisy group of phase oscillators, high frequency perturbations can separate the population into multiple clusters, each with a nearly identical proportion of the overall population. This phenomenon can be understood by studying maps of the underlying deterministic system and is guaranteed to be observed for small noise strengths. When we apply this framework to populations of Type I and Type II neurons, we observe clustered desynchronization at many pulsing frequencies. PMID:26713619

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

    PubMed

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

    2016-07-01

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

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

    PubMed

    Hedera, Peter

    2014-05-01

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

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

    PubMed

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

    2015-04-29

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

  17. Dystonia and the Role of Deep Brain Stimulation

    PubMed Central

    Ellis, Thomas L.

    2011-01-01

    Dystonia is a painful, disabling disease whose cause in many cases remains unknown. It has historically been treated with a variety methodologies including baclofen pumps, Botox injection, peripheral denervation, and stereotactic surgery. Deep brain stimulation (DBS) is emerging as a viable treatment option for selected patients with dystonia. Results of DBS for dystonia appear to be more consistently superior in patients with primary versus secondary forms of the disorder. Patients with secondary dystonia, due to a variety of causes, may still be candidates for DBS surgery, although the results may not be as consistently good. The procedure is relatively safe with a small likelihood of morbidity and mortality. A randomized trial is needed to determine who are the best patients and when it is best to proceed with surgery. PMID:22084748

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2016-08-01

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

  20. Clustered Desynchronization from High-Frequency Deep Brain Stimulation.

    PubMed

    Wilson, Dan; Moehlis, Jeff

    2015-12-01

    While high-frequency deep brain stimulation is a well established treatment for Parkinson's disease, its underlying mechanisms remain elusive. Here, we show that two competing hypotheses, desynchronization and entrainment in a population of model neurons, may not be mutually exclusive. We find that in a noisy group of phase oscillators, high frequency perturbations can separate the population into multiple clusters, each with a nearly identical proportion of the overall population. This phenomenon can be understood by studying maps of the underlying deterministic system and is guaranteed to be observed for small noise strengths. When we apply this framework to populations of Type I and Type II neurons, we observe clustered desynchronization at many pulsing frequencies. PMID:26713619

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

    PubMed

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

    2011-02-01

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

  2. Deep brain stimulation for severe autism: from pathophysiology to procedure.

    PubMed

    Sinha, Saurabh; McGovern, Robert A; Sheth, Sameer A

    2015-06-01

    Autism is a heterogeneous neurodevelopmental disorder characterized by early-onset impairment in social interaction and communication and by repetitive, restricted behaviors and interests. Because the degree of impairment may vary, a spectrum of clinical manifestations exists. Severe autism is characterized by complete lack of language development and potentially life-threatening self-injurious behavior, the latter of which may be refractory to medical therapy and devastating for affected individuals and their caretakers. New treatment strategies are therefore needed. Here, the authors propose deep brain stimulation (DBS) of the basolateral nucleus of the amygdala (BLA) as a therapeutic intervention to treat severe autism. The authors review recent developments in the understanding of the pathophysiology of autism. Specifically, they describe the genetic and environmental alterations that affect neurodevelopment. The authors also highlight the resultant microstructural, macrostructural, and functional abnormalities that emerge during brain development, which create a pattern of dysfunctional neural networks involved in socioemotional processing. They then discuss how these findings implicate the BLA as a key node in the pathophysiology of autism and review a reported case of BLA DBS for treatment of severe autism. Much progress has been made in recent years in understanding the pathophysiology of autism. The BLA represents a logical neurosurgical target for treating severe autism. Further study is needed that considers mechanistic and operative challenges. PMID:26030703

  3. In vivo impedance spectroscopy of deep brain stimulation electrodes

    NASA Astrophysics Data System (ADS)

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

    2009-08-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. Central thalamic deep brain stimulation to support anterior forebrain mesocircuit function in the severely injured brain.

    PubMed

    Schiff, Nicholas D

    2016-07-01

    This integrative review frames a general rationale for the use of central thalamic deep brain stimulation (CT-DBS) to support arousal regulation mechanisms in the severely injured brain. The organizing role of the anterior forebrain mesocircuit in recovery mechanisms following widespread deafferentation produced by multi-focal structural brain injuries is emphasized. The mesocircuit model provides the conceptual foundation for the key role of the central thalamus as a privileged node for neuromodulation to support forebrain arousal regulation. In this context, cellular mechanisms arising at the neocortical, striatal, and thalamic population level are considered in the assessment of an individual patient's capacity for harboring underlying reserve that could be recruited for further recovery. Recent preclinical studies and pilot clinical results are compared to frame the detailed rationale for CT-DBS. Application of CT-DBS across the range of outcomes following severe-to-moderate brain injuries is discussed with the aim of improving consciousness and cognition in patients with non-progressive brain injuries. PMID:27113938

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

    Using internal illumination with an optical fiber in the oral cavity, we demonstrate, for the first time, photoacoustic computed tomography (PACT) of the deep brain of rats in vivo. The experiment was performed on a full-ring-array PACT system, with the capability of providing high-speed cross-sectional imaging of the brain. Compared with external illumination through the cranial skull, internal illumination delivers more light to the base of the brain. Consequently, in vivo photoacoustic images clearly reveal deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.

  9. Deep brain optical measurements of cell type–specific neural activity in behaving mice

    PubMed Central

    Cui, Guohong; Jun, Sang Beom; Jin, Xin; Luo, Guoxiang; Pham, Michael D; Lovinger, David M; Vogel, Steven S; Costa, Rui M

    2014-01-01

    Recent advances in genetically encoded fluorescent sensors enable the monitoring of cellular events from genetically defined groups of neurons in vivo. In this protocol, we describe how to use a time-correlated single-photon counting (tcspc)–based fiber optics system to measure the intensity, emission spectra and lifetime of fluorescent biosensors expressed in deep brain structures in freely moving mice. When combined with cre-dependent selective expression of genetically encoded ca2+ indicators (GecIs), this system can be used to measure the average neural activity from a specific population of cells in mice performing complex behavioral tasks. as an example, we used viral expression of GcaMps in striatal projection neurons (spns) and recorded the fluorescence changes associated with calcium spikes from mice performing a lever-pressing operant task. the whole procedure, consisting of virus injection, behavior training and optical recording, takes 3–4 weeks to complete. With minor adaptations, this protocol can also be applied to recording cellular events from other cell types in deep brain regions, such as dopaminergic neurons in the ventral tegmental area. the simultaneously recorded fluorescence signals and behavior events can be used to explore the relationship between the neural activity of specific brain circuits and behavior. PMID:24784819

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

    PubMed

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

    2012-01-01

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

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

    PubMed

    Sugiyama, Kenji; Nozaki, Takao; Asakawa, Tetsuya; Koizumi, Shinichiro; Saitoh, Osamu; Namba, Hiroki

    2015-01-01

    The use of electrical stimulation to treat pain in human disease dates back to ancient Rome or Greece. Modern deep brain stimulation (DBS) was initially applied for pain treatment in the 1960s, and was later used to treat movement disorders in the 1990s. After recognition of DBS as a therapy for central nervous system (CNS) circuit disorders, DBS use showed drastic increase in terms of adaptability to disease and the patient's population. More than 100,000 patients have received DBS therapy worldwide. The established indications for DBS are Parkinson's disease, tremor, and dystonia, whereas global indications of DBS expanded to other neuronal diseases or disorders such as neuropathic pain, epilepsy, and tinnitus. DBS is also experimentally used to manage cognitive disorders and psychiatric diseases such as major depression, obsessive-compulsive disorder (OCD), Tourette's syndrome, and eating disorders. The importance of ethics and conflicts surrounding the regulation and freedom of choice associated with the application of DBS therapy for new diseases or disorders is increasing. These debates are centered on the use of DBS to treat new diseases and disorders as well as its potential to enhance ability in normal healthy individuals. Here we present three issues that need to be addressed in the future: (1) elucidation of the mechanisms of DBS, (2) development of new DBS methods, and (3) miniaturization of the DBS system. With the use of DBS, functional neurosurgery entered into the new era that man can manage and control the brain circuit to treat intractable neuronal diseases and disorders. PMID:25925757

  12. The Present Indication and Future of Deep Brain Stimulation

    PubMed Central

    SUGIYAMA, Kenji; NOZAKI, Takao; ASAKAWA, Tetsuya; KOIZUMI, Shinichiro; SAITOH, Osamu; NAMBA, Hiroki

    2015-01-01

    The use of electrical stimulation to treat pain in human disease dates back to ancient Rome or Greece. Modern deep brain stimulation (DBS) was initially applied for pain treatment in the 1960s, and was later used to treat movement disorders in the 1990s. After recognition of DBS as a therapy for central nervous system (CNS) circuit disorders, DBS use showed drastic increase in terms of adaptability to disease and the patient’s population. More than 100,000 patients have received DBS therapy worldwide. The established indications for DBS are Parkinson’s disease, tremor, and dystonia, whereas global indications of DBS expanded to other neuronal diseases or disorders such as neuropathic pain, epilepsy, and tinnitus. DBS is also experimentally used to manage cognitive disorders and psychiatric diseases such as major depression, obsessive-compulsive disorder (OCD), Tourette’s syndrome, and eating disorders. The importance of ethics and conflicts surrounding the regulation and freedom of choice associated with the application of DBS therapy for new diseases or disorders is increasing. These debates are centered on the use of DBS to treat new diseases and disorders as well as its potential to enhance ability in normal healthy individuals. Here we present three issues that need to be addressed in the future: (1) elucidation of the mechanisms of DBS, (2) development of new DBS methods, and (3) miniaturization of the DBS system. With the use of DBS, functional neurosurgery entered into the new era that man can manage and control the brain circuit to treat intractable neuronal diseases and disorders. PMID:25925757

  13. Lesion Analysis of the Brain Areas Involved in Language Comprehension

    ERIC Educational Resources Information Center

    Dronkers, Nina F.; Wilkins, David P.; Van Valin, Robert D., Jr.; Redfern, Brenda B.; Jaeger, Jeri J.

    2004-01-01

    The cortical regions of the brain traditionally associated with the comprehension of language are Wernicke's area and Broca's area. However, recent evidence suggests that other brain regions might also be involved in this complex process. This paper describes the opportunity to evaluate a large number of brain-injured patients to determine which…

  14. Deep brain stimulation for Parkinson's disease - patient selection.

    PubMed

    Pollak, Pierre

    2013-01-01

    Proper selection of patients who will reliably benefit from deep brain stimulation (DBS) is critical to its success. This requires careful evaluation that should be delivered by an expert multidisciplinary team involving a movement disorder neurologist, a neurosurgeon, a neuropsychologist, and a psychiatrist. The most suitable candidates for DBS suffer from Parkinson's disease with motor fluctuations and/or dyskinesias that are not adequately controlled with optimized medical therapy, or with medication-refractory tremor. During the best on-motor periods, gait difficulties, instability, and speech problems should be minimal, reflecting an excellent response to levodopa in the ideal candidate. The cognitive, psychiatric, and behavioral status must be normal or minimally affected, with the exception of dopamine agonist drug-induced impulse control disorders, which are usually improved after successful surgery and drug withdrawal. Moreover, the patients have no serious comorbidities. Most patients corresponding to this profile suffer from a relatively young onset of Parkinson's disease, and are aged less than 70 years at the time of surgery. Indeed, most patients fall outside this ideal description, and the medical art is to appreciate for each patient the extent to which the alterations of these features can be accepted. Eventually, patients make their own decision from detailed information of their individualized risks and benefits of DBS. Patient expectations, cooperation, and familial support are also important considerations. PMID:24112888

  15. Deep Brain Stimulation Can Preserve Working Status in Parkinson's Disease

    PubMed Central

    Deli, Gabriella; Balás, István; Dóczi, Tamás; Janszky, József; Karádi, Kázmér; Aschermann, Zsuzsanna; Nagy, Ferenc; Makkos, Attila; Kovács, Márton; Bosnyák, Edit; Kovács, Norbert; Komoly, Sámuel

    2015-01-01

    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. PMID:26295005

  16. Presurgical Rehearsals for Patients Considering "Awake" Deep Brain Stimulation.

    PubMed

    Falconer, Ramsey A; Rogers, Sean L; Brewer, Cristie M; Piscitani, Franco; Shenai, Mahesh B

    2016-01-01

    Simulated surgical environments are rapidly gaining adoption in training students, residents, and members of specialized surgical teams. However, minimal attention has been given to the use of simulated surgical environments to educate patients on surgical processes, particularly procedures that require the active participation of the patient. "Awake" neurosurgery provides a unique situation in which patients openly participate in their operation. We describe a case report, in which a 62-year-old male was referred for "awake" deep brain stimulation implantation, in relation to medically refractory Parkinson's disease. The patient had significant concerns regarding anxiety and claustrophobia, and toleration of the "awake" procedure. Consequently, we designed a simulated OR environment and process, to recreate the physical experience of the procedure, with minimal cost or risk. This experience was crucial in determining the care plan, as after this experience, the patient opted for an "asleep" alternative. Thus, in certain settings, presurgical rehearsals may have a dramatic impact in the overall course of care. PMID:27532036

  17. Deep brain stimulation abolishes slowing of reactions to unlikely stimuli.

    PubMed

    Antoniades, Chrystalina A; Bogacz, Rafal; Kennard, Christopher; FitzGerald, James J; Aziz, Tipu; Green, Alexander L

    2014-08-13

    The cortico-basal-ganglia circuit plays a critical role in decision making on the basis of probabilistic information. Computational models have suggested how this circuit could compute the probabilities of actions being appropriate according to Bayes' theorem. These models predict that the subthalamic nucleus (STN) provides feedback that normalizes the neural representation of probabilities, such that if the probability of one action increases, the probabilities of all other available actions decrease. Here we report the results of an experiment testing a prediction of this theory that disrupting information processing in the STN with deep brain stimulation should abolish the normalization of the neural representation of probabilities. In our experiment, we asked patients with Parkinson's disease to saccade to a target that could appear in one of two locations, and the probability of the target appearing in each location was periodically changed. When the stimulator was switched off, the target probability affected the reaction times (RT) of patients in a similar way to healthy participants. Specifically, the RTs were shorter for more probable targets and, importantly, they were longer for the unlikely targets. When the stimulator was switched on, the patients were still faster for more probable targets, but critically they did not increase RTs as the target was becoming less likely. This pattern of results is consistent with the prediction of the model that the patients on DBS no longer normalized their neural representation of prior probabilities. We discuss alternative explanations for the data in the context of other published results. PMID:25122887

  18. Deep brain stimulation for dystonia: review of the literature.

    PubMed

    Mehdorn, Hubertus M

    2016-06-01

    Deep brain stimulation (DBS) has become one of the major therapy options for movement disorders including dystonia. This article should give a review of the current literature from a neurosurgical perspective. Since dystonia is a rare disease, only few studies on larger cohorts have been published, and very few randomized controlled studies are avaialable in the international literature. Our experiences gained treating 134 patients with various types of dystonia, between 1999 and 2015, will serve a guide to interpret the current literature. Symptoms of dystonia are due to a variety of medical conditions. A careful and extensive neurological evaluation is mandatory before medical and surgical treatment options are considered, since the clinical benefits of more aggressive treatment e.g. by DBS depend to a large extent on the etiology of the disease. Diagnostic steps should include also magnetic resonance imaging (MRI) and possibly genetic evaluation. Therapy consists of physiotherapy, medical therapy including botulinum toxin injections in focal dystonia and DBS. This neurosurgical therapy is considered a highly effective therapy in well selected patients, which should be discussed, depending on the etiology, early in the patient's career. Patients with primary dystonia will benefit the most from DBS to the ventromediolateral part of the globus pallidus internus (GPi) with acceptable low complication rates; in order to optimize longterm results in these groups of patient, they will require an interdisciplinary individualized approach both pre- and postoperatively as well as longterm care adjusting to their needs. PMID:26977634

  19. The use of deep brain stimulation in Tourette's syndrome.

    PubMed

    Rotsides, Janine; Mammis, Antonios

    2013-11-01

    Tourette's syndrome (TS) is a childhood neuropsychiatric disorder characterized by multiple involuntary motor and vocal tics. It is commonly associated with other behavioral disorders including attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, depression, and self-injurious behaviors. Tourette's syndrome can be effectively managed with psychobehavioral and pharmacological treatments, and many patients experience an improvement in tics in adulthood. However, symptoms may persist and cause severe impairment in a small subset of patients despite available therapies. In recent years, deep brain stimulation (DBS) has been shown to be a promising treatment option for such patients. Since the advent of its use in 1999, multiple targets have been identified in DBS for TS, including the medial thalamus, globus pallidus internus, globus pallidus externus, anterior limb of the internal capsule/nucleus accumbens, and subthalamic nucleus. While the medial thalamus is the most commonly reported trajectory, the optimal surgical target for TS is still a topic of much debate. This paper provides a review of the available literature regarding the use of DBS for TS. PMID:24175864

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

    PubMed

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

    2005-03-30

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

  1. In vivo multiphoton microscopy of deep brain tissue.

    PubMed

    Levene, Michael J; Dombeck, Daniel A; Kasischke, Karl A; Molloy, Raymond P; Webb, Watt W

    2004-04-01

    Although fluorescence microscopy has proven to be one of the most powerful tools in biology, its application to the intact animal has been limited to imaging several hundred micrometers below the surface. The rest of the animal has eluded investigation at the microscopic level without excising tissue or performing extensive surgery. However, the ability to image with subcellular resolution in the intact animal enables a contextual setting that may be critical for understanding proper function. Clinical applications such as disease diagnosis and optical biopsy may benefit from minimally invasive in vivo approaches. Gradient index (GRIN) lenses with needle-like dimensions can transfer high-quality images many centimeters from the object plane. Here, we show that multiphoton microscopy through GRIN lenses enables minimally invasive, subcellular resolution several millimeters in the anesthetized, intact animal, and we present in vivo images of cortical layer V and hippocampus in the anesthetized Thy1-YFP line H mouse. Microangiographies from deep capillaries and blood vessels containing fluorescein-dextran and quantum dot-labeled serum in wild-type mouse brain are also demonstrated. PMID:14668300

  2. Deep brain stimulation in the treatment of depression

    PubMed Central

    Delaloye, Sibylle; Holtzheimer, Paul E.

    2014-01-01

    Major depressive disorder is a worldwide disease with debilitating effects on a patient's life. Common treatments include pharmacotherapy, psychotherapy, and electroconvulsive therapy. Many patients do not respond to these treatments; this has led to the investigation of alternative therapeutic modalities. Deep brain stimulation (DBS) is one of these modalities. It was first used with success for treating movement disorders and has since been extended to the treatment of psychiatric disorders. Although DBS is still an emerging treatment, promising efficacy and safety have been demonstrated in preliminary trials in patients with treatment-resistant depression (TRD). Further, neuroimaging has played a pivotal role in identifying some DBS targets and remains an important tool for evaluating the mechanism of action of this novel intervention. Preclinical animal studies have broadened knowledge about the possible mechanisms of action of DBS for TRD, Given that DBS involves neurosurgery in patients with severe psychiatric impairment, ethical questions concerning capacity to consent arise; these issues must continue to be carefully considered. PMID:24733973

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

    PubMed

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

    2015-06-01

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

  4. Deep brain stimulation in the globus pallidus externa promotes sleep.

    PubMed

    Qiu, M H; Chen, M C; Wu, J; Nelson, D; Lu, J

    2016-05-13

    The basal ganglia, a network of subcortical structures, play a critical role in movements, sleep and mental behavior. Basal ganglia disorders such as Parkinson's disease and Huntington's disease affect sleep. Deep brain stimulation (DBS) to treat motor symptoms in Parkinson's disease can ameliorate sleep disturbances. Our series of previous studies lead the hypothesis that dopamine, acting on D2 receptors on the striatopallidal terminals, enhances activity in the globus pallidus externa (GPe) and promotes sleep. Here, we tested if DBS in the GPe promotes sleep in rats. We found that unilateral DBS (180Hz at 100μA) in the GPe in rats significantly increased both non-rapid eye movement and rapid eye movement sleep compared to sham DBS stimulation. The EEG power spectrum of sleep induced by DBS was similar to that of the baseline sleep, and sleep latency was not affected by DBS. The GPe is potentially a better site for DBS to treat both insomnia and motor disorders caused by basal ganglia dysfunction. PMID:26917269

  5. Personality Changes after Deep Brain Stimulation in Parkinson's Disease

    PubMed Central

    Pham, Uyen; Solbakk, Anne-Kristin; Skogseid, Inger-Marie; Pripp, Are Hugo; Konglund, Ane Eidahl; Andersson, Stein; Haraldsen, Ira Ronit; Aarsland, Dag; Dietrichs, Espen; Malt, Ulrik Fredrik

    2015-01-01

    Objectives. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a recognized therapy that improves motor symptoms in advanced Parkinson's disease (PD). However, little is known about its impact on personality. To address this topic, we have assessed personality traits before and after STN-DBS in PD patients. Methods. Forty patients with advanced PD were assessed with the Temperament and Character Inventory (TCI): the Urgency, Premeditation, Perseverance, Sensation Seeking impulsive behaviour scale (UPPS), and the Neuroticism and Lie subscales of the Eysenck Personality Questionnaire (EPQ-N, EPQ-L) before surgery and after three months of STN-DBS. Collateral information obtained from the UPPS was also reported. Results. Despite improvement in motor function and reduction in dopaminergic dosage patients reported lower score on the TCI Persistence and Self-Transcendence scales, after three months of STN-DBS, compared to baseline (P = 0.006; P = 0.024). Relatives reported significantly increased scores on the UPPS Lack of Premeditation scale at follow-up (P = 0.027). Conclusion. STN-DBS in PD patients is associated with personality changes in the direction of increased impulsivity. PMID:25705545

  6. Deep brain stimulation for levodopa-refractory benign tremulous parkinsonism.

    PubMed

    Konno, Takuya; Ross, Owen A; Wharen, Robert E; Uitti, Ryan J; Wszolek, Zbigniew K

    2016-01-01

    Benign tremulous parkinsonism (BTP) is characterized by prominent resting tremor combined with action and postural components, and with only subtle rigidity and bradykinesia. This tremor is frequently disabling and poorly responsive to therapy with levodopa. Thus, BTP could be considered either as a distinct clinical disorder or a variant of PD. We present a case of a 57-year-old man who had a 3-year history of severe and functionally disabling resting tremor with action and postural features bilaterally but with left dominant hand predominance. There was only very mild rigidity and bradykinesia and no postural instability. His tremor was refractory to dopaminergic therapy, including carbidopa/levodopa. The dopamine transporter (DAT) imaging showed reduced tracer uptake in the putamen bilaterally, more so on the right side. He was treated with deep brain stimulation (DBS) targeting the right ventral intermediate nucleus of the thalamus. His tremor resolved immediately after procedure. The DAT imaging abnormalities indicate the presynaptic dopamine deficiency. In some autopsied BTP cases classic alpha-synuclein pathology of PD was observed. Thus, despite the lack of levodopa responsiveness BTP likely represents a variant of PD and not a distinct neurodegenerative disorder. DBS should be considered for patients with BTP PD variant despite their poor responsiveness to levodopa treatment. PMID:27591066

  7. Evaluation of novel stimulus waveforms for deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Foutz, Thomas J.; McIntyre, Cameron C.

    2010-12-01

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

  8. Microendoscopic Removal of Deep-Seated Brain Tumors Using Tubular Retraction System.

    PubMed

    Ratre, Shailendra; Yadav, Yad Ram; Parihar, Vijay Singh; Kher, Yatin

    2016-07-01

    Background Retraction of the overlying brain can be difficult without causing significant trauma when using traditional brain retractors with blades. These retractors may produce focal pressure and may result in brain contusion or infarction. Tubular retractors offer the advantage of low retracting pressure that is less likely to be traumatic. Low retraction pressure in the tubular retractor is due to the distribution of retraction force in all directions in a larger area. Material and Methods We conducted a retrospective study of 100 patients with deep-seated tumors operated on from January 2010 to December 2014. Tumor removal was accomplished with the help of a microscope and/or endoscope. Tubular brain retractors sizes 23, 18, and 15 mm were used. Folding of the tubular retractor after making a longitudinal cut allowed a small corticectomy. Larger retractor sizes were used in the earlier part of the study and in larger tumors. All the patients were evaluated postoperatively by computed tomography scan on the first postoperative day, and subsequent scans were done as and when needed. Any brain contusion or infarctions and the amount of tumor removal were recorded. Results A total of 74 patients had astrocytomas; 12, meningiomas; 4, colloid cyst of the third ventricle; 4, metastases; 4, primitive neuroectodermal tumor; 1, neurocytoma; and 1, ependymoma. Pure endoscopic excision without using a microscope was performed in 12 patients. Lesions were in the frontal (n = 34), parietal (n = 22), intraventricular (n = 16), basal ganglion or thalamic (n = 14), occipital (n = 10), and cerebellar (n = 4) areas. Total, near-total, and partial excision was achieved in 49, 29, and 22 patients, respectively. Use of a conventional retractor for excision of peripheral and superficial parts of a large tumor, small brain contusions, and technical failure were observed in 7, 4, and 1 patient, respectively. The low incidence of contusion may be partly

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

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

    PubMed Central

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

    2008-01-01

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

  11. Material and physical model for evaluation of deep brain activity contribution to EEG recordings

    NASA Astrophysics Data System (ADS)

    Ye, Yan; Li, Xiaoping; Wu, Tiecheng; Li, Zhe; Xie, Wenwen

    2015-12-01

    Deep brain activity is conventionally recorded with surgical implantation of electrodes. During the neurosurgery, brain tissue damage and the consequent side effects to patients are inevitably incurred. In order to eliminate undesired risks, we propose that deep brain activity should be measured using the noninvasive scalp electroencephalography (EEG) technique. However, the deeper the neuronal activity is located, the noisier the corresponding scalp EEG signals are. Thus, the present study aims to evaluate whether deep brain activity could be observed from EEG recordings. In the experiment, a three-layer cylindrical head model was constructed to mimic a human head. A single dipole source (sine wave, 10 Hz, altering amplitudes) was embedded inside the model to simulate neuronal activity. When the dipole source was activated, surface potential was measured via electrodes attached on the top surface of the model and raw data were recorded for signal analysis. Results show that the dipole source activity positioned at 66 mm depth in the model, equivalent to the depth of deep brain structures, is clearly observed from surface potential recordings. Therefore, it is highly possible that deep brain activity could be observed from EEG recordings and deep brain activity could be measured using the noninvasive scalp EEG technique.

  12. Dopamine Dysregulation Syndrome and Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease

    PubMed Central

    De la Casa-Fages, Beatriz; Grandas, Francisco

    2011-01-01

    Dopamine dysregulation syndrome is a complication of the dopaminergic treatment in Parkinson's disease that may be very disabling due to the negative impact that compulsive medication use may have on patients' social, psychological, and physical functioning. The relationship between subthalamic nucleus deep brain stimulation and dopamine dysregulation syndrome in patients with Parkinson's disease remains unclear. Deep brain stimulation may improve, worsen, or have no effect on preoperative dopamine dysregulation syndrome. Moreover, dopamine dysregulation syndrome may appear for the first time after deep brain stimulation of the subthalamic nucleus. The outcome of postoperative dopamine dysregulation syndrome is poor despite stimulation and medication adjustments. Here we review the phenomenology and neurobiology of this disorder, discuss possible mechanisms that may underlie the diverse outcomes of dopamine dysregulation syndrome after subthalamic nucleus deep brain stimulation, and propose management strategies. PMID:22135744

  13. The Impact of Deep Brain Stimulation on Sleep and Olfactory Function in Parkinson’s Disease

    PubMed Central

    Breen, David P; Low, Hu Liang; Misbahuddin, Anjum

    2015-01-01

    Objective: Relatively little is known about the effects of deep brain stimulation on non-motor symptoms. The aim of this pilot study was to assess the impact of deep brain stimulation on sleep and olfactory function in Parkinson’s disease. Methods: Subjective sleep quality and olfactory testing were performed on 11 consecutive Parkinson’s disease patients (eight men and three women) undergoing bilateral subthalamic nucleus stimulation. All patients consented to undergo clinical assessments prior to the procedure, and at regular intervals afterwards. Results: Subjective sleep quality improved at six months following deep brain stimulation and this benefit was sustained in the majority of patients at later follow-up assessments. There was no significant change in olfactory function following deep brain stimulation. Conclusions: In addition to having beneficial effects on motor function and quality of life, bilateral subthalamic nucleus stimulation improves subjective sleep quality in Parkinson’s disease. PMID:26535069

  14. Computational modeling of pedunculopontine nucleus deep brain stimulation

    NASA Astrophysics Data System (ADS)

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

    2013-08-01

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

  15. Delayed awakening in dystonia patients undergoing deep brain stimulation surgery.

    PubMed

    Trombetta, Carlos; Deogaonkar, Anupa; Deogaonkar, Milind; Ebrahim, Zeyd; Rezai, Ali; Machado, Andre; Farag, Ehab

    2010-07-01

    We aimed to identify the incidence, duration and causes of delayed emergence from anesthesia in patients with dystonia undergoing surgery for deep brain stimulation (DBS) placement. A retrospective review of patients with dystonia who underwent DBS placement was conducted and the following characteristics were noted: age, gender, comorbid conditions, American Society of Anesthesiologists classification, anesthetic agents used, amount of initial dose, amount of infusion dose, duration of the infusion and the time needed for emergence. Twenty-four patients underwent 33 DBS procedures for dystonia. Propofol was administered to 21 patients, in 29 of the 33 procedures. Dexmedetomidine was administered to three patients, in four procedures. The average propofol loading dose was 0.7mg/kg, and the infusion rate was 80microg/kg per minute (min), for an average duration of 89min. The average time of emergence was 36min. Only 31% of patients emerged from propofol anesthesia during the expected time frame, 69% of patients had some degree of delayed emergence, and 24% had a significant delay in emergence. Delayed emergence was more common in younger patients due to the higher loading doses these patients received. This study shows a 69% incidence of delayed emergence in dystonia patients undergoing DBS surgery. It also suggests an association between delayed emergence and younger patients who receive higher loading doses. A possible cause of delayed emergence is excessive anesthetic potentiation of the low output pallidal state in dystonia which may depress the pallido-thalamo-cortical circuitry. Delayed emergence could also result from depression of the previously affected ventral pallidal inputs to the septo-hippocampal system that mediates general anesthesia and awareness. Complex neurotransmitter disturbances may also be involved. PMID:20466547

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

    PubMed

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

    2011-07-01

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

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

    PubMed

    Saleh, Christian; Fontaine, Denys

    2015-05-01

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

  18. Measurement of evoked potentials during thalamic deep brain stimulation

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  20. Embedded Ultrathin Cluster Electrodes for Long-Term Recordings in Deep Brain Centers

    PubMed Central

    Thorbergsson, Palmi Thor; Ekstrand, Joakim; Friberg, Annika; Granmo, Marcus; Pettersson, Lina M. E.; Schouenborg, Jens

    2016-01-01

    Neural interfaces which allow long-term recordings in deep brain structures in awake freely moving animals have the potential of becoming highly valuable tools in neuroscience. However, the recording quality usually deteriorates over time, probably at least partly due to tissue reactions caused by injuries during implantation, and subsequently micro-forces due to a lack of mechanical compliance between the tissue and neural interface. To address this challenge, we developed a gelatin embedded neural interface comprising highly flexible electrodes and evaluated its long term recording properties. Bundles of ultrathin parylene C coated platinum electrodes (N = 29) were embedded in a hard gelatin based matrix shaped like a needle, and coated with Kollicoat™ to retard dissolution of gelatin during the implantation. The implantation parameters were established in an in vitro model of the brain (0.5% agarose). Following a craniotomy in the anesthetized rat, the gelatin embedded electrodes were stereotactically inserted to a pre-target position, and after gelatin dissolution the electrodes were further advanced and spread out in the area of the subthalamic nucleus (STN). The performance of the implanted electrodes was evaluated under anesthesia, during 8 weeks. Apart from an increase in the median-noise level during the first 4 weeks, the electrode impedance and signal-to-noise ratio of single-units remained stable throughout the experiment. Histological postmortem analysis confirmed implantation in the area of STN in most animals. In conclusion, by combining novel biocompatible implantation techniques and ultra-flexible electrodes, long-term neuronal recordings from deep brain structures with no significant deterioration of electrode function were achieved. PMID:27159159

  1. Deep Brain Stimulation for the Treatment of Severe, Medically Refractory Obsessive-Compulsive Disorder

    PubMed Central

    Sedrak, Mark; Wong, William; Wilson, Paul; Bruce, Diana; Bernstein, Ivan; Khandhar, Suketu; Pappas, Conrad; Heit, Gary; Sabelman, Eric

    2013-01-01

    Deep brain stimulation is a rapidly expanding therapy initially designed for the treatment of movement disorders and pain syndromes. The therapy includes implantation of electrodes in specific targets of the brain, delivering programmable small and safe electric impulses, like a pacemaker, that modulates both local and broad neurologic networks. The effects are thought to primarily involve a focus in the brain, probably inhibitory, which then restores a network of neural circuitry. Psychiatric diseases can be refractory and severe, leading to high medical costs, significant morbidity, and even death. Whereas surgery for psychiatric disease used to include destructive procedures, deep brain stimulation allows safe, reversible, and adjustable treatment that can be tailored for each patient. Deep brain stimulation offers new hope for these unfortunate patients, and the preliminary results are promising. PMID:24361021

  2. Inferring deep-brain activity from cortical activity using functional near-infrared spectroscopy

    PubMed Central

    Liu, Ning; Cui, Xu; Bryant, Daniel M.; Glover, Gary H.; Reiss, Allan L.

    2015-01-01

    Functional near-infrared spectroscopy (fNIRS) is an increasingly popular technology for studying brain function because it is non-invasive, non-irradiating and relatively inexpensive. Further, fNIRS potentially allows measurement of hemodynamic activity with high temporal resolution (milliseconds) and in naturalistic settings. However, in comparison with other imaging modalities, namely fMRI, fNIRS has a significant drawback: limited sensitivity to hemodynamic changes in deep-brain regions. To overcome this limitation, we developed a computational method to infer deep-brain activity using fNIRS measurements of cortical activity. Using simultaneous fNIRS and fMRI, we measured brain activity in 17 participants as they completed three cognitive tasks. A support vector regression (SVR) learning algorithm was used to predict activity in twelve deep-brain regions using information from surface fNIRS measurements. We compared these predictions against actual fMRI-measured activity using Pearson’s correlation to quantify prediction performance. To provide a benchmark for comparison, we also used fMRI measurements of cortical activity to infer deep-brain activity. When using fMRI-measured activity from the entire cortex, we were able to predict deep-brain activity in the fusiform cortex with an average correlation coefficient of 0.80 and in all deep-brain regions with an average correlation coefficient of 0.67. The top 15% of predictions using fNIRS signal achieved an accuracy of 0.7. To our knowledge, this study is the first to investigate the feasibility of using cortical activity to infer deep-brain activity. This new method has the potential to extend fNIRS applications in cognitive and clinical neuroscience research. PMID:25798327

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

    PubMed Central

    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.

    2016-01-01

    Background 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. Methods 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. Results: Consistent with previous studies, deep brain stimulation improved the overall the Burkee–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. Conclusion 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. PMID:25465373

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

    PubMed

    Hickey, Patrick; Stacy, Mark

    2016-01-01

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

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

    PubMed Central

    Hickey, Patrick; Stacy, Mark

    2016-01-01

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

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

    PubMed

    Mindermann, Thomas; Mendelowitsch, Aminadav

    2016-05-01

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

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

    NASA Astrophysics Data System (ADS)

    Kent, Alexander R.; Grill, Warren M.

    2014-08-01

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

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

    PubMed

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

    2016-08-01

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

  9. Deep brain stimulation versus anterior capsulotomy for obsessive-compulsive disorder: a review of the literature.

    PubMed

    Pepper, Joshua; Hariz, Marwan; Zrinzo, Ludvic

    2015-05-01

    Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition. Traditionally, anterior capsulotomy (AC) was an established procedure for treatment of patients with refractory OCD. Over recent decades, deep brain stimulation (DBS) has gained popularity. In this paper the authors review the published literature and compare the outcome of AC and DBS targeting of the area of the ventral capsule/ventral striatum (VC/VS) and nucleus accumbens (NAcc). Patients in published cases were grouped according to whether they received AC or DBS and according to their preoperative scores on the Yale-Brown Obsessive-Compulsive Scale (YBOCS), and then separated according to outcome measures: remission (YBOCS score < 8); response (≥ 35% improvement in YBOCS score); nonresponse (< 35% improvement in YBOCS score); and unfavorable (i.e., worsening of the baseline YBOCS score). Twenty studies were identified reporting on 170 patients; 62 patients underwent DBS of the VC/VS or the NAcc (mean age 38 years, follow-up 19 months, baseline YBOCS score of 33), and 108 patients underwent AC (mean age 36 years, follow-up 61 months, baseline YBOCS score of 30). In patients treated with DBS there was a 40% decrease in YBOCS score, compared with a 51% decrease for those who underwent AC (p = 0.004). Patients who underwent AC were 9% more likely to go into remission than patients treated with DBS (p = 0.02). No difference in complication rates was noted. Anterior capsulotomy is an efficient procedure for refractory OCD. Deep brain stimulation in the VC/VS and NAcc area is an emerging and promising therapy. The current popularity of DBS over ablative surgery for OCD is not due to nonefficacy of AC, but possibly because DBS is perceived as more acceptable by clinicians and patients. PMID:25635480

  10. A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research

    PubMed Central

    Abulseoud, Osama A.; Tye, Susannah J.; Hosain, Md Kamal; Berk, Michael

    2013-01-01

    Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented. PMID:27170861

  11. A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research.

    PubMed

    Kouzani, Abbas Z; Abulseoud, Osama A; Tye, Susannah J; Hosain, M D Kamal; Berk, Michael

    2013-01-01

    Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented. PMID:27170861

  12. Segmenting hippocampus from infant brains by sparse patch matching with deep-learned features.

    PubMed

    Guo, Yanrong; Wu, Guorong; Commander, Leah A; Szary, Stephanie; Jewells, Valerie; Lin, Weili; Shent, Dinggang

    2014-01-01

    Accurate segmentation of the hippocampus from infant MR brain images is a critical step for investigating early brain development. Unfortunately, the previous tools developed for adult hippocampus segmentation are not suitable for infant brain images acquired from the first year of life, which often have poor tissue contrast and variable structural patterns of early hippocampal development. From our point of view, the main problem is lack of discriminative and robust feature representations for distinguishing the hippocampus from the surrounding brain structures. Thus, instead of directly using the predefined features as popularly used in the conventional methods, we propose to learn the latent feature representations of infant MR brain images by unsupervised deep learning. Since deep learning paradigms can learn low-level features and then successfully build up more comprehensive high-level features in a layer-by-layer manner, such hierarchical feature representations can be more competitive for distinguishing the hippocampus from entire brain images. To this end, we apply Stacked Auto Encoder (SAE) to learn the deep feature representations from both T1- and T2-weighed MR images combining their complementary information, which is important for characterizing different development stages of infant brains after birth. Then, we present a sparse patch matching method for transferring hippocampus labels from multiple atlases to the new infant brain image, by using deep-learned feature representations to measure the interpatch similarity. Experimental results on 2-week-old to 9-month-old infant brain images show the effectiveness of the proposed method, especially compared to the state-of-the-art counterpart methods. PMID:25485393

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    PubMed

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

    2006-01-30

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

  15. Deep brain stimulation of the ventral striatum increases BDNF in the fear extinction circuit.

    PubMed

    Do-Monte, Fabricio H; Rodriguez-Romaguera, Jose; Rosas-Vidal, Luis E; Quirk, Gregory J

    2013-01-01

    Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces the symptoms of treatment-resistant obsessive compulsive disorder (OCD), and improves response to extinction-based therapies. We recently reported that DBS-like stimulation of a rat homologue of VC/VS, the dorsal-VS, reduced conditioned fear and enhanced extinction memory (Rodriguez-Romaguera et al., 2012). In contrast, DBS of the ventral-VS had the opposite effects. To examine possible mechanisms of these effects, we assessed the effects of VS DBS on the expression of the neural activity marker Fos and brain-derived neurotrophic factor (BDNF), a key mediator of extinction plasticity in prefrontal-amygdala circuits. Consistent with decreased fear expression, DBS of dorsal-VS increased Fos expression in prelimbic and infralimbic prefrontal cortices and in the lateral division of the central nucleus of amygdala, an area that inhibits amygdala output. Consistent with improved extinction memory, we found that DBS of dorsal-VS, but not ventral-VS, increased neuronal BDNF expression in prelimbic and infralimbic prefrontal cortices. These rodent findings are consistent with the idea that clinical DBS of VC/VS may augment fear extinction through an increase in BDNF expression. PMID:23964215

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

    PubMed

    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

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

    PubMed Central

    Rebelo, Pedro; Kennard, Christopher; Aziz, Tipu Z.; Green, Alexander L.

    2015-01-01

    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

  18. Scientists Zero in On Brain Area Linked to 'Parkinson's Gait'

    MedlinePlus

    ... Scientists Zero in on Brain Area Linked to 'Parkinson's Gait' Discovery could lead to new treatments for ... play a role in walking difficulties that afflict Parkinson's disease patients, new research suggests. The prefrontal cortex ...

  19. Computer-Based Visualization System for the Study of Deep Brain Structures Involved in Parkinson's Disease.

    PubMed

    Juanes, Juan A; Ruisoto, Pablo; Obeso, José A; Prats, Alberto; San-Molina, Joan

    2015-11-01

    Parkinson's Disease is characterized by alterations in deep brain structures and pathways involved in movement control. However, the understanding of neuroanatomy and spatial relationships of deep brain structures remains a challenge for medical students. Recent developments in information technology may help provide new instructional material that addresses this problem. This paper aims to develop an interactive and digital tool to enhance the study of the anatomical and functional neurological basis involved in Parkinson's Disease. This tool allows the organization and exploration of complex neuroanatomical contents related with Parkinson's Disease in an attractive and interactive way. Educational implications of this tool are analyzed. PMID:26370536

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

    PubMed Central

    Prata, Cecilia; Vieceli Dalla Sega, Francesco; Piperno, Roberto; Hrelia, Silvana

    2015-01-01

    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. PMID:25918580

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

    SciTech Connect

    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.

  2. Cavitation-enhanced nonthermal ablation in deep brain targets: feasibility in a large animal model.

    PubMed

    Arvanitis, Costas D; Vykhodtseva, Natalia; Jolesz, Ferenc; Livingstone, Margaret; McDannold, Nathan

    2016-05-01

    OBJECT Transcranial MRI-guided focused ultrasound (TcMRgFUS) is an emerging noninvasive alternative to surgery and radiosurgery that is undergoing testing for tumor ablation and functional neurosurgery. The method is currently limited to central brain targets due to skull heating and other factors. An alternative ablative approach combines very low intensity ultrasound bursts and an intravenously administered microbubble agent to locally destroy the vasculature. The objective of this work was to investigate whether it is feasible to use this approach at deep brain targets near the skull base in nonhuman primates. METHODS In 4 rhesus macaques, targets near the skull base were ablated using a clinical TcMRgFUS system operating at 220 kHz. Low-duty-cycle ultrasound exposures (sonications) were applied for 5 minutes in conjunction with the ultrasound contrast agent Definity, which was administered as a bolus injection or continuous infusion. The acoustic power level was set to be near the inertial cavitation threshold, which was measured using passive monitoring of the acoustic emissions. The resulting tissue effects were investigated with MRI and with histological analysis performed 3 hours to 1 week after sonication. RESULTS Thirteen targets were sonicated in regions next to the optic tract in the 4 animals. Inertial cavitation, indicated by broadband acoustic emissions, occurred at acoustic pressure amplitudes ranging from 340 to 540 kPa. MRI analysis suggested that the lesions had a central region containing red blood cell extravasations that was surrounded by edema. Blood-brain barrier disruption was observed on contrast-enhanced MRI in the lesions and in a surrounding region corresponding to the prefocal area of the FUS system. In histology, lesions consisting of tissue undergoing ischemic necrosis were found in all regions that were sonicated above the inertial cavitation threshold. Tissue damage in prefocal areas was found in several cases, suggesting that in

  3. No Effect of Subthalamic Deep Brain Stimulation on Intertemporal Decision-Making in Parkinson Patients123

    PubMed Central

    Wojtecki, Lars; Storzer, Lena; Schnitzler, Alfons

    2016-01-01

    Abstract Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a widely used treatment for the motor symptoms of Parkinson’s disease (PD). DBS or pharmacological treatment is believed to modulate the tendency to, or reverse, impulse control disorders. Several brain areas involved in impulsivity and reward valuation, such as the prefrontal cortex and striatum, are linked to the STN, and activity in these areas might be affected by STN-DBS. To investigate the effect of STN-DBS on one type of impulsive decision-making—delay discounting (i.e., the devaluation of reward with increasing delay until its receipt)—we tested 40 human PD patients receiving STN-DBS treatment and medication for at least 3 months. Patients were pseudo-randomly assigned to one of four groups to test the effects of DBS on/off states as well as medication on/off states on delay discounting. The delay-discounting task consisted of a series of choices among a smaller. sooner or a larger, later monetary reward. Despite considerable effects of DBS on motor performance, patients receiving STN-DBS did not choose more or less impulsively compared with those in the off-DBS group, as well as when controlling for risk attitude. Although null results have to be interpreted with caution, our findings are of significance to other researchers studying the effects of PD treatment on impulsive decision-making, and they are of clinical relevance for determining the therapeutic benefits of using STN-DBS. PMID:27257622

  4. No Effect of Subthalamic Deep Brain Stimulation on Intertemporal Decision-Making in Parkinson Patients.

    PubMed

    Seinstra, Maayke; Wojtecki, Lars; Storzer, Lena; Schnitzler, Alfons; Kalenscher, Tobias

    2016-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a widely used treatment for the motor symptoms of Parkinson's disease (PD). DBS or pharmacological treatment is believed to modulate the tendency to, or reverse, impulse control disorders. Several brain areas involved in impulsivity and reward valuation, such as the prefrontal cortex and striatum, are linked to the STN, and activity in these areas might be affected by STN-DBS. To investigate the effect of STN-DBS on one type of impulsive decision-making-delay discounting (i.e., the devaluation of reward with increasing delay until its receipt)-we tested 40 human PD patients receiving STN-DBS treatment and medication for at least 3 months. Patients were pseudo-randomly assigned to one of four groups to test the effects of DBS on/off states as well as medication on/off states on delay discounting. The delay-discounting task consisted of a series of choices among a smaller. sooner or a larger, later monetary reward. Despite considerable effects of DBS on motor performance, patients receiving STN-DBS did not choose more or less impulsively compared with those in the off-DBS group, as well as when controlling for risk attitude. Although null results have to be interpreted with caution, our findings are of significance to other researchers studying the effects of PD treatment on impulsive decision-making, and they are of clinical relevance for determining the therapeutic benefits of using STN-DBS. PMID:27257622

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

    PubMed

    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. PMID:26556561

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

    PubMed Central

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

    2016-01-01

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

  7. The Effect of Deep Brain Stimulation on the Speech Motor System

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    ERIC Educational Resources Information Center

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

    2008-01-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2016-05-15

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Howell, Bryan; Grill, Warren M.

    2014-08-01

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

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

    PubMed

    Valente, Virgilio; Demosthenous, Andreas; Bayford, Richard

    2012-06-01

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

  16. Broca's Area: A Problem in Language-Brain Relationships

    ERIC Educational Resources Information Center

    Whitaker, H. A.; Selnes, O. A.

    1975-01-01

    How significantly is Broca's Area related to speech? It is considered here to be definitely a component in the language mechanism of the brain. It is also stated that this area is unique to people and that it has no unitary function, yet it is specialized for certain expressive (motor) functions. (SCC)

  17. Atlas-based segmentation of deep brain structures using non-rigid registration

    NASA Astrophysics Data System (ADS)

    Khan, Muhammad Faisal; Mewes, Klaus; Gross, Robert E.; Škrinjar, Oskar

    2008-03-01

    Deep brain structures are frequently used as targets in neurosurgical procedures. However, the boundaries of these structures are often not visible in clinically used MR and CT images. Techniques based on anatomical atlases and indirect targeting are used to infer the location of these targets intraoperatively. Initial errors of such approaches may be up to a few millimeters, which is not negligible. E.g. subthalamic nucleus is approximately 4x6 mm in the axial plane and the diameter of globus pallidus internus is approximately 8 mm, both of which are used as targets in deep brain stimulation surgery. To increase the initial localization accuracy of deep brain structures we have developed an atlas-based segmentation method that can be used for the surgery planning. The atlas is a high resolution MR head scan of a healthy volunteer with nine deep brain structures manually segmented. The quality of the atlas image allowed for the segmentation of the deep brain structures, which is not possible from the clinical MR head scans of patients. The subject image is non-rigidly registered to the atlas image using thin plate splines to represent the transformation and normalized mutual information as a similarity measure. The obtained transformation is used to map the segmented structures from the atlas to the subject image. We tested the approach on five subjects. The quality of the atlas-based segmentation was evaluated by visual inspection of the third and lateral ventricles, putamena, and caudate nuclei, which are visible in the subject MR images. The agreement of these structures for the five tested subjects was approximately 1 to 2 mm.

  18. Decoupling of the brain's default mode network during deep sleep

    PubMed Central

    Horovitz, Silvina G.; Braun, Allen R.; Carr, Walter S.; Picchioni, Dante; Balkin, Thomas J.; Fukunaga, Masaki; Duyn, Jeff H.

    2009-01-01

    The recent discovery of a circuit of brain regions that is highly active in the absence of overt behavior has led to a quest for revealing the possible function of this so-called default-mode network (DMN). A very recent study, finding similarities in awake humans and anesthetized primates, has suggested that DMN activity might not simply reflect ongoing conscious mentation but rather a more general form of network dynamics typical of complex systems. Here, by performing functional MRI in humans, it is shown that a natural, sleep-induced reduction of consciousness is reflected in altered correlation between DMN network components, most notably a reduced involvement of frontal cortex. This suggests that DMN may play an important role in the sustenance of conscious awareness. PMID:19549821

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

    PubMed Central

    Ekmekci, Hakan; Kaptan, Hulagu

    2016-01-01

    Background: Camptocormia is known as “bent spine syndrome” and defined as a forward hyperflexion. The most common etiologic factor is related with the movement disorders, mainly in Parkinson's disease (PD). Case Description: We present the case of a 51-year-old woman who has been followed with PD for the last 10 years, and also under the therapy for PD. An unappreciated correlation low back pain with camptocormia developed. She underwent deep brain stimulation (DBS) in the subthalamic nucleus bilaterally and improved her bending posture. Conclusion: The relationship between the DBS and camptocormia is discussed in this unique condition. PMID:26958425

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2016-09-01

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

  2. Cross-frequency coupling in deep brain structures upon processing the painful sensory inputs.

    PubMed

    Liu, C C; Chien, J H; Kim, J H; Chuang, Y F; Cheng, D T; Anderson, W S; Lenz, F A

    2015-09-10

    Cross-frequency coupling has been shown to be functionally significant in cortical information processing, potentially serving as a mechanism for integrating functionally relevant regions in the brain. In this study, we evaluate the hypothesis that pain-related gamma oscillatory responses are coupled with low-frequency oscillations in the frontal lobe, amygdala and hippocampus, areas known to have roles in pain processing. We delivered painful laser pulses to random locations on the dorsal hand of five patients with uncontrolled epilepsy requiring depth electrode implantation for seizure monitoring. Two blocks of 40 laser stimulations were delivered to each subject and the pain-intensity was controlled at five in a 0-10 scale by adjusting the energy level of the laser pulses. Local-field-potentials (LFPs) were recorded through bilaterally implanted depth electrode contacts to study the oscillatory responses upon processing the painful laser stimulations. Our results show that painful laser stimulations enhanced low-gamma (LH, 40-70 Hz) and high-gamma (HG, 70-110 Hz) oscillatory responses in the amygdala and hippocampal regions on the right hemisphere and these gamma responses were significantly coupled with the phases of theta (4-7 Hz) and alpha (8-1 2 Hz) rhythms during pain processing. Given the roles of these deep brain structures in emotion, these findings suggest that the oscillatory responses in these regions may play a role in integrating the affective component of pain, which may contribute to our understanding of the mechanisms underlying the affective information processing in humans. PMID:26168707

  3. Non-invasive Parenchymal, Vascular and Metabolic High-frequency Ultrasound and Photoacoustic Rat Deep Brain Imaging

    PubMed Central

    Giustetto, Pierangela; Filippi, Miriam; Castano, Mauro; Terreno, Enzo

    2015-01-01

    Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central nervous system of small animals. However, transdermal and transcranial neuroimaging is frequently affected by low sensitivity, image aberrations and loss of space resolution, requiring scalp or even skull removal before imaging. To overcome this challenge, a new protocol is presented to gain significant insights in brain hemodynamics by photoacoustic and high-frequency ultrasounds imaging with the animal skin and skull intact. The procedure relies on the passage of ultrasound (US) waves and laser directly through the fissures that are naturally present on the animal cranium. By juxtaposing the imaging transducer device exactly in correspondence to these selected areas where the skull has a reduced thickness or is totally absent, one can acquire high quality deep images and explore internal brain regions that are usually difficult to anatomically or functionally describe without an invasive approach. By applying this experimental procedure, significant data can be collected in both sonic and optoacoustic modalities, enabling to image the parenchymal and the vascular anatomy far below the head surface. Deep brain features such as parenchymal convolutions and fissures separating the lobes were clearly visible. Moreover, the configuration of large and small blood vessels was imaged at several millimeters of depth, and precise information were collected about blood fluxes, vascular stream velocities and the hemoglobin chemical state. This repertoire of data could be crucial in several research contests, ranging from brain vascular disease studies to experimental techniques involving the systemic administration of exogenous chemicals or other objects endowed with imaging contrast enhancement properties. In conclusion, thanks to the presented protocol, the US and PA techniques become an attractive noninvasive

  4. Non-invasive parenchymal, vascular and metabolic high-frequency ultrasound and photoacoustic rat deep brain imaging.

    PubMed

    Giustetto, Pierangela; Filippi, Miriam; Castano, Mauro; Terreno, Enzo

    2015-01-01

    Photoacoustics and high frequency ultrasound stands out as powerful tools for neurobiological applications enabling high-resolution imaging on the central nervous system of small animals. However, transdermal and transcranial neuroimaging is frequently affected by low sensitivity, image aberrations and loss of space resolution, requiring scalp or even skull removal before imaging. To overcome this challenge, a new protocol is presented to gain significant insights in brain hemodynamics by photoacoustic and high-frequency ultrasounds imaging with the animal skin and skull intact. The procedure relies on the passage of ultrasound (US) waves and laser directly through the fissures that are naturally present on the animal cranium. By juxtaposing the imaging transducer device exactly in correspondence to these selected areas where the skull has a reduced thickness or is totally absent, one can acquire high quality deep images and explore internal brain regions that are usually difficult to anatomically or functionally describe without an invasive approach. By applying this experimental procedure, significant data can be collected in both sonic and optoacoustic modalities, enabling to image the parenchymal and the vascular anatomy far below the head surface. Deep brain features such as parenchymal convolutions and fissures separating the lobes were clearly visible. Moreover, the configuration of large and small blood vessels was imaged at several millimeters of depth, and precise information were collected about blood fluxes, vascular stream velocities and the hemoglobin chemical state. This repertoire of data could be crucial in several research contests, ranging from brain vascular disease studies to experimental techniques involving the systemic administration of exogenous chemicals or other objects endowed with imaging contrast enhancement properties. In conclusion, thanks to the presented protocol, the US and PA techniques become an attractive noninvasive

  5. Efficacy of endoport-guided endoscopic resection for deep-seated brain lesions.

    PubMed

    Jo, Kwang-Wook; Shin, Hyung Jin; Nam, Do-Hyun; Lee, Jung-Il; Park, Kwan; Kim, Jong Hyun; Kong, Doo-Sik

    2011-10-01

    Surgery for deep-seated brain lesions without causing significant trauma to the overlying cortex is difficult because brain retraction is required to approach these lesions. The aim of this study was to determine the efficacy of endoport-guided endoscopic or microscopic removal for deep-seated lesions using the neuronavigation system. Between October 2008 and December 2009, 21 patients (17 men and 4 women; average age, 40.8 years) underwent endoport-guided endoscopic tumor removal. We adapted the transparent tubular conduit, so-called "endoport," to target the lesions under the guidance of neuronavigation. We then determined the efficacy and limitations of this technique with fully endoscopic removal, compared with standard approaches using a spatula retractor. Gross total resection of the lesions was achieved in 14 of 21 patients (66%), and partial removal occurred in four (19%) patients. However, there was failure to remove the lesion through the endoport in three patients (14.3%), requiring the use of blade spatula retractors. In reviewing the seven cases with either failure or partial removal, it was found that a large tumor size (≥ 3 cm) and calcified lesions were the major factors limiting the application of this technique. Endoport-guided endoscopic surgery facilitated an accurate and minimally invasive technique for removal of these deep-seated brain lesions. This procedure required a protracted learning curve although, when successful, this approach can minimize brain retraction and provide satisfactory visualization. PMID:21614427

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

    PubMed

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

    2016-01-01

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

  7. Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear.

    PubMed

    Rodriguez-Romaguera, Jose; Do Monte, Fabricio H M; Quirk, Gregory J

    2012-05-29

    Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces symptoms of intractable obsessive-compulsive disorder (OCD), but the mechanism of action is unknown. OCD is characterized by avoidance behaviors that fail to extinguish, and DBS could act, in part, by facilitating extinction of fear. We investigated this possibility by using auditory fear conditioning in rats, for which the circuits of fear extinction are well characterized. We found that DBS of the VS (the VC/VS homolog in rats) during extinction training reduced fear expression and strengthened extinction memory. Facilitation of extinction was observed for a specific zone of dorsomedial VS, just above the anterior commissure; stimulation of more ventrolateral sites in VS impaired extinction. DBS effects could not be obtained with pharmacological inactivation of either dorsomedial VS or ventrolateral VS, suggesting an extrastriatal mechanism. Accordingly, DBS of dorsomedial VS (but not ventrolateral VS) increased expression of a plasticity marker in the prelimbic and infralimbic prefrontal cortices, the orbitofrontal cortex, the amygdala central nucleus (lateral division), and intercalated cells, areas known to learn and express extinction. Facilitation of fear extinction suggests that, in accord with clinical observations, DBS could augment the effectiveness of cognitive behavioral therapies for OCD. PMID:22586125

  8. Deep Brain Stimulation for Obesity: From a Theoretical Framework to Practical Application

    PubMed Central

    Nangunoori, Raj K.; Tomycz, Nestor D.; Oh, Michael Y.; Whiting, Donald M.

    2016-01-01

    Obesity remains a pervasive global health problem. While there are a number of nonsurgical and surgical options for treatment, the incidence of obesity continues to increase at an alarming rate. The inability to curtail the growing rise of the obesity epidemic may be related to a combination of increased food availability and palatability. Research into feeding behavior has yielded a number of insights into the homeostatic and reward mechanisms that govern feeding. However, there remains a gap between laboratory investigations of feeding physiology in animals and translation into meaningful treatment options for humans. In addition, laboratory investigation may not be able to recapitulate all aspects of human food consumption. In a landmark pilot study of deep brain stimulation (DBS) of the lateral hypothalamic area for obesity, we found that there was an increase in resting metabolic rate as well as a decreased urge to eat. In this review, the authors will review some of the work relating to feeding physiology and research surrounding two nodes involved in feeding homeostasis, nucleus accumbens (NAc) and hypothalamus, and use this to provide a framework for future investigations of DBS as a viable therapeutic modality for obesity. PMID:26819774

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

    PubMed Central

    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 structure of clinical trial funding and the current regulation of device research threaten investigator-initiated efforts in neurologic disorders. The current atmosphere dissuades clinical investigators from pursuing formal and prospective research with novel devices or novel indications. We review our experience in conducting a federally funded, investigator-initiated, device-based clinical trial that utilized DBS for thalamic pain syndrome. We also explore barriers that clinical investigators face in conducting device-based clinical trials, particularly in early-stage studies or small disease populations. We discuss 5 specific areas for potential reform and integration: (1) alternative pathways for device approval; (2) eliminating right of reference requirements; (3) combining federal grant awards with regulatory approval; (4) consolidation of oversight for human subjects research; and (5) private insurance coverage for clinical trials. Careful reformulation of regulatory policy and funding mechanisms is critical for expanding investigator-initiated device research, which has great potential to benefit science, industry, and, most importantly, patients. PMID:24670888

  10. Axial disability and deep brain stimulation in patients with Parkinson disease.

    PubMed

    Fasano, Alfonso; Aquino, Camila C; Krauss, Joachim K; Honey, Christopher R; Bloem, Bastiaan R

    2015-02-01

    Axial motor signs-including gait impairment, postural instability and postural abnormalities-are common and debilitating symptoms in patients with advanced Parkinson disease. Dopamine replacement therapy and physiotherapy provide, at best, partial relief from axial motor symptoms. In carefully selected candidates, deep brain stimulation (DBS) of the subthalamic nucleus or globus pallidus internus is an established treatment for 'appendicular' motor signs (limb tremor, bradykinesia and rigidity). However, the effects of DBS on axial signs are much less clear, presumably because motor control of axial and appendicular functions is mediated by different anatomical-functional pathways. Here, we discuss the successes and failures of DBS in managing axial motor signs. We systematically address a series of common clinical questions associated with the preoperative phase, during which patients presenting with prominent axial signs are considered for DBS implantation surgery, and the postoperative phase, in particular, the management of axial motor signs that newly develop as postoperative complications, either acutely or with a delay. We also address the possible merits of new targets-including the pedunculopontine nucleus area, zona incerta and substantia nigra pars reticulata-to specifically alleviate axial symptoms. Supported by a rapidly growing body of evidence, this practically oriented Review aims to support decision-making in the management of axial symptoms. PMID:25582445

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

    NASA Technical Reports Server (NTRS)

    Koehne, Jessica E.

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-04-22

    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 structure of clinical trial funding and the current regulation of device research threaten investigator-initiated efforts in neurologic disorders. The current atmosphere dissuades clinical investigators from pursuing formal and prospective research with novel devices or novel indications. We review our experience in conducting a federally funded, investigator-initiated, device-based clinical trial that utilized DBS for thalamic pain syndrome. We also explore barriers that clinical investigators face in conducting device-based clinical trials, particularly in early-stage studies or small disease populations. We discuss 5 specific areas for potential reform and integration: (1) alternative pathways for device approval; (2) eliminating right of reference requirements; (3) combining federal grant awards with regulatory approval; (4) consolidation of oversight for human subjects research; and (5) private insurance coverage for clinical trials. Careful reformulation of regulatory policy and funding mechanisms is critical for expanding investigator-initiated device research, which has great potential to benefit science, industry, and, most importantly, patients. PMID:24670888

  14. A Brain Area for Visual Numerals

    PubMed Central

    Shum, Jennifer; Hermes, Dora; Foster, Brett L.; Dastjerdi, Mohammad; Rangarajan, Vinitha; Winawer, Jonathan; Miller, Kai J.; Parvizi, Josef

    2014-01-01

    Is there a distinct area within the human visual system that has a preferential response to numerals, as there is for faces, words, or scenes? We addressed this question using intracranial electrophysiological recordings and observed a significantly higher response in the high-frequency broadband range (high γ, 65–150 Hz) to visually presented numerals, compared with morphologically similar (i.e., letters and false fonts) or semantically and phonologically similar stimuli (i.e., number words and non-number words). Anatomically, this preferential response was consistently localized in the inferior temporal gyrus and anterior to the temporo-occipital incisure. This region lies within or close to the fMRI signal-dropout zone produced by the nearby auditory canal and venous sinus artifacts, an observation that may account for negative findings in previous fMRI studies of preferential response to numerals. Because visual numerals are culturally dependent symbols that are only learned through education, our novel finding of anatomically localized preferential response to such symbols provides a new example of acquired category-specific responses in the human visual system. PMID:23595729

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

    NASA Astrophysics Data System (ADS)

    Butson, Christopher R.; McIntyre, Cameron C.

    2006-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

  17. Age-dependent expression of VEGFR2 in deep brain arteries in small vessel disease, CADASIL, and healthy brains.

    PubMed

    Ahmed-Jushuf, Fiyyaz; Jiwa, Nadim S; Arwani, Anum S; Foot, Peter; Bridges, Leslie R; Kalaria, Raj N; Esiri, Margaret M; Hainsworth, Atticus H

    2016-06-01

    Vascular myocytes are central to brain aging. Small vessel disease (SVD; arteriolosclerosis) is a widespread cause of lacunar stroke and vascular dementia and is characterized by fibrosis and depletion of vascular myocytes in small penetrating arteries. Vascular endothelial growth factor (VEGF) is associated with brain aging, and Immunolabeling for vascular endothelial growth factor receptor 2 (VEGFR2) is a potent determinant of cell fate. Here, we tested whether VEGFR2 in vascular myocytes is associated with older age and SVD in human brain. Immunolabeling for VEGFR2 in deep gray matter was assessed in older people with or without moderate-severe SVD or in younger people without brain pathology or with a monogenic form of SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). All cases were without Alzheimer's disease pathology. Myocyte VEGFR2 was associated with increasing age (p = 0.0026) but not with SVD pathology or with sclerotic index or blood vessel density. We conclude that VEGFR2 is consistently expressed in small artery myocytes of older people and may mediate effects of VEGF on brain vascular aging. PMID:27143427

  18. STED Nanoscopy of Actin Dynamics in Synapses Deep Inside Living Brain Slices

    PubMed Central

    Urban, Nicolai T.; Willig, Katrin I.; Hell, Stefan W.; Nägerl, U. Valentin

    2011-01-01

    It is difficult to investigate the mechanisms that mediate long-term changes in synapse function because synapses are small and deeply embedded inside brain tissue. Although recent fluorescence nanoscopy techniques afford improved resolution, they have so far been restricted to dissociated cells or tissue surfaces. However, to study synapses under realistic conditions, one must image several cell layers deep inside more-intact, three-dimensional preparations that exhibit strong light scattering, such as brain slices or brains in vivo. Using aberration-reducing optics, we demonstrate that it is possible to achieve stimulated emission depletion superresolution imaging deep inside scattering biological tissue. To illustrate the power of this novel (to our knowledge) approach, we resolved distinct distributions of actin inside dendrites and spines with a resolution of 60–80 nm in living organotypic brain slices at depths up to 120 μm. In addition, time-lapse stimulated emission depletion imaging revealed changes in actin-based structures inside spines and spine necks, and showed that these dynamics can be modulated by neuronal activity. Our approach greatly facilitates investigations of actin dynamics at the nanoscale within functionally intact brain tissue. PMID:21889466

  19. Preanesthetic evaluation of a patient with a deep brain stimulator: a practical guide and checklist for patient safety.

    PubMed

    Weinstein, Adam S; Aglio, Linda S

    2016-06-01

    As the patient population with deep brain stimulators grows, medical personnel need to be comfortable managing these patients because they will likely encounter them in practice. Caring for a patient with a deep brain stimulator during surgery or a procedure requires technical knowledge of the device and its possible interactions in order to take the correct precautionary measures. Here we discuss the key issues and questions that should be covered in every preanesthetic evaluation visit of a patient with a deep brain stimulator along with an evaluation checklist. PMID:27185727

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

    PubMed

    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. PMID:25570219

  1. Development of Demand-Controlled Deep Brain Stimulation Techniques Based on Stochastic Phase Resetting

    NASA Astrophysics Data System (ADS)

    Tass, Peter A.

    2003-05-01

    Stimulation techniques are discussed here which make it possible to effectively desynchronize a synchronized cluster of globally coupled phase oscillators in the presence of noise. To this end composite stimuli are used which consist of a first, stronger stimulus followed by a second, weaker stimulus after a constant time delay. The first stimulus controls the dynamics of the cluster by resetting it, whereas the second stimulus desynchronizes the cluster by hitting it in a vulnerable state. The first, resetting stimulus can be a strong single pulse, a high-frequency pulse train or a low-frequency pulse train. The cluster's resynchronization can effectively be blocked by repeated administration of a composite stimulus. Demand controlled deep brain stimulation with these desynchronizing stimulation techniques is suggested for the therapy of patients suffering from tremor-dominant Parkinson's disease or essential tremor as a milder and more efficient therapy compared to the standard permanent high-frequency deep brain stimulation.

  2. Deep brain stimulation for Parkinson's disease: current status and future outlook.

    PubMed

    Smith, Kyle A; Pahwa, Rajesh; Lyons, Kelly E; Nazzaro, Jules M

    2016-08-01

    Parkinson's disease is a neurodegenerative condition secondary to loss of dopaminergic neurons in the substantia nigra pars compacta. Surgical therapy serves as an adjunct when unwanted medication side effects become apparent or additional therapy is needed. Deep brain stimulation emerged into the forefront in the 1990s. Studies have demonstrated improvement in all of the cardinal parkinsonian signs with stimulation. Frameless and 'mini-frame' stereotactic systems, improved MRI for anatomic visualization, and intraoperative MRI-guided placement are a few of the surgical advances in deep brain stimulation. Other advances include rechargeable pulse generators, voltage- or current-based stimulation, and enhanced abilities to 'steer' stimulation. Work is ongoing investigating closed-loop 'smart' stimulation in which stimulation is predicated on neuronal feedback. PMID:27409150

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Bae, Dae-Woong; Son, Byung-chul; Kim, Joong-Seok

    2014-01-01

    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. PMID:25360233

  5. Deep Brain Stimulation in Huntington's Disease-Preliminary Evidence on Pathophysiology, Efficacy and Safety.

    PubMed

    Wojtecki, Lars; Groiss, Stefan Jun; Hartmann, Christian Johannes; Elben, Saskia; Omlor, Sonja; Schnitzler, Alfons; Vesper, Jan

    2016-01-01

    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. PMID:27589813

  6. Beyond nine years of continuous subthalamic nucleus deep brain stimulation in Parkinson's disease.

    PubMed

    Zibetti, Maurizio; Merola, Aristide; Rizzi, Laura; Ricchi, Valeria; Angrisano, Serena; Azzaro, Corrado; Artusi, Carlo Alberto; Arduino, Nichy; Marchisio, Alice; Lanotte, Michele; Rizzone, Mario; Lopiano, Leonardo

    2011-11-01

    Deep brain stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease. The benefits of bilateral subthalamic stimulation are well documented, and some studies reported outcomes with a follow-up of 5 to 6 years; nevertheless, few data are available beyond 5 years. We report a long-term prospective evaluation of 14 consecutive parkinsonian patients, treated by bilateral subthalamic stimulation for at least 9 years. Motor symptoms, activity of daily living, and motor complications were evaluated by means of the Unified Parkinson's Disease Rating Scale, while cognition and mood were assessed with a specific neuropsychological test battery; medication intake, stimulation parameters, comorbidity, and adverse events were also recorded. Patients were evaluated before surgery and at 1, 5, and ≥ 9 years after surgery. At last follow-up, deep brain stimulation significantly improved the motor score by 42% compared to baseline, whereas activities of daily living were no longer improved; there was a 39% reduction in the dosage of dopaminergic drugs and a 59% improvement of L-dopa-related motor complications. The neuropsychological assessment showed that 4 patients (29%) developed a significant cognitive decline over the follow-up period. These results indicate a persistent effect of deep brain stimulation of the subthalamic nucleus on the cardinal motor symptoms in advanced Parkinson's disease patients in the long-term; however, a worsening of patients' disability, mainly due to disease progression, was observed. PMID:22012750

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:27173938

  9. Nonthermal ablation of deep brain targets: A simulation study on a large animal model

    PubMed Central

    Top, Can Barış; White, P. Jason; McDannold, Nathan J.

    2016-01-01

    Purpose: Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is currently limited to central brain targets because of heating and other beam effects caused by the presence of the skull. Recently, it was shown that it is possible to ablate tissues without depositing thermal energy by driving intravenously administered microbubbles to inertial cavitation using low-duty-cycle burst sonications. A recent study demonstrated that this ablation method could ablate tissue volumes near the skull base in nonhuman primates without thermally damaging the nearby bone. However, blood–brain disruption was observed in the prefocal region, and in some cases, this region contained small areas of tissue damage. The objective of this study was to analyze the experimental model with simulations and to interpret the cause of these effects. Methods: The authors simulated prior experiments where nonthermal ablation was performed in the brain in anesthetized rhesus macaques using a 220 kHz clinical prototype transcranial MRI-guided FUS system. Low-duty-cycle sonications were applied at deep brain targets with the ultrasound contrast agent Definity. For simulations, a 3D pseudospectral finite difference time domain tool was used. The effects of shear mode conversion, focal steering, skull aberrations, nonlinear propagation, and the presence of skull base on the pressure field were investigated using acoustic and elastic wave propagation models. Results: The simulation results were in agreement with the experimental findings in the prefocal region. In the postfocal region, however, side lobes were predicted by the simulations, but no effects were evident in the experiments. The main beam was not affected by the different simulated scenarios except for a shift of about 1 mm in peak position due to skull aberrations. However, the authors observed differences in the volume, amplitude, and distribution of the side lobes. In the experiments, a single element passive

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

    NASA Astrophysics Data System (ADS)

    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.

  11. Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning.

    PubMed

    Katnani, Husam A; Patel, Shaun R; Kwon, Churl-Su; Abdel-Aziz, Samer; Gale, John T; Eskandar, Emad N

    2016-01-01

    The primate brain has the remarkable ability of mapping sensory stimuli into motor behaviors that can lead to positive outcomes. We have previously shown that during the reinforcement of visual-motor behavior, activity in the caudate nucleus is correlated with the rate of learning. Moreover, phasic microstimulation in the caudate during the reinforcement period was shown to enhance associative learning, demonstrating the importance of temporal specificity to manipulate learning related changes. Here we present evidence that extends upon our previous finding by demonstrating that temporally coordinated phasic deep brain stimulation across both the nucleus accumbens and caudate can further enhance associative learning. Monkeys performed a visual-motor associative learning task and received stimulation at time points critical to learning related changes. Resulting performance revealed an enhancement in the rate, ceiling, and reaction times of learning. Stimulation of each brain region alone or at different time points did not generate the same effect. PMID:26725509

  12. Temporally Coordinated Deep Brain Stimulation in the Dorsal and Ventral Striatum Synergistically Enhances Associative Learning

    PubMed Central

    Katnani, Husam A.; Patel, Shaun R.; Kwon, Churl-Su; Abdel-Aziz, Samer; Gale, John T.; Eskandar, Emad N.

    2016-01-01

    The primate brain has the remarkable ability of mapping sensory stimuli into motor behaviors that can lead to positive outcomes. We have previously shown that during the reinforcement of visual-motor behavior, activity in the caudate nucleus is correlated with the rate of learning. Moreover, phasic microstimulation in the caudate during the reinforcement period was shown to enhance associative learning, demonstrating the importance of temporal specificity to manipulate learning related changes. Here we present evidence that extends upon our previous finding by demonstrating that temporally coordinated phasic deep brain stimulation across both the nucleus accumbens and caudate can further enhance associative learning. Monkeys performed a visual-motor associative learning task and received stimulation at time points critical to learning related changes. Resulting performance revealed an enhancement in the rate, ceiling, and reaction times of learning. Stimulation of each brain region alone or at different time points did not generate the same effect. PMID:26725509

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2011-07-01

    Clinical findings in Parkinson's disease suggest that most patients progressively develop disabling non-levodopa-responsive symptoms during the course of the disease. Nevertheless, several heterogeneous factors, such as clinical phenotype, age at onset and genetic aspects may influence the long-term clinical picture. In order to investigate the main features of long-term Parkinson's disease progression, we studied a cohort of 19 subjects treated with subthalamic nucleus deep brain stimulation after >20 years of disease, reporting clinical and neuropsychological data up to a mean of 30 years from disease onset. This group of patients was characterized by an early onset of disease, with a mean age of 38.63 years at Parkinson's disease onset, which was significantly lower than in the other long-term subthalamic nucleus deep brain stimulation follow-up cohorts reported in the literature. All subjects were regularly evaluated by a complete Unified Parkinson's Disease Rating Scale, a battery of neuropsychological tests and a clinical interview, intended to assess the rate of non-levodopa-responsive symptom progression. Clinical data were available for all patients at presurgical baseline and at 1, 3 and 5 years from the subthalamic nucleus deep brain stimulation surgical procedure, while follow-up data after >7 years were additionally reported in a subgroup of 14 patients. The clinical and neuropsychological performance progressively worsened during the course of follow-up; 64% of patients gradually developed falls, 86% dysphagia, 57% urinary incontinence and 43% dementia. A progressive worsening of motor symptoms was observed both in 'medication-ON' condition and in 'stimulation-ON' condition, with a parallel reduction in the synergistic effect of 'medication-ON/stimulation-ON' condition. Neuropsychological data also showed a gradual decline in the performances of all main cognitive domains, with an initial involvement of executive functions, followed by the impairment

  15. How Localized are Language Brain Areas? A Review of Brodmann Areas Involvement in Oral Language.

    PubMed

    Ardila, Alfredo; Bernal, Byron; Rosselli, Monica

    2016-02-01

    The interest in understanding how language is "localized" in the brain has existed for centuries. Departing from seven meta-analytic studies of functional magnetic resonance imaging activity during the performance of different language activities, it is proposed here that there are two different language networks in the brain: first, a language reception/understanding system, including a "core Wernicke's area" involved in word recognition (BA21, BA22, BA41, and BA42), and a fringe or peripheral area ("extended Wernicke's area:" BA20, BA37, BA38, BA39, and BA40) involved in language associations (associating words with other information); second, a language production system ("Broca's complex:" BA44, BA45, and also BA46, BA47, partially BA6-mainly its mesial supplementary motor area-and extending toward the basal ganglia and the thalamus). This paper additionally proposes that the insula (BA13) plays a certain coordinating role in interconnecting these two brain language systems. PMID:26663825

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

    PubMed

    Kroeger, Daniel; Florea, Bogdan; Amzica, Florin

    2013-01-01

    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. PMID:24058669

  17. Human Brain Activity Patterns beyond the Isoelectric Line of Extreme Deep Coma

    PubMed Central

    Kroeger, Daniel; Florea, Bogdan; Amzica, Florin

    2013-01-01

    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. PMID:24058669

  18. Neuroprotection trek--the next generation: neuromodulation I. Techniques--deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation

    NASA Technical Reports Server (NTRS)

    Andrews, Russell J.

    2003-01-01

    Neuromodulation denotes controlled electrical stimulation of the central or peripheral nervous system. The three forms of neuromodulation described in this paper-deep brain stimulation, vagus nerve stimulation, and transcranial magnetic stimulation-were chosen primarily for their demonstrated or potential clinical usefulness. Deep brain stimulation is a completely implanted technique for improving movement disorders, such as Parkinson's disease, by very focal electrical stimulation of the brain-a technique that employs well-established hardware (electrode and pulse generator/battery). Vagus nerve stimulation is similar to deep brain stimulation in being well-established (for the treatment of refractory epilepsy), completely implanted, and having hardware that can be considered standard at the present time. Vagus nerve stimulation differs from deep brain stimulation, however, in that afferent stimulation of the vagus nerve results in diffuse effects on many regions throughout the brain. Although use of deep brain stimulation for applications beyond movement disorders will no doubt involve placing the stimulating electrode(s) in regions other than the thalamus, subthalamus, or globus pallidus, the use of vagus nerve stimulation for applications beyond epilepsy-for example, depression and eating disorders-is unlikely to require altering the hardware significantly (although stimulation protocols may differ). Transcranial magnetic stimulation is an example of an external or non-implanted, intermittent (at least given the current state of the hardware) stimulation technique, the clinical value of which for neuromodulation and neuroprotection remains to be determined.

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

    PubMed

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

    2016-02-01

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

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

    PubMed

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

    2003-12-01

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

  1. Improved Sequence Learning with Subthalamic Nucleus Deep Brain Stimulation: Evidence for Treatment-Specific Network Modulation

    PubMed Central

    Mure, Hideo; Tang, Chris C.; Argyelan, Miklos; Ghilardi, Maria-Felice; Kaplitt, Michael G.; Dhawan, Vijay; Eidelberg, David

    2015-01-01

    We used a network approach to study the effects of anti-parkinsonian treatment on motor sequence learning in humans. Eight Parkinson’s disease (PD) patients with bilateral subthalamic nucleus (STN) deep brain stimulation underwent H2 15Opositron emission tomography (PET) imaging to measure regional cerebral blood flow (rCBF) while they performed kinematically matched sequence learning and movement tasks at baseline and during stimulation. Network analysis revealed a significant learning-related spatial covariance pattern characterized by consistent increases in subject expression during stimulation (p = 0.008, permutation test). The network was associated with increased activity in the lateral cerebellum, dorsal premotor cortex, and parahippocampal gyrus, with covarying reductions in the supplementary motor area (SMA) and orbitofrontal cortex. Stimulation-mediated increases in network activity correlated with concurrent improvement in learning performance (p < 0.02). To determine whether similar changes occurred during dopaminergic pharmacotherapy, we studied the subjects during an intravenous levodopa infusion titrated to achieve a motor response equivalent to stimulation. Despite consistent improvement in motor ratings during infusion, levodopa did not alter learning performance or network activity. Analysis of learning-related rCBF in network regions revealed improvement in baseline abnormalities with STN stimulation but not levodopa. These effects were most pronounced in the SMA. In this region, a consistent rCBF response to stimulation was observed across subjects and trials (p = 0.01), although the levodopa response was not significant. These findings link the cognitive treatment response in PD to changes in the activity of a specific cerebello-premotor cortical network. Selective modulation of overactive SMA–STN projection pathways may underlie the improvement in learning found with stimulation. PMID:22357863

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

    PubMed

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

    2015-01-01

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

  3. Disruption in proprioception from long-term thalamic deep brain stimulation: a pilot study

    PubMed Central

    Semrau, Jennifer A.; Herter, Troy M.; Kiss, Zelma H.; Dukelow, Sean P.

    2015-01-01

    Deep brain stimulation (DBS) is an excellent treatment for tremor and is generally thought to be reversible by turning off stimulation. For tremor, DBS is implanted in the ventrointermedius (Vim) nucleus of the thalamus, a region that relays proprioceptive information for movement sensation (kinaesthesia). Gait disturbances have been observed with bilateral Vim DBS, but the long-term effects on proprioceptive processing are unknown. We aimed to determine whether Vim DBS surgical implantation or stimulation leads to proprioceptive deficits in the upper limb. We assessed two groups of tremor subjects on measures of proprioception (kinaesthesia, position sense) and motor function using a robotic exoskeleton. In the first group (Surgery), we tested patients before and after implantation of Vim DBS, but before DBS was turned on to determine if proprioceptive deficits were inherent to tremor or caused by DBS implantation. In the second group (Stim), we tested subjects with chronically implanted Vim DBS ON and OFF stimulation. Compared to controls, there were no proprioceptive deficits before or after DBS implantation in the Surgery group. Surprisingly, those that received chronic long-term stimulation (LT-stim, 3–10 years) displayed significant proprioceptive deficits ON and OFF stimulation not present in subjects with chronic short-term stimulation (ST-stim, 0.5–2 years). LT-stim had significantly larger variability and reduced workspace area during the position sense assessment. During the kinesthetic assessment, LT-stim made significantly larger directional errors and consistently underestimated the speed of the robot, despite generating normal movement speeds during motor assessment. Chronic long-term Vim DBS may potentially disrupt proprioceptive processing, possibly inducing irreversible plasticity in the Vim nucleus and/or its network connections. Our findings in the upper limb may help explain some of the gait disturbances seen by others following Vim DBS

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

    PubMed

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

    2013-01-01

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

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

    PubMed

    Motevakel, Amir; Medvedev, Alexander

    2014-01-01

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

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

    PubMed

    Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

    2016-01-01

    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. PMID:27057543

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

    PubMed Central

    Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

    2016-01-01

    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. PMID:27057543

  8. Toward Deep Brain Monitoring with Superficial EEG Sensors Plus Neuromodulatory Focused Ultrasound.

    PubMed

    Darvas, Felix; Mehić, Edin; Caler, Connor J; Ojemann, Jeff G; Mourad, Pierre D

    2016-08-01

    Noninvasive recordings of electrophysiological activity have limited anatomic specificity and depth. We hypothesized that spatially tagging a small volume of brain with a unique electroencephalography (EEG) signal induced by pulsed focused ultrasound could overcome those limitations. As a first step toward testing this hypothesis, we applied transcranial ultrasound (2 MHz, 200-ms pulses applied at 1050 Hz for 1 s at a spatial peak temporal average intensity of 1.4 W/cm(2)) to the brains of anesthetized rats while simultaneously recording EEG signals. We observed a significant 1050-Hz electrophysiological signal only when ultrasound was applied to a living brain. Moreover, amplitude demodulation of the EEG signal at 1050 Hz yielded measurement of gamma band (>30 Hz) brain activity consistent with direct measurements of that activity. These results represent preliminary support for use of pulsed focused ultrasound as a spatial tagging mechanism for non-invasive EEG-based mapping of deep brain activity with high spatial resolution. PMID:27181686

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2016-07-01

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

  11. Development of tube tetrodes and a multi-tetrode drive for deep structure electrophysiological recordings in the macaque brain.

    PubMed

    Kapoor, Vishal; Krampe, Eduard; Klug, Axel; Logothetis, Nikos K; Panagiotaropoulos, Theofanis I

    2013-05-30

    Understanding the principles that underlie information processing by neuronal networks requires simultaneous recordings from large populations of well isolated single units. Twisted wire tetrodes (TWTs), typically made by winding together four ultrathin wires (diameter: 12-25 μm), are ideally suited for such population recordings. They are advantageous over single electrodes; both with respect to quality of isolation as well as the number of single units isolated and have therefore been used extensively for superficial cortical recordings. However, their limited tensile strength poses a difficulty to their use for recordings in deep brain areas. We therefore developed a method to overcome this limitation and utilize tetrodes for electrophysiological recordings in the inferotemporal cortex of rhesus macaque. We fabricated a novel, stiff tetrode called the tube tetrode (TuTe) and developed a multi-tetrode driving system for advancing up to 5 TuTes through a ball and socket chamber to precise locations in the temporal lobe of a rhesus macaque. The signal quality acquired with TuTes was comparable to conventional TWTs and allowed excellent isolation of multiple single units. We describe here a simple method for constructing TuTes, which requires only standard laboratory equipment. Further, our TuTes can be easily adapted to work with other microdrives commonly used for electrophysiological investigation in the macaque brain and produce minimal damage to the cortex along its path because of their ultrathin diameter. The tetrode development described here could allow studying neuronal populations in deep lying brain structures previously difficult to reach with the current technology. PMID:23549063

  12. Testosterone affects language areas of the adult human brain

    PubMed Central

    Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  13. Testosterone affects language areas of the adult human brain.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

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

    PubMed

    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

  15. Identification and Management of Deep Brain Stimulation Intra- and Postoperative Urgencies and Emergencies

    PubMed Central

    Morishita, Takashi; Foote, Kelly D.; Burdick, Adam P.; Katayama, Yoichi; Yamamoto, Takamitsu; Frucht, Steven J.; Okun, Michael S.

    2009-01-01

    Deep brain stimulation (DBS) has been increasingly utilized for the therapeutic treatment of movement disorders, and with the advent of this therapy more postoperative urgencies and emergencies have emerged. In this paper, we will review, identify, and suggest management strategies for both intra- and postoperative urgencies and emergencies. We have separated the scenarios into 1- surgery/procedure related, 2- hardware related, 3- stimulation induced difficulties, and 4- others. We have included ten illustrative (and actual) case vignettes to augment the discussion of each issue. PMID:19896407

  16. Proceedings of the second annual deep brain stimulation think tank: What's in the pipeline

    SciTech Connect

    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; Troster, Alexander I.; Verhagen, Leo; Walker, Harrison; Okun, Michael S.

    2015-05-25

    Here 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.

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

    PubMed Central

    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

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

    PubMed Central

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

    2012-01-01

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

  19. Hold your horses: impulsivity, deep brain stimulation, and medication in parkinsonism.

    PubMed

    Frank, Michael J; Samanta, Johan; Moustafa, Ahmed A; Sherman, Scott J

    2007-11-23

    Deep brain stimulation (DBS) of the subthalamic nucleus markedly improves the motor symptoms of Parkinson's disease, but causes cognitive side effects such as impulsivity. We showed that DBS selectively interferes with the normal ability to slow down when faced with decision conflict. While on DBS, patients actually sped up their decisions under high-conflict conditions. This form of impulsivity was not affected by dopaminergic medication status. Instead, medication impaired patients' ability to learn from negative decision outcomes. These findings implicate independent mechanisms leading to impulsivity in treated Parkinson's patients and were predicted by a single neurocomputational model of the basal ganglia. PMID:17962524

  20. Cellular mechanisms of deep brain stimulation: activity-dependent focal circuit reprogramming?

    PubMed Central

    Veerakumar, Avin; Berton, Olivier

    2015-01-01

    Deep brain stimulation (DBS) is a well-established treatment modality for movement disorders. As more behavioral disorders are becoming understood as specific disruptions in neural circuitry, the therapeutic realm of DBS is broadening to encompass a wider range of domains, including disorders of compulsion, affect, and memory, but current understanding of the cellular mechanisms of DBS remains limited. We review progress made during the last decade focusing in particular on how recent methods for targeted circuit manipulations, imaging and reconstruction are fostering preclinical and translational advances that improve our neurobiological understanding of DBS’s action in psychiatric disorders. PMID:26719852

  1. Deep Brain Stimulation in Persistent Vegetative States: Ethical Issues Governing Decision Making

    PubMed Central

    Patuzzo, Sara; Manganotti, Paolo

    2014-01-01

    The aim of the present paper was to investigate the fundamental ethical issues of Deep Brain Stimulation (DBS) on patients remaining in Persistent Vegetative State (PVS). First, the purpose of this analysis was to discuss the nature of this intervention in order to classify it such as an ordinary clinical practice, or otherwise as an extraordinary clinical practice or as experimental research. Second, ethical issues, criticisms, and methodological issues of this intervention, also in the future perspectives, are discussed, attempting to identify who could give informed consent for a patient in PVS. PMID:24803730

  2. [Cardiac Surgery in Two Patients with Parkinson's Disease who were Using Deep Brain Stimulation Devices].

    PubMed

    Horiuchi, Kazutaka; Nakata, Shunsuke; Komoda, Satsuki; Yuasa, Takeshi

    2015-09-01

    For the treatment of Parkinson's disease, deep brain stimulation( DBS) devices are implanted for the control of motor symptoms including tremor. We performed cardiac surgery in 2 patients with Parkinson's disease who were using DBS devices. Coronary artery bypass was performed in one patient, and closure of ventricular septal perforation after acute myocardial infarction was performed in the other. There is a risk of injury and electromagnetic interference of DBS devices. No device failure or aggravation of Parkinson's symptom was observed in these cases. In many cases of cardiac surgery, various devices are concomitantly used, and the potential interference with the devices should be carefully examined in perioperative management. PMID:26329628

  3. Value of serial stereotactic biopsies and impedance monitoring in the treatment of deep brain tumours.

    PubMed Central

    Broggi, G; Franzini, A

    1981-01-01

    Thirty-five patients with deep brain tumours have been submitted to transtumoral stereotactic impedance monitoring and serial biopsy. The direct examination of the biopsy samples confirmed the presumptive clinical and neuroradiological diagnosis in 25 patients, but in 10 patients the histological diagnosis differed from the presumptive one. In this second group the treatment was changed as a result of the histological findings. Stereotactic biopsy avoided the risks of "blind" management. The technique, the indications and the diagnostic advantages of stereotactic biopsy are reported with two illustrative cases. Images PMID:7021770

  4. Deep Brain Stimulation of the Ventroposteromedial (VPM) Thalamus 10 Years after VPM Thalamotomy to Treat a Recurrent Facial Pain.

    PubMed

    Yamgoue, Yves; Pralong, Etienne; Levivier, Marc; Bloch, Jocelyne

    2016-01-01

    We report the successful treatment of recurrent facial pain by deep brain stimulation (DBS) of the ventroposteromedial thalamic nucleus (VPM-DBS), 10 years after VPM thalamotomy. A 62-year-old woman who suffered from an atypical right-sided trigeminal neuralgia of the V1 and V2 branches was successfully treated a decade ago with a radiofrequency VPM thermocoagulation. Ten years later, the same burning right-sided trigeminal pain progressively recurred and was resistant to medical treatments. A DBS procedure was proposed to the patient aiming to stimulate the vicinity of the preexisting stereotactic lesion. Intraoperatively, the pain relief was immediate at low stimulation intensities. Eleven months later, the patient remains pain free. This case report suggests that DBS targeting an area of the VPM close to the previous stereotactic lesion is possible as a salvage therapy, and can successfully achieve relief of facial pain 10 years after VPM thalamotomy. PMID:27096946

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

    PubMed Central

    Gandhi, Ranju; Chawla, Reeta

    2014-01-01

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

  6. A Novel Human Body Area Network for Brain Diseases Analysis.

    PubMed

    Lin, Kai; Xu, Tianlang

    2016-10-01

    Development of wireless sensor and mobile communication technology provide an unprecedented opportunity for realizing smart and interactive healthcare systems. Designing such systems aims to remotely monitor the health and diagnose the diseases for users. In this paper, we design a novel human body area network for brain diseases analysis, which is named BABDA. Considering the brain is one of the most complex organs in the human body, the BABDA system provides four function modules to ensure the high quality of the analysis result, which includes initial data collection, data correction, data transmission and comprehensive data analysis. The performance evaluation conducted in a realistic environment with several criteria shows the availability and practicability of the BABDA system. PMID:27526187

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

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  8. Deep Brain Stimulation for Obsessive Compulsive Disorder Reduces Symptoms of Irritable Bowel Syndrome in a Single Patient

    PubMed Central

    Langguth, Berthold; Sturm, Kornelia; Wetter, Thomas C.; Lange, Max; Gabriels, Loes; Mayer, Emeran A.; Schlaier, Juergen

    2016-01-01

    Irritable bowel syndrome (IBS) is a frequent gastrointestinal disorder that is difficult to treat. We describe findings from evaluation of a woman (55 years old) with obsessive compulsive disorder, which was treated with bilateral deep brain stimulation in the anterior limb of the internal capsule, and IBS. After the brain stimulation treatment she reported substantial relief of her IBS symptoms. This reduction depended on specific stimulation parameters, was reproducible over time, and was not directly associated with improvements in obsessive compulsive disorder symptoms. These observations indicate a specific effect of deep brain stimulation on IBS. This observation confirms involvement of specific brain structures in the pathophysiology of IBS and shows that symptoms can be reduced through modulation of neuronal activity in the central nervous system. Further studies of the effects of brain stimulation on IBS are required. PMID:25638586

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

    PubMed

    Seymour, Ben; Barbe, Michael; Dayan, Peter; Shiner, Tamara; Dolan, Ray; Fink, Gereon R

    2016-01-01

    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. PMID:27624437

  10. Recording, labeling, and transfection of single neurons in deep brain structures.

    PubMed

    Dempsey, Bowen; Turner, Anita J; Le, Sheng; Sun, Qi-Jian; Bou Farah, Lama; Allen, Andrew M; Goodchild, Ann K; McMullan, Simon

    2015-01-01

    Genetic tools that permit functional or connectomic analysis of neuronal circuits are rapidly transforming neuroscience. The key to deployment of such tools is selective transfection of target neurons, but to date this has largely been achieved using transgenic animals or viral vectors that transduce subpopulations of cells chosen according to anatomical rather than functional criteria. Here, we combine single-cell transfection with conventional electrophysiological recording techniques, resulting in three novel protocols that can be used for reliable delivery of conventional dyes or genetic material in vitro and in vivo. We report that techniques based on single cell electroporation yield reproducible transfection in vitro, and offer a simple, rapid and reliable alternative to established dye-labeling techniques in vivo, but are incompatible with targeted transfection in deep brain structures. In contrast, we show that intracellular electrophoresis of plasmid DNA transfects brainstem neurons recorded up to 9 mm deep in the anesthetized rat. The protocols presented here require minimal, if any, modification to recording hardware, take seconds to deploy, and yield high recovery rates in vitro (dye labeling: 89%, plasmid transfection: 49%) and in vivo (dye labeling: 66%, plasmid transfection: 27%). They offer improved simplicity compared to the juxtacellular labeling technique and for the first time offer genetic manipulation of functionally characterized neurons in previously inaccessible brain regions. PMID:25602013

  11. Deep potential of Hugoton - evaluation of unexplored and underexplored areas

    SciTech Connect

    Woltz, D.

    1986-05-01

    Structurally, the Hugoton embayment is a large, southward-plunging syncline that represents a northerly extension of the Anadarko basin. It is bounded on the east by the Pratt anticline, on the northeast by the Central Kansas uplift, on the northwest by the Las Animas arch, on the west by the Sierra Grande uplift, and on the southwest by the Amarillo uplift. The embayment is approximately 150 mi wide and 250 mi long. Subsidence began during the Early Ordovician and reached a maximum from the middle Mississippi through the early middle Permian. Rocks of Paleozoic, Mesozoic, and Cenozoic ages are present in the embayment. The section thickens toward the axis of the embayment where it is about 9500 ft. The Ordovician through Cambrian section attains a thickness of about 650 ft. The Devonian and Silurian are largely absent from the area. The Mississippian and Pennsylvanian sections are about 3000 ft thick. Excluding the Permian, the Mississippian and Pennsylvanian contain the highest exploration potential. An evaluation of the deeper zones in the underexplored areas of the embayment identified several structural and stratigraphic trends that are presently untested or remain underexplored. The trends can be separated into those controlled by early structural developments which persisted through the section and later structural stratigraphic events. The probability of finding new fields in the 500,000 to 5,000,000-bbl range is good.

  12. Deep Brain Stimulation: In Search of Reliable Instruments for Assessing Complex Personality-Related Changes.

    PubMed

    Ineichen, Christian; Baumann-Vogel, Heide; Christen, Markus

    2016-01-01

    During the last 25 years, more than 100,000 patients have been treated with Deep Brain Stimulation (DBS). While human clinical and animal preclinical research has shed light on the complex brain-signaling disturbances that underpin e.g., Parkinson's disease (PD), less information is available when it comes to complex psychosocial changes following DBS interventions. In this contribution, we propose to more thoroughly investigate complex personality-related changes following deep brain stimulation through refined and reliable instruments in order to help patients and their relatives in the post-surgery phase. By pursuing this goal, we first outline the clinical importance DBS has attained followed by discussing problematic and undesired non-motor problems that accompany some DBS interventions. After providing a brief definition of complex changes, we move on by outlining the measurement problem complex changes relating to non-motor symptoms currently are associated with. The latter circumstance substantiates the need for refined instruments that are able to validly assess personality-related changes. After providing a brief paragraph with regard to conceptions of personality, we argue that the latter is significantly influenced by certain competencies which themselves currently play only a tangential role in the clinical DBS-discourse. Increasing awareness of the latter circumstance is crucial in the context of DBS because it could illuminate a link between competencies and the emergence of personality-related changes, such as new-onset impulse control disorders that have relevance for patients and their relatives. Finally, we elaborate on the field of application of instruments that are able to measure personality-related changes. PMID:27618110

  13. Statistical significance of task related deep brain EEG dynamic changes in the time-frequency domain.

    PubMed

    Chládek, J; Brázdil, M; Halámek, J; Plešinger, F; Jurák, P

    2013-01-01

    We present an off-line analysis procedure for exploring brain activity recorded from intra-cerebral electroencephalographic data (SEEG). The objective is to determine the statistical differences between different types of stimulations in the time-frequency domain. The procedure is based on computing relative signal power change and subsequent statistical analysis. An example of characteristic statistically significant event-related de/synchronization (ERD/ERS) detected across different frequency bands following different oddball stimuli is presented. The method is used for off-line functional classification of different brain areas. PMID:24109865

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

    PubMed

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

    2012-01-01

    Deep brain stimulation was first developed for movement disorders but is now being offered as a therapeutic alternative in severe psychiatric disorders after the failure of conventional therapies. One of such pathologies is obsessive-compulsive disorder. This disorder which associates intrusive thoughts (obsessions) and repetitive irrepressible rituals (compulsions) is characterized by a dysfunction of a cortico-subcortical loop. After having reviewed the pathophysiological evidence to show why deep brain stimulation was an interesting path to take for severe and resistant cases of obsessive-compulsive disorder, we will present the results of the different clinical trials. Finally, we will provide possible mechanisms for the effects of deep brain stimulation in this pathology. PMID:22898561

  15. Large field-of-view wavefront control for deep brain imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Park, Jung-Hoon; Cui, Meng

    2016-03-01

    The biggest obstacle for deep tissue imaging is the scattering of light due to the heterogeneous distribution of biological tissue. In this respect, multiphoton microscopy has an inherent advantage as the scattering is significantly reduced by the use of longer excitation wavelengths. However, as we go deeper into the brain, effects of scattering still accumulate resulting in a loss of resolution and increased background noise. Adaptive optics is an ideal tool of choice to correct for such distortions of the excitation wavefront; the incident light can be tuned to cancel out the wavefront distortion experienced while propagating into greater depths resulting in a diffraction limited focus at the depth of interest. However, the biggest limitation of adaptive optics for in vivo brain imaging is its limited corrected field-of-view (FOV). For typical multiphoton laser scanning microscopes, the wavefront corrector for adaptive optics is placed at the pupil plane. This means that a single correction wavefront is applied to the entire scanned FOV which results in inefficient correction as the correction is averaged over the entire FOV. In this work, we demonstrate a novel approach to measure and display different correction wavefronts over different segments of the FOV. The application of the different correction wavefronts for each segment is realized in parallel resulting in fast aberration corrected imaging over a large FOV for high resolution in vivo brain imaging.

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

    PubMed

    Hebb, Adam O; Miller, Kai J

    2010-03-15

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

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

    PubMed

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

    2013-01-01

    Rewards have various effects on human behavior and multiple representations in the human brain. Behaviorally, rewards notably enhance response vigor in incentive motivation paradigms and bias subsequent choices in instrumental learning paradigms. Neurally, rewards affect activity in different fronto-striatal regions attached to different motor effectors, for instance in left and right hemispheres for the two hands. Here we address the question of whether manipulating reward-related brain activity has local or general effects, with respect to behavioral paradigms and motor effectors. Neuronal activity was manipulated in a single hemisphere using unilateral deep brain stimulation (DBS) in patients with Parkinson's disease. Results suggest that DBS amplifies the representation of reward magnitude within the targeted hemisphere, so as to affect the behavior of the contralateral hand specifically. These unilateral DBS effects on behavior include both boosting incentive motivation and biasing instrumental choices. Furthermore, using computational modeling we show that DBS effects on incentive motivation can predict DBS effects on instrumental learning (or vice versa). Thus, we demonstrate the feasibility of causally manipulating reward-related neuronal activity in humans, in a manner that is specific to a class of motor effectors but that generalizes to different computational processes. As these findings proved independent from therapeutic effects on parkinsonian motor symptoms, they might provide insight into DBS impact on non-motor disorders, such as apathy or hypomania. PMID:23643244

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

    PubMed

    Okun, Michael S

    2012-01-01

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

  19. Exploring avian deep-brain photoreceptors and their role in activating the neuroendocrine regulation of gonadal development1

    PubMed Central

    Kuenzel, Wayne J.; Kang, Seong W.; Zhou, Z. Jimmy

    2015-01-01

    In the eyes of mammals, specialized photoreceptors called intrinsically photosensitive retinal ganglion cells (ipRGC) have been identified that sense photoperiodic or daylight exposure, providing them over time with seasonal information. Detectors of photoperiods are critical in vertebrates, particularly for timing the onset of reproduction each year. In birds, the eyes do not appear to monitor photoperiodic information; rather, neurons within at least 4 different brain structures have been proposed to function in this capacity. Specialized neurons, called deep brain photoreceptors (DBP), have been found in the septum and 3 hypothalamic areas. Within each of the 4 brain loci, one or more of 3 unique photopigments, including melanopsin, neuropsin, and vertebrate ancient opsin, have been identified. An experiment was designed to characterize electrophysiological responses of neurons proposed to be avian DBP following light stimulation. A second study used immature chicks raised under short-day photoperiods and transferred to long day lengths. Gene expression of photopigments was then determined in 3 septal-hypothalamic regions. Preliminary electrophysiological data obtained from patch-clamping neurons in brain slices have shown that bipolar neurons in the lateral septal organ responded to photostimulation comparable with mammalian ipRGC, particularly by showing depolarization and a delayed, slow response to directed light stimulation. Utilizing real-time reverse-transcription PCR, it was found that all 3 photopigments showed significantly increased gene expression in the septal-hypothalamic regions in chicks on the third day after being transferred to long-day photoperiods. Each dissected region contained structures previously proposed to have DBP. The highly significant increased gene expression for all 3 photopigments on the third, long-day photoperiod in brain regions proposed to contain 4 structures with DBP suggests that all 3 types of DBP (melanopsin, neuropsin

  20. Deep brain stimulation of the subthalamic nucleus transiently enhances loss-chasing behaviour in patients with Parkinson's disease.

    PubMed

    Rogers, Robert D; Wielenberg, Birgit; Wojtecki, Lars; Elben, Saskia; Campbell-Meiklejohn, Daniel; Schnitzler, Alfons

    2011-09-01

    Dopaminergic treatments are associated with impulse control disorders such as pathological gambling in a subset of patients with Parkinson's Disease. While deep brain stimulation of the subthalamic nucleus has been reported to reduce symptoms of impulse control disorders in some Parkinson's Disease patients, little is known about its specific effects on gambling behaviour. In this experiment, we investigated the effects of deep brain stimulation of the subthalamic nucleus on one of the central features of pathological gambling: the tendency to chase losses. Loss-chasing is associated with impaired control over gambling behaviour and it is one of the most salient features of pathological gambling as it presents in the clinic. Twenty two patients with advanced idiopathic Parkinson's Disease and chronically implanted subthalamic nucleus electrodes for deep brain stimulation completed a simple laboratory model of loss-chasing behaviour twice: once with and once without stimulation. Exploratory analysis indicated that deep brain stimulation of the subthalamic nucleus increased the value of losses chased by patients with Parkinson's Disease when shifting from off- to on-stimulation. These effects were not attributable to changes in state affect or to the motor impairments produced by the withdrawal of deep brain stimulation of the subthalamic nucleus. The effects of the stimulation on the value of losses chased were more pronounced in female than in male patients and reduced in patients taking dopamine receptor agonists. Collectively, these results suggest that deep brain stimulation of the subthalamic nucleus can transiently alter the evaluation of accumulated losses during gambling episodes in idiopathic Parkinson's Disease. PMID:21726554

  1. Towards fully automated closed-loop Deep Brain Stimulation in Parkinson's disease patients: A LAMSTAR-based tremor predictor.

    PubMed

    Khobragade, Nivedita; Graupe, Daniel; Tuninetti, Daniela

    2015-08-01

    This paper describes the application of the LAMSTAR (LArge Memory STorage and Retrieval) neural network for prediction of onset of tremor in Parkinson's disease (PD) patients to allow for on-off adaptive control of Deep Brain Stimulation (DBS). Currently, the therapeutic treatment of PD by DBS is an open-loop system where continuous stimulation is applied to a target area in the brain. This work demonstrates a fully automated closed-loop DBS system so that stimulation can be applied on-demand only when needed to treat PD symptoms. The proposed LAMSTAR network uses spectral, entropy and recurrence rate parameters for prediction of the advent of tremor after the DBS stimulation is switched off. These parameters are extracted from non-invasively collected surface electromyography and accelerometry signals. The LAMSTAR network has useful characteristics, such as fast retrieval of patterns and ability to handle large amount of data of different types, which make it attractive for medical applications. Out of 21 trials blue from one subject, the average ratio of delay in prediction of tremor to the actual delay in observed tremor from the time stimulation was switched off achieved by the proposed LAMSTAR network is 0.77. Moreover, sensitivity of 100% and overall performance better than previously proposed Back Propagation neural networks is obtained. PMID:26736828

  2. Activation of AMPA Receptors Mediates the Antidepressant Action of Deep Brain Stimulation of the Infralimbic Prefrontal Cortex.

    PubMed

    Jiménez-Sánchez, Laura; Castañé, Anna; Pérez-Caballero, Laura; Grifoll-Escoda, Marc; López-Gil, Xavier; Campa, Leticia; Galofré, Mireia; Berrocoso, Esther; Adell, Albert

    2016-06-01

    Although deep brain stimulation (DBS) has been used with success in treatment-resistant depression, little is known about its mechanism of action. We examined the antidepressant-like activity of short (1 h) DBS applied to the infralimbic prefrontal cortex in the forced swim test (FST) and the novelty-suppressed feeding test (NSFT). We also used in vivo microdialysis to evaluate the release of glutamate, γ-aminobutyric acid, serotonin, dopamine, and noradrenaline in the prefrontal cortex and c-Fos immunohistochemistry to determine the brain regions activated by DBS. One hour of DBS of the infralimbic prefrontal cortex has antidepressant-like effects in FST and NSFT, and increases prefrontal efflux of glutamate, which would activate AMPA receptors (AMPARs). This effect is specific of the infralimbic area since it is not observed after DBS of the prelimbic subregion. The activation of prefrontal AMPARs would result in a stimulation of prefrontal output to the brainstem, thus increasing serotonin, dopamine, and noradrenaline in the prefrontal cortex. Further, the activation of prefrontal AMPARs is necessary and sufficient condition for the antidepressant response of 1 h DBS. PMID:26088969

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

    PubMed

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

    2015-10-01

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

  4. Using species-area relationships to inform baseline conservation targets for the deep North East Atlantic.

    PubMed

    Foster, Nicola L; Foggo, Andrew; Howell, Kerry L

    2013-01-01

    Demands on the resources of the deep-sea have increased in recent years. Consequently, the need to create and implement a comprehensive network of Marine Protected Areas (MPAs) to help manage and protect these resources has become a global political priority. Efforts are currently underway to implement MPA networks in the deep North East Atlantic. To ensure these networks are effective, it is essential that baseline information be available to inform the conservation planning process. Using empirical data, we calculated conservation targets for sessile benthic invertebrates in the deep North East Atlantic for consideration during the planning process. We assessed Species-Area Relationships across two depth bands (200-1100 m and 1100-1800 m) and nine substrata. Conservation targets were predicted for each substratum within each depth band using z-values obtained from fitting a power model to the Species-Area Relationships of observed and estimated species richness (Chao1). Results suggest an MPA network incorporating 10% of the North East Atlantic's deep-sea area would protect approximately 58% and 49% of sessile benthic species for the depth bands 200-1100 m and 1100-1800 m, respectively. Species richness was shown to vary with substratum type indicating that, along with depth, substratum information needs to be incorporated into the conservation planning process to ensure the most effective MPA network is implemented in the deep North East Atlantic. PMID:23527053

  5. Using Species-Area Relationships to Inform Baseline Conservation Targets for the Deep North East Atlantic

    PubMed Central

    Foster, Nicola L.; Foggo, Andrew; Howell, Kerry L.

    2013-01-01

    Demands on the resources of the deep-sea have increased in recent years. Consequently, the need to create and implement a comprehensive network of Marine Protected Areas (MPAs) to help manage and protect these resources has become a global political priority. Efforts are currently underway to implement MPA networks in the deep North East Atlantic. To ensure these networks are effective, it is essential that baseline information be available to inform the conservation planning process. Using empirical data, we calculated conservation targets for sessile benthic invertebrates in the deep North East Atlantic for consideration during the planning process. We assessed Species-Area Relationships across two depth bands (200–1100 m and 1100–1800 m) and nine substrata. Conservation targets were predicted for each substratum within each depth band using z-values obtained from fitting a power model to the Species-Area Relationships of observed and estimated species richness (Chao1). Results suggest an MPA network incorporating 10% of the North East Atlantic’s deep-sea area would protect approximately 58% and 49% of sessile benthic species for the depth bands 200–1100 m and 1100–1800 m, respectively. Species richness was shown to vary with substratum type indicating that, along with depth, substratum information needs to be incorporated into the conservation planning process to ensure the most effective MPA network is implemented in the deep North East Atlantic. PMID:23527053

  6. Repeated BOLD-fMRI imaging of deep brain stimulation responses in rats.

    PubMed

    Chao, Tzu-Hao Harry; Chen, Jyh-Horng; Yen, Chen-Tung

    2014-01-01

    Functional magnetic resonance imaging (fMRI) provides a picture of the global spatial activation pattern of the brain. Interest is growing regarding the application of fMRI to rodent models to investigate adult brain plasticity. To date, most rodent studies used an electrical forepaw stimulation model to acquire fMRI data, with α-chloralose as the anesthetic. However, α-chloralose is harmful to animals, and not suitable for longitudinal studies. Moreover, peripheral stimulation models enable only a limited number of brain regions to be studied. Processing between peripheral regions and the brain is multisynaptic, and renders interpretation difficult and uncertain. In the present study, we combined the medetomidine-based fMRI protocol (a noninvasive rodent fMRI protocol) with chronic implantation of an MRI-compatible stimulation electrode in the ventroposterior (VP) thalamus to repetitively sample thalamocortical responses in the rat brain. Using this model, we scanned the forebrain responses evoked by the VP stimulation repeatedly of individual rats over 1 week. Cortical BOLD responses were compared between the 2 profiles obtained at day1 and day8. We discovered reproducible frequency- and amplitude-dependent BOLD responses in the ipsilateral somatosensory cortex (S1). The S1 BOLD responses during the 2 sessions were conserved in maximal response amplitude, area size (size ratio from 0.88 to 0.91), and location (overlap ratio from 0.61 to 0.67). The present study provides a long-term chronic brain stimulation protocol for studying the plasticity of specific neural circuits in the rodent brain by BOLD-fMRI. PMID:24825464

  7. Repeated BOLD-fMRI Imaging of Deep Brain Stimulation Responses in Rats

    PubMed Central

    Chao, Tzu-Hao Harry; Chen, Jyh-Horng; Yen, Chen-Tung

    2014-01-01

    Functional magnetic resonance imaging (fMRI) provides a picture of the global spatial activation pattern of the brain. Interest is growing regarding the application of fMRI to rodent models to investigate adult brain plasticity. To date, most rodent studies used an electrical forepaw stimulation model to acquire fMRI data, with α-chloralose as the anesthetic. However, α-chloralose is harmful to animals, and not suitable for longitudinal studies. Moreover, peripheral stimulation models enable only a limited number of brain regions to be studied. Processing between peripheral regions and the brain is multisynaptic, and renders interpretation difficult and uncertain. In the present study, we combined the medetomidine-based fMRI protocol (a noninvasive rodent fMRI protocol) with chronic implantation of an MRI-compatible stimulation electrode in the ventroposterior (VP) thalamus to repetitively sample thalamocortical responses in the rat brain. Using this model, we scanned the forebrain responses evoked by the VP stimulation repeatedly of individual rats over 1 week. Cortical BOLD responses were compared between the 2 profiles obtained at day1 and day8. We discovered reproducible frequency- and amplitude-dependent BOLD responses in the ipsilateral somatosensory cortex (S1). The S1 BOLD responses during the 2 sessions were conserved in maximal response amplitude, area size (size ratio from 0.88 to 0.91), and location (overlap ratio from 0.61 to 0.67). The present study provides a long-term chronic brain stimulation protocol for studying the plasticity of specific neural circuits in the rodent brain by BOLD-fMRI. PMID:24825464

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

    NASA Astrophysics Data System (ADS)

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

    2012-02-01

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

  9. Tractographical model of the cortico-basal ganglia and corticothalamic connections: Improving Our Understanding of Deep Brain Stimulation.

    PubMed

    Avecillas-Chasin, Josué M; Rascón-Ramírez, Fernando; Barcia, Juan A

    2016-05-01

    The cortico-basal ganglia and corticothalamic projections have been extensively studied in the context of neurological and psychiatric disorders. Deep brain stimulation (DBS) is known to modulate many of these pathways to produce the desired clinical effect. The aim of this work is to describe the anatomy of the main circuits of the basal ganglia using tractography in a surgical planning station. We used imaging studies of 20 patients who underwent DBS for movement and psychiatric disorders. We segmented the putamen, caudate nucleus (CN), thalamus, and subthalamic nucleus (STN), and we also segmented the cortical areas connected with these subcortical areas. We used tractography to define the subdivisions of the basal ganglia and thalamus through the generation of fibers from the cortical areas to the subcortical structures. We were able to generate the corticostriatal and corticothalamic connections involved in the motor, associative and limbic circuits. Furthermore, we were able to reconstruct the hyperdirect pathway through the corticosubthalamic connections and we found subregions in the STN. Finally, we reconstructed the cortico-subcortical connections of the ventral intermediate nucleus, the nucleus accumbens and the CN. We identified a feasible delineation of the basal ganglia and thalamus connections using tractography. These results could be potentially useful in DBS if the parcellations are used as targets during surgery. Clin. Anat. 29:481-492, 2016. © 2016 Wiley Periodicals, Inc. PMID:26779936

  10. Dyslexic brain activation abnormalities in deep and shallow orthographies: A meta-analysis of 28 functional neuroimaging studies.

    PubMed

    Martin, Anna; Kronbichler, Martin; Richlan, Fabio

    2016-07-01

    We used coordinate-based meta-analysis to objectively quantify commonalities and differences of dyslexic functional brain abnormalities between alphabetic languages differing in orthographic depth. Specifically, we compared foci of under- and overactivation in dyslexic readers relative to nonimpaired readers reported in 14 studies in deep orthographies (DO: English) and in 14 studies in shallow orthographies (SO: Dutch, German, Italian, Swedish). The separate meta-analyses of the two sets of studies showed universal reading-related dyslexic underactivation in the left occipitotemporal cortex (including the visual word form area (VWFA)). The direct statistical comparison revealed higher convergence of underactivation for DO compared with SO in bilateral inferior parietal regions, but this abnormality disappeared when foci resulting from stronger dyslexic task-negative activation (i.e., deactivation relative to baseline) were excluded. Higher convergence of underactivation for DO compared with SO was further identified in the left inferior frontal gyrus (IFG) pars triangularis, left precuneus, and right superior temporal gyrus, together with higher convergence of overactivation in the left anterior insula. Higher convergence of underactivation for SO compared with DO was found in the left fusiform gyrus, left temporoparietal cortex, left IFG pars orbitalis, and left frontal operculum, together with higher convergence of overactivation in the left precentral gyrus. Taken together, the findings support the notion of a biological unity of dyslexia, with additional orthography-specific abnormalities and presumably different compensatory mechanisms. The results are discussed in relation to current functional neuroanatomical models of developmental dyslexia. Hum Brain Mapp 37:2676-2699, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27061464

  11. A Battery-Less, Implantable Neuro-Electronic Interface for Studying the Mechanisms of Deep Brain Stimulation in Rat Models.

    PubMed

    Lin, Yu-Po; Yeh, Chun-Yi; Huang, Pin-Yang; Wang, Zong-Ye; Cheng, Hsiang-Hui; Li, Yi-Ting; Chuang, Chi-Fen; Huang, Po-Chiun; Tang, Kea-Tiong; Ma, Hsi-Pin; Chang, Yen-Chung; Yeh, Shih-Rung; Chen, Hsin

    2016-02-01

    Although deep brain stimulation (DBS) has been a promising alternative for treating several neural disorders, the mechanisms underlying the DBS remain not fully understood. As rat models provide the advantage of recording and stimulating different disease-related regions simultaneously, this paper proposes a battery-less, implantable neuro-electronic interface suitable for studying DBS mechanisms with a freely-moving rat. The neuro-electronic interface mainly consists of a microsystem able to interact with eight different brain regions bi-directionally and simultaneously. To minimize the size of the implant, the microsystem receives power and transmits data through a single coil. In addition, particular attention is paid to the capability of recording neural activities right after each stimulation, so as to acquire information on how stimulations modulate neural activities. The microsystem has been fabricated with the standard 0.18 μm CMOS technology. The chip area is 7.74 mm (2) , and the microsystem is able to operate with a single supply voltage of 1 V. The wireless interface allows a maximum power of 10 mW to be transmitted together with either uplink or downlink data at a rate of 2 Mbps or 100 kbps, respectively. The input referred noise of recording amplifiers is 1.16 μVrms, and the stimulation voltage is tunable from 1.5 V to 4.5 V with 5-bit resolution. After the electrical functionality of the microsystem is tested, the capability of the microsystem to interface with rat brain is further examined and compared with conventional instruments. All experimental results are presented and discussed in this paper. PMID:25838526

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

    PubMed

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

    2013-01-01

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

  13. Clinical and Neurophysiological Improvement of SGCE Myoclonus-Dystonia with GPi Deep Brain Stimulation

    PubMed Central

    Kurtis, Monica M; San Luciano, Marta; Yu, Qiping; Goodman, Robert R; Ford, Blair; Raymond, Deborah; Pullman, Seth

    2009-01-01

    Myoclonus-dystonia (M-D) is characterized by early onset myoclonus and dystonia. It is thought to be subcortical in origin. Response to oral medications may be incomplete, such that deep brain stimulation (DBS) surgery to the globus pallidum interna (GPi) or ventral intermediate thalamic nucleus (VIM) may be considered. The optimal site is not known. The physiology and surgical response for a 63 year-old woman who underwent GPi DBS for M-D with onset at age 2 and related to a mutation in the epsilon-sarcoglycan gene (SGCE) is described. She showed excellent clinical and neurophysiological improvement of both myoclonus and dystonia, suggesting that modulation by DBS is effective even after long disease duration and only partial response to oral medications. PMID:19896264

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

    PubMed

    Mantione, Mariska; Figee, Martijn; Denys, Damiaan

    2014-01-01

    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 (NAcc), 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 (DBS) targeted at the NAcc. This case report substantiates the assumption that the NAcc is involved in musical preference, based on the observation of direct stimulation of the accumbens with DBS. It also shows that accumbens DBS can change musical preference without habituation of its rewarding properties. PMID:24834035

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

    PubMed Central

    Mantione, Mariska; Figee, Martijn; Denys, Damiaan

    2014-01-01

    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 (NAcc), 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 (DBS) targeted at the NAcc. This case report substantiates the assumption that the NAcc is involved in musical preference, based on the observation of direct stimulation of the accumbens with DBS. It also shows that accumbens DBS can change musical preference without habituation of its rewarding properties. PMID:24834035

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

    PubMed Central

    Williams, Nolan R.; Okun, Michael S.

    2013-01-01

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

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

    PubMed

    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. PMID:27007543

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

    PubMed

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

    2001-10-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-05-01

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

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

    PubMed Central

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

    2014-01-01

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

  3. Deep Learning Based Imaging Data Completion for Improved Brain Disease Diagnosis

    PubMed Central

    Li, Rongjian; Zhang, Wenlu; Suk, Heung-Il; Wang, Li; Li, Jiang; Shen, Dinggang; Ji, Shuiwang

    2015-01-01

    Combining multi-modality brain data for disease diagnosis commonly leads to improved performance. A challenge in using multi-modality data is that the data are commonly incomplete; namely, some modality might be missing for some subjects. In this work, we proposed a deep learning based framework for estimating multi-modality imaging data. Our method takes the form of convolutional neural networks, where the input and output are two volumetric modalities. The network contains a large number of trainable parameters that capture the relationship between input and output modalities. When trained on subjects with all modalities, the network can estimate the output modality given the input modality. We evaluated our method on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, where the input and output modalities are MRI and PET images, respectively. Results showed that our method significantly outperformed prior methods. PMID:25320813

  4. [New indications for deep brain stimulation: ethical criteria for research and therapy].

    PubMed

    Synofzik, M

    2013-10-01

    The applications of deep brain stimulation (DBS) are rapidly increasing and now include a large variety of neurological and psychiatric diseases, such as depression, obsessive compulsive disorders, addiction, Alzheimer's disease, anorexia nervosa and rare movement disorders. These new applications confer a huge therapeutic potential in diseases for which often no treatment exists or which are refractory to existing therapies. This spread of applications, however, implies ethical problems in several domains: clinical use, research and presentation in the media and public. Thus, a systematic ethical analysis is needed to inform and guide this process. In this article we identify ethical problems involved in research and clinical use of novel DBS applications, suggest criteria and distinctions for structuring the ethical analysis, and articulate ethical demands for DBS research of novel applications. PMID:23979358

  5. The costs and benefits of deep brain stimulation surgery for patients with dystonia: an initial exploration.

    PubMed

    Yianni, John; Green, Alexander L; McIntosh, Emma; Bittar, Richard G; Joint, Carol; Scott, Richard; Gregory, Ralph; Bain, Peter G; Aziz, Tipu Z

    2005-07-01

    Objectives.  To perform a preliminary cost-utility and cost-benefit of deep brain stimulation (DBS) in the treatment of dystonia, Materials and Methods.  We conducted a prospective study of 26 patients undergoing DBS for the treatment of dystonia. We performed a cost-utility analysis using the Euroquol (EQ-5D) questionnaire. A cost-benefit analysis used the willingness-to-pay principle and costs of treatment were calculated retrospectively in order to calculate the cost-benefit. Results.  We found that the EQ-5D score improved from 29 to 76.2 points after surgery, an incremental utility of 0.47. There was an overall gain of 0.94 quality-adjusted life-years (QALY) with a cost of £33,980 per QALY. Conclusions.  DBS for dystonia, while an expensive treatment, compares favorably to therapies that are commonly used for other conditions. PMID:22151484

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

    PubMed

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

    2016-08-01

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

  7. Eligibility Criteria for Deep Brain Stimulation in Parkinson's Disease, Tremor, and Dystonia.

    PubMed

    Munhoz, Renato P; Picillo, Marina; Fox, Susan H; Bruno, Veronica; Panisset, Michel; Honey, Christopher R; Fasano, Alfonso

    2016-07-01

    In this review, the available evidence to guide clinicians regarding eligibility for deep brain stimulation (DBS) in the main conditions in which these forms of therapy are generally indicated-Parkinson's disease (PD), tremor, and dystonia-is presented. In general, the literature shows that DBS is effective for PD, essential tremor, and idiopathic dystonia. In these cases, key points in patient selection must include the level of disability and inability to manage symptoms using the best available medical therapy. Results are, however, still not optimal when dealing with other aetiologies, such as secondary tremors and symptomatic dystonia. Also, in PD, issues such as age and neuropsychiatric profile are still debatable parameters. Overall, currently available literature is able to guide physicians on basic aspects of patient selection and indications for DBS; however, a few points are still debatable and controversial. These issues should be refined and clarified in future studies. PMID:27139127

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

    PubMed

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

    2014-05-01

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

  9. An Unusual Case of Asystole Occurring during Deep Brain Stimulation Surgery

    PubMed Central

    Nguyen, Ha Son; Woehlck, Harvey; Pahapill, Peter

    2016-01-01

    Background. Symptomatic bradycardia and hypotension in neurosurgery can produce severe consequences if not managed appropriately. The literature is scarce regarding its occurrence during deep brain stimulation (DBS) surgery. Case Presentation. A 67-year-old female presented for left DBS lead placement for essential tremors. During lead implantation, heart rate and blood pressure dropped rapidly; the patient became unresponsive and asystolic. Chest compressions were initiated and epinephrine was given. Within 30 seconds, the patient became hemodynamically stable and conscious. A head CT demonstrated no acute findings. After deliberation, a decision was made to complete the procedure. Assuming the etiology of the episode was the Bezold-Jarisch reflex (BJR), appropriate accommodations were made. The procedure was completed uneventfully. Conclusion. The episode was consistent with a manifestation of the BJR. The patient had a history of neurocardiogenic syncope and a relatively low-volume state, factors prone to the BJR. Overall, lead implantation can still occur safely if preventive measures are employed. PMID:27217962

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

    PubMed

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

    2015-02-01

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

  11. Voice and fluency changes as a function of speech task and deep brain stimulation

    PubMed Central

    Sidtis, D.; Rogers, T.; Godier, V.; Tagliati, M.; Sidtis, J.J.

    2015-01-01

    Speaking, which naturally occurs in different modes or “tasks” such as conversation and repetition, relies on intact basal ganglia nuclei. Recent studies suggest that voice and fluency parameters are differentially affected by speech task. This study examines the effects of subcortical functionality on voice and fluency, comparing measures obtained from spontaneous and matched repeated speech samples. Parkinson subjects who are being treated with bilateral deep brain stimulation (DBS) of the subthalamic nuclei (STN) were tested with stimulators ON and OFF. Results indicated that a voice measure, harmonic to noise ratio, is improved in repetition and in DBS-ON, and that dysfluencies are more plentiful in conversation with little or variable influence of DBS condition. These findings suggest that voice and fluency are differentially affected by DBS treatment and that task conditions, interacting with subcortical functionality, influence motor speech performance. PMID:20643796

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

    NASA Astrophysics Data System (ADS)

    Beuter, Anne; Modolo, Julien

    2009-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

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

    PubMed Central

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

    2012-01-01

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

  15. Cognitive effects of deep brain stimulation in patients with obsessive–compulsive disorder

    PubMed Central

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

    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 between clinical changes and cognitive functioning. Methods Patients with treatment-refractory OCD treated with DBS targeted at the nucleus accumbens (NAcc) were compared with a control group of 14 patients with treatment-refractory OCD treated with care as usual. We assessed cognitive functioning at baseline, 3 weeks postoperatively and following 8 months of DBS. We compared change in clinical symptoms with cognitive changes. Results There were 16 patients in the DBS group and 14 patients in the control group. Three weeks postoperatively, the DBS group showed a significantly reduced performance on measures of visual organization and verbal fluency and a trend toward reduced performance on measures of visual memory and abstract reasoning. Cognitive functioning was found to be stable on all other measures. After 8 months of DBS, reduced performances persisted, except for a significant improvement in verbal fluency. Cognitive functioning in all other domains remained unaffected. We found no correlation between improvement of clinical symptoms and cognitive changes. Limitations A limitation of this study was its relatively small sample size. Conclusion Deep brain stimulation targeted at the NAcc may be considered a safe method in terms of cognition because cognitive functioning was unaffected on most neuropsychological measures. Nevertheless, we observed some minor reduced performance on specific measures of executive functioning that were possibly associated with surgical intervention. Our results suggest that severity of OCD symptoms is independent of cognitive functioning. PMID:26107159

  16. Age-Related Differences in the Brain Areas outside the Classical Language Areas among Adults Using Category Decision Task

    ERIC Educational Resources Information Center

    Cho, Yong Won; Song, Hui-Jin; Lee, Jae Jun; Lee, Joo Hwa; Lee, Hui Joong; Yi, Sang Doe; Chang, Hyuk Won; Berl, Madison M.; Gaillard, William D.; Chang, Yongmin

    2012-01-01

    Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that…

  17. Deep brain stimulation and ablation for obsessive compulsive disorder: evolution of contemporary indications, targets and techniques.

    PubMed

    Tierney, Travis S; Abd-El-Barr, Muhammad M; Stanford, Arielle D; Foote, Kelly D; Okun, Michael S

    2014-06-01

    Surgical therapy for treatment-resistant obsessive compulsive disorder (OCD) remains an effective option for well-selected patients managed within a multidisciplinary setting. Historically, lesions within the limbic system have been used to control both obsessive thoughts and repetitive compulsions associated with this disease. We discuss classical targets as well as contemporary neuromodulatory approaches that have been shown to provide symptomatic relief. Recently, deep brain stimulation (DBS) of the anterior limb of the internal capsule/ventral striatum received Conformité Européene (CE) mark and Food and Drug Administration (FDA) approvals for treatment of intractable OCD. Remarkably, this is the first such approval for neurosurgical intervention in a strictly psychiatric indication in modern times. This target is discussed in detail along with alternative targets currently being proposed. We close with a discussion of gamma knife capsulotomy, a modality with deep historical roots. Further directions in the surgical treatment of OCD will require better preoperative predictors of postoperative responses, optimal selection of individualized targets, and rigorous reporting of adverse events and standardized outcomes. To meet these challenges, centers must be equipped with a multidisciplinary team and patient-centered approach to ensure adequate screening and follow up of patients with this difficult-to-treat condition. PMID:24099662

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

    PubMed Central

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

    2016-01-01

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

  19. Individual Human Brain Areas Can Be Identified from Their Characteristic Spectral Activation Fingerprints.

    PubMed

    Keitel, Anne; Gross, Joachim

    2016-06-01

    The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles ("fingerprints"), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified from these spectral profiles with high accuracy. Our results suggest that each brain area engages in different spectral modes that are characteristic for individual areas. Clustering of brain areas according to similarity of spectral profiles reveals well-known brain networks. Furthermore, we demonstrate task-specific modulations of auditory spectral profiles during auditory processing. These findings have important implications for the classification of regional spectral activity and allow for novel approaches in neuroimaging and neurostimulation in health and disease. PMID:27355236

  20. Individual Human Brain Areas Can Be Identified from Their Characteristic Spectral Activation Fingerprints

    PubMed Central

    Keitel, Anne; Gross, Joachim

    2016-01-01

    The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles (“fingerprints”), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified from these spectral profiles with high accuracy. Our results suggest that each brain area engages in different spectral modes that are characteristic for individual areas. Clustering of brain areas according to similarity of spectral profiles reveals well-known brain networks. Furthermore, we demonstrate task-specific modulations of auditory spectral profiles during auditory processing. These findings have important implications for the classification of regional spectral activity and allow for novel approaches in neuroimaging and neurostimulation in health and disease. PMID:27355236

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Paffi, Alessandra; Camera, Francesca; Apollonio, Francesca; d’Inzeo, Guglielmo; Liberti, Micaela

    2015-01-01

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

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

    PubMed

    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. PMID:27375149

  4. Central Thalamic Deep-Brain Stimulation Alters Striatal-Thalamic Connectivity in Cognitive Neural Behavior.

    PubMed

    Lin, Hui-Ching; Pan, Han-Chi; Lin, Sheng-Huang; Lo, Yu-Chun; Shen, Elise Ting-Hsin; Liao, Lun-De; Liao, Pei-Han; Chien, Yi-Wei; Liao, Kuei-Da; Jaw, Fu-Shan; Chu, Kai-Wen; Lai, Hsin-Yi; Chen, You-Yin

    2015-01-01

    Central thalamic deep brain stimulation (CT-DBS) has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs) induced by CT-DBS from the thalamic central lateral nuclei (CL) and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr), and dorsal striatum (Dstr). LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2), and α4-nicotinic acetylcholine receptor (α4-nAChR) occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity's ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning. PMID:26793069

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

    PubMed

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

    2014-05-01

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

  6. Neurodegeneration of lateral habenula efferent fibers after intermittent cocaine administration: implications for deep brain stimulation.

    PubMed

    Lax, Elad; Friedman, Alexander; Croitoru, Ofri; Sudai, Einav; Ben-Moshe, Hila; Redlus, Lior; Sasson, Efrat; Blumenfeld-Katzir, Tamar; Assaf, Yaniv; Yadid, Gal

    2013-12-01

    Deep brain stimulation (DBS) is an emerging technique for effective, non-pharmacological intervention in the course of neurological and neuropsychiatric diseases. Several brain targets have been suggested as suitable for DBS treatment of drug addiction. Previously, we showed that DBS of the lateral habenula (LHb) can reduce cocaine intake, facilitate extinction and attenuate drug-induced relapse in rats trained to self-administrate cocaine. Herein, we demonstrated that cocaine self-administration dose-dependently decreased connectivity between the LHb and midbrain, as shown by neurodegeneration of the main LHb efferent fiber, the fasciculus retroflexus (FR). FR degeneration, in turn, may have caused lack of response to LHb stimulation in rats trained to self-administer high-dose cocaine (1.5 mg/kg; i.v.). Furthermore, we show that the micro-structural changes caused by cocaine can be non-invasively detected using magnetic resonance imaging and diffusion tensor imaging. Detection of cocaine-induced alterations in FR anatomy can aid the selection of potential responders to LHb stimulation for treatment of drug addiction. PMID:23891640

  7. Deep-brain photoreception links luminance detection to motor output in Xenopus frog tadpoles.

    PubMed

    Currie, Stephen P; Doherty, Gayle H; Sillar, Keith T

    2016-05-24

    Nonvisual photoreceptors are widely distributed in the retina and brain, but their roles in animal behavior remain poorly understood. Here we document a previously unidentified form of deep-brain photoreception in Xenopus laevis frog tadpoles. The isolated nervous system retains sensitivity to light even when devoid of input from classical eye and pineal photoreceptors. These preparations produce regular bouts of rhythmic swimming activity in ambient light but fall silent in the dark. This sensitivity is tuned to short-wavelength UV light; illumination at 400 nm initiates motor activity over a broad range of intensities, whereas longer wavelengths do not cause a response. The photosensitive tissue is located in a small region of caudal diencephalon-this region is necessary to retain responses to illumination, whereas its focal illumination is sufficient to drive them. We present evidence for photoreception via the light-sensitive proteins opsin (OPN)5 and/or cryptochrome 1, because populations of OPN5-positive and cryptochrome-positive cells reside within the caudal diencephalon. This discovery represents a hitherto undescribed vertebrate pathway that links luminance detection to motor output. The pathway provides a simple mechanism for light avoidance and/or may reinforce classical circadian systems. PMID:27166423

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

    PubMed

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

    2016-01-01

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

  9. Deep Brain Stimulation of the Human Reward System for Major Depression—Rationale, Outcomes and Outlook

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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. PMID:25521796

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

    PubMed Central

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

    2015-01-01

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

  15. Investigating irregularly patterned deep brain stimulation signal design using biophysical models

    PubMed Central

    Summerson, Samantha R.; Aazhang, Behnaam; Kemere, Caleb

    2015-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder which follows from cell loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), a nucleus in the basal ganglia (BG). Deep brain stimulation (DBS) is an electrical therapy that modulates the pathological activity to treat the motor symptoms of PD. Although this therapy is currently used in clinical practice, the sufficient conditions for therapeutic efficacy are unknown. In this work we develop a model of critical motor circuit structures in the brain using biophysical cell models as the base components and then evaluate performance of different DBS signals in this model to perform comparative studies of their efficacy. Biological models are an important tool for gaining insights into neural function and, in this case, serve as effective tools for investigating innovative new DBS paradigms. Experiments were performed using the hemi-parkinsonian rodent model to test the same set of signals, verifying the obedience of the model to physiological trends. We show that antidromic spiking from DBS of the subthalamic nucleus (STN) has a significant impact on cortical neural activity, which is frequency dependent and additionally modulated by the regularity of the stimulus pulse train used. Irregular spacing between stimulus pulses, where the amount of variability added is bounded, is shown to increase diversification of response of basal ganglia neurons and reduce entropic noise in cortical neurons, which may be fundamentally important to restoration of information flow in the motor circuit. PMID:26167150

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

    PubMed

    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). PMID:25337356

  17. No Impact of Deep Brain Stimulation on Fear-Potentiated Startle in Obsessive–Compulsive Disorder

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Schermer, Maartje

    2013-01-01

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

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

    PubMed

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

    2014-01-01

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

  20. A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

    PubMed Central

    Batra, Vinita; Guerin, Glenn F.; Goeders, Nicholas E.; Wilden, Jessica A.

    2016-01-01

    Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug. PMID:26863392

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

    PubMed

    Mahlknecht, Philipp; Limousin, Patricia; Foltynie, Thomas

    2015-11-01

    Modern deep brain stimulation (DBS) has become a routine therapy for patients with movement disorders such as Parkinson's disease, generalized or segmental dystonia and for multiple forms of tremor. Growing numbers of publications also report beneficial effects in other movement disorders such as Tourette's syndrome, various forms of chorea and DBS is even being studied for Parkinson's-related dementia. While exerting remarkable effects on many motor symptoms, DBS does not restore normal neurophysiology and therefore may also have undesirable side effects including speech and gait deterioration. Furthermore, its efficacy might be compromised in the long term, due to progression of the underlying disease. Various programming strategies have been studied to try and address these issues, e.g., the use of low-frequency rather than high-frequency stimulation or the targeting of alternative brain structures such as the pedunculopontine nucleus. In addition, further technical developments will soon provide clinicians with an expanded choice of hardware such as segmented electrodes allowing for a steering of the current to optimize beneficial effects and reduce side effects as well as the possibility of adaptive stimulation systems based on closed-loop concepts with or without accompanying advances in programming and imaging software. In the present article, we will provide an update on the most recent achievements and discoveries relevant to the application of DBS in the treatment of movement disorder patients and give an outlook on future clinical and technical developments. PMID:26037016

  2. Central Thalamic Deep-Brain Stimulation Alters Striatal-Thalamic Connectivity in Cognitive Neural Behavior

    PubMed Central

    Lin, Hui-Ching; Pan, Han-Chi; Lin, Sheng-Huang; Lo, Yu-Chun; Shen, Elise Ting-Hsin; Liao, Lun-De; Liao, Pei-Han; Chien, Yi-Wei; Liao, Kuei-Da; Jaw, Fu-Shan; Chu, Kai-Wen; Lai, Hsin-Yi; Chen, You-Yin

    2016-01-01

    Central thalamic deep brain stimulation (CT-DBS) has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs) induced by CT-DBS from the thalamic central lateral nuclei (CL) and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr), and dorsal striatum (Dstr). LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2), and α4-nicotinic acetylcholine receptor (α4-nAChR) occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity's ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning. PMID:26793069

  3. Numerical analysis and design of single-source multicoil TMS for deep and focused brain stimulation.

    PubMed

    Gomez, Luis; Cajko, Frantishek; Hernandez-Garcia, Luis; Grbic, Anthony; Michielssen, Eric

    2013-10-01

    Transcranial magnetic stimulation (TMS) is a tool for noninvasive stimulation of neuronal tissue used for research in cognitive neuroscience and to treat neurological disorders. Many TMS applications call for large electric fields to be sharply focused on regions that often lie deep inside the brain. Unfortunately, the fields generated by present-day TMS coils diffuse and decay rapidly as they penetrate into the head. As a result, they tend to stimulate relatively large regions of tissue near the brain surface. Earlier studies suggested that a focused TMS excitation can be attained using multiple nonuniformly fed coils in a multichannel array. We propose a systematic, genetic algorithm-based technique for synthesizing multichannel arrays that minimize the volume of the excited region required to achieve a prescribed penetration depth and maintain realistic values for the input driving currents. Because multichannel arrays are costly to build, we also propose a method to convert the multichannel arrays into single-channel ones while minimally materially deteriorating performance. Numerical results show that the new multi- and single-channel arrays stimulate tissue 2.4 cm into the head while exciting 3.0 and 2.6 times less volume than conventional Figure-8 coils, respectively. PMID:23708768

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

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

  5. Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series.

    PubMed

    Dy, Marisela E; Chang, Florence C F; Jesus, Sol De; Anselm, Irina; Mahant, Neil; Zeilman, Pamela; Rodan, Lance H; Foote, Kelly D; Tan, Wen-Hann; Eskandar, Emad; Sharma, Nutan; Okun, Michael S; Fung, Victor S C; Waugh, Jeff L

    2016-07-01

    ADCY5 mutations have been reported as a cause of early onset hyperkinetic movements associated with delayed motor milestones, hypotonia, and exacerbation during sleep. The movement disorder may be continuous or episodic, and can vary considerably in severity within families and in individuals. The authors report a case series of 3 patients with ADCY5 mutations treated with deep brain stimulation after unsuccessful medication trials. All had extensive imaging, metabolic, and genetic testing prior to confirmation of their ADCY5 mutation. Two of the patients had the c.1252C>T; p.R418W mutation, while the youngest and most severely affected had a de novo c.2080_2088del; p.K694_M696 mutation. All had variable and incomplete, but positive responses to deep brain stimulation. The authors conclude that deep brain stimulation may provide benefit in ADCY5-related movement disorders. Long-term efficacy remains to be confirmed by longitudinal observation. ADCY5 should be considered in the differential diagnosis of early onset hyperkinetic movement disorders, and may respond to deep brain stimulation. PMID:27052971

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

    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…

  8. Recognition of emotional prosody is altered after subthalamic nucleus deep brain stimulation in Parkinson's disease.

    PubMed

    Péron, Julie; Grandjean, Didier; Le Jeune, Florence; Sauleau, Paul; Haegelen, Claire; Drapier, Dominique; Rouaud, Tiphaine; Drapier, Sophie; Vérin, Marc

    2010-03-01

    The recognition of facial emotions is impaired following subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD). These changes have been linked to a disturbance in the STN's limbic territory, which is thought to be involved in emotional processing. This was confirmed by a recent PET study where these emotional modifications were correlated with changes in glucose metabolism in different brain regions, including the amygdala and the orbitofrontal regions that are well known for their involvement in emotional processing. Nevertheless, the question as to whether these emotional changes induced by STN DBS in PD are modality-specific has yet to be answered. The objective of this study was therefore to examine the effects of STN DBS in PD on the recognition of emotional prosody. An original emotional prosody paradigm was administered to twenty-one post-operative PD patients, twenty-one pre-operative PD patients and twenty-one matched controls. Results showed that both the pre- and post-operative groups differed from the healthy controls. There was also a significant difference between the pre and post groups. More specifically, an analysis of their continuous judgments revealed that the performance of the post-operative group compared with that of the other two groups was characterized by a systematic emotional bias whereby they perceived emotions more strongly. These results suggest that the impaired recognition of emotions may not be specific to the visual modality but may also be present when emotions are expressed through the human voice, implying the involvement of the STN in the brain network underlying the recognition of emotional prosody. PMID:20005239

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

    PubMed

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

    2013-08-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Higuchi, Masa-aki; Topiol, Dan D.; Ahmed, Bilal; Morita, Hokuto; Carbunaru, Samuel; Hess, Christopher W.; Bowers, Dawn; Ward, Herbert E.; Warren, Lisa R.; DeFranco, Meredith M.; Troche, Michelle S.; Kulkarni, Shankar J.; Hastings, Erin; Foote, Kelly D.; Okun, Michael S.; Martinez-Ramirez, Daniel

    2015-01-01

    Objective To investigate the relationship of our interdisciplinary screening process on post-operative unintended hospitalizations and quality of life. Background 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. Methods 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. Results 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. Conclusions 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

  12. Disentangling linear and nonlinear brain responses to evoked deep tissue pain

    PubMed Central

    Loggia, Marco L.; Edwards, Robert R.; Kim, Jieun; Vangel, Mark G.; Wasan, Ajay; Gollub, Randy L.; Harris, Richard E.; Park, Kyungmo; Napadow, Vitaly

    2012-01-01

    Pain stimuli evoke widespread responses in the brain. However, our understanding of the physiological significance underlying heterogeneous response within different pain-activated and -deactivated regions is still limited. Using functional MRI, we evaluated brain responses to a wide range of stimulus intensity levels (1 innocuous, 7 painful) in order to estimate region-specific stimulus-response functions, which we hypothesized could illuminate that region’s functional relationship to pain. Linear and nonlinear brain responses to pain were estimated through independent Legendre polynomial transformations of pain ratings within a general linear model. This approach identified at least five different, regionally-specific activity profiles in the brain. Linearly increasing (e.g., primary somatosensory/motor cortex, insulae) and intensity-independent (e.g., secondary somatosensory cortex) activation was noted in traditional pain processing areas, potentially reflecting sensory encoding and all-or-none salience responses, respectively. Multiple activity profiles were seen in areas of the default mode network (DMN): intensity-independent deactivation (e.g., posterior cingulate cortex), linearly decreasing (e.g., contralateral inferior parietal lobule), and quadratic (U-shaped; e.g., medial prefrontal cortex). The latter observation suggests that: 1) different DMN subregions exhibit functional heterogeneity and 2) some DMN subregions respond in a percept-related manner to pain, suggesting closer linkage between the DMN and pain processing than previously thought. Future studies should apply a similar approach using innocuous stimuli of multiple intensities in order to evaluate whether the response profiles reported here can also be generalized to nonpainful somatosensory processing. PMID:22883925

  13. Effect of Deep Brain Stimulation on Regional Cerebral Blood Flow in Patients with Medically Refractory Tourette Syndrome.

    PubMed

    Haense, Cathleen; Müller-Vahl, Kirsten R; Wilke, Florian; Schrader, Christoph; Capelle, Holger H; Geworski, Lilli; Bengel, Frank M; Krauss, Joachim K; Berding, Georg

    2016-01-01

    In this study, alterations in brain perfusion have been investigated in patients with Tourette syndrome (TS) compared with control subjects. In addition, we investigated the effects of deep brain stimulation (DBS) in both globus pallidus internus (GPi) and centromedian-parafascicular/ventralis oralis internus nuclei of the thalamus (CM/Voi) and sham (SHAM) stimulation on cerebral blood flow. In a prospective controlled, randomized, double-blind setting, five severely affected adult patients with TS with predominant motor or vocal tics (mean total tic score on the Yale Global Tic Severity Scale: 39) underwent serial brain perfusion single photon emission computed tomography with (99m)Tc-ECD. Results were compared with data from six age-matched control subjects. All patients were investigated at four different time points: once before DBS implantation (preOP) and three times postoperatively. Postoperative scans were performed in a randomized order, each after 3 months of either GPi, CM/Voi, or SHAM stimulation. At each investigation, patients were injected at rest while awake, but scanned during anesthesia. This procedure ensured that neither anesthesia nor movement artifacts influenced our results. Control subjects were investigated only once at baseline (without DBS or anesthesia). At baseline, cerebral blood flow was significantly reduced in patients with TS (preOP) compared with controls in the central region, frontal, and parietal lobe, specifically in Brodmann areas 1, 4-9, 30, 31, and 40. Significantly increased perfusion was found in the cerebellum. When comparing SHAM stimulation to preOP condition, we found significantly decreased perfusion in basal ganglia and thalamus, but increased perfusion in different parts of the frontal cortex. Compared with SHAM condition both GPi and thalamic stimulation resulted in a significant decrease in cerebral blood flow in basal ganglia and cerebellum, while perfusion in the frontal cortex was significantly increased

  14. Effect of Deep Brain Stimulation on Regional Cerebral Blood Flow in Patients with Medically Refractory Tourette Syndrome

    PubMed Central

    Haense, Cathleen; Müller-Vahl, Kirsten R.; Wilke, Florian; Schrader, Christoph; Capelle, Holger H.; Geworski, Lilli; Bengel, Frank M.; Krauss, Joachim K.; Berding, Georg

    2016-01-01

    In this study, alterations in brain perfusion have been investigated in patients with Tourette syndrome (TS) compared with control subjects. In addition, we investigated the effects of deep brain stimulation (DBS) in both globus pallidus internus (GPi) and centromedian-parafascicular/ventralis oralis internus nuclei of the thalamus (CM/Voi) and sham (SHAM) stimulation on cerebral blood flow. In a prospective controlled, randomized, double-blind setting, five severely affected adult patients with TS with predominant motor or vocal tics (mean total tic score on the Yale Global Tic Severity Scale: 39) underwent serial brain perfusion single photon emission computed tomography with 99mTc-ECD. Results were compared with data from six age-matched control subjects. All patients were investigated at four different time points: once before DBS implantation (preOP) and three times postoperatively. Postoperative scans were performed in a randomized order, each after 3 months of either GPi, CM/Voi, or SHAM stimulation. At each investigation, patients were injected at rest while awake, but scanned during anesthesia. This procedure ensured that neither anesthesia nor movement artifacts influenced our results. Control subjects were investigated only once at baseline (without DBS or anesthesia). At baseline, cerebral blood flow was significantly reduced in patients with TS (preOP) compared with controls in the central region, frontal, and parietal lobe, specifically in Brodmann areas 1, 4–9, 30, 31, and 40. Significantly increased perfusion was found in the cerebellum. When comparing SHAM stimulation to preOP condition, we found significantly decreased perfusion in basal ganglia and thalamus, but increased perfusion in different parts of the frontal cortex. Compared with SHAM condition both GPi and thalamic stimulation resulted in a significant decrease in cerebral blood flow in basal ganglia and cerebellum, while perfusion in the frontal cortex was significantly increased

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

    PubMed

    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. PMID:26315009

  16. Deep two-photon brain imaging with a red-shifted fluorometric Ca2+ indicator

    PubMed Central

    Tischbirek, Carsten; Birkner, Antje; Jia, Hongbo; Sakmann, Bert; Konnerth, Arthur

    2015-01-01

    In vivo Ca2+ imaging of neuronal populations in deep cortical layers has remained a major challenge, as the recording depth of two-photon microscopy is limited because of the scattering and absorption of photons in brain tissue. A possible strategy to increase the imaging depth is the use of red-shifted fluorescent dyes, as scattering of photons is reduced at long wavelengths. Here, we tested the red-shifted fluorescent Ca2+ indicator Cal-590 for deep tissue experiments in the mouse cortex in vivo. In experiments involving bulk loading of neurons with the acetoxymethyl (AM) ester version of Cal-590, combined two-photon imaging and cell-attached recordings revealed that, despite the relatively low affinity of Cal-590 for Ca2+ (Kd = 561 nM), single-action potential-evoked Ca2+ transients were discernable in most neurons with a good signal-to-noise ratio. Action potential-dependent Ca2+ transients were recorded in neurons of all six layers of the cortex at depths of up to −900 µm below the pial surface. We demonstrate that Cal-590 is also suited for multicolor functional imaging experiments in combination with other Ca2+ indicators. Ca2+ transients in the dendrites of an individual Oregon green 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid-1 (OGB-1)-labeled neuron and the surrounding population of Cal-590-labeled cells were recorded simultaneously on two spectrally separated detection channels. We conclude that the red-shifted Ca2+ indicator Cal-590 is well suited for in vivo two-photon Ca2+ imaging experiments in all layers of mouse cortex. In combination with spectrally different Ca2+ indicators, such as OGB-1, Cal-590 can be readily used for simultaneous multicolor functional imaging experiments. PMID:26305966

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

    PubMed Central

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

    2015-01-01

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

  18. Deep Sequencing for the Detection of Virus-Like Sequences in the Brains of Patients with Multiple Sclerosis: Detection of GBV-C in Human Brain

    PubMed Central

    Kriesel, John D.; Hobbs, Maurine R.; Jones, Brandt B.; Milash, Brett; Nagra, Rashed M.; Fischer, Kael F.

    2012-01-01

    Multiple sclerosis (MS) is a demyelinating disease of unknown origin that affects the central nervous system of an estimated 400,000 Americans. GBV-C or hepatitis G is a flavivirus that is found in the serum of 1–2% of blood donors. It was originally associated with hepatitis, but is now believed to be a relatively non-pathogenic lymphotropic virus. Fifty frozen specimens from the brains of deceased persons affected by MS were obtained along with 15 normal control brain specimens. RNA was extracted and ribosomal RNAs were depleted before sequencing on the Illumina GAII. These 36 bp reads were compared with a non-redundant database derived from the 600,000+ viral sequences in GenBank organized into 4080 taxa. An individual read successfully aligned to the viral database was considered to be a “hit”. Normalized MS specimen hit rates for each viral taxon were compared to the distribution of hits in the normal controls. Seventeen MS and 11 control brain extracts were sequenced, yielding 4–10 million sequences (“reads”) each. Over-representation of sequence from at least one of 12 viral taxa was observed in 7 of the 17 MS samples. Sequences resembling other viruses previously implicated in the pathogenesis of MS were not significantly enriched in any of the diseased brain specimens. Sequences from GB virus C (GBV-C), a flavivirus not previously isolated from brain, were enriched in one of the MS samples. GBV-C in this brain specimen was confirmed by specific amplification in this single MS brain specimen, but not in the 30 other MS brain samples available. The entire 9.4 kb sequence of this GBV-C isolate is reported here. This study shows the feasibility of deep sequencing for the detection of occult viral infections in the brains of deceased persons with MS. The first isolation of GBV-C from human brain is reported here. PMID:22412845

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

    PubMed

    Dovzhenok, Andrey; Park, Choongseok; Worth, Robert M; Rubchinsky, Leonid L

    2013-01-01

    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. PMID:23469272

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Deep MRI brain extraction: A 3D convolutional neural network for skull stripping.

    PubMed

    Kleesiek, Jens; Urban, Gregor; Hubert, Alexander; Schwarz, Daniel; Maier-Hein, Klaus; Bendszus, Martin; Biller, Armin

    2016-04-01

    Brain extraction from magnetic resonance imaging (MRI) is crucial for many neuroimaging workflows. Current methods demonstrate good results on non-enhanced T1-weighted images, but struggle when confronted with other modalities and pathologically altered tissue. In this paper we present a 3D convolutional deep learning architecture to address these shortcomings. In contrast to existing methods, we are not limited to non-enhanced T1w images. When trained appropriately, our approach handles an arbitrary number of modalities including contrast-enhanced scans. Its applicability to MRI data, comprising four channels: non-enhanced and contrast-enhanced T1w, T2w and FLAIR contrasts, is demonstrated on a challenging clinical data set containing brain tumors (N=53), where our approach significantly outperforms six commonly used tools with a mean Dice score of 95.19. Further, the proposed method at least matches state-of-the-art performance as demonstrated on three publicly available data sets: IBSR, LPBA40 and OASIS, totaling N=135 volumes. For the IBSR (96.32) and LPBA40 (96.96) data set the convolutional neuronal network (CNN) obtains the highest average Dice scores, albeit not being significantly different from the second best performing method. For the OASIS data the second best Dice (95.02) results are achieved, with no statistical difference in comparison to the best performing tool. For all data sets the highest average specificity measures are evaluated, whereas the sensitivity displays about average results. Adjusting the cut-off threshold for generating the binary masks from the CNN's probability output can be used to increase the sensitivity of the method. Of course, this comes at the cost of a decreased specificity and has to be decided application specific. Using an optimized GPU implementation predictions can be achieved in less than one minute. The proposed method may prove useful for large-scale studies and clinical trials. PMID:26808333

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2016-06-01

    Deep brain stimulation (DBS) is a therapeutic intervention used for a variety of neurological and psychiatric disorders, but its mechanism of action is not well understood. It is known that DBS modulates neural activity which changes metabolic demands and thus the cerebral circulation state. However, it is unclear whether there are correlations between electrophysiological, hemodynamic and behavioral changes and whether they have any implications for clinical benefits. In order to investigate these questions, we present a miniaturized system for spectroscopic imaging of brain hemodynamics. The system consists of a 144 ×144, [Formula: see text] pixel pitch, high-sensitivity, analog-output CMOS imager fabricated in a standard 0.35 μm CMOS process, along with a miniaturized imaging system comprising illumination, focusing, analog-to-digital conversion and μSD card based data storage. This enables stand alone operation without a computer, nor electrical or fiberoptic tethers. To achieve high sensitivity, the pixel uses a capacitive transimpedance amplifier (CTIA). The nMOS transistors are in the pixel while pMOS transistors are column-parallel, resulting in a fill factor (FF) of 26%. Running at 60 fps and exposed to 470 nm light, the CMOS imager has a minimum detectable intensity of 2.3 nW/cm(2) , a maximum signal-to-noise ratio (SNR) of 49 dB at 2.45 μW/cm(2) leading to a dynamic range (DR) of 61 dB while consuming 167 μA from a 3.3 V supply. In anesthetized rats, the system was able to detect temporal, spatial and spectral hemodynamic changes in response to DBS. PMID:26357405

  8. Deep Brain Stimulation of the Subthalamic Nucleus Improves Reward-Based Decision-Learning in Parkinson's Disease

    PubMed Central

    van Wouwe, Nelleke 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). We determined computational measures of outcome evaluation and reward prediction from PD patients who performed a probabilistic reward-based decision-learning task. In previous work, these measures covaried with activation in the nucleus caudatus (outcome evaluation during the early phases of learning) and the putamen (reward prediction during later phases of learning). We observed that stimulation of the STN motor regions in PD patients served to improve reward-based decision-learning, probably through its effect on activity in frontostriatal motor loops (prominently involving the putamen and, hence, reward prediction). In a subset of relatively younger patients with relatively shorter disease duration, the effects of DBS appeared to spread to more cognitive regions of the STN, benefiting loops that connect the caudate to various prefrontal areas importantfor outcome evaluation. These results highlight positive effects of STN stimulation on cognitive functions that may benefit PD patients in daily-life association-learning situations. PMID:21519377

  9. Neuropsychological impact of Cg25 deep brain stimulation for treatment-resistant depression: preliminary results over 12 months.

    PubMed

    McNeely, Heather E; Mayberg, Helen S; Lozano, Andres M; Kennedy, Sidney H

    2008-05-01

    The purpose of this study was to evaluate preservation of cognitive function after deep brain stimulation (DBS) of the subgenual cingulate (Cg25) for treatment-resistant depression (TRD). We have previously reported on the treatment methods, safety, and 6-month clinical outcome (Mayberg et al., Neuron. 2005;45:651-660). Comprehensive neuropsychological assessments tapping 4 domains of frontal lobe function, and general cognitive abilities, were completed before implantation and at 3, 6, and 12 months postonset of continuous DBS in 6 TRD patients. No adverse neuropsychological effects were noted following surgery, onset and maintenance of DBS with the exception of transient motor slowing noted at 3 and 6 months that improved to normative levels by 12 months. Several areas of cognition that were below average or impaired at baseline improved over follow-up, and these changes were not correlated with improvements in mood. Though the sample size is small, these results support cognitive safety of Cg25 DBS for TRD. PMID:18477883

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

    PubMed

    Willsie, Andrew; Dorval, Alan

    2015-01-01

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

  11. Assessment of Potential Targets for Deep Brain Stimulation in Patients With Alzheimer’s Disease

    PubMed Central

    Sharma, Mayur; Deogaonkar, Milind; Rezai, Ali

    2015-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting 36 million people worldwide and 5.2 million in the United States. The pathogenesis of AD is still elusive. Accumulations of abnormal proteins (beta amyloid and tau protein), inflammatory cascades, abnormal responses to oxidative stress and alteration in oxidative metabolism have been implicated in AD. There are few effective therapeutic options available for this disorder at present. Neuromodulation offers a novel treatment modality for patients with AD. The databases of Medline and PubMed were searched for various studies in English literature describing the deep brain stimulation (DBS) in patients with AD. Various animal and human clinical studies have shown promising initial results with bilateral DBS targeting various anatomical nodes. In this review, we attempt to highlight the pathophysiology, neural circuitry and potential neuromodulation options in patients with AD. In appropriately selected patients, DBS can potentially delay the cognitive decline, enhance memory functions and can improve the overall quality of life. However, further randomized controlled trials are required to validate the efficacy of neuromodulation and to determine the most optimal target for AD. PMID:26015813

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

    PubMed

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

    2012-07-01

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

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

    PubMed

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

    2016-01-15

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

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

    PubMed Central

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

    2015-01-01

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

  15. Deep Brain Stimulation Significantly Decreases Disability from Low Back Pain in Patients with Advanced Parkinson's Disease

    PubMed Central

    Smith, Heather; Gee, Lucy; Kumar, Vignessh; Ramirez-Zamora, Adolfo; Durphy, Jennifer; Hanspal, Era; Barba, Anne; Molho, Eric; Shin, Damian; Pilitsis, Julie G.

    2015-01-01

    Background Up to 60% of Parkinson's patients suffer from low back pain (LBP) during the course of their disease. How LBP affects daily functional status and how to manage this aspect of PD has not been adequately explored. Methods We examined sixteen patients undergoing bilateral subthalamic nucleus deep brain stimulation (STN DBS) who met inclusion criteria for moderate disability from LBP, as classified by the Oswestry Low Back Pain Disability Index (OLBPD). Results Thirteen of 16 patients had attempted additional treatments for LBP including medical management, massage, chiropractic, epidural steroid injections and/or surgery and with minimal relief. Following DBS, there was a significant improvement in OLBPD at both the 6-month and 1-year time points (p < 0.02, p < 0.005 respectively). A mean improvement of 31.7% on OLBPD score was noted. Visual Analogue Scale (VAS) similarly decreased significantly at 1 year (p = 0.015). There was no correlation between OLBPD score and other measures including UPDRS, age, and other non-motor symptoms. Conclusion Given the prevalent yet undertreated disability associated with LBP in PD, these results are novel in that they show STN DBS has a significant positive effect on disability associated with LBP. PMID:25895600

  16. Rapid assessment of gait and speech after subthalamic deep brain stimulation

    PubMed Central

    Farris, Sierra M.; Giroux, Monique L.

    2016-01-01

    Background: Describe a rapid assessment for patients with idiopathic Parkinson's disease (PD) and deep brain stimulation of the subthalamic nucleus reporting worsening speech and/or gait problems. Methods: We retrospectively reviewed 29 patients that had improvement in gait and/or speech within 30 min after turning stimulation off. Clinical data analyzed include unified PD rating scale motor scores and stimulation parameters before and after adjusting stimulation. All patients received electrode efficacy and side effect threshold testing. Stimulation parameters were adjusted to maximize efficacy, avoid side effects, and maximize battery longevity. Results: Turning stimulation off revealed reversible speech and/or gait stimulation side effects within 30 min. Focusing on six factors revealed stimulation modifications that improved motor symptoms, eliminated stimulation side effects, and reduced battery drain. Primary stimulation parameters modified were cathode selection and pulse width reduction. Conclusions: Stimulation-induced side effects impacting gait and speech can be identified within 30 min. A systematic evaluation can distinguish disease progression from reversible stimulation side effects and improve motor outcomes over the long term. PMID:27583181

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

    PubMed Central

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

    2008-01-01

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

  18. Two-Photon Enzymatic Probes Visualizing Sub-cellular/Deep-brain Caspase Activities in Neurodegenerative Models

    PubMed Central

    Qian, Linghui; Zhang, Cheng-Wu; Mao, Yanli; Li, Lin; Gao, Nengyue; Lim, Kah-Leong; Xu, Qing-Hua; Yao, Shao Q.

    2016-01-01

    Caspases work as a double-edged sword in maintaining cell homeostasis. Highly regulated caspase activities are essential during animal development, but dysregulation might lead to different diseases, e.g. extreme caspase activation is known to promote neurodegeneration. At present, visualization of caspase activation has mostly remained at the cellular level, in part due to a lack of cell-permeable imaging probes capable of direct, real-time investigations of endogenous caspase activities in deep tissues. Herein, we report a suite of two-photon, small molecule/peptide probes which enable sensitive and dynamic imaging of individual caspase activities in neurodegenerative models under physiological conditions. With no apparent toxicity and the ability of imaging endogenous caspases both in different subcellular organelles of mammalian cells and in brain tissues, these probes serve as complementary tools to conventional histological analysis. They should facilitate future explorations of caspases at molecular, cellular and organism levels and inspire development of novel two-photon probes against other enzymes. PMID:27210613

  19. A Power-Efficient Wireless System With Adaptive Supply Control for Deep Brain Stimulation.

    PubMed

    Lee, Hyung-Min; Park, Hangue; Ghovanloo, Maysam

    2013-09-01

    A power-efficient wireless stimulating system for a head-mounted deep brain stimulator (DBS) is presented. A new adaptive rectifier generates a variable DC supply voltage from a constant AC power carrier utilizing phase control feedback, while achieving high AC-DC power conversion efficiency (PCE) through active synchronous switching. A current-controlled stimulator adopts closed-loop supply control to automatically adjust the stimulation compliance voltage by detecting stimulation site potentials through a voltage readout channel, and improve the stimulation efficiency. The stimulator also utilizes closed-loop active charge balancing to maintain the residual charge at each site within a safe limit, while receiving the stimulation parameters wirelessly from the amplitude-shift-keyed power carrier. A 4-ch wireless stimulating system prototype was fabricated in a 0.5-μm 3M2P standard CMOS process, occupying 2.25 mm². With 5 V peak AC input at 2 MHz, the adaptive rectifier provides an adjustable DC output between 2.5 V and 4.6 V at 2.8 mA loading, resulting in measured PCE of 72 ~ 87%. The adaptive supply control increases the stimulation efficiency up to 30% higher than a fixed supply voltage to 58 ~ 68%. The prototype wireless stimulating system was verified in vitro. PMID:24678126

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

    PubMed Central

    Ramdhani, Ritesh A.; Frucht, Steven J.; Behnegar, Anousheh; Kopell, Brian H.

    2016-01-01

    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. PMID:26989574

  1. Effects of Deep Brain Stimulation on Pausing During Spontaneous Speech in Parkinson’s Disease

    PubMed Central

    Ahn, Ji Sook; Van Lancker Sidtis, Diana; Sidtis, John J.

    2016-01-01

    The present study examined pausing patterns in spontaneous speech as a measure of the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on parkinsonian speech. Pauses reflect various aspects of speech and language processes, including motor initiation and linguistic planning. Relatively little attention has been given to pauses in determining the effect of STN-DBS. An examination of pausing may be helpful to understanding how this form of therapy affects these behaviors. Seven individuals with Parkinson’s disease who received surgery for bilateral STN-DBS participated. Spontaneous speech samples were elicited in both the ON and OFF STN-DBS condition. Findings indicated that long pauses (250–3000 ms) in spontaneous speech were significantly shorter and more frequent in the STN-DBS ON condition. Furthermore, the proportion of nonlinguistic boundary pauses was significantly greater with stimulation. The findings support previous studies suggesting that speech motor control and lexical retrieval may be affected by STN-DBS. PMID:26848252

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

    SciTech Connect

    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.

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

    PubMed

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

    2015-06-01

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

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

    PubMed

    Wichmann, Thomas; DeLong, Mahlon R

    2016-04-01

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

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

    PubMed

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

    2015-06-01

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

  6. Two-Photon Enzymatic Probes Visualizing Sub-cellular/Deep-brain Caspase Activities in Neurodegenerative Models.

    PubMed

    Qian, Linghui; Zhang, Cheng-Wu; Mao, Yanli; Li, Lin; Gao, Nengyue; Lim, Kah-Leong; Xu, Qing-Hua; Yao, Shao Q

    2016-01-01

    Caspases work as a double-edged sword in maintaining cell homeostasis. Highly regulated caspase activities are essential during animal development, but dysregulation might lead to different diseases, e.g. extreme caspase activation is known to promote neurodegeneration. At present, visualization of caspase activation has mostly remained at the cellular level, in part due to a lack of cell-permeable imaging probes capable of direct, real-time investigations of endogenous caspase activities in deep tissues. Herein, we report a suite of two-photon, small molecule/peptide probes which enable sensitive and dynamic imaging of individual caspase activities in neurodegenerative models under physiological conditions. With no apparent toxicity and the ability of imaging endogenous caspases both in different subcellular organelles of mammalian cells and in brain tissues, these probes serve as complementary tools to conventional histological analysis. They should facilitate future explorations of caspases at molecular, cellular and organism levels and inspire development of novel two-photon probes against other enzymes. PMID:27210613

  7. Compact stacked planar inverted-F antenna for passive deep brain stimulation implants.

    PubMed

    Hosain, Md Kamal; Kouzani, Abbas Z; Tye, Susannah; Mortazavi, Daryoush; Kaynak, Akif

    2012-01-01

    A compact meandered three-layer stacked circular planar inverted-F antenna is designed and simulated at the UHF band (902.75 - 927.25 MHz) for passive deep brain stimulation implants. The UHF band is used because it offers small antenna size, and high data rate. The top and middle radiating layers are meandered, and low cost substrate and superstrate materials are used to limit the radius and height of the antenna to 5 mm and 1.64 mm, respectively. A dielectric substrate of FR-4 of ε(r)= 4.7 and δ= 0.018, and a biocompatible superstrate of silicone of er= 3.7 and d= 0.003 with thickness of 0.2 mm are used in the design. The resonance frequency of the proposed antenna is 918 MHz with a bandwidth of 24 MHz at return loss of -10 dB in free space. The antenna parameter such as 3D gain pattern of the designed antenna within a skin-tissue model is evaluated by using the finite element method. The compactness, wide bandwidth, round shape, and stable characteristics in skin make this antenna suitable for DBS. The feasibility of the wireless power transmission to the implant in the human head is also examined. PMID:23366026

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

    PubMed

    Udupa, Kaviraja; Chen, Robert

    2015-10-01

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

  9. Deep brain stimulation for obesity: rationale and approach to trial design.

    PubMed

    Ho, Allen L; Sussman, Eric S; Pendharkar, Arjun V; Azagury, Dan E; Bohon, Cara; Halpern, Casey H

    2015-06-01

    Obesity is one of the most serious public health concerns in the US. While bariatric surgery has been shown to be successful for treatment of morbid obesity for those who have undergone unsuccessful behavioral modification, its associated risks and rates of relapse are not insignificant. There exists a neurological basis for the binge-like feeding behavior observed in morbid obesity that is believed to be due to dysregulation of the reward circuitry. The authors present a review of the evidence of the neuroanatomical basis for obesity, the potential neural targets for deep brain stimulation (DBS), as well as a rationale for DBS and future trial design. Identification of an appropriate patient population that would most likely benefit from this type of therapy is essential. There are also significant cost and ethical considerations for such a neuromodulatory intervention designed to alter maladaptive behavior. Finally, the authors present a consolidated set of inclusion criteria and study end points that should serve as the basis for any trial of DBS for obesity. PMID:26030708

  10. Timing of deep brain stimulation in Parkinson disease: a need for reappraisal?

    PubMed

    deSouza, Ruth-Mary; Moro, Elena; Lang, Anthony E; Schapira, Anthony H V

    2013-05-01

    We review the current application of deep brain stimulation (DBS) in Parkinson disease (PD) and consider the evidence that earlier use of DBS confers long-term symptomatic benefit for patients compared to best medical therapy. Electronic searches were performed of PubMed, Web of Knowledge, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials to identify all article types relating to the timing of DBS in PD. Current evidence suggests that DBS is typically performed in late stage PD, a mean of 14 to 15 years after diagnosis. Current guidelines recommend that PD patients who are resistant to medical therapies, have significant medication side effects and lengthening off periods, but are otherwise cognitively intact and medically fit for surgery be considered for DBS. If these criteria are rigidly interpreted, it may be that, by the time medical treatment options have been exhausted, the disease has progressed to the point that the patient may no longer be fit for neurosurgical intervention. From the evidence available, we conclude that surgical management of PD alone or in combination with medical therapy results in greater improvement of motor symptoms and quality of life than medical treatment alone. There is evidence to support the use of DBS in less advanced PD and that it may be appropriate for earlier stages of the disease than for which it is currently used. The improving short and long-term safety profile of DBS makes early application a realistic possibility. PMID:23483564

  11. Transcranial Magnetic Stimulation and Deep Brain Stimulation in the treatment of alcohol dependence

    PubMed Central

    Alba-Ferrara, L.; Fernandez, F.; Salas, R.; de Erausquin, G. A.

    2013-01-01

    Alcohol dependence is a major social, economic, and public health problem. Alcoholism can lead to damage of the gastrointestinal, nervous, cardiovascular, and respiratory systems and it can be lethal, costing hundreds of billions to the health care system. Despite the existence of cognitive-behavioral therapy, psychosocial interventions, and spiritually integrated treatment to treat it, alcohol dependence has a high relapse rate and poor prognosis, albeit with high interindividual variability. In this review, we discuss the use of two neuromodulation techniques, namely repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation (DBS), and their advantages and disadvantages compared to first-line pharmacological treatment for alcohol dependence. We also discuss rTMS and DBS targets for alcohol dependence treatment, considering experimental animal and human evidence, with careful consideration of methodological issues preventing the identification of feasible targets for neuromodulation treatments, as well as inter-individual variability factors influencing alcoholism prognosis. Lastly, we anticipate future research aiming to tailor the treatment to each individual patient by combining neurofunctional, neuroanatomical and neurodisruptive techniques optimizing the outcome. PMID:25598743

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

    PubMed

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

    2016-01-01

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

  13. A Power-Efficient Wireless System With Adaptive Supply Control for Deep Brain Stimulation

    PubMed Central

    Lee, Hyung-Min; Park, Hangue; Ghovanloo, Maysam

    2014-01-01

    A power-efficient wireless stimulating system for a head-mounted deep brain stimulator (DBS) is presented. A new adaptive rectifier generates a variable DC supply voltage from a constant AC power carrier utilizing phase control feedback, while achieving high AC-DC power conversion efficiency (PCE) through active synchronous switching. A current-controlled stimulator adopts closed-loop supply control to automatically adjust the stimulation compliance voltage by detecting stimulation site potentials through a voltage readout channel, and improve the stimulation efficiency. The stimulator also utilizes closed-loop active charge balancing to maintain the residual charge at each site within a safe limit, while receiving the stimulation parameters wirelessly from the amplitude-shift-keyed power carrier. A 4-ch wireless stimulating system prototype was fabricated in a 0.5-μm 3M2P standard CMOS process, occupying 2.25 mm². With 5 V peak AC input at 2 MHz, the adaptive rectifier provides an adjustable DC output between 2.5 V and 4.6 V at 2.8 mA loading, resulting in measured PCE of 72 ~ 87%. The adaptive supply control increases the stimulation efficiency up to 30% higher than a fixed supply voltage to 58 ~ 68%. The prototype wireless stimulating system was verified in vitro. PMID:24678126

  14. Thyroid-induced worsening of parkinsonian tremor resistant to drugs and subthalamic nucleus deep brain stimulation.

    PubMed

    Minár, Michal; Valkovič, Peter

    2014-01-01

    Introduction. Symptoms of both hypothyroidism and thyrotoxicosis can be easily overlooked in patients with Parkinson's disease (PD). We report on a patient whose parkinsonian tremor worsened and proved refractory not only to common treatment, but also to deep brain stimulation (DBS). Case Presentation. A 61-year-old woman with advanced PD underwent bilateral subthalamic DBS, with an excellent outcome. Twenty-one months after the surgery, however, patient's resting/postural tremor markedly worsened. There was a slight improvement for 1 month after repeated adjustments of DBS parameters, but then the tremor worsened again. Since even a minimal increase of the dose of dopaminergic drugs caused extremely severe dyskinesias, an anticholinergic drug biperiden and benzodiazepine clonazepam were introduced, what helped for another month. With the onset of severe diarrhoea, a laboratory workup was performed. Thyrotoxicosis was detected. During treatment with the antithyroid agent carbimazole, the parkinsonian tremor clearly improved within two weeks. Conclusion. A hyperthyroid state can markedly exaggerate all forms of tremor, as well as other types of movement disorders. This condition can be overlooked or masked by other symptoms. Therefore, if the tremor in a patient with PD gradually worsens and proves resistant to the usual treatment, examine the thyroid gland. PMID:25628904

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

    PubMed Central

    Strumpf, Hendrik; Noesselt, Toemme; Schoenfeld, Mircea Ariel; Voges, Jürgen; Panther, Patricia; Kaufmann, Joern; Heinze, Hans-Jochen; Hopf, Jens-Max

    2016-01-01

    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. PMID:27167979

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

    PubMed

    Sweeney-Reed, Catherine M; Zaehle, Tino; Voges, Jürgen; Schmitt, Friedhelm C; Buentjen, Lars; Kopitzki, Klaus; Richardson-Klavehn, Alan; Hinrichs, Hermann; Heinze, Hans-Jochen; Knight, Robert T; Rugg, Michael D

    2016-09-01

    The data presented here comprise clinical, neuropsychological, and intrathalamic electrophysiological data from 7 patients with pharmacoresistant focal epilepsy and are related to the article "Pre-stimulus thalamic theta power predicts human memory formation" C.M. Sweeney-Reed, T. Zaehle, J. Voges, F.C. Schmitt, L. Buentjen, K. Kopitzki, et al. (2016) [1]. The patients participated in a memory paradigm after receiving electrodes implanted in the DMTN due to the surgical approach taken in electrode insertion for deep brain stimulation of the anterior thalamic nucleus. Epilepsy duration and pre-operative neuropsychological tests provide an indication of the profile of patients receiving intrathalamic electrode implantation and the memory capabilities in such a patient group. The electrophysiological data were recorded from the right DMTN preceding stimulus presentation during intentional memory encoding. The patients viewed a series of photographic scenes, which they judged as indoors or outdoors. The 900 ms epochs prior to stimulus presentation were labeled as preceding successful or unsuccessful subsequent memory formation according to a subsequent memory test for the items. The difference between theta power preceding successful versus unsuccessful subsequent memory formation is shown against time for each patient individually. PMID:27508216

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

    PubMed

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

    2015-06-01

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

  18. Deep brain stimulation of the subthalamic nucleus facilitates coordination of hand preshaping in Parkinson's disease.

    PubMed

    Schettino, L F; Van Erp, E; Hening, W; Lessig, S; Song, D; Barba, D; Poizner, H

    2009-01-01

    Several studies have found that Parkinson's disease (PD) disrupts the organization of complex motor sequences regardless of the influence of parkinsonian medications. A clear candidate for the neural bases of such deficits, which we term "coordinative," is the failure to integrate propioceptive and visual information by cortico-striatal circuits in a timed fashion. Recent reports, however, have indicated that deep-brain stimulation of the subthalamic nucleus (STN DBS) may result in an improvement in coordinative deficits beyond the amelioration of "intensive deficits" such as bradykinesia and scaling errors. The present study examined the spatio-temporal organization underlying the shaping of the hand during reaching to grasp objects differing in shape. Six PD patients ON and OFF their STN DBS when OFF their concomitant medications and six age-matched controls participated in this study. STN DBS improved the coordination involved in preshaping the hand while grasping. We discuss these results in light of our earlier work with PD patients on and off dopamine replacement therapy. PMID:19922392

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

    PubMed

    Schmetz, M-K; Heinemann, T

    2010-05-01

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

  20. Towards a Switched-Capacitor based Stimulator for efficient deep-brain stimulation.

    PubMed

    Vidal, Jose; Ghovanloo, Maysam

    2010-01-01

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

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

    PubMed

    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. PMID:22823486

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

    PubMed Central

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

    2016-01-01

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

  3. Patient and Caregiver Perspectives of Preoperative Teaching for Deep Brain Stimulation Surgery.

    PubMed

    Lanier-Bohan, Elaine M; Heath, Susan L

    2016-10-01

    Deep brain stimulation (DBS) has developed into an important therapy for Parkinson disease, essential tremor, and dystonia with more nurses in varied settings often preparing patients and families for this type of surgery. This exploratory study sought to obtain patient and caregiver perspectives of the current DBS teaching for Parkinson disease, essential tremor, and dystonia; to improve the teaching; and to standardize the education. Using survey methodology, 41 patients with movement disorder and 32 caregivers completed surveys about the preoperative instructions they received. Data analysis calculated frequencies for response rate, demographic information, multiple-choice questions, and Likert scale responses. Fill-in questions were summarized. Results overall showed that, because of the teaching, two thirds of patients and nearly two thirds of caregivers felt fully prepared for the DBS surgery. Patients' and caregivers' suggested recommendations for nurses and surgeons included requests for specific information such as attention to delivery of the education, more individualized care during the education, attention to pain during and after procedure, and postdischarge follow-up. The study identified unmet patient and caregiver needs, resulted in changes in practice, and serves as a guide toward standardization of educational approach and/or content. PMID:27579958

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

    PubMed

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

    2013-08-01

    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 to study whether DBS affects the HPA axis in OCD patients. We compared a stimulation ON and OFF condition with a one-week interval in 16 therapy-refractory OCD patients, treated with DBS for at least one year, targeted at the nucleus accumbens (NAc). We measured changes in 24-h urinary excretion of free cortisol (UFC), adrenaline and noradrenaline and changes in obsessive-compulsive (Y-BOCS), depressive (HAM-D) and anxiety (HAM-A) symptom scores. Median UFC levels increased with 53% in the OFF condition (from 93 to 143nmol/24h, p=0.12). There were no changes in urinary adrenaline or noradrenaline excretion. The increase in Y-BOCS (39%), and HAM-D (78%) scores correlated strongly with increased UFC levels in the OFF condition. Our findings indicate that symptom changes following DBS for OCD patients are associated with changes in UFC levels. PMID:23333254

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

    PubMed Central

    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

  6. Deep brain stimulation in obsessive-compulsive disorder: neurocircuitry and clinical experience.

    PubMed

    Lipsman, Nir; Giacobbe, Peter; Lozano, Andres M

    2013-01-01

    The last decade has seen a significant rise in interest in the use of deep brain stimulation (DBS) for the management of obsessive-compulsive disorder (OCD), one of psychiatry's most challenging conditions. The prominent role of both thought (obsessions) and motor (compulsions) dysfunction in OCD place the condition at the border between the neurological and the psychiatric. This is supported by a growing body of literature that implicates structures in decision-making, reward, and action-selection circuits in the disorder. Here, we provide an overview of the neurocircuitry of OCD while reviewing the DBS literature to date for the condition. Results of DBS trials in treatment- resistant OCD have been remarkably similar, with clinical response rates in the range of 40-60%, despite the use of a diverse range of targets. These results imply that a common underlying circuit is being modulated, and moreover that there is room for improvement, and debate, in the development of an evidence-driven DBS treatment for this chronic, debilitating illness. PMID:24112898

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed

    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. PMID:23726461

  11. Cerebral Venous Infarction: A Potentially Avoidable Complication of Deep Brain Stimulation Surgery

    PubMed Central

    Morishita, Takashi; Okun, Michael S.; Burdick, Adam; Jacobson, Charles E; Foote, Kelly D.

    2013-01-01

    Object Despite numerous reports on the morbidity and mortality of deep brain stimulation (DBS), cerebral venous infarction has rarely been reported. We present four cases of venous infarct secondary to DBS surgery. Methods The diagnosis of venous infarction was based on: 1) delayed onset of new neurologic deficits on post-operative day 1 or 2, and 2) significant edema surrounding the superficial aspect of the implanted lead, with or without subcortical hemorrhage on CT scan. Results Four cases (0.8%/lead, 1.3%/patient) of symptomatic cerebral venous infarction were identified out of 500 DBS lead implantation procedures between July 2002 and August 2009. All four patients had Parkinson’s disease (PD). Their DBS leads were implanted in the subthalamic nucleus (STN) (n=2), and the internal globus pallidus (GPi) (n=2). Retrospective review of the targeting confirmed that the planned trajectory passed within 3mm of a cortical vein in two cases for which contrast-enhanced pre-operative MRI was available. In the other two cases, contrasted targeting images were not obtained preoperatively. Conclusion Cerebral venous infarction is a potentially avoidable, but serious complication. To minimize its incidence, we propose the use of high resolution, contrast-enhanced, T1 weighted MR images to delineate cerebral venous anatomy, along with careful stereotactic planning of the lead trajectory to avoid injury to venous structures. PMID:23738501

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

    PubMed Central

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

    2016-01-01

    Objective Reduced verbal fluency (VF) has been reported in patients with Parkinson’s disease (PD), especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS). To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS. Method Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., ‘clusters’ as correlates of automatic activation spread within lexical fields) from slower cluster transitions (i.e., ‘switches’ reflecting set-shifting towards new lexical fields). The results were compared to those of eleven healthy control subjects. Results PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls. Discussion Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones. PMID:27575379

  13. Presurgical Rehearsals for Patients Considering “Awake” Deep Brain Stimulation

    PubMed Central

    Falconer, Ramsey A.; Rogers, Sean L.; Brewer, Cristie M.; Piscitani, Franco; Shenai, Mahesh B.

    2016-01-01

    Simulated surgical environments are rapidly gaining adoption in training students, residents, and members of specialized surgical teams. However, minimal attention has been given to the use of simulated surgical environments to educate patients on surgical processes, particularly procedures that require the active participation of the patient. “Awake” neurosurgery provides a unique situation in which patients openly participate in their operation. We describe a case report, in which a 62-year-old male was referred for “awake” deep brain stimulation implantation, in relation to medically refractory Parkinson’s disease. The patient had significant concerns regarding anxiety and claustrophobia, and toleration of the “awake” procedure. Consequently, we designed a simulated OR environment and process, to recreate the physical experience of the procedure, with minimal cost or risk. This experience was crucial in determining the care plan, as after this experience, the patient opted for an “asleep” alternative. Thus, in certain settings, presurgical rehearsals may have a dramatic impact in the overall course of care. PMID:27532036

  14. Preserving cortico-striatal function: deep brain stimulation in Huntington’s disease

    PubMed Central

    Nagel, Sean J.; Machado, Andre G.; Gale, John T.; Lobel, Darlene A.; Pandya, Mayur

    2015-01-01

    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. PMID:25814939

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

    PubMed Central

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

    2011-01-01

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

  16. The ethics of research on deep brain stimulation for depression: decisional capacity and therapeutic misconception

    PubMed Central

    Fisher, Carl Erik; Dunn, Laura B.; Christopher, Paul P.; Holtzheimer, Paul E.; Leykin, Yan; Mayberg, Helen S.; Lisanby, Sarah H.; Appelbaum, Paul S.

    2013-01-01

    Research on deep brain stimulation (DBS) for treatment-resistant depression appears promising, but concerns have been raised about the decisional capacity of severely depressed patients and their potential misconceptions about the research. We assessed 31 DBS research participants with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), a well-validated capacity measure, and with a scale to measure therapeutic misconception, which occurs when subjects do not recognize key differences between treatment and clinical research. Correlations with baseline depressive symptoms were explored. Subjects’ performance on the MacCAT-CR was excellent, but therapeutic misconception was still apparent. A trend toward significance was found in the correlation between baseline depression ratings and total therapeutic misconception score. Responses to open-ended prompts revealed both reassuring and concerning statements related to expectations of risk, benefit, and individualization. Even severely depressed patients did not manifest impairments in their capacity to consent to DBS research. Therapeutic misconception, however, remained prevalent. PMID:22812719

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2014-01-01

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

  19. Deep brain recordings using an implanted pulse generator in Parkinson’s disease

    PubMed Central

    Neumann, Wolf-Julian; Staub, Franziska; Horn, Andreas; Schanda, Julia; Mueller, Joerg; Schneider, Gerd-Helge

    2016-01-01

    Objectives Recent studies suggest that oscillatory beta activity could be used as a state biomarker in patients with Parkinson’s disease for subthalamic closed-loop stimulation with the intention of improving clinical benefit. Here we investigate the feasibility of subthalamic recordings via a novel chronically implanted pulse generator. Methods Subthalamic local field potential recordings were obtained from eight patients before and during deep brain stimulation (DBS). All data were analyzed in the frequency domain using Fourier transform based methods and compared between ON and OFF stimulation conditions. Results Distinct peaks of oscillatory beta band activity were found in 12 of 15 electrodes. DBS induced a significant frequency specific suppression of oscillatory beta activity (p = 0.002). Conclusion The results of the study suggest that oscillatory beta band synchronization and it’s modulation by DBS is recordable with a system suitable for chronic implantation and may serve as a biomarker for subthalamic closed-loop stimulation in patients with Parkinson’s disease. PMID:26387795

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

    PubMed Central

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

    2013-01-01

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

  1. Real-time classification of activated brain areas for fMRI-based human-brain-interfaces

    NASA Astrophysics Data System (ADS)

    Moench, Tobias; Hollmann, Maurice; Grzeschik, Ramona; Mueller, Charles; Luetzkendorf, Ralf; Baecke, Sebastian; Luchtmann, Michael; Wagegg, Daniela; Bernarding, Johannes

    2008-03-01

    Functional MR imaging (fMRI) enables to detect different activated brain areas according to the performed tasks. However, data are usually evaluated after the experiment, which prohibits intra-experiment optimization or more sophisticated applications such as biofeedback experiments. Using a human-brain-interface (HBI), subjects are able to communicate with external programs, e.g. to navigate through virtual scenes, or to experience and modify their own brain activation. These applications require the real-time analysis and classification of activated brain areas. Our paper presents first results of different strategies for real-time pattern analysis and classification realized within a flexible experiment control system that enables the volunteers to move through a 3D virtual scene in real-time using finger tapping tasks, and alternatively only thought-based tasks.

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

    PubMed

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

    2015-01-01

    Essential tremor (ET) is a highly prevalent movement disorder. Patients with ET exhibit a complex progressive and disabling tremor, and medical management often fails. Deep brain stimulation (DBS) has been successfully applied to this disorder, however there has been no quantifiable way to measure tremor severity or treatment efficacy in this patient population. The quantified amelioration of kinetic tremor via DBS is herein demonstrated through the application of a smartphone (iPhone) as a wireless accelerometer platform. The recorded acceleration signal can be obtained at a setting of the subject's convenience and conveyed by wireless transmission through the Internet for post-processing anywhere in the world. Further post-processing of the acceleration signal can be classified through a machine learning application, such as the support vector machine. Preliminary application of deep brain stimulation with a smartphone for acquisition of a feature set and machine learning for classification has been successfully applied. The support vector machine achieved 100% classification between deep brain stimulation in `on' and `off' mode based on the recording of an accelerometer signal through a smartphone as a wireless accelerometer platform. PMID:26737848

  3. The influence of bilateral subthalamic nucleus deep brain stimulation on impulsivity and prepulse inhibition in Parkinson’s disease patients

    PubMed Central

    Gee, Lucy; Smith, Heather; Cruz, Priscilla De La; Campbell, Joannalee; Fama, Chris; Haller, Jessica; Ramirez-Zamora, Adolfo; Durphy, Jennifer; Hanspal, Era; Molho, Eric; Barba, Anne; Shin, Damian; Pilitsis, Julie G.

    2015-01-01

    Background At least 14% of Parkinson disease (PD) patients develop impulse control disorders (ICDs). The pathophysiology behind these behaviors and the impact of deep brain stimulation in a real-life setting remains unclear. Objectives We prospectively examined the impact of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on ICDs in PD patients, as well as the relationship between impaired sensorimotor gaiting and impulsivity. Methods Patients undergoing bilateral STN-DBS were assessed for ICDs preoperatively and 1-year postoperatively using a validated questionnaire (QUIP-RS). A subset of patients completed the Balloon Analog Risk Task (BART) and auditory pre-pulse inhibition (PPI) testing. Results Analysis revealed 12 patients had an improvement in score assessing ICDs (“good responders” – GR; p = 0.006) while 4 had a worse or stable score (“poor responders” – PR; p > 0.05). GR further exemplified a significant decrease in hypersexual behavior (p = 0.005) and binge eating (p = 0.01). Impaired PPI responses also significantly correlated with impulsivity in BART (r = −0.72, p = 0.044). Discussion Following bilateral STN-DBS 75% of our cohort had a reduction in ICDs, thus suggesting deep brain stimulation effectively manages ICDs in PD. The role of impaired PPI in predisposition to ICDs in PD warrants further investigation. PMID:26066569

  4. Hypothalamic deep brain stimulation in the treatment of chronic cluster headache

    PubMed Central

    Leone, Massimo; Franzini, Angelo; Cecchini, Alberto Proietti; Broggi, Giovanni; Bussone, Gennaro

    2010-01-01

    Cluster headache (CH) is a short-lasting unilateral headache associated with ipsilateral craniofacial autonomic manifestations. A positron emission tomography (PET) study has shown that the posterior hypothalamus is activated during CH attacks, suggesting that hypothalamic hyperactivity plays a key role in CH pathophysiology. On this basis, stimulation of the ipsilateral posterior hypothalamus was hypothesized to counteract such hyperactivity to prevent intractable CH. Ten years after its introduction, hypothalamic stimulation has been proved to successfully prevent attacks in more than 60% of 58 hypothalamic implanted drug-resistant chronic CH patients. The implantation procedure has generally been proved to be safe, although it carries a small risk of brain haemorrhage. Long-term stimulation is safe, and nonsymptomatic impairment of orthostatic adaptation is the only noteworthy change. Microrecording studies will make it possible to better identify the target site. Neuroimaging investigations have shown that hypothalamic stimulation activates ipsilateral trigeminal complex, but with no immediate perceived sensation within the trigeminal distribution. Other studies on the pain threshold in chronically stimulated patients showed increased threshold for cold pain in the distribution of the first trigeminal branch ipsilateral to stimulation. These studies suggest that activation of the hypothalamus and of the trigeminal system are both necessary, but not sufficient to generate CH attacks. In addition to the hypothalamus, other unknown brain areas are likely to play a role in the pathophysiology of this illness. Hypothalamus implantation is associated with a small risk of intracerebral haemorrhage and must be performed by an expert neurosurgical team, in selected patients. PMID:21179610

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

    NASA Astrophysics Data System (ADS)

    Fan, Denggui; Wang, Zhihui; Wang, Qingyun

    2016-07-01

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

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

    PubMed Central

    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

  7. Brain activity monitoring by compressed spectral array during deep hypothermic circulatory arrest in acute aortic dissection surgery

    PubMed Central

    Budniak, Wiktor; Buczkowski, Piotr; Perek, Bartłomiej; Walczak, Maciej; Tomczyk, Jadwiga; Katarzyński, Sławomir; Jemielity, Marek

    2014-01-01

    Introduction Monitoring the central nervous system during aortic dissection repair may improve the understanding of the intraoperative changes related to its bioactivity. Aim The aim of the study was to evaluate the influence of deep hypothermia on intraoperative brain bioactivity measured by the compressed spectral array (CSA) method and to assess the influence of the operations on postoperative cognitive function. Material and methods The study enrolled 40 patients (31 men and 9 women) at the mean age of 60.2 ± 8.6 years, diagnosed with acute aortic dissection. They underwent emergency operations in deep hypothermic circulatory arrest (DHCA). During the operations, brain bioactivity was monitored with the compressed spectral array method. Results There were no intraoperative deaths. Electrocerebral silence during DHCA was observed in 31 patients (74%). The lowest activity was observed during DHCA: it was 0.01 ± 0.05 nW in the left hemisphere and 0.01 ± 0.03 nW in the right hemisphere. The postoperative results of neurological tests deteriorated statistically significantly (26.9 ± 1.7 points vs. 22.0 ± 1.7 points; p < 0.001), especially among patients who exhibited brain activity during DHCA. Conclusions The compressed spectral array method is clinically useful in monitoring brain bioactivity during emergency operations of acute aortic dissections. Electrocerebral silence occurs in 75% of patients during DHCA. The cognitive function of patients deteriorates significantly after operations with DHCA. PMID:26336458

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

    PubMed

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

    2016-06-01

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

  9. Long-Term Clinical Outcome of Internal Globus Pallidus Deep Brain Stimulation for Dystonia

    PubMed Central

    Park, Hye Ran; Lee, Jae Meen; Ehm, Gwanhee; Yang, Hui-Jun; Song, In Ho; Lim, Yong Hoon; Kim, Mi-Ryoung; Kim, Keyoung Ran; Lee, Woong-Woo; Kim, Young Eun; Hwang, Jae Ha; Shin, Chae Won; Park, Hyeyoung; Kim, Jin Wook; Kim, Han-Joon; Kim, Cheolyoung; Kim, Dong Gyu; Jeon, Beom Seok; Paek, Sun Ha

    2016-01-01

    Background GPi (Internal globus pallidus) DBS (deep brain stimulation) is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia. Objectives This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital. Methods 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) Results 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. Conclusions 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. PMID:26745717

  10. Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice.

    PubMed

    Hao, Shuang; Tang, Bin; Wu, Zhenyu; Ure, Kerstin; Sun, Yaling; Tao, Huifang; Gao, Yan; Patel, Akash J; Curry, Daniel J; Samaco, Rodney C; Zoghbi, Huda Y; Tang, Jianrong

    2015-10-15

    Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnesic rats have demonstrated that DBS targeted to the fimbria-fornix, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder. Such disorders are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We proposed that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP2 (ref. 6), RTT appears by the second year of life in humans, causing profound impairment in cognitive, motor and social skills, along with an array of neurological features. RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity. Here we show that forniceal DBS in RTT mice rescues contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restores in vivo hippocampal long-term potentiation and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT. PMID:26469053

  11. Interventional magnetic resonance imaging-guided subthalamic nucleus deep brain stimulation for Parkinson's disease: Patient selection

    PubMed Central

    Azmi, Hooman; Gupta, Fiona; Vukic, Mario; Kreitner, Jason; Kera, Elizabeth; Nicola, Gregory; Pierce, Sean; Panush, David; Cohen, Randy

    2016-01-01

    Background: Interventional magnetic resonance imaging (iMRI) guided deep brain stimulation (DBS) for Parkinson's disease (PD) has been shown to be effective. The costs of a dedicated intraoperative MRI may be prohibitive. The procedure can also be performed in a diagnostic scanner, however this presents challenges for utilization of time when the scanner is used both as a diagnostic and an interventional unit. This report outlines our novel methodology for patient selection for implantation in a diagnostic MR scanner, as an attempt to streamline the use of resources. A retrospective review of our outcomes is also presented. Methods: DBS candidacy evaluation included a PD questionnaire-39. Anxiety, age, difficulties in communication and body habitus were factors that were assessed in selecting patients for this technique. Eleven patients underwent iMRI-guided DBS implantation in the subthalamic nucleus. All patients were implanted bilaterally. Unified PD rating scale (UPDRS) part III and L-dopa dose were compared pre- and post-stimulation. A cohort of 11 DBS patients not selected for iMRI-guided DBS were also reported for comparison. Results: For the iMRI-guided patients, mean “Off” UPDRS III score was 47.6 (standard deviation [SD] 8.26). Postoperative “On” medication, “On” stimulation UPDRS III was 13.6 (SD 5.23). Mean preoperative L-dopa dose was 1060 mg (SD 474.3) and mean postoperative L-dopa dose was 320 (SD 298.3). Conclusion: iMRI-guided DBS is a newly emerging technique for surgical treatment of patients with PD. We present a novel scoring system for patient selection assessing anxiety, age, ability to communicate, and body habitus to identify patients who will be benefited most from this technique.

  12. Referring Parkinson's disease patients for deep brain stimulation: a RAND/UCLA appropriateness study.

    PubMed

    Moro, Elena; Schüpbach, Michael; Wächter, Tobias; Allert, Niels; Eleopra, Roberto; Honey, Christopher R; Rueda, Mauricio; Schiess, Mya C; Shimo, Yasushi; Valkovic, Peter; Whone, Alan; Stoevelaar, Herman

    2016-01-01

    In 2005, a European expert panel developed and validated an electronic tool to support the appropriate referral of patients with Parkinson's disease (PD) for the consideration of deep brain stimulation (DBS). Since new evidence has become available over the last decade an update of the tool is necessary. A world-wide expert panel (71 neurologists and 11 neurosurgeons) used the RAND/UCLA Appropriateness Method to assess the appropriateness of referral for 1296 scenarios (9-point scale). Scenarios were permutations of 8 clinical variables relevant to the decision of referral. Appropriateness of referral was calculated on the basis of the median score and the extent of agreement. Compared to 2005, the impact of clinical variables on the appropriateness of referral was similar for severity of on-off fluctuations, dyskinesias and refractory tremor (positive association, p < 0.001), and cognitive impairment (negative association, p < 0.001). A relatively stronger negative impact was seen for levodopa-unresponsive gait and balance disturbances as well as older age, the latter most likely due to a higher cut-off value (75 versus 70 years in the previous study). The impact of PD duration on the appropriateness of referral was less pronounced than in 2005. The contribution of the newly included variable 'non-motor side effects of anti-PD medication' was very modest. Based on these results the panel produced new recommendations on the appropriateness of referral for the evaluation of DBS in PD patients. Differences from the previous study reflect the new clinical evidence, particularly related to the use of DBS in an earlier stage of PD. The validation of the updated recommendations is in progress. PMID:26530503

  13. Quantitative Methods for Evaluating the Efficacy of Thalamic Deep Brain Stimulation in Patients with Essential Tremor

    PubMed Central

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

    2013-01-01

    Background Deep brain stimulation (DBS) of the thalamus is a safe and efficient method for treatment of disabling tremor in patient with essential tremor (ET). However, successful tremor suppression after surgery requires careful selection of stimulus parameters. Our aim was to examine the possible use of certain quantitative methods for evaluating the efficacy of thalamic DBS in ET patients in clinical practice, and to compare these methods with traditional clinical tests. Methods We examined 22 patients using the Essential Tremor Rating Scale (ETRS) and quantitative assessment of tremor with the stimulator both activated and deactivated. We used an accelerometer (CATSYS tremor Pen) for quantitative measurement of postural tremor, and a eurythmokinesimeter (EKM) to evaluate kinetic tremor in a rapid pointing task. Results The efficacy of DBS on tremor suppression was prominent irrespective of the method used. The agreement between clinical rating of postural tremor and tremor intensity as measured by the CATSYS tremor pen was relatively high (rs = 0.74). The agreement between kinetic tremor as assessed by the ETRS and the main outcome variable from the EKM test was low (rs = 0.34). The lack of agreement indicates that the EKM test is not comparable with the clinical test. Discussion Quantitative methods, such as the CATSYS tremor pen, could be a useful complement to clinical tremor assessment in evaluating the efficacy of DBS in clinical practice. Future studies should evaluate the precision of these methods and long-term impact on tremor suppression, activities of daily living (ADL) function and quality of life. PMID:24255800

  14. Kilohertz Frequency Deep Brain Stimulation Is Ineffective at Regularizing the Firing of Model Thalamic Neurons

    PubMed Central

    Couto, João; Grill, Warren M.

    2016-01-01

    Deep brain stimulation (DBS) is an established therapy for movement disorders, including tremor, dystonia, and Parkinson's disease, but the mechanisms of action are not well understood. Symptom suppression by DBS typically requires stimulation frequencies ≥100 Hz, but when the frequency is increased above ~2 kHz, the effectiveness in tremor suppression declines (Benabid et al., 1991). We sought to test the hypothesis that the decline in efficacy at high frequencies is associated with desynchronization of the activity generated within a population of stimulated neurons. Regularization of neuronal firing is strongly correlated with tremor suppression by DBS, and desynchronization would disrupt the regularization of neuronal activity. We implemented computational models of CNS axons with either deterministic or stochastic membrane dynamics, and quantified the response of populations of model nerve fibers to extracellular stimulation at different frequencies and amplitudes. As stimulation frequency was increased from 2 to 80 Hz the regularity of neuronal firing increased (as assessed with direct estimates of entropy), in accord with the clinical effects on tremor of increasing stimulation frequency (Kuncel et al., 2006). Further, at frequencies between 80 and 500 Hz, increasing the stimulation amplitude (i.e., the proportion of neurons activated by the stimulus) increased the regularity of neuronal activity across the population, in accord with the clinical effects on tremor of stimulation amplitude (Kuncel et al., 2007). However, at stimulation frequencies above 1 kHz the regularity of neuronal firing declined due to irregular patterns of action potential generation and conduction block. The reductions in neuronal regularity that occurred at high frequencies paralleled the previously reported decline in tremor reduction and may be responsible for the loss of efficacy of DBS at very high frequencies. This analysis provides further support for the hypothesis that

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    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 degrees of freedom in shaping the stimulating electric field. The objective of this study is to compare the performances of a new HD lead with a conventional cylindrical contact (CC) lead. Approach. A computational model, consisting of a finite element electric field model combined with multi-compartment neuron and axon models representing different neural populations in the subthalamic region, was used to evaluate the two leads. We compared ring-mode and steering-mode stimulation with the HD lead to single contact stimulation with the CC lead. These stimulation modes were tested for the lead: (1) positioned in the centroid of the STN, (2) shifted 1 mm towards the internal capsule (IC), and (3) shifted 2 mm towards the IC. Under these conditions, we quantified the number of STN neurons that were activated without activating IC fibers, which are known to cause side-effects. Main results. The modeling results show that the HD lead is able to mimic the stimulation effect of the CC lead. Additionally, in steering-mode stimulation there was a significant increase of activated STN neurons compared to the CC mode. Significance. From the model simulations we conclude that the HD lead in steering-mode with optimized stimulation parameter selection can stimulate more STN cells. Next, the clinical impact of the increased number of activated STN cells should be tested and balanced across the increased complexity of identifying the optimized stimulation parameter settings for the HD lead.

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2007-01-01

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

  18. A Fuzzy Inference System for Closed-Loop Deep Brain Stimulation in Parkinson's Disease.

    PubMed

    Camara, Carmen; Warwick, Kevin; Bruña, Ricardo; Aziz, Tipu; del Pozo, Francisco; Maestú, Fernando

    2015-11-01

    Parkinsons disease is a complex neurodegenerative disorder for which patients present many symptoms, tremor being the main one. In advanced stages of the disease, Deep Brain Stimulation is a generalized therapy which can significantly improve the motor symptoms. However despite its beneficial effects on treating the symptomatology, the technique can be improved. One of its main limitations is that the parameters are fixed, and the stimulation is provided uninterruptedly, not taking into account any fluctuation in the patients state. A closed-loop system which provides stimulation by demand would adjust the stimulation to the variations in the state of the patient, stimulating only when it is necessary. It would not only perform a more intelligent stimulation, capable of adapting to the changes in real time, but also extending the devices battery life, thereby avoiding surgical interventions. In this work we design a tool that learns to recognize the principal symptom of Parkinsons disease and particularly the tremor. The goal of the designed system is to detect the moments the patient is suffering from a tremor episode and consequently to decide whether stimulation is needed or not. For that, local field potentials were recorded in the subthalamic nucleus of ten Parkinsonian patients, who were diagnosed with tremor-dominant Parkinsons disease and who underwent surgery for the implantation of a neurostimulator. Electromyographic activity in the forearm was simultaneously recorded, and the relation between both signals was evaluated using two different synchronization measures. The results of evaluating the synchronization indexes on each moment represent the inputs to the designed system. Finally, a fuzzy inference system was applied with the goal of identifying tremor episodes. Results are favourable, reaching accuracies of higher 98.7% in 70% of the patients. PMID:26385550

  19. Analyzing 7000 texts on deep brain stimulation: what do they tell us?

    PubMed

    Ineichen, Christian; Christen, Markus

    2015-01-01

    The enormous increase in numbers of scientific publications in the last decades requires quantitative methods for obtaining a better understanding of topics and developments in various fields. In this exploratory study, we investigate the emergence, trends, and connections of topics within the whole text corpus of the deep brain stimulation (DBS) literature based on more than 7000 papers (title and abstracts) published between 1991 to 2014 using a network approach. Taking the co-occurrence of basic terms that represent important topics within DBS as starting point, we outline the statistics of interconnections between DBS indications, anatomical targets, positive, and negative effects, as well as methodological, technological, and economic issues. This quantitative approach confirms known trends within the literature (e.g., regarding the emergence of psychiatric indications). The data also reflect an increased discussion about complex issues such as personality connected tightly to the ethical context, as well as an apparent focus on depression as important DBS indication, where the co-occurrence of terms related to negative effects is low both for the indication as well as the related anatomical targets. We also discuss consequences of the analysis from a bioethical perspective, i.e., how such a quantitative analysis could uncover hidden subject matters that have ethical relevance. For example, we find that hardware-related issues in DBS are far more robustly connected to an ethical context compared to impulsivity, concrete side-effects or death/suicide. Our contribution also outlines the methodology of quantitative text analysis that combines statistical approaches with expert knowledge. It thus serves as an example how innovative quantitative tools can be made useful for gaining a better understanding in the field of DBS. PMID:26578908

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

    PubMed

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

    2013-05-15

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

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

    PubMed Central

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

    2014-01-01

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

  2. Neuronavigation using susceptibility-weighted venography: application to deep brain stimulation and comparison with gadolinium contrast.

    PubMed

    Bériault, Silvain; Sadikot, Abbas F; Alsubaie, Fahd; Drouin, Simon; Collins, D Louis; Pike, G Bruce

    2014-07-01

    Careful trajectory planning on preoperative vascular imaging is an essential step in deep brain stimulation (DBS) to minimize risks of hemorrhagic complications and postoperative neurological deficits. This paper compares 2 MRI methods for visualizing cerebral vasculature and planning DBS probe trajectories: a single data set T1-weighted scan with double-dose gadolinium contrast (T1w-Gd) and a multi-data set protocol consisting of a T1-weighted structural, susceptibility-weighted venography, and time-of-flight angiography (T1w-SWI-TOF). Two neurosurgeons who specialize in neuromodulation surgery planned bilateral STN DBS in 18 patients with Parkinson's disease (36 hemispheres) using each protocol separately. Planned trajectories were then evaluated across all vascular data sets (T1w-Gd, SWI, and TOF) to detect possible intersection with blood vessels along the entire path via an objective vesselness measure. The authors' results show that trajectories planned on T1w-SWI-TOF successfully avoided the cerebral vasculature imaged by conventional T1w-Gd and did not suffer from missing vascular information or imprecise data set registration. Furthermore, with appropriate planning and visualization software, trajectory corridors planned on T1w-SWI-TOF intersected significantly less fine vasculature that was not detected on the T1w-Gd (p < 0.01 within 2 mm and p < 0.001 within 4 mm of the track centerline). The proposed T1w-SWI-TOF protocol comes with minimal effects on the imaging and surgical workflow, improves vessel avoidance, and provides a safe cost-effective alternative to injection of gadolinium contrast. PMID:24834941

  3. Centromedian-Parafascicular Complex Deep Brain Stimulation for Tourette Syndrome: A Retrospective Study.

    PubMed

    Testini, Paola; Zhao, Cong Z; Stead, Matt; Duffy, Penelope S; Klassen, Bryan T; Lee, Kendall H

    2016-02-01

    Deep brain stimulation (DBS) of the thalamic centromedian/parafascicular (CM-Pf) complex has been reported as a promising treatment for patients with severe, treatment-resistant Tourette syndrome (TS). In this study, safety and clinical outcomes of bilateral thalamic CM-Pf DBS were reviewed in a series of 12 consecutive patients with medically refractory TS, 11 of whom met the criteria of postsurgical follow-up at our institution for at least 2 months. Five patients were followed for a year or longer. Consistent with many patients with TS, all patients had psychiatric comorbidities. Tic severity and frequency were measured by using the Yale Global Tic Severity Scale (YGTSS) over time (average, 26 months) in 10 subjects. One patient was tested at 2-week follow-up only and thus was excluded from group YGTSS analysis. Final YGTSS scores differed significantly from the preoperative baseline score. The average (n=10) improvement relative to baseline in the total score was 54% (95% CI, 37-70); average improvement relative to baseline in the YGTSS Motor tic, Phonic tic, and Impairment subtests was 46% (95% CI, 34-64), 52% (95% CI, 34-72), and 59% (95% CI, 39-78), respectively. There were no intraoperative complications. After surgery, 1 subject underwent wound revision because of a scalp erosion and wound infection; the implanted DBS system was successfully salvaged with surgical revision and combined antibiotic therapy. Stimulation-induced adverse effects did not prevent the use of the DBS system, although 1 subject is undergoing a trial period with the stimulator off. This surgical series adds to the literature on CM-Pf DBS and supports its use as an effective and safe therapeutic option for severe refractory TS. PMID:26848003

  4. An automated approach towards detecting complex behaviours in deep brain oscillations.

    PubMed

    Mace, Michael; Yousif, Nada; Naushahi, Mohammad; Abdullah-Al-Mamun, Khondaker; Wang, Shouyan; Nandi, Dipankar; Vaidyanathan, Ravi

    2014-03-15

    Extracting event-related potentials (ERPs) from neurological rhythms is of fundamental importance in neuroscience research. Standard ERP techniques typically require the associated ERP waveform to have low variance, be shape and latency invariant and require many repeated trials. Additionally, the non-ERP part of the signal needs to be sampled from an uncorrelated Gaussian process. This limits methods of analysis to quantifying simple behaviours and movements only when multi-trial data-sets are available. We introduce a method for automatically detecting events associated with complex or large-scale behaviours, where the ERP need not conform to the aforementioned requirements. The algorithm is based on the calculation of a detection contour and adaptive threshold. These are combined using logical operations to produce a binary signal indicating the presence (or absence) of an event with the associated detection parameters tuned using a multi-objective genetic algorithm. To validate the proposed methodology, deep brain signals were recorded from implanted electrodes in patients with Parkinson's disease as they participated in a large movement-based behavioural paradigm. The experiment involved bilateral recordings of local field potentials from the sub-thalamic nucleus (STN) and pedunculopontine nucleus (PPN) during an orientation task. After tuning, the algorithm is able to extract events achieving training set sensitivities and specificities of [87.5 ± 6.5, 76.7 ± 12.8, 90.0 ± 4.1] and [92.6 ± 6.3, 86.0 ± 9.0, 29.8 ± 12.3] (mean ± 1 std) for the three subjects, averaged across the four neural sites. Furthermore, the methodology has the potential for utility in real-time applications as only a single-trial ERP is required. PMID:24370598

  5. Understanding the impact of deep brain stimulation on ambulatory activity in advanced Parkinson's disease.

    PubMed

    Rochester, Lynn; Chastin, Sebastien Francois Martin; Lord, Sue; Baker, Katherine; Burn, David John

    2012-06-01

    Whilst deep brain stimulation of the subthalamic nucleus (DBS-STN) improves the motor symptoms of Parkinson's disease (PD), its effect on daily activity is unknown. We aimed to quantify changes in ambulatory activity following DBS-STN in advanced PD using novel accelerometry based measures that describe changes to the volume and pattern of walking. Seventeen participants with advanced PD were measured over a 7-day period using an activPAL (™) activity monitor. Data were collected 6 weeks before and 6 months after surgery and included measures that describe the volume and pattern of ambulatory activity (number of steps per day, accumulation, diversity and variability of walking time), alongside standard measures for disease severity, freezing of gait, gait speed, and extended activities of daily living. Activity outcomes were compared pre- and 6 months post-surgery using linear mixed models and correlated with standard outcomes. The results of this study are despite significant improvements in motor symptoms after surgery, the volume of ambulatory activity (total number of steps per day) did not change (P = 0.468). However, significant increases in length and variability of walking bouts emerged, suggesting improvements in diversity and flexibility of walking patterns. Motor severity and extended activities of daily living scores were significantly correlated with walking bout variability but not with volume of walking. Thus, the conclusions are reduction in motor symptom severity after DBS-STN translated into selective improvements in daily activity. Novel measures derived from accelerometry provide a discrete measure of performance and allow closer interpretation of the impact of DBS-STN on real-world activity. PMID:22086738

  6. Long-lasting hyperpolarization underlies seizure reduction by low frequency deep brain electrical stimulation

    PubMed Central

    Toprani, Sheela; Durand, Dominique M

    2013-01-01

    Mesial temporal lobe epilepsy (MTLE) is a common medically refractory neurological disease. Deep brain electrical stimulation (DBS) of grey matter has been used for MTLE with limited success. However, stimulation of a white matter tract connecting the hippocampi, the ventral hippocampal commissure (VHC), with low frequencies that simulate interictal discharges has shown promising results, with seizure reduction greater than 98% in bilateral hippocampi during stimulation and greater than 50% seizure reduction in bilateral hippocampi after treatment. A major hurdle to the implementation and optimization of this treatment is that the mechanisms of seizure reduction by low frequency electrical stimulation (LFS) are not known. The goal of this study is to understand how commissural fibre tract stimulation reduces bilateral hippocampal epileptic activity in an in vitro slice preparation containing bilateral hippocampi connected by the VHC. It is our hypothesis that electrical stimuli induce hyperpolarization lasting hundreds of milliseconds following each pulse which reduces spontaneous epileptic activity during each inter-stimulus interval (ISI). Stimulus-induced long-lasting-hyperpolarization (LLH) can be mediated by GABAB inhibitory post-synaptic potentials (IPSPs) or slow after-hyperpolarization (sAHP). To test the role of LLH in effective bilateral seizure reduction by fibre tract stimulation, we measured stimulus-induced hyperpolarization during LFS of the VHC using electrophysiology techniques. Antagonism of the GABAB IPSP and/or sAHP diminished stimulus-induced hyperpolarization concurrently with LFS efficacy (greater than 50% reduction). Blocking both the GABAB IPSP and sAHP simultaneously eliminated the effect of electrical stimulation on seizure reduction entirely. These data show that LFS of the VHC is an effective protocol for bilateral hippocampal seizure reduction and that its efficacy relies on the induction of long-lasting hyperpolarization mediated

  7. A decade of emerging indications: deep brain stimulation in the United States.

    PubMed

    Youngerman, Brett E; Chan, Andrew K; Mikell, Charles B; McKhann, Guy M; Sheth, Sameer A

    2016-08-01

    OBJECTIVE Deep brain stimulation (DBS) is an emerging treatment option for an expanding set of neurological and psychiatric diseases. Despite growing enthusiasm, the patterns and implications of this rapid adoption are largely unknown. National trends in DBS surgery performed for all indications between 2002 and 2011 are reported. METHODS Using a national database of hospital discharges, admissions for DBS for 14 indications were identified and categorized as either FDA approved, humanitarian device exempt (HDE), or emerging. Trends over time were examined, differences were analyzed by univariate analyses, and outcomes were analyzed by hierarchical regression analyses. RESULTS Between 2002 and 2011, there were an estimated 30,490 discharges following DBS for approved indications, 1647 for HDE indications, and 2014 for emerging indications. The volume for HDE and emerging indications grew at 36.1% annually in comparison with 7.0% for approved indications. DBS for emerging indications occurred at hospitals with more neurosurgeons and neurologists locally, but not necessarily at those with the highest DBS caseloads. Patients treated for HDE and emerging indications were younger with lower comorbidity scores. HDE and emerging indications were associated with greater rates of reported complications, longer lengths of stay, and greater total costs. CONCLUSIONS DBS for HDE and emerging indications underwent rapid growth in the last decade, and it is not exclusively the most experienced DBS practitioners leading the charge to treat the newest indications. Surgeons may be selecting younger and healthier patients for their early experiences. Differences in reported complication rates warrant further attention and additional costs should be anticipated as surgeons gain experience with new patient populations and targets. PMID:26722851

  8. Disease-specific longevity of impulse generators in deep brain stimulation and review of the literature.

    PubMed

    van Riesen, Christoph; Tsironis, Georg; Gruber, Doreen; Klostermann, Fabian; Krause, Patricia; Schneider, Gerd Helge; Kupsch, Andreas

    2016-06-01

    Deep brain stimulation (DBS) represents an established and internationally approved therapy for movement disorders. In the present retrospective analysis, we evaluated disease-specific longevity of dual channel impulse generators (IPG) used in different movement disorders. We correlated the battery lifetime with electrical stimulation settings, "total electrical energy delivered" (TEED), stimulation modi (monopolar, double monopolar and bipolar) and targets. Specifically, we reviewed the longevity and stimulation settings of 464 IPGs implanted between 1996 until 2011 in a single university center. Disease entities comprised Parkinson's disease (PD, n = 257), dystonia (n = 130) and essential tremor (ET, n = 50). Further subanalyses aimed at assessing differential longevity in different subtypes of PD and dystonia. The main finding relates to longer IPG longevity in ET (thalamic DBS) and PD (subthalamic DBS) vs. dystonia (pallidal DBS; 71.9 ± 6.7 vs. 51.5 ± 2.3 vs. 37 ± 2 months). In PD the tremor-dominant type was associated with a significant shorter battery survival than in the akinetic-rigid type without tremor or the "balanced" type with tremor, bradykinesia and rigidity (38.8 ± 3.9 vs. 53.6 ± 3.4 vs. 58.8 ± 4.1 months), while there were no significant differences in longevity between the subtypes of dystonia. Frequency, amplitude, pulse widths and TEED correlated inversely with battery lifetime. Pallidal DBS in dystonia is associated with a shorter lifetime of IPGs than subthalamic or thalamic DBS for PD or ET. The present results may contribute to the rapidly evolving refinement of DBS devices. Future studies that assess energy consumption both in patients with and without IPG replacement could help to avoid potential underestimation of longevity of IPGs. PMID:27198700

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

    PubMed

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

    2016-10-15

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

  10. Effects of thalamic deep brain stimulation based on tremor type and diagnosis.

    PubMed

    Hubble, J P; Busenbark, K L; Wilkinson, S; Pahwa, R; Paulson, G W; Lyons, K; Koller, W C

    1997-05-01

    It has been suggested that deep brain stimulation (DBS) is less effective in alleviating proximal than distal postural arm tremor reduction is said to be less in essential tremor (ET) than in Parkinson's disease (PD). We analyzed blinded rater's tremor scores and subjects' disability ratings at 3-month follow-up to examine the effects of DBS based on tremor type (rest, kinetic, distal postural, proximal postural) and diagnosis (ET, PD). An independent examiner provided tremor scores using randomized videotaped footage of 19 ET and 10 PD subjects at baseline and at follow-up with DBS "on." Subjects provided self-ratings of disability at baseline and at follow-up. Comparisons of baseline and follow-up tremor scores and disability ratings were made using the Mann-Whitney U and Wilcoxon rank sum W test; correlation analyses were performed using Spearman rank order correlation test. There were significant and essentially equal improvements in tremor scores of test, kinetic, distal postural, and proximal postural tremor at follow-up. Only one subject had no improvement in tremor. Tremor improved significantly and to the same extent in ET and PD subjects in each position except "at rest," which was most improved in PD (p = 0.0003). ET and PD subjects did not differ in the extent of disability improvement. Improved disability correlated only with improved postural tremor scores; proximal postural and distal postural (r = 0.41, p = 0.03; r = 0.47, p = 0.01). DBS is effective in alleviating tremor and disability in both ET and PD. Resting, kinetic, distal postural, and proximal postural tremor can be reduced to an equal degree. However, DBS produces the greatest improvement in disability in association with improved postural tremor in both ET and PD. PMID:9159728

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

    NASA Astrophysics Data System (ADS)

    Zhang, Tianhe C.; Grill, Warren M.

    2010-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-08-01

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

  13. Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice

    PubMed Central

    Hao, Shuang; Tang, Bin; Wu, Zhenyu; Ure, Kerstin; Sun, Yaling; Tao, Huifang; Gao, Yan; Patel, Akash J.; Curry, Daniel J.; Samaco, Rodney C.; Zoghbi, Huda Y.; Tang, Jianrong

    2016-01-01

    Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnestic rats have demonstrated that DBS targeted to the fimbria-fornix1-3, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory3-5. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder (IDD). IDDs are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We hypothesized that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett Syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP26, RTT appears by the second year of life, causing profound impairment in cognitive, motor, and social skills along with an array of neurological features7; RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity8-11. Here we show that forniceal DBS in RTT mice rescued contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restored in vivo hippocampal long-term potentiation (LTP) and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT. PMID:26469053

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

  15. Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson’s Disease

    PubMed Central

    Hacker, Mallory L.; Currie, Amanda D.; Molinari, Anna L.; Turchan, Maxim; Millan, Sarah M.; Heusinkveld, Lauren E.; Roach, Jonathon; Konrad, Peter E.; Davis, Thomas L.; Neimat, Joseph S.; Phibbs, Fenna T.; Hedera, Peter; Byrne, Daniel W.; Charles, David

    2016-01-01

    Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson’s disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). Objective: The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. Methods: Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. Results: Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months (p <  0.05; OR = 0.2; 95% CI: 0.04–0.97). Conclusions: STN-DBS in early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD. PMID:26967937

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

    PubMed

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

    2016-02-01

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

  17. Deep Brain Stimulation for Parkinson’s Disease: Recent Trends and Future Direction

    PubMed Central

    FUKAYA, Chikashi; YAMAMOTO, Takamitsu

    2015-01-01

    To date, deep brain stimulation (DBS) has already been performed on more than 120,000 patients worldwide and in more than 7,000 patients in Japan. However, fundamental understanding of DBS effects on the pathological neural circuitry remains insufficient. Recent studies have specifically shown the importance of cortico-striato-thalamo-cortical (CSTC) loops, which were identified as functionally and anatomically discrete units. Three main circuits exist in the CSTC loops, namely, the motor, associative, and limbic circuits. From these theoretical backgrounds, it is determined that DBS sometimes influences not only motor functions but also the cognitive and affective functions of Parkinson’s disease (PD) patients. The main targets of DBS for PD are subthalamic nucleus (STN) and globus pallidus interna (GPi). Ventralis intermedius (Vim)-DBS was found to be effective in improving tremor. However, Vim-DBS cannot sufficiently improve akinesia and rigidity. Therefore, Vim-DBS is seldom carried out for the treatment of PD. In this article, we review the present state of DBS, mainly STN-DBS and GPi-DBS, for PD. In the first part of the article, appropriate indications and practical effects established in previous studies are discussed. The findings of previous investigations on the complications caused by the surgical procedure and on the adverse events induced by DBS itself are reviewed. In the second part, we discuss target selection (GPi vs. STN) and the effect of DBS on nonmotor symptoms. In the final part, as issues that should be resolved, the suitable timing of surgery, symptoms unresponsive to DBS such as on-period axial symptoms, and the related postoperative programing of stimulation parameters, are discussed. PMID:25925761

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

    PubMed

    Bourne, Sarah K; Eckhardt, Christine A; Sheth, Sameer A; Eskandar, Emad N

    2012-01-01

    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 (OFC), anterior cingulate cortex (ACC), ventral striatum, and mediodorsal (MD) thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule (ALIC), ventral capsule/ventral striatum (VC/VS), ventral caudate nucleus, subthalamic nucleus (STN), and nucleus accumbens (NAc) 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. PMID:22712007

  19. Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

    PubMed

    Yágüez, Lidia; Costello, Angela; Moriarty, John; Hulse, Natasha; Selway, Richard; Clough, Chris; Samuel, Michael; Ashkan, Keyoumars

    2014-03-01

    The beneficial effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the motor symptoms in advanced Parkinson's disease (PD) are well established. Early in PD, mild cognitive impairment is present in a proportion of patients. Hence, it can also be present in PD patients considered for DBS. The potential impact of even a modest decline post-surgically is a concern because it could result in impaired cognitive function. Therefore, attempts to determine which pre-operative cognitive measures predict post-operative cognitive change warrant further attention. We report our findings in a cohort of 30 routinely operated non-demented patients who underwent detailed neuropsychological assessments on average 7.1 months before and 9.4 months after STN DBS. We report the individual and group differences pre- and post-DBS. Stepwise regression analysis was used to analyse the best cognitive predictors of post-operative cognitive changes. We describe our data in relation to published normative data. Post-STN DBS, the immediate story recall component of verbal memory was the most affected cognitive function showing a significant decline in its group mean with a large effect size. The best predictors for this change were pre-surgical list learning and Full Scale Intelligence Quotient. These results suggest that non-demented patients, with even mild impairments in both general intellectual functions and list learning, may be at greater risk of decline in other aspects of verbal memory after STN DBS. Pre-existing mild executive dysfunction was not influenced post-operatively. These findings may help selection and consent for STN DBS. PMID:24231557

  20. The combined depletion of monoamines alters the effectiveness of subthalamic deep brain stimulation.

    PubMed

    Faggiani, Emilie; Delaville, Claire; Benazzouz, Abdelhamid

    2015-10-01

    Non-motor symptoms of Parkinson's disease are under-studied and therefore not well treated. Here, we investigated the role of combined depletions of dopamine, norepinephrine and/or serotonin in the manifestation of motor and non-motor deficits in the rat. Then, we studied the impact of these depletions on the efficacy of deep brain stimulation of the subthalamic nucleus (STN-DBS). We performed selective depletions of dopamine, norepinephrine and serotonin, and the behavioral effects of different combined depletions were investigated using the open field, the elevated plus maze and the forced swim test. Bilateral dopamine depletion alone induced locomotor deficits associated with anxiety and mild "depressive-like" behaviors. Although additional depletions of norepinephrine and/or serotonin did not potentiate locomotor and anxiety disorders, combined depletions of the three monoamines dramatically exacerbated "depressive-like" behavior. STN-DBS markedly reversed locomotor deficits and anxiety behavior in animals with bilateral dopamine depletion alone. However, these improvements were reduced or lost by the additional depletion of norepinephrine and/or serotonin, indicating that the depletion of these monoamines may interfere with the antiparkinsonian efficacy of STN-DBS. Furthermore, our results showed that acute STN-DBS improved "depressive-like" disorder in animals with bilateral depletion of dopamine and also in animals with combined depletions of the three monoamines, which induced severe immobility in the forced swim test. Our data highlight the key role of monoamine depletions in the pathophysiology of anxiety and depressive-like disorders and provide the first evidence of their negative consequences on the efficacy of STN-DBS upon the motor and anxiety disorders in the context of Parkinson's disease. PMID:26206409

  1. Early deep brain stimulation in patients with myoclonus-dystonia syndrome.

    PubMed

    Rocha, Helena; Linhares, Paulo; Chamadoira, Clara; Rosas, Maria José; Vaz, Rui

    2016-05-01

    Myoclonus-dystonia (MD) is a rare movement disorder which is disabling and frequently refractory to medical treatment. Deep brain stimulation (DBS) of the globus pallidus interna (GPi) has been used to treat some patients. Although there is significant motor improvement with DBS, the impact on disability and on quality of life has been infrequently reported. Also, the benefit of the procedure is not established in patients without ε-sarcoglycan gene (SGCE) mutations. We present two patients with severe MD treated with GPi-DBS, one of the patients without a SGCE mutation. Motor improvements (rest/action/total subscores of the Unified Myoclonus Rating Scale and movement subscore of the Burke-Fahn-Marsden Dystonia Rating Scale [BFMRS]) and disability (BFMRS disability subscore) were carefully evaluated preoperatively and at 6 and 12months after surgery. Quality of life (addressed using the Portuguese version of the Medical Outcomes Study 36-item Short-Form General Health Survey, version 2.0 [SF-36v2]) was tested preoperatively and 12months after DBS. At 12-month follow-up, myoclonus improved 78.6% in Patient 1 and 80.7% in Patient 2, while dystonia improved 37% and 86.7%, respectively. Improvements in disability ranged from 71.4% to 75%. With regard to quality of life, all parameters addressed by the SF-36v2 improved or stabilized in both patients. No major adverse effects were noticed. Improvements in motor symptoms are consistent with reports in the literature and were obtained regardless of the identification of a SGCE gene mutation. There were also significant benefits on disability and quality of life. DBS should be considered for MD. PMID:26810467

  2. RF rectifiers for EM power harvesting in a Deep Brain Stimulating device.

    PubMed

    Hosain, Md Kamal; Kouzani, Abbas Z; Tye, Susannah; Kaynak, Akif; Berk, Michael

    2015-03-01

    A passive deep brain stimulation (DBS) device can be equipped with a rectenna, consisting of an antenna and a rectifier, to harvest energy from electromagnetic fields for its operation. This paper presents optimization of radio frequency rectifier circuits for wireless energy harvesting in a passive head-mountable DBS device. The aim is to achieve a compact size, high conversion efficiency, and high output voltage rectifier. Four different rectifiers based on the Delon doubler, Greinacher voltage tripler, Delon voltage quadrupler, and 2-stage charge pumped architectures are designed, simulated, fabricated, and evaluated. The design and simulation are conducted using Agilent Genesys at operating frequency of 915 MHz. A dielectric substrate of FR-4 with thickness of 1.6 mm, and surface mount devices (SMD) components are used to fabricate the designed rectifiers. The performance of the fabricated rectifiers is evaluated using a 915 MHz radio frequency (RF) energy source. The maximum measured conversion efficiency of the Delon doubler, Greinacher tripler, Delon quadrupler, and 2-stage charge pumped rectifiers are 78, 75, 73, and 76 % at -5 dBm input power and for load resistances of 5-15 kΩ. The conversion efficiency of the rectifiers decreases significantly with the increase in the input power level. The Delon doubler rectifier provides the highest efficiency at both -5 and 5 dBm input power levels, whereas the Delon quadrupler rectifier gives the lowest efficiency for the same inputs. By considering both efficiency and DC output voltage, the charge pump rectifier outperforms the other three rectifiers. Accordingly, the optimised 2-stage charge pumped rectifier is used together with an antenna to harvest energy in our DBS device. PMID:25600671

  3. Subthalamic Nucleus Deep Brain Stimulation Impacts Language in Early Parkinson's Disease

    PubMed Central

    Phillips, Lara; Litcofsky, Kaitlyn A.; Pelster, Michael; Gelfand, Matthew

    2012-01-01

    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. PMID:22880117

  4. Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

    PubMed Central

    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 C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

    2014-01-01

    Background 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. Methods 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. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum 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. Conclusions 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. PMID:24768120

  5. Area Estimation of Deep-Sea Surfaces from Oblique Still Images

    PubMed Central

    Souto, Miguel; Afonso, Andreia; Calado, António; Madureira, Pedro; Campos, Aldino

    2015-01-01

    Estimating the area of seabed surfaces from pictures or videos is an important problem in seafloor surveys. This task is complex to achieve with moving platforms such as submersibles, towed or remotely operated vehicles (ROV), where the recording camera is typically not static and provides an oblique view of the seafloor. A new method for obtaining seabed surface area estimates is presented here, using the classical set up of two laser devices fixed to the ROV frame projecting two parallel lines over the seabed. By combining lengths measured directly from the image containing the laser lines, the area of seabed surfaces is estimated, as well as the camera’s distance to the seabed, pan and tilt angles. The only parameters required are the distance between the parallel laser lines and the camera’s horizontal and vertical angles of view. The method was validated with a controlled in situ experiment using a deep-sea ROV, yielding an area estimate error of 1.5%. Further applications and generalizations of the method are discussed, with emphasis on deep-sea applications. PMID:26177287

  6. Area Estimation of Deep-Sea Surfaces from Oblique Still Images.

    PubMed

    Dias, Frederico Carvalho; Gomes-Pereira, José; Tojeira, Inês; Souto, Miguel; Afonso, Andreia; Calado, António; Madureira, Pedro; Campos, Aldino

    2015-01-01

    Estimating the area of seabed surfaces from pictures or videos is an important problem in seafloor surveys. This task is complex to achieve with moving platforms such as submersibles, towed or remotely operated vehicles (ROV), where the recording camera is typically not static and provides an oblique view of the seafloor. A new method for obtaining seabed surface area estimates is presented here, using the classical set up of two laser devices fixed to the ROV frame projecting two parallel lines over the seabed. By combining lengths measured directly from the image containing the laser lines, the area of seabed surfaces is estimated, as well as the camera's distance to the seabed, pan and tilt angles. The only parameters required are the distance between the parallel laser lines and the camera's horizontal and vertical angles of view. The method was validated with a controlled in situ experiment using a deep-sea ROV, yielding an area estimate error of 1.5%. Further applications and generalizations of the method are discussed, with emphasis on deep-sea applications. PMID:26177287

  7. The CLAIR model: Extension of Brodmann areas based on brain oscillations and connectivity.

    PubMed

    Başar, Erol; Düzgün, Aysel

    2016-05-01

    Since the beginning of the last century, the localization of brain function has been represented by Brodmann areas, maps of the anatomic organization of the brain. They are used to broadly represent cortical structures with their given sensory-cognitive functions. In recent decades, the analysis of brain oscillations has become important in the correlation of brain functions. Moreover, spectral connectivity can provide further information on the dynamic connectivity between various structures. In addition, brain responses are dynamic in nature and structural localization is almost impossible, according to Luria (1966). Therefore, brain functions are very difficult to localize; hence, a combined analysis of oscillation and event-related coherences is required. In this study, a model termed as "CLAIR" is described to enrich and possibly replace the concept of the Brodmann areas. A CLAIR model with optimum function may take several years to develop, but this study sets out to lay its foundation. PMID:25700996

  8. Violence, mental illness, and the brain - A brief history of psychosurgery: Part 2 - From the limbic system and cingulotomy to deep brain stimulation.

    PubMed

    Faria, Miguel A

    2013-01-01

    Knowledge of neuroscience flourished during and in the wake of the era of frontal lobotomy, as a byproduct of psychosurgery in the late 1930s and 1940s, revealing fascinating neural pathways and neurophysiologic mechanisms of the limbic system for the formulation of emotions, memory, and human behavior. The creation of the Klüver-Bucy syndrome in monkeys opened new horizons in the pursuit of knowledge in human behavior and neuropathology. In the 1950s specialized functional neurosurgery was developed in association with stereotactic neurosurgery; deep brain electrodes were implanted for more precise recording of brain electrical activity in the evaluation and treatment of intractable mental disorders, including schizophrenia, "pathologic aggression," and psychomotor seizures in temporal lobe epilepsy. Psychosurgical procedures involved deep brain stimulation of the limbic system, as well as ablative procedures, such as cingulotomy and thalamotomy. The history of these developments up to the 21(st) century will continue in this three-part essay-editorial, exclusively researched and written for the readers of Surgical Neurology International. PMID:23776761

  9. The geomorphological features of a large scale deep-seated landslide in the Luchang area, Taiwan

    NASA Astrophysics Data System (ADS)

    Huang, Ming-Wan; Liao, Jyh-Jong; Pan, Yii-Wen

    2016-04-01

    Landslides events are frequently induced by high-intensity precipitation and active tectonic in Taiwan. Several catastrophic deep-seated landslides have been occurred in past few decades. The pre-existing landslides are the potential sites to occur again. The geomorphology features could provide their important information in reflection of landslide activity. The large scale deep-seated landslide of Luchang locates in the mountain area of Miaoli County, west-northern Taiwan. The site is about 60 hectares in area and from west to east is comprised of a ridge (El. 1100~950 m), main scarp, terrace (El. 925~900 m), hilly slope (El. 900~700 m), and the Luchang River. The regional geology is mainly the middle Miocene sedimentary rock which composed of thick sandstone, interlayered sandstone and shale, and coal. The major structures include the Luchang fault and the Shibi anticline, which the location of the former is approximately coincidental to the Luchang River and the latter is approximately coincidental to the ridge. In this study, we identify the geomorphology features by viewing stereo pairs of aerial photographs and examine in the field. UAV (Unmanned Aerial Vehicle) is adopted to assist in unreachable area. Several clear topographic features including scarps, anti-slopes, bulges, etc. are observed in this site. Active bedrock incision has caused many slope collapsed in the Luchang River, which could possibly be the important factors affecting the stability of this site. We also compared the topographic changes through the chronological aerial photographs. The topographic changes likely include several small-scale landslides. The preliminary evolution model of the large scale landslide is proposed in this study. The results help us to evaluate the recurrence potential of a large scale deep-seated landslide.

  10. Geology of the Deep Creek area, Washington, and its regional significance

    USGS Publications Warehouse

    Yates, Robert Giertz

    1976-01-01

    This report, although primarily concerned with the stratigraphy and structure of a lead-zinc mining district in northern Stevens County, Washington, discusses and integrates the geology of the region about the Deep Creek area. Although the study centers in an area of about 200 square miles immediately south of the International Boundary, the regional background comes from: (1)the previously undescribed Northport quadrangle to the west, (2) published reports and reconnaissance of the Metaline quadrangle to the east, and (3) from published reports and maps of a 16 mile wide area that lies to the north adjacent to these three quadrangles in British Columbia. The report is divided into three parts: (1) descriptions of rocks and structures of the Deep Creek area, (2) descriptions of the regional setting of the Deep Creek area, and (3) an analysis and interpretation of the depositional and tectonic events that produced the geologic features exposed today. In the Deep Creek area surficial deposits of sand and gravel of glacial origin cover much of the consolidated rocks, which range in age from greenschist of the late Precambrlan to albite granite of the Eocene. Three broad divisions of depositional history are represented: (1) Precambrian, (2) lower Paleozoic and (3) upper Paleozoic; the record of the Mesozoic and Eocene is fragmentary. The lower Paleozoic division is the only fossil-controlled sequence; the age of the other two divisions were established by less direct methods. Both Precambrian and upper Paleozoic sequences are dominated by fine-grained detrital sediments, the Precambrian tending towards the alumina-rich and the upper Paleozoic tending towards the black shale facies with high silica. Neither sequence has more than trivial amounts of coarse clastics. Both include limestones, but in minor abundance. The lower Paleozoic sequence, on the other hand, represents a progressive change in deposition. The sequence began during the very late Precambrian with the

  11. The Chandra Deep Survey of the Hubble Deep Field-North Area. II. Results from the Caltech Faint Field Galaxy Redshift Survey Area

    NASA Astrophysics Data System (ADS)

    Hornschemeier, A. E.; Brandt, W. N.; Garmire, G. P.; Schneider, D. P.; Barger, A. J.; Broos, P. S.; Cowie, L. L.; Townsley, L. K.; Bautz, M. W.; Burrows, D. N.; Chartas, G.; Feigelson, E. D.; Griffiths, R. E.; Lumb, D.; Nousek, J. A.; Ramsey, L. W.; Sargent, W. L. W.

    2001-06-01

    A deep X-ray survey of the Hubble Deep Field-North (HDF-N) and its environs is performed using data collected by the Advanced CCD Imaging Spectrometer (ACIS) on board the Chandra X-Ray Observatory. Currently a 221.9 ks exposure is available, the deepest ever presented, and here we give results on X-ray sources located in the 8.6‧×8.7‧ area covered by the Caltech Faint Field Galaxy Redshift Survey (the ``Caltech area''). This area has (1) deep photometric coverage in several optical and near-infrared bands; (2) extensive coverage at radio, submillimeter, and mid-infrared wavelengths; and (3) some of the deepest and most complete spectroscopic coverage ever obtained. It is also where the X-ray data have the greatest sensitivity; the minimum detectable fluxes in the 0.5-2 keV (soft) and 2-8 keV (hard) bands are ~1.3×10-16 and ~6.5×10-16 ergs cm-2 s-1, respectively. More than ~80% of the extragalactic X-ray background in the hard band is resolved. The 82 Chandra sources detected in the Caltech area are correlated with more than 25 multiwavelength source catalogs, and the results of these correlations as well as spectroscopic follow-up results obtained with the Keck and Hobby-Eberly Telescopes are presented. All but nine of the Chandra sources are detected optically with R<~26.5. Redshifts are available for 39% of the Chandra sources, including 96% of the sources with R<23 the redshift range is 0.1-3.5, with most sources having z<1.5. Eight of the X-ray sources are located in the HDF-N itself, including two not previously reported. A population of X-ray faint, optically bright, nearby galaxies emerges at soft-band fluxes of <~3×10-16 ergs cm-2 s-1. Our multiwavelength correlations have set the tightest constraints to date on the X-ray emission properties of μJy radio sources, mid-infrared sources detected by the Infrared Space Observatory (ISO), and very red (R-Ks>5.0) objects. A total of 16 of the 67 1.4 GHz μJy sources in the Caltech area are detected in the

  12. Seismic signature of crustal magma and fluid from deep seismic sounding data across Tengchong volcanic area

    NASA Astrophysics Data System (ADS)

    Bai, Z. M.; Zhang, Z. Z.; Wang, C. Y.; Klemperer, S. L.

    2012-04-01

    The weakened lithosphere around eastern syntax of Tibet plateau has been revealed by the Average Pn and Sn velocities, the 3D upper mantle velocity variations of P wave and S wave, and the iimaging results of magnetotelluric data. Tengchong volcanic area is neighboring to core of eastern syntax and famous for its springs, volcanic-geothermal activities and remarkable seismicity in mainland China. To probe the deep environment for the Tengchong volcanic-geothermal activity a deep seismic sounding (DSS) project was carried out across the this area in 1999. In this paper the seismic signature of crustal magma and fluid is explored from the DSS data with the seismic attribute fusion (SAF) technique, hence four possible positions for magma generation together with some locations for porous and fractured fluid beneath the Tengchong volcanic area were disclosed from the final fusion image of multi seismic attributes. The adopted attributes include the Vp, Vs and Vp/Vs results derived from a new inversion method based on the No-Ray-Tomography technique, and the migrated instantaneous attributes of central frequency, bandwidth and high frequency energy of pressure wave. Moreover, the back-projected ones which are mainly consisted by the attenuation factor Qp , the delay-time of shear wave splitting, and the amplitude ratio between S wave and P wave + S wave were also considered in this fusion process. Our fusion image indicates such a mechanism for the surface springs: a large amount of heat and the fluid released by the crystallization of magma were transmitted upward into the fluid-filled rock, and the fluid upwells along some pipeline since the high pressure in deep, thus the widespread springs of Tengchong volcanic area were developed. Moreover, the fusion image, regional volcanic and geothermal activities, and the seismicity suggest that the main risk of volcanic eruption was concentrated to the south of Tengchong city, especially around the shot point (SP) Tuantian

  13. Simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo.

    PubMed

    Hirai, Yasuharu; Nishino, Eri; Ohmori, Harunori

    2015-06-01

    Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices. PMID:25761950

  14. Simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo

    PubMed Central

    Hirai, Yasuharu; Nishino, Eri

    2015-01-01

    Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices. PMID:25761950

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

    PubMed

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

    2013-01-30

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

  16. A glass-coated tungsten microelectrode enclosing optical fibers for optogenetic exploration in primate deep brain structures.

    PubMed

    Tamura, Keita; Ohashi, Yohei; Tsubota, Tadashi; Takeuchi, Daigo; Hirabayashi, Toshiyuki; Yaguchi, Masae; Matsuyama, Makoto; Sekine, Takeru; Miyashita, Yasushi

    2012-10-15

    The optogenetic approach to primate brain circuitry has unparalleled potential for uncovering genetically and temporally resolved neuronal mechanisms of higher brain functions. In order to optogenetically investigate the large and complex primate brain, an optical-/electrical probe, or "optrode", must be inserted deeply, which requires the optrode to be not only long and stiff, but also sharp and smooth to reduce possible tissue damage. This study presents a tungsten microelectrode-based optrode that encloses optical fibers within its insulation glass. Optical fibers and a tungsten wire were tightly bound to each other and integrally coated with a smooth, thin layer of glass. This design satisfied the structural requirements for use in deep brain structures. The performance of the optrode was then examined in the thalamus of the rat and macaque monkeys which were injected with lentiviral vectors carrying the channelrhodopsin-2-enhanced yellow fluorescent protein (ChR2-EYFP) transgene. With fluorescence measurements via the optical fiber, ChR2-EYFP expression was detected clearly in vivo, which was confirmed by histological analysis in the rat. With photostimulation and extracellular recording, photo-responsive single-unit activities were isolated in the monkeys. The depth distribution of these units and the peak of the EYFP fluorescence profile overlapped consistently with each other. Thus, by developing a new probe, optogenetic methodology was successfully applied to a primate subcortical structure. This smooth glass-coated optrode is a promising tool for chronic in vivo experiments with various research targets including deep brain structures in behaving monkeys. PMID:22971353

  17. Compromised Blood-Brain Barrier Competence in Remote Brain Areas in Ischemic Stroke Rats at Chronic Stage

    PubMed Central

    Garbuzova-Davis, Svitlana; Haller, Edward; Williams, Stephanie N.; Haim, Eithan D.; Tajiri, Naoki; Hernandez-Ontiveros, Diana G.; Frisina-Deyo, Aric; Boffeli, Sean M.; Sanberg, Paul R.; Borlongan, Cesario V.

    2014-01-01

    Stroke is a life threatening disease leading to long-term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from initial ischemic lesion, i.e. diaschisis. Previously, we showed that the damaged blood-brain barrier (BBB) was implicated in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included: (1) vacuolated endothelial cells containing large autophagosomes, (2) degenerated pericytes displaying mitochondria with cristae disruption, (3) degenerated astrocytes and perivascular edema, (4) Evans Blue extravasation, and (5) appearance of parenchymal astrogliosis. Importantly, discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke. PMID:24610730

  18. Remote effect of deep-seated vascular brain lesions on cerebral blood flow

    SciTech Connect

    Attig, E.; Capon, A.; Demeurisse, G.; Verhas, M. )

    1990-11-01

    We measured regional cerebral blood flow using the xenon-133 inhalation method, at approximately 1 month after onset, in 60 stroke patients who had no evidence of major carotid artery stenosis or occlusion. Their single lesions (43 infarcts and 17 hematomas) were located in the capsulothalamolenticular region, sparing the cortex. Hemispheric mean cerebral blood flow was reduced on the side of the lesion in 25 patients and on both sides in 20. Regional hypoperfusion was observed in 46 patients (ipsilaterally in 34, bilaterally in 10, and contralaterally in two). Regional hypoperfusion was observed most frequently in the frontal lobe, particularly in the motor and premotor cortices of the prerolandic area. The 46 patients with regional hypoperfusion were compared with the 14 patients without regional hypoperfusion, considering the size and location of the lesion as well as the functional and analytic motor performances. As a rule, the lesion was slightly smaller and more posterior and the functional (p less than 0.001) and analytic (p less than 0.05) motor performances were significantly better in the 14 patients without regional hypoperfusion. Since the xenon-133 inhalation method examines cortical blood flow, we can attribute blood flow reductions resulting from deep-seated lesions to a functional depression akin to diaschisis. Interpretation of the clinical consequences and pathogenesis of this phenomenon requires further sequential and pathologic studies.

  19. The Safety of Using Body-Transmit MRI in Patients with Implanted Deep Brain Stimulation Devices

    PubMed Central

    Kahan, Joshua; Papadaki, Anastasia; White, Mark; Mancini, Laura; Yousry, Tarek; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Thornton, John

    2015-01-01

    Background Deep brain stimulation (DBS) is an established treatment for patients with movement disorders. Patients receiving chronic DBS provide a unique opportunity to explore the underlying mechanisms of DBS using functional MRI. It has been shown that the main safety concern with MRI in these patients is heating at the electrode tips – which can be minimised with strict adherence to a supervised acquisition protocol using a head-transmit/receive coil at 1.5T. MRI using the body-transmit coil with a multi-channel receive head coil has a number of potential advantages including an improved signal-to-noise ratio. Study outline We compared the safety of cranial MRI in an in vitro model of bilateral DBS using both head-transmit and body-transmit coils. We performed fibre-optic thermometry at a Medtronic ActivaPC device and Medtronic 3389 electrodes during turbo-spin echo (TSE) MRI using both coil arrangements at 1.5T and 3T, in addition to gradient-echo echo-planar fMRI exposure at 1.5T. Finally, we investigated the effect of transmit-coil choice on DBS stimulus delivery during MRI. Results Temperature increases were consistently largest at the electrode tips. Changing from head- to body-transmit coil significantly increased the electrode temperature elevation during TSE scans with scanner-reported head SAR 0.2W/kg from 0.45°C to 0.79°C (p<0.001) at 1.5T, and from 1.25°C to 1.44°C (p<0.001) at 3T. The position of the phantom relative to the body coil significantly impacted on electrode heating at 1.5T; however, the greatest heating observed in any position tested remained <1°C at this field strength. Conclusions We conclude that (1) with our specific hardware and SAR-limited protocol, body-transmit cranial MRI at 1.5T does not produce heating exceeding international guidelines, even in cases of poorly positioned patients, (2) cranial MRI at 3T can readily produce heating exceeding international guidelines, (3) patients with ActivaPC Medtronic systems are safe

  20. Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial.

    PubMed

    Ponce, Francisco A; Asaad, Wael F; Foote, Kelly D; Anderson, William S; Rees Cosgrove, G; Baltuch, Gordon H; Beasley, Kara; Reymers, Donald E; Oh, Esther S; Targum, Steven D; Smith, Gwenn S; Lyketsos, Constantine G; Lozano, Andres M

    2016-07-01

    OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer's disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0-79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0-7.9 mm), y = 9.6 ± 0.9 mm (range 8.0-11.6 mm), z = -7.5 ± 1.2 mm (range -5.4 to -10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2-4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with

  1. Cost analysis of awake versus asleep deep brain stimulation: a single academic health center experience.

    PubMed

    Jacob, R Lorie; Geddes, Jonah; McCartney, Shirley; Burchiel, Kim J

    2016-05-01

    OBJECT The objective of this study was to compare the cost of deep brain stimulation (DBS) performed awake versus asleep at a single US academic health center and to compare costs across the University HealthSystem Consortium (UHC) Clinical Database. METHODS Inpatient and outpatient demographic and hospital financial data for patients receiving a neurostimulator lead implant (from the first quarter of 2009 to the second quarter of 2014) were collected and analyzed. Inpatient charges included those associated with International Classification of Diseases, Ninth Revision (ICD-9) procedure code 0293 (implantation or replacement of intracranial neurostimulator lead). Outpatient charges included all preoperative charges ≤ 30 days prior to implant and all postoperative charges ≤ 30 days after implant. The cost of care based on reported charges and a cost-to-charge ratio was estimated. The UHC database was queried (January 2011 to March 2014) with the same ICD-9 code. Procedure cost data across like hospitals (27 UHC hospitals) conducting similar DBS procedures were compared. RESULTS Two hundred eleven DBS procedures (53 awake and 158 asleep) were performed at a single US academic health center during the study period. The average patient age ( ± SD) was 65 ± 9 years old and 39% of patients were female. The most common primary diagnosis was Parkinson's disease (61.1%) followed by essential and other forms of tremor (36%). Overall average DBS procedure cost was $39,152 ± $5340. Asleep DBS cost $38,850 ± $4830, which was not significantly different than the awake DBS cost of $40,052 ± $6604. The standard deviation for asleep DBS was significantly lower (p ≤ 0.05). In 2013, the median cost for a neurostimulator implant lead was $34,052 at UHC-affiliated hospitals that performed at least 5 procedures a year. At Oregon Health & Science University, the median cost was $17,150 and the observed single academic health center cost for a neurostimulator lead implant was

  2. Management of Deep Brain Stimulator Battery Failure: Battery Estimators, Charge Density, and Importance of Clinical Symptoms

    PubMed Central

    Fakhar, Kaihan; Hastings, Erin; Butson, Christopher R.; Foote, Kelly D.; Zeilman, Pam; Okun, Michael S.

    2013-01-01

    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/cm2/phase (SD = 3.82), for dystonia was 17.5 µC/cm2/phase (SD = 8.53), for essential tremor was 8.3 µC/cm2/phase (SD = 4.85), and for OCD was 18.0 µC/cm2/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. PMID:23536810

  3. Areas of Brain Damage Underlying Increased Reports of Behavioral Disinhibition.

    PubMed

    Knutson, Kristine M; Dal Monte, Olga; Schintu, Selene; Wassermann, Eric M; Raymont, Vanessa; Grafman, Jordan; Krueger, Frank

    2015-01-01

    Disinhibition, the inability to inhibit inappropriate behavior, is seen in frontal-temporal degeneration, Alzheimer's disease, and stroke. Behavioral disinhibition leads to social and emotional impairments, including impulsive behavior and disregard for social conventions. The authors investigated the effects of lesions on behavioral disinhibition measured by the Neuropsychiatric Inventory in 177 veterans with traumatic brain injuries. The authors performed voxel-based lesion-symptom mapping using MEDx. Damage in the frontal and temporal lobes, gyrus rectus, and insula was associated with greater behavioral disinhibition, providing further evidence of the frontal lobe's involvement in behavioral inhibition and suggesting that these regions are necessary to inhibit improper behavior. PMID:25959040

  4. Magnesium, aluminum and lead in various brain areas

    SciTech Connect

    Zumkley, H.; Bertram, H.P.; Brandt, M.; Roedig, M.; Spieker, C.

    1986-01-01

    Whereas the lead concentrations were increased in brain tissue of patients with chronic alcoholism, the aluminum concentrations remained within the normal range. The magnesium concentrations were found decreased in patients with chronic alcoholism compared to normal controls. The sources for the elevated lead levels seem to be the increased intake of alcohol. The decreased magnesium levels are probably caused by an increased loss of magnesium with the urine, malnutrition, malabsorption, hormonal factors and drugs. Various neurological disorders which often accompanied chronic alcoholism may be caused or aggravated by lead encephalopathy and hypomagnesemia. Therapeutical implications may be the early substitution of magnesium deficiency in chronic alcoholism. 10 references, 5 figures.

  5. The effect of media area on the dust holding capacity of deep pleat HEPA filters

    SciTech Connect

    Dyment, J.; Loughborough, D.

    1997-08-01

    The high potential cost of storage, treatment and disposal of radioactive wastes places a premium on the longevity of installed HEPA filters in situations in radioactive processing facilities where dust capacity is a life determining factor. Previous work investigated the dust holding capacity v pressure drop characteristics of different designs of HEPA filter and also the effect of using graded density papers. This paper records an investigation of the effect of media area variation on the dust holding capacity of the {open_quotes}deep-pleat{close_quotes} design of HEPA filter. As in the previously reported work two test dusts (carbon black and sub micron sodium chloride) in the range (0.15 - 0.4{mu}m) were used. Media area adjustment was effected by varying the number of separators within the range 60 - 90. Results with the coarser dust allowed an optimum media area to be identified. Media areas greater or smaller than this optimum retained less dust than the optimum for the same terminal pressure drop. Conversely with the finer sodium chloride aerosol the dust holding capacity continued to increase up to the maximum area investigated. 7 refs., 4 figs.

  6. A wirelessly controlled implantable LED system for deep brain optogenetic stimulation

    PubMed Central

    Rossi, Mark A.; Go, Vinson; Murphy, Tracy; Fu, Quanhai; Morizio, James; Yin, Henry H.

    2015-01-01

    In recent years optogenetics has rapidly become an essential technique in neuroscience. Its temporal and spatial specificity, combined with efficacy in manipulating neuronal activity, are especially useful in studying the behavior of awake behaving animals. Conventional optogenetics, however, requires the use of lasers and optic fibers, which can place considerable restrictions on behavior. Here we combined a wirelessly controlled interface and small implantable light-emitting diode (LED) that allows flexible and precise placement of light source to illuminate any brain area. We tested this wireless LED system in vivo, in transgenic mice expressing channelrhodopsin-2 in striatonigral neurons expressing D1-like dopamine receptors. In all mice tested, we were able to elicit movements reliably. The frequency of twitches induced by high power stimulation is proportional to the frequency of stimulation. At lower power, contraversive turning was observed. Moreover, the implanted LED remains effective over 50 days after surgery, demonstrating the long-term stability of the light source. Our results show that the wireless LED system can be used to manipulate neural activity chronically in behaving mice without impeding natural movements. PMID:25713516

  7. Induced seismicity caused by hydraulic fracturing in deep geothermal wells in Germany and adjacent areas

    NASA Astrophysics Data System (ADS)

    Plenefisch, Thomas; Brückner, Lisa; Ceranna, Lars; Gestermann, Nicolai; Houben, Georg; Tischner, Torsten; Wegler, Ulrich; Wellbrink, Matthias; Bönnemann, Christian; Bertram, Andreas; Kirschbaum, Bernd

    2016-04-01

    Recently, the BGR has worked out a study on the potential environmental impact caused by hydraulic fracturing or chemical stimulations in deep geothermal reservoirs in Germany and adjacent areas. The investigations and analyses are based on existing studies and information provided by operators. The two environmental impacts being essentially considered in the report are induced seismicity and possible contamination of the groundwater reservoirs which serve for drinking water supply. Altogether, in this study, information on 30 hydraulic frac operations and 26 chemical stimulations including information from neighboring countries were compiled and analyzed. Out of the hydraulic stimulations two thirds were carried out as waterfracs and one third as fracturing with proppants. Parameters used in the study to characterize the induced seismicity are maximum magnitude, number of seismic events, size of the seismically active volume, and the relation of this volume to fault zones and the cap rock, as well as, finally, the impacts at the Earth's surface. The response of the subsurface to hydraulic fracturing is variable: There are some activities, which cause perceptible seismic events, others, where no perceptible but instrumentally detected events occurred, and moreover activities without even any instrumentally detected events. A classification of seismic hazard with respect to tectonic region, geology, or depth of the layer is still difficult, since the number of hydraulic fracturing measures in deep geothermal wells is small making a statistically sound analysis impossible. However, there are some indications, that hydraulic fracturing in granite in tectonically active regions like the Upper Rhine Graben results in comparatively stronger, perceptible seismicity compared to hydraulic fracturing in the sedimentary rocks of the North German basin. The maximum magnitudes of induced earthquakes caused by hydraulic fracturing of deep geothermal wells in Germany are

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

    PubMed

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

    2016-01-01

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

  9. Capgras Syndrome in a Patient with Parkinson's Disease after Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Case Report

    PubMed Central

    Kyrtsos, Christina Rose; Stahl, Mark C.; Eslinger, Paul; Subramanian, Thyagarajan; Lucassen, Elisabeth B.

    2015-01-01

    Capgras syndrome is a delusional misidentification syndrome (DMS) which can be seen in neurodegenerative diseases such as Lewy body dementia and, to a lesser extent, in Parkinson's disease (PD). Here, we report the case of a 78-year-old man with a history of idiopathic PD who developed Capgras syndrome following bilateral subthalamic nucleus deep brain stimulation (DBS) implantation. As the risk of DMS has been related to deficits in executive, memory, and visuospatial function preoperatively, this case highlights the importance of continuing to improve patient selection for DBS surgery. Capgras syndrome is a rare potential complication of DBS surgery in PD patients with preexisting cognitive decline. PMID:26078747

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

    PubMed Central

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