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Sample records for directional migration stimulated

  1. Hypoxia stimulates invasion and migration of human cervical cancer ...

    Indian Academy of Sciences (India)

    Here we show that hypoxiaincreases tumour cell invasion and migration by the modulation of Rab11, an important molecule for vesicular trafficking.In our study, we found that Rab11, together with the activation of Rac1, could stimulate invasion and migration of cervicalcancer cell lines HeLa/SiHa in hypoxia. Activation of ...

  2. Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes

    Science.gov (United States)

    Clatworthy, Menna R.; Aronin, Caren E. Petrie; Mathews, Rebeccah J.; Morgan, Nicole; Smith, Kenneth G.C.; Germain, Ronald N.

    2014-01-01

    Antibodies are critical for defence against a variety of microbes but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). DCs are important antigen presenting cells and play a central role in inducing antigen-specific tolerance or immunity1,2. Following antigen acquisition in peripheral tissues, DCs migrate to draining lymph nodes via lymphatics to present antigen to T cells. In this study we demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC-stimulated murine and human DCs showed enhanced directional migration in a CCL19 gradient and increased CCR7 expression. Using intravital two-photon microscopy, we observed that local administration of IC resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. These observations have relevance to autoimmunity, because autoantibody-containing serum from mice and humans with SLE also increased dermal DC migration to lymph nodes in vivo, suggesting that this process may occur in lupus, potentially driving the inappropriate localisation of autoantigen-bearing DCs. PMID:25384086

  3. Analysis of primary cilia in directional cell migration in fibroblasts

    DEFF Research Database (Denmark)

    Christensen, Søren Tvorup; Veland, Iben; Schwab, Albrecht

    2013-01-01

    summarize selected methods in analyzing ciliary function in directional cell migration, including immunofluorescence microscopy, scratch assay, and chemotaxis assay by micropipette addition of PDGFRα ligands to cultures of fibroblasts. These methods should be useful not only in studying cell migration....... In particular, platelet-derived growth factor receptor alpha (PDGFRα) is compartmentalized to the primary cilium to activate signaling pathways that regulate reorganization of the cytoskeleton required for lamellipodium formation and directional migration in the presence of a specific ligand gradient. We...

  4. Transcranial Direct Current Stimulation in Epilepsy.

    Science.gov (United States)

    San-Juan, Daniel; Morales-Quezada, León; Orozco Garduño, Adolfo Josué; Alonso-Vanegas, Mario; González-Aragón, Maricarmen Fernández; Espinoza López, Dulce Anabel; Vázquez Gregorio, Rafael; Anschel, David J; Fregni, Felipe

    2015-01-01

    Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation therapy in epilepsy with conflicting results in terms of efficacy and safety. Review the literature about the efficacy and safety of tDCS in epilepsy in humans and animals. We searched studies in PubMed, MedLine, Scopus, Web of Science and Google Scholar (January 1969 to October 2013) using the keywords 'transcranial direct current stimulation' or 'tDCS' or 'brain polarization' or 'galvanic stimulation' and 'epilepsy' in animals and humans. Original articles that reported tDCS safety and efficacy in epileptic animals or humans were included. Four review authors independently selected the studies, extracted data and assessed the methodological quality of the studies using the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines and Jadad Scale. A meta-analysis was not possible due to methodological, clinical and statistical heterogeneity of included studies. We analyzed 9 articles with different methodologies (3 animals/6 humans) with a total of 174 stimulated individuals; 109 animals and 65 humans. In vivo and in vitro animal studies showed that direct current stimulation can successfully induce suppression of epileptiform activity without neurological injury and 4/6 (67%) clinical studies showed an effective decrease in epileptic seizures and 5/6 (83%) reduction of inter-ictal epileptiform activity. All patients tolerated tDCS well. tDCS trials have demonstrated preliminary safety and efficacy in animals and patients with epilepsy. Further larger studies are needed to define the best stimulation protocols and long-term follow-up. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Transnational nurse migration: future directions for medical anthropological research.

    Science.gov (United States)

    Prescott, Megan; Nichter, Mark

    2014-04-01

    Transnational nurse migration is a serious global health issue in which inequitably distributed shortages hinder health and development goals. This article selectively reviews the literature on nurse migration that has emerged from nursing, health planning, and the social sciences and offers productive directions for future anthropological research. The literature on global nurse migration has largely focused on push/pull economic logic and the concept of brain drain to understand the causes and effects of nurse migration. These concepts obscure political-economic, historical, and cultural factors that pattern nurse migration and influence the complex effects of nurse migration. Global nurse care chain analysis helps illuminate the numerous nodes in the production and migration of nurses, and management of this transnational process. Examples are provided from the Philippines and India to illustrate ways in which this analysis may be deepened, refined and rendered more critical by anthropological research. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Directional Cell Migration in Response to Repeated Substratum Stretching

    Science.gov (United States)

    Okimura, Chika; Iwadate, Yoshiaki

    2017-10-01

    Crawling migration plays an essential role in a variety of biological phenomena, including development, wound healing, and immune system function. Migration properties such as anterior-posterior polarity, directionality, and velocity are regulated not only by the reception of a chemoattractant but also by sensing mechanical inputs from the external environment. In this review, we describe the mechanical response of migrating cells, particularly under repeated stretching of the elastic substratum, highlighting the fact that there appear to be two independent mechanosensing systems that generate the polarity needed for migration. Cells that have no stress fibers, such as Dictyostelium cells and neutrophil-like differentiated HL-60 cells, migrate perpendicular to the stretching direction via myosin II localization. Cells that do possess stress fibers, however, such as fish keratocytes, migrate parallel to the stretching via a stress-fiber-dependent process.

  7. Silk Film Topography Directs Collective Epithelial Cell Migration

    Science.gov (United States)

    Rosenblatt, Mark I.

    2012-01-01

    The following study provides new insight into how surface topography dictates directed collective epithelial cell sheet growth through the guidance of individual cell movement. Collective cell behavior of migrating human corneal limbal-epithelial cell sheets were studied on highly biocompatible flat and micro-patterned silk film surfaces. The silk film edge topography guided the migratory direction of individual cells making up the collective epithelial sheet, which resulted in a 75% increase in total culture elongation. This was due to a 3-fold decrease in cell sheet migration rate efficiency for movement perpendicular to the topography edge. Individual cell migration direction is preferred in the parallel approach to the edge topography where localization of cytoskeletal proteins to the topography’s edge region is reduced, which results in the directed growth of the collective epithelial sheet. Findings indicate customized biomaterial surfaces may be created to direct both the migration rate and direction of tissue epithelialization. PMID:23185573

  8. Proinflammatory mediators stimulate neutrophil-directed angiogenesis.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Vascular endothelial growth factor (VEGF; vascular permeability factor) is one of the most potent proangiogenic cytokines, and it plays a central role in mediating the process of angiogenesis or new blood vessel formation. Neutrophils (PMNs) recently have been shown to produce VEGF. HYPOTHESIS: The acute inflammatory response is a potent stimulus for PMN-directed angiogenesis. METHODS: Neutrophils were isolated from healthy volunteers and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and anti-human Fas monoclonal antibody. Culture supernatants were assayed for VEGF using enzyme-linked immunosorbent assays. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs were then added to human umbilical vein endothelial cells and human microvessel endothelial cells and assessed for endothelial cell proliferation using 5-bromodeoxyuridine labeling. Tubule formation was also assessed on MATRIGEL basement membrane matrix. Neutrophils were lysed to measure total VEGF release, and VEGF expression was detected using Western blot analysis. RESULTS: Lipopolysaccharide and TNF-alpha stimulation resulted in significantly increased release of PMN VEGF (532+\\/-49 and 484+\\/-80 pg\\/mL, respectively; for all, presented as mean +\\/- SEM) compared with control experiments (32+\\/-4 pg\\/mL). Interleukin 6 and Fas had no effect. Culture supernatants from LPS- and TNF-alpha-stimulated PMNs also resulted in significant increases (P<.005) in macrovascular and microvascular endothelial cell proliferation and tubule formation. Adding anti-human VEGF-neutralizing polyclonal antibody to stimulated PMN supernatant inhibited these effects. Total VEGF release following cell lysis and Western blot analysis suggests that the VEGF is released from an intracellular store. CONCLUSION: Activated human PMNs are directly angiogenic by releasing VEGF, and this has important implications for inflammation, capillary leak syndrome

  9. Electric Signals Regulate the Directional Migration of Oligodendrocyte Progenitor Cells (OPCs via β1 Integrin

    Directory of Open Access Journals (Sweden)

    Bangfu Zhu

    2016-11-01

    Full Text Available The guided migration of neural cells is essential for repair in the central nervous system (CNS. Oligodendrocyte progenitor cells (OPCs will normally migrate towards an injury site to re-sheath demyelinated axons; however the mechanisms underlying this process are not well understood. Endogenous electric fields (EFs are known to influence cell migration in vivo, and have been utilised in this study to direct the migration of OPCs isolated from neonatal Sprague-Dawley rats. The OPCs were exposed to physiological levels of electrical stimulation, and displayed a marked electrotactic response that was dependent on β1 integrin, one of the key subunits of integrin receptors. We also observed that F-actin, an important component of the cytoskeleton, was re-distributed towards the leading edge of the migrating cells, and that this asymmetric rearrangement was associated with β1 integrin function.

  10. Exploration of molecular pathways mediating electric field-directed Schwann cell migration by RNA-Seq

    Science.gov (United States)

    Yao, Li; Li, Yongchao; Knapp, Jennifer; Smith, Peter

    2015-01-01

    In peripheral nervous systems, Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. Following spinal cord injury, Schwann cells regenerate and migrate to the lesion and are involved in the spinal cord regeneration process. Transplantation of Schwann cells into injured neural tissue results in enhanced spinal axonal regeneration. Effective directional migration of Schwann cells is critical in the neural regeneration process. In this study, we report that Schwann cells migrate anodally in an applied electric field (EF). The directedness and displacement of anodal migration increased significantly when the strength of the EF increased from 50 mV/mm to 200 mV/mm. The EF did not significantly affect the cell migration speed. To explore the genes and signaling pathways that regulate cell migration in EFs, we performed a comparative analysis of differential gene expression between cells stimulated with an EF (100 mV/mm) and those without using next-generation RNA sequencing, verified by RT-qPCR. Based on the cut-off criteria (FC > 1.2, q cells versus EF-stimulated cells. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found that compared to the control group, 21 pathways are down-regulated, while 10 pathways are up-regulated. Differentially expressed genes participate in multiple cellular signaling pathways involved in the regulation of cell migration, including pathways of regulation of actin cytoskeleton, focal adhesion, and PI3K-Akt. PMID:25557037

  11. Comments in reply: new directions in migration research.

    Science.gov (United States)

    Shaw, R P

    1986-01-01

    The author comments on a review of his recent book NEW DIRECTIONS IN MIGRATION RESEARCH and reflects on theory and model specification, problems of estimation and statistical inference, realities of temporal and spatial heterogeneity, choices of explanatory variables, and the importance of broader political issues in migration studies. A core hypothesis is that market forces have declined as influences on internal migration in Canada over the last 30 years. Theoretical underpinnings include declining relevance of wage considerations in the decision to migrate on the assumption that marginal utility of money diminishes and marginal utility of leisure increases as society becomes wealthier. The author perceives the human capital model to have limitations and is especially troubled by the "as if" clause--that all migrants behave "as if" they calculate benefits and risks with equal rigor. The author has "shadowed" and not quantified the costs involved. He implies that normative frameworks for future migration research and planning should be established.

  12. Foreign Direct Investments and the New Migration Pattern for Europe

    Directory of Open Access Journals (Sweden)

    Ana María Aragonés

    2012-04-01

    Full Text Available The present paper explores the relationship between Foreign Direct Investments (FDI and immigrant workers. Two different groups of countries are compared: traditional host (United Kingdom, France and Germany and new host (Spain, Portugal and Ireland EU Member States, in order to highlight that the actual reasons for the flows of immigrants are the needs of international movements of capital. FDI features are studied along with its stimulating impact, mainly on job generation. A comparative approach is used to evaluate both the demographic situation of each country and the difficulties they face to fulfil the gaps in their labour markets as the diminishing native workforce calls for foreign labour. This article primarily focuses on the “pull” factor. Finally, an econometric dynamic panel model is presented; the empirical evidence indicates that the economic-demographic pull factors in the receiving countries like unemployment rate, the real Gross Domestic Product and the inflows of FDI and the ratio of the economically active population over the total population, are significant variables related to the migration flows in both groups of countries, new and traditional.

  13. Transcranial direct current stimulation in psychiatric disorders

    Science.gov (United States)

    Tortella, Gabriel; Casati, Roberta; Aparicio, Luana V M; Mantovani, Antonio; Senço, Natasha; D’Urso, Giordano; Brunelin, Jerome; Guarienti, Fabiana; Selingardi, Priscila Mara Lorencini; Muszkat, Débora; Junior, Bernardo de Sampaio Pereira; Valiengo, Leandro; Moffa, Adriano H; Simis, Marcel; Borrione, Lucas; Brunoni, André R

    2015-01-01

    The interest in non-invasive brain stimulation techniques is increasing in recent years. Among these techniques, transcranial direct current stimulation (tDCS) has been the subject of great interest among researchers because of its easiness to use, low cost, benign profile of side effects and encouraging results of research in the field. This interest has generated several studies and randomized clinical trials, particularly in psychiatry. In this review, we provide a summary of the development of the technique and its mechanism of action as well as a review of the methodological aspects of randomized clinical trials in psychiatry, including studies in affective disorders, schizophrenia, obsessive compulsive disorder, child psychiatry and substance use disorder. Finally, we provide an overview of tDCS use in cognitive enhancement as well as a discussion regarding its clinical use and regulatory and ethical issues. Although many promising results regarding tDCS efficacy were described, the total number of studies is still low, highlighting the need of further studies aiming to replicate these findings in larger samples as to provide a definite picture regarding tDCS efficacy in psychiatry. PMID:25815258

  14. Electrical stimulation enhances cell migration and integrative repair in the meniscus

    Science.gov (United States)

    Yuan, Xiaoning; Arkonac, Derya E.; Chao, Pen-hsiu Grace; Vunjak-Novakovic, Gordana

    2014-01-01

    Electrical signals have been applied towards the repair of articular tissues in the laboratory and clinical settings for over seventy years. We focus on healing of the meniscus, a tissue essential to knee function with limited innate repair potential, which has been largely unexplored in the context of electrical stimulation. Here we demonstrate for the first time that electrical stimulation enhances meniscus cell migration and integrative tissue repair. We optimize pulsatile direct current electrical stimulation parameters on cells at the micro-scale, and apply these to healing of full-thickness defects in explants at the macro-scale. We report increased expression of the adenosine A2b receptor in meniscus cells after stimulation at the micro- and macro-scale, and propose a role for A2bR in meniscus electrotransduction. Taken together, these findings advance our understanding of the effects of electrical signals and their mechanisms of action, and contribute to developing electrotherapeutic strategies for meniscus repair. PMID:24419206

  15. Transcranial Direct Current Stimulation in Neurodegenerative Disease

    Directory of Open Access Journals (Sweden)

    Argye E. Hillis

    2014-04-01

    Full Text Available We review rationale, challenges, study designs, reported results, and future directions in the use of transcranial direct cranial stimulation (tDCS in neurodegenerative disease, focusing on treatment of spelling in primary progressive aphasia (PPA. Rationale Evidence from both animal studies and human studies indicates that anodal and cathodal tDCS over the brain result in a temporary change in membrane potentials, reducing the threshold for long-term potentiation of neurons in the affected area. This may allow unaffected brain regions to assume functions of diseased regions. Challenges Special challenges in treating individuals with progressive conditions include altered goals of treatment and the possibility that participants may accumulate new deficits over the course of the treatment program that interfere with their ability to understand, retain, or cooperate with aspects of the program. The most serious challenge – particularly for single case designs - is that there may be no stable baseline against which to measure change with treatment. Thus, it is essential to demonstrate that treatment results in a statistically significant change in the slope of decline or improvement. Therefore, demonstration of a significant difference between tDCS and control (sham requires either a large number of participants or a large effect size. Designs The choice of a treatment design reflects these limitations. Group studies with a randomized, double-blind, sham control trial design (without cross-over provide the greatest power to detect a difference between intervention and control conditions, with the fewest participants. A cross-over design, in which all participants (from 1 to many receive both active and sham conditions, in randomized order, requires a larger effect size for the active condition relative to the control condition (or little to no maintenance of treatment gains or carry-over effect to show significant differences between treatment

  16. p21-Activated kinase (PAK regulates cytoskeletal reorganization and directional migration in human neutrophils.

    Directory of Open Access Journals (Sweden)

    Asako Itakura

    Full Text Available Neutrophils serve as a first line of defense in innate immunity owing in part to their ability to rapidly migrate towards chemotactic factors derived from invading pathogens. As a migratory function, neutrophil chemotaxis is regulated by the Rho family of small GTPases. However, the mechanisms by which Rho GTPases orchestrate cytoskeletal dynamics in migrating neutrophils remain ill-defined. In this study, we characterized the role of p21-activated kinase (PAK downstream of Rho GTPases in cytoskeletal remodeling and chemotactic processes of human neutrophils. We found that PAK activation occurred upon stimulation of neutrophils with f-Met-Leu-Phe (fMLP, and PAK accumulated at the actin-rich leading edge of stimulated neutrophils, suggesting a role for PAK in Rac-dependent actin remodeling. Treatment with the pharmacological PAK inhibitor, PF3758309, abrogated the integrity of RhoA-mediated actomyosin contractility and surface adhesion. Moreover, inhibition of PAK activity impaired neutrophil morphological polarization and directional migration under a gradient of fMLP, and was associated with dysregulated Ca(2+ signaling. These results suggest that PAK serves as an important effector of Rho-family GTPases in neutrophil cytoskeletal reorganization, and plays a key role in driving efficient directional migration of human neutrophils.

  17. Measuring directional urban spatial interaction in China: A migration perspective.

    Science.gov (United States)

    Li, Fangzhou; Feng, Zhiming; Li, Peng; You, Zhen

    2017-01-01

    The study of urban spatial interaction is closely linked to that of economic geography, urban planning, regional development, and so on. Currently, this topic is generating a great deal of interest among researchers who are striving to find accurate ways to measure urban spatial interaction. Classical spatial interaction models lack theoretical guidance and require complicated parameter-adjusting processes. The radiation model, however, as proposed by Simini et al. with rigorous formula derivation, can simulate directional urban spatial interaction. We applied the radiation model in China to simulate the directional migration number among 337 nationwide research units, comprising 4 municipalities and 333 prefecture-level cities. We then analyzed the overall situation in Chinese cities, the interaction intensity hierarchy, and the prime urban agglomerations from the perspective of migration. This was done to ascertain China's urban spatial interaction and regional development from 2000 to 2010 to reveal ground realities.

  18. Cellular Mechanisms of Transcranial Direct Current Stimulation

    Science.gov (United States)

    2016-07-14

    fEPSP responses are significantly (P < 0.05, *) facilitated with +8 V/m fields ( left ) and reduced with -8 V/m ( right ) in three pathways. In each...cortex results in a sustained modulation of synaptic efficacy. A) Schematic of anodal ( left ) and cathodal ( right ) DCS with current flow along the...current stimulation (tDCS) delivered 1day vs . 1week after cerebral ischemia in rats. Brain Res. Zimerman M, Nitsch M, Giraux P, Gerloff C, Cohen LG

  19. Annexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions.

    Directory of Open Access Journals (Sweden)

    Valentina Bizzarro

    Full Text Available Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we have evaluated whether Annexin A1 derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions. Using normal human skin fibroblasts WS1 in low glucose (LG or high glucose (HG we observed the enrichment of Annexin A1 protein at cell movement structures like lamellipodial extrusions and interestingly, a significant decrease in levels of the protein in HG conditions. The analysis of the translocation of Annexin A1 to cell membrane showed lower levels of Annexin A1 in both membrane pool and supernatants of WS1 cells treated with HG. Wound-healing assays using cell line transfected with Annexin A1 siRNAs indicated a slowing down in migration speed of cells suggesting that Annexin A1 has a role in the migration of WS1 cells. In order to analyze the role of extracellular Annexin A1 in cell migration, we have performed wound-healing assays using Ac2-26 showing that peptide was able to increase fibroblast cell migration in HG conditions. Experiments on the mobilization of intracellular calcium and analysis of p-ERK expression confirmed the activity of the FPR1 following stimulation with the peptide Ac2-26. A wound-healing assay on WS1 cells in the presence of the FPR agonist fMLP, of the FPR antagonist CsH and in the presence of Ac2-26 indicated that Annexin A1 influences fibroblast cell migration under HG conditions acting through FPR receptors whose expression was slightly increased in HG. In conclusion, these data demonstrate that (i Annexin A1 is involved in migration of WS1 cells, through interaction with FPRs; (ii N- terminal peptide of Annexin A1 Ac2-26 is able to stimulate direct migration of WS1 cells in high glucose treatment possibly due to the increased receptor expression observed in hyperglycemia conditions.

  20. Stimulating thought: a functional MRI study of transcranial direct current stimulation in schizophrenia.

    Science.gov (United States)

    Orlov, Natasza D; O'Daly, Owen; Tracy, Derek K; Daniju, Yusuf; Hodsoll, John; Valdearenas, Lorena; Rothwell, John; Shergill, Sukhi S

    2017-09-01

    Individuals with schizophrenia typically suffer a range of cognitive deficits, including prominent deficits in working memory and executive function. These difficulties are strongly predictive of functional outcomes, but there is a paucity of effective therapeutic interventions targeting these deficits. Transcranial direct current stimulation is a novel neuromodulatory technique with emerging evidence of potential pro-cognitive effects; however, there is limited understanding of its mechanism. This was a double-blind randomized sham controlled pilot study of transcranial direct current stimulation on a working memory (n-back) and executive function (Stroop) task in 28 individuals with schizophrenia using functional magnetic resonance imaging. Study participants received 30 min of real or sham transcranial direct current stimulation applied to the left frontal cortex. The 'real' and 'sham' groups did not differ in online working memory task performance, but the transcranial direct current stimulation group demonstrated significant improvement in performance at 24 h post-transcranial direct current stimulation. Transcranial direct current stimulation was associated with increased activation in the medial frontal cortex beneath the anode; showing a positive correlation with consolidated working memory performance 24 h post-stimulation. There was reduced activation in the left cerebellum in the transcranial direct current stimulation group, with no change in the middle frontal gyrus or parietal cortices. Improved performance on the executive function task was associated with reduced activity in the anterior cingulate cortex. Transcranial direct current stimulation modulated functional activation in local task-related regions, and in more distal nodes in the network. Transcranial direct current stimulation offers a potential novel approach to altering frontal cortical activity and exerting pro-cognitive effects in schizophrenia. © The Author (2017). Published by Oxford

  1. A new technique of "midline anchoring" in spinal cord stimulation dramatically reduces lead migration.

    Science.gov (United States)

    Mironer, Y Eugene; Brown, Christopher; Satterthwaite, John R; Cohen, Mary; Tonder, Lisa M; Grumman, Steve

    2004-01-01

    Spinal cord stimulation (SCS) is a popular method of treatment of chronic pain. Unfortunately, migration of the lead continues to be a serious complication of this therapy. In an attempt to reduce lateral migration of the SCS lead, we performed a retrospective assessment of a new technique of percutaneous lead placement. This new method of "midline anchoring" of the lead using the plica mediana dorsalis was tested against conventional technique in a retrospective study involving 122 trials and 91 implants of SCS over a period of five years. The use of "midline anchoring" resulted in a decrease in lead migration from 23% to 6% after trial insertion and from 24% to 7% after implantation. We conclude that "midline anchoring" of the SCS lead is an effective method of preventing lead migration.

  2. Transcranial Direct Current Stimulation Improves Audioverbal Memory in Stroke Patients.

    Science.gov (United States)

    Kazuta, Toshinari; Takeda, Kotaro; Osu, Rieko; Tanaka, Satoshi; Oishi, Ayako; Kondo, Kunitsugu; Liu, Meigen

    2017-08-01

    The aim of this study was to investigate whether anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance in stroke patients. Twelve stroke patients with audioverbal memory impairment participated in a single-masked, crossover, and sham-controlled experiment. The anodal or sham transcranial direct current stimulation was applied during the Rey Auditory Verbal Learning Test, which evaluates the ability to recall a list of 15 heard words over five trials. The number of correctly recalled words was compared between the anodal and sham conditions and the influence of transcranial direct current stimulation on serial position effect of the 15 words was also examined. The increase in the number of correctly recalled words from the first to the fifth trial was significantly greater in the anodal condition than in the sham condition (P transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance and induced the primacy effect in stroke patients.

  3. Macrophage migration inhibitory factor stimulated by Helicobacter pylori increases proliferation of gastric epithelial cells

    Science.gov (United States)

    Xia, Harry Hua-Xiang; Lam, Shiu Kum; Chan, Annie O.O.; Lin, Marie Chia Mi; Kung, Hsiang Fu; Ogura, Keiji; Berg, Douglas E.; Wong, Benjamin C. Y.

    2005-01-01

    AIM: Helicobacter pylori (H pylori) is associated with increased gastric inflammatory and epithelial expression of macrophage migration inhibitory factor (MIF) and gastric epithelial cell proliferation. This study aimed at determining whether H pylori directly stimulates release of MIF in monocytes, whether the cag pathogenicity island (PAI) is involved for this function, and whether MIF stimulated by H pylori increases gastric epithelial cell proliferation in vitro. METHODS: A cytotoxic wild-type H pylori strain (TN2)and its three isogenic mutants (TN2△cag, TN2△cagA and TN2△cagE) were co-cultured with cells of a human monocyte cell line, THP-1, for 24 h at different organism/cell ratios. MIF in the supernatants was measured by an ELISA. Cells of a human gastric cancer cell line, MKN45, were then co-cultured with the supernatants, with and without monoclonal anti-MIF antibody for 24 h. The cells were further incubated for 12 h after addition of 3H-thymidine, and the levels of incorporation of 3H-thymidine were measured with a liquid scintillation counter. RESULTS: The wild-type strain and the isogenic mutants, TN2△cagA and TN2△cagE, increased MIF release at organism/cell ratios of 200/1 and 400/1, but not at the ratios of 50/1 and 100/1. However, the mutant TN2△cag did not increase the release of MIF at any of the four ratios. 3H-thymidine readings for MKN-45 cells were significantly increased with supernatants derived from the wild-type strain and the mutants TN2△cagA and TN2△cagE, but not from the mutant TN2△cag. Moreover, in the presence of monoclonal anti-MIF antibody, the stimulatory effects of the wild-type strain on cell proliferation disappeared. CONCLUSION: H pylori stimulates MIF release in monocytes, likely through its cag PAI, but not related to cagA or cagE. H pylori-stimulated monocyte culture supernatant increases gastric cell proliferation, which is blocked by anti-MIF antibody, suggesting that MIF plays an important role in H

  4. Luteolin Inhibits Angiotensin II-Stimulated VSMC Proliferation and Migration through Downregulation of Akt Phosphorylation

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    Tongda Xu

    2015-01-01

    Full Text Available Luteolin is a naturally occurring flavonoid found in many plants that possesses cardioprotective properties. The purpose of this study was to elucidate the effect of luteolin on vascular smooth muscle cells (VSMCs proliferation and migration induced by Angiotensin II (Ang II and to investigate the mechanism(s of action of this compound. Rat VSMCs were cultured in vitro, and the proliferation and migration of these cells following Ang II stimulation were monitored. Different doses of luteolin were added to VSMC cultures, and the proliferation and migration rate were observed by MTT and Transwell chamber assays, respectively. In addition, the expressions of p-Akt (308, p-Akt (473, and proliferative cell nuclear antigen (PCNA in VSMCs were monitored by Western blotting. This study demonstrated that luteolin has an inhibitory effect on Ang II-induced VSMC proliferation and migration. Further, the levels of p-Akt (308, p-Akt (473, and PCNA were reduced in VSMCs treated with both Ang II and luteolin compared to VSMCs treated with only Ang II. These findings strongly suggest that luteolin inhibits Ang II-stimulated proliferation and migration of VSMCs, which is partially due to downregulation of the Akt signaling pathway.

  5. The Activity of the Neutral Sphingomyelinase Is Important in T Cell Recruitment and Directional Migration

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    Lena Collenburg

    2017-08-01

    Full Text Available Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation and co-stimulation in a spatiotemporally controlled manner, the neutral sphingomyelinase (NSM has proven to be important in T cell activation, where it appears to play a particularly important role in cytoskeletal reorganization and cell polarization. Because these are important parameters in directional T cell migration and motility in tissues, we analyzed the role of the NSM in these processes. Pharmacological inhibition of NSM interfered with early lymph node homing of T cells in vivo indicating that the enzyme impacts on endothelial adhesion, transendothelial migration, sensing of chemokine gradients or, at a cellular level, acquisition of a polarized phenotype. NSM inhibition reduced adhesion of T cells to TNF-α/IFN-γ activated, but not resting endothelial cells, most likely via inhibiting high-affinity LFA-1 clustering. NSM activity proved to be highly important in directional T cell motility in response to SDF1-α, indicating that their ability to sense and translate chemokine gradients might be NSM dependent. In fact, pharmacological or genetic NSM ablation interfered with T cell polarization both at an overall morphological level and redistribution of CXCR4 and pERM proteins on endothelial cells or fibronectin, as well as with F-actin polymerization in response to SDF1-α stimulation, indicating that efficient directional perception and signaling relay depend on NSM activity. Altogether, these data support a central role of the NSM in T cell recruitment and migration both under homeostatic and inflamed conditions by regulating polarized redistribution of receptors and their coupling to the cytoskeleton.

  6. Fibroin and sericin from Bombyx mori silk stimulate cell migration through upregulation and phosphorylation of c-Jun.

    Directory of Open Access Journals (Sweden)

    Celia Martínez-Mora

    Full Text Available Wound healing is a biological process directed to the restoration of tissue that has suffered an injury. An important phase of wound healing is the generation of a basal epithelium able to wholly replace the epidermis of the wound. A broad range of products derived from fibroin and sericin from Bombyx mori silk are used to stimulate wound healing. However, so far the molecular mechanism underlying this phenomenon has not been elucidated. The aim of this work was to determine the molecular basis underlying wound healing properties of silk proteins using a cell model. For this purpose, we assayed fibroin and sericin in a wound healing scratch assay using MDA-MB-231 and Mv1Lu cells. Both proteins stimulated cell migration. Furthermore, treatment with sericin and fibroin involved key factors of the wound healing process such as upregulation of c-Jun and c-Jun protein phosphorylation. Moreover, fibroin and sericin stimulated the phosphorylation of ERK 1/2 and JNK 1/2 kinases. All these experiments were done in the presence of specific inhibitors for some of the cell signalling pathways referred above. The obtained results revealed that MEK, JNK and PI3K pathways are involved in fibroin and sericin stimulated cells migration. Inhibition of these three kinases prevented c-Jun upregulation and phosphorylation by fibroin or sericin. Fibroin and sericin were tested in the human keratinocyte cell line, HaCaT, with similar results. Altogether, our results showed that fibroin and sericin initiate cell migration by activating the MEK, JNK and PI3K signalling pathways ending in c-Jun activation.

  7. Burn injury reduces neutrophil directional migration speed in microfluidic devices.

    Directory of Open Access Journals (Sweden)

    Kathryn L Butler

    2010-07-01

    Full Text Available Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72-120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions.

  8. Tamarind Seed Xyloglucans Promote Proliferation and Migration of Human Skin Cells through Internalization via Stimulation of Proproliferative Signal Transduction Pathways

    Directory of Open Access Journals (Sweden)

    W. Nie

    2013-01-01

    Full Text Available Xyloglucans (XGs of Tamarindus indica L. Fabaceae are used as drug vehicles or as ingredients of cosmetics. Two xyloglucans were extracted from T. indica seed with cold water (TSw and copper complex precipitation (TSc. Both were analyzed in regard to composition and influence on cell viability, proliferation, cell cycle progression, migration, MAPK phosphorylation, and gene expression of human skin keratinocytes (NHEK and HaCaT and fibroblasts (NHDF in vitro. TSw and TSc differed in molecular weight, rhamnose content, and ratios of xylose, arabinose, galactose, and glucose. Both XGs improved keratinocytes and fibroblast proliferation, promoted the cell cycle, and stimulated migration and intracellular enzyme activity of NHDF after endosomal uptake. Only TSw significantly enhanced HaCaT migration and extracellular enzyme activity of NHDF and HaCaT. TSw and TSc predominantly enhanced the phosphorylation of molecules that referred to Erk signaling in NHEK. In NHDF parts of the integrin signaling and SAPK/JNK pathway were affected. Independent of cell type TSw marginally regulated the expression of genes, which referred to membrane proteins, cytoskeleton, cytokine signaling, and ECM as well as to processes of metabolism and transcription. Results show that T. indica xyloglucans promote skin regeneration by a direct influence on cell proliferation and migration.

  9. Transcranial direct-current stimulation as treatment in epilepsy.

    Science.gov (United States)

    Gschwind, Markus; Seeck, Margitta

    2016-12-01

    Neuromodulation (NM) is a complementary therapy for patients with drug-resistant epilepsy. Vagal nerve stimulation and deep brain stimulation of the anterior thalamus are established techniques and have shown their efficacy in lowering seizure frequency, but they are invasive and rarely render patients seizure-free. Non-invasive NM techniques are therefore increasingly investigated in a clinical context. Areas covered: Current knowledge about transcranial direct-current stimulation (tDCS) and other non-invasive NM in patients with epilepsy, based on the available animal and clinical studies from PubMed search. Expert commentary: tDCS modulates neuronal membrane potentials, and consequently alters cortical excitability. Cathodal stimulation leads to cortical inhibition, which is of particular importance in epilepsy treatment. The antiepileptic efficacy is promising but still lacks systematic studies. The beneficial effect, seen in ~20%, outlasts the duration of stimulation, indicating neuronal plasticity and is therefore of great interest to obtain long-term effects.

  10. Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway.

    Science.gov (United States)

    Mizoguchi, Takamasa; Ikeda, Shoko; Watanabe, Saori; Sugawara, Michiko; Itoh, Motoyuki

    2017-10-31

    Persistent directional cell migration is involved in animal development and diseases. The small GTPase Rac1 is involved in F-actin and focal adhesion dynamics. Local Rac1 activity is required for persistent directional migration, whereas global, hyperactivated Rac1 enhances random cell migration. Therefore, precise control of Rac1 activity is important for proper directional cell migration. However, the molecular mechanism underlying the regulation of Rac1 activity in persistent directional cell migration is not fully understood. Here, we show that the ubiquitin ligase mind bomb 1 (Mib1) is involved in persistent directional cell migration. We found that knockdown of MIB1 led to an increase in random cell migration in HeLa cells in a wound-closure assay. Furthermore, we explored novel Mib1 substrates for cell migration and found that Mib1 ubiquitinates Ctnnd1. Mib1-mediated ubiquitination of Ctnnd1 K547 attenuated Rac1 activation in cultured cells. In addition, we found that posterior lateral line primordium cells in the zebrafish mib1 ta52b mutant showed increased random migration and loss of directional F-actin-based protrusion formation. Knockdown of Ctnnd1 partially rescued posterior lateral line primordium cell migration defects in the mib1 ta52b mutant. Taken together, our data suggest that Mib1 plays an important role in cell migration and that persistent directional cell migration is regulated, at least in part, by the Mib1-Ctnnd1-Rac1 pathway. Published under the PNAS license.

  11. TRPV2 mediates adrenomedullin stimulation of prostate and urothelial cancer cell adhesion, migration and invasion.

    Directory of Open Access Journals (Sweden)

    Agathe Oulidi

    Full Text Available Adrenomedullin (AM is a 52-amino acid peptide initially isolated from human pheochromocytoma. AM is expressed in a variety of malignant tissues and cancer cell lines and was shown to be a mitogenic factor capable of stimulating growth of several cancer cell types. In addition, AM is a survival factor for certain cancer cells. Some data suggest that AM might be involved in the progression cancer metastasis via angiogenesis and cell migration and invasion control. The Transient Receptor Potential channel TRPV2 is known to promote in prostate cancer cell migration and invasive phenotype and is correlated with the stage and grade of bladder cancer. In this work we show that AM induces prostate and urothelial cancer cell migration and invasion through TRPV2 translocation to plasma membrane and the subsequent increase in resting calcium level.

  12. Sphingosine kinase-1 is a hypoxia-regulated gene that stimulates migration of human endothelial cells

    International Nuclear Information System (INIS)

    Schwalm, Stephanie; Doell, Frauke; Roemer, Isolde; Bubnova, Svetlana; Pfeilschifter, Josef; Huwiler, Andrea

    2008-01-01

    Sphingosine kinases (SK) catalyze the production of sphingosine-1-phosphate which in turn regulates cell responses such as proliferation and migration. Here, we show that exposure of the human endothelial cell line EA.hy 926 to hypoxia stimulates a increased SK-1, but not SK-2, mRNA, protein expression, and activity. This effect was due to stimulated SK-1 promoter activity which contains two putative hypoxia-inducible factor-responsive-elements (HRE). By deletion of one of the two HREs, hypoxia-induced promoter activation was abrogated. Furthermore, hypoxia upregulated the expression of HIF-1α and HIF-2α, and both contributed to SK-1 gene transcription as shown by selective depletion of HIF-1α or HIF-2α by siRNA. The hypoxia-stimulated SK-1 upregulation was functionally coupled to increased migration since the selective depletion of SK-1, but not of SK-2, by siRNAs abolished the migratory response. In summary, these data show that hypoxia upregulates SK-1 activity and results in an accelerated migratory capacity of endothelial cells. SK-1 may thus serve as an attractive therapeutic target to treat diseases associated with increased endothelial migration and angiogenesis such as cancer growth and progression

  13. The Codacs™ direct acoustic cochlear implant actuator: exploring alternative stimulation sites and their stimulation efficiency.

    Science.gov (United States)

    Grossöhmichen, Martin; Salcher, Rolf; Kreipe, Hans-Heinrich; Lenarz, Thomas; Maier, Hannes

    2015-01-01

    This work assesses the efficiency of the Codacs system actuator (Cochlear Ltd., Sydney Australia) in different inner ear stimulation modalities. Originally the actuator was intended for direct perilymph stimulation after stapedotomy using a piston prosthesis. A possible alternative application is the stimulation of middle ear structures or the round window (RW). Here the perilymph stimulation with a K-piston through a stapes footplate (SFP) fenestration (N = 10) as well as stimulation of the stapes head (SH) with a Bell prosthesis (N = 9), SFP stimulation with an Omega/Aerial prosthesis (N = 8) and reverse RW stimulation (N = 10) were performed in cadaveric human temporal bones (TBs). Codacs actuator output is expressed as equivalent sound pressure level (eq. SPL) using RW and SFP displacement responses, measured by Laser Doppler velocimetry as reference. The axial actuator coupling force in stimulation of stapes and RW was adjusted to ~5 mN. The Bell prosthesis and Omega/Aerial prosthesis stimulation generated similar mean eq. SPLs (Bell: 127.5-141.8 eq. dB SPL; Omega/Aerial: 123.6-143.9 eq. dB SPL), being significantly more efficient than K-piston perilymph stimulation (108.6-131.6 eq. dB SPL) and RW stimulation (108.3-128.2 eq. dB SPL). Our results demonstrate that SH, SFP and RW are adequate alternative stimulation sites for the Codacs actuator using coupling prostheses and an axial coupling force of ~5 mN. Based on the eq. SPLs, all investigated methods were adequate for in vivo hearing aid applications, provided that experimental conditions including constant coupling force will be implemented.

  14. The Codacs™ direct acoustic cochlear implant actuator: exploring alternative stimulation sites and their stimulation efficiency.

    Directory of Open Access Journals (Sweden)

    Martin Grossöhmichen

    Full Text Available This work assesses the efficiency of the Codacs system actuator (Cochlear Ltd., Sydney Australia in different inner ear stimulation modalities. Originally the actuator was intended for direct perilymph stimulation after stapedotomy using a piston prosthesis. A possible alternative application is the stimulation of middle ear structures or the round window (RW. Here the perilymph stimulation with a K-piston through a stapes footplate (SFP fenestration (N = 10 as well as stimulation of the stapes head (SH with a Bell prosthesis (N = 9, SFP stimulation with an Omega/Aerial prosthesis (N = 8 and reverse RW stimulation (N = 10 were performed in cadaveric human temporal bones (TBs. Codacs actuator output is expressed as equivalent sound pressure level (eq. SPL using RW and SFP displacement responses, measured by Laser Doppler velocimetry as reference. The axial actuator coupling force in stimulation of stapes and RW was adjusted to ~5 mN. The Bell prosthesis and Omega/Aerial prosthesis stimulation generated similar mean eq. SPLs (Bell: 127.5-141.8 eq. dB SPL; Omega/Aerial: 123.6-143.9 eq. dB SPL, being significantly more efficient than K-piston perilymph stimulation (108.6-131.6 eq. dB SPL and RW stimulation (108.3-128.2 eq. dB SPL. Our results demonstrate that SH, SFP and RW are adequate alternative stimulation sites for the Codacs actuator using coupling prostheses and an axial coupling force of ~5 mN. Based on the eq. SPLs, all investigated methods were adequate for in vivo hearing aid applications, provided that experimental conditions including constant coupling force will be implemented.

  15. Transcutaneous Spinal Direct Current Stimulation (tsDCS

    Directory of Open Access Journals (Sweden)

    Filippo eCogiamanian

    2012-07-01

    Full Text Available In the past ten years renewed interest has centered on non-invasive transcutaneous weak direct currents applied over the scalp to modulate cortical excitability (brain polarization or transcranial direct current stimulation, tDCS. Extensive literature shows that tDCS induces marked changes in cortical excitability that outlast stimulation.Aiming at developing a new, non invasive, approach to spinal cord neuromodulation we assessed the after-effects of thoracic transcutaneous spinal DC stimulation (tsDCS on somatosensory potentials (SEPs evoked in healthy subjects by posterior tibial nerve (PTN stimulation. Our findings showed that thoracic anodal tsDCS depresses the cervico-medullary PTN-SEP component (P30 without eliciting adverse effects. tsDCS also modulates post-activation H-reflex dynamics. Later works further confirmed that transcutaneous electric fields modulate spinal cord function. Subsequent studies in our laboratory showed that tsDCS modulates the flexion reflex in the human lower limb. Besides influencing the laser evoked potentials, tsDCS increases pain tolerance in healthy subjects. Hence, though the underlying mechanisms remain speculative, tsDCS modulates activity in lemniscal, spinothalamic and segmental motor systems.Here we review currently available experimental evidence that non-invasive spinal cord stimulation influences spinal function in humans and argue that, by focally modulating spinal excitability, tsDCS could provide a novel therapeutic tool complementary to drugs and invasive spinal cord stimulation in managing various pathologic conditions, including pain.

  16. Leader Cells Define Directionality of Trunk, but Not Cranial, Neural Crest Cell Migration

    Directory of Open Access Journals (Sweden)

    Jo Richardson

    2016-05-01

    Full Text Available Collective cell migration is fundamental for life and a hallmark of cancer. Neural crest (NC cells migrate collectively, but the mechanisms governing this process remain controversial. Previous analyses in Xenopus indicate that cranial NC (CNC cells are a homogeneous population relying on cell-cell interactions for directional migration, while chick embryo analyses suggest a heterogeneous population with leader cells instructing directionality. Our data in chick and zebrafish embryos show that CNC cells do not require leader cells for migration and all cells present similar migratory capacities. In contrast, laser ablation of trunk NC (TNC cells shows that leader cells direct movement and cell-cell contacts are required for migration. Moreover, leader and follower identities are acquired before the initiation of migration and remain fixed thereafter. Thus, two distinct mechanisms establish the directionality of CNC cells and TNC cells. This implies the existence of multiple molecular mechanisms for collective cell migration.

  17. Transcranial direct current stimulation enhances propulsion during walking

    NARCIS (Netherlands)

    van Asseldonk, Edwin H.F.; Jensen, W.; Andersen, O.K.; Akay, M

    2014-01-01

    Transcranial direct current stimulation (tDCS) has been shown to improve force generation and control in single leg joints in healthy subjects and stroke survivors. However, it is unknown whether these effects also result in improved force production and coordination during walking. Here we

  18. Direct foreign investment: a migration push-factor?

    Science.gov (United States)

    Sassen-koob, S

    1984-01-01

    Policymakers and analysts now recognize that US military activities abroad contribute to the creation of refugee flows into the US. Previously, immigration into the US was viewed as a result of inept and failed domestic policies in the countries of origin. Results show that recent immigrants to the US come from countries with neither the poorest nor the largest population growth rate in the less developed world. However, the sending countries received US direct foreign investment (DFI) in the 1970s, particularly labor intensive investment in export manufacturing. Significant levels and concentrations of DFI promote emigration through: 1) the incorporation of new segments of the population into wage labor and the associated disruption of traditional work structures, 2) the feminization of the new industrial work force and its impact on the work opportunities of men, and 3) the consolidation of objective and ideological links with the highly industrialized countries where most foreign capital originates. The data suggest an examination of the causes of emigration on a much more specific level than that of underdevelopment, poverty, and population growth. These facts carry immediate policy implications for US immigration organizations: 1) if US firms in export processing zones recruited workers from the pool of unemployed--mostly prime-age males--rather than expanding the labor supply by recruiting young women, thereby disrupting unwaged work structures, and 2) if these firms would desist from having high turnover rates among workers, then the migration impact of this type of development would be minimized.

  19. IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration.

    Science.gov (United States)

    Johansson, M W; Khanna, M; Bortnov, V; Annis, D S; Nguyen, C L; Mosher, D F

    2017-10-01

    IL-5 causes suspended eosinophils to polarize with filamentous (F)-actin and granules at one pole and the nucleus in a specialized uropod, the "nucleopod," which is capped with P-selectin glycoprotein ligand-1 (PSGL-1). IL-5 enhances eosinophil adhesion and migration on periostin, an extracellular matrix protein upregulated in asthma by type 2 immunity mediators. Determine how the polarized morphology evolves to foster migration of IL-5-stimulated eosinophils on a surface coated with periostin. Blood eosinophils adhering to adsorbed periostin were imaged at different time points by fluorescent microscopy, and migration of eosinophils on periostin was assayed. After 10 minutes in the presence of IL-5, adherent eosinophils were polarized with PSGL-1 at the nucleopod tip and F-actin distributed diffusely at the opposite end. After 30-60 minutes, the nucleopod had dissipated such that PSGL-1 was localized in a crescent or ring away from the cell periphery, and F-actin was found in podosome-like structures. The periostin layer, detected with monoclonal antibody Stiny-1, shown here to recognize the FAS1 4 module, was cleared in wide areas around adherent eosinophils. Clearance was attenuated by metalloproteinase inhibitors or antibodies to disintegrin metalloproteinase 8 (ADAM8), a major eosinophil metalloproteinase previously implicated in asthma pathogenesis. ADAM8 was not found in podosome-like structures, which are associated with proteolytic activity in other cell types. Instead, immunoblotting demonstrated proteoforms of ADAM8 that lack the cytoplasmic tail in the supernatant. Anti-ADAM8 inhibited migration of IL-5-stimulated eosinophils on periostin. Migrating IL-5-activated eosinophils on periostin exhibit loss of nucleopodal features and appearance of prominent podosomes along with clearance of the Stiny-1 periostin epitope. Migration and epitope clearance are both attenuated by inhibitors of ADAM8. We propose, therefore, that eosinophils remodel and migrate

  20. Frontal transcranial direct current stimulation (tDCS) abolishes list-method directed forgetting.

    Science.gov (United States)

    Silas, Jonathan; Brandt, Karen R

    2016-03-11

    It is a point of controversy as to whether directed forgetting effects are a result of active inhibition or a change of context initiated by the instruction to forget. In this study we test the causal role of active inhibition in directed forgetting. By applying cathodal transcranial direct current stimulation (tDCS) over the right prefrontal cortex we suppressed cortical activity commonly associated with inhibitory control. Participants who underwent real brain stimulation before completing the directed forgetting paradigm showed no directed forgetting effects. Conversely, those who underwent sham brain stimulation demonstrated classical directed forgetting effects. We argue that these findings suggest that inhibition is the primary mechanism that results in directed forgetting costs and benefits. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Determinants of the electric field during transcranial direct current stimulation

    DEFF Research Database (Denmark)

    Opitz, Alexander; Paulus, Walter; Will, Susanne

    2015-01-01

    Transcranial direct current stimulation (tDCS) causes a complex spatial distribution of the electric current flow in the head which hampers the accurate localization of the stimulated brain areas. In this study we show how various anatomical features systematically shape the electric field...... over the motor cortex in small steps to examine the resulting changes of the electric field distribution in the underlying cortex. We examined the effect of skull thickness and composition on the passing currents showing that thinner skull regions lead to higher electric field strengths. This effect...... fluid and the skull, the gyral depth and the distance to the anode and cathode. These factors account for up to 50% of the spatial variation of the electric field strength. Further, we demonstrate that individual anatomical factors can lead to stimulation "hotspots" which are partly resistant...

  2. Navigating a 2D Virtual World using Direct Brain Stimulation

    Directory of Open Access Journals (Sweden)

    Darby M. Losey

    2016-11-01

    Full Text Available Can the human brain learn to interpret inputs from a virtual world delivered directly through brain stimulation? We answer this question by describing the first demonstration of humans playing a computer game utilizing only direct brain stimulation and no other sensory inputs. The demonstration also provides the first instance of artificial sensory information, in this case depth, being delivered directly to the human brain through noninvasive methods. Our approach utilizes transcranial magnetic stimulation (TMS of the human visual cortex to convey binary information about obstacles in a virtual maze. At certain intensities, TMS elicits visual percepts known as phosphenes, which transmits information to the subject about their current location within the maze. Using this computer-brain interface (CBI, five subjects successfully navigated an average of 92% of all the steps in a variety of virtual maze worlds. They also became more accurate in solving the task over time. These results suggest that humans can learn to utilize information delivered directly and noninvasively to their brains to solve tasks that cannot be solved using their natural senses, opening the door to human sensory augmentation and novel modes of human-computer interaction.

  3. Japanese direct investment and its impact on migration in the ASEAN 4.

    Science.gov (United States)

    Ito, S; Iguchi, Y

    1994-01-01

    "The purpose of this article is to show the relationship among Japanese direct investment...,domestic labor markets, and international labor migration in ASEAN-4 countries (Indonesia, Malaysia, Philippines, and Thailand). The effects of foreign direct investment on skilled labor migration are also considered." excerpt

  4. Direct Intracochlear Acoustic Stimulation Using a PZT Microactuator.

    Science.gov (United States)

    Luo, Chuan; Omelchenko, Irina; Manson, Robert; Robbins, Carol; Oesterle, Elizabeth C; Cao, Guo Zhong; Shen, I Y; Hume, Clifford R

    2015-12-01

    Combined electric and acoustic stimulation has proven to be an effective strategy to improve hearing in some cochlear implant users. We describe an acoustic microactuator to directly deliver stimuli to the perilymph in the scala tympani. The 800 µm by 800 µm actuator has a silicon diaphragm driven by a piezoelectric thin film (e.g., lead-zirconium-titanium oxide or PZT). This device could also be used as a component of a bimodal acoustic-electric electrode array. In the current study, we established a guinea pig model to test the actuator for its ability to deliver auditory signals to the cochlea in vivo. The actuator was placed through the round window of the cochlea. Auditory brainstem response (ABR) thresholds, peak latencies, and amplitude growth were calculated for an ear canal speaker versus the intracochlear actuator for tone burst stimuli at 4, 8, 16, and 24 kHz. An ABR was obtained after removal of the probe to assess loss of hearing related to the procedure. In some animals, the temporal bone was harvested for histologic analysis of cochlear damage. We show that the device is capable of stimulating ABRs in vivo with latencies and growth functions comparable to stimulation in the ear canal. Further experiments will be necessary to evaluate the efficiency and safety of this modality in long-term auditory stimulation and its ability to be integrated with conventional cochlear implant arrays. © The Author(s) 2015.

  5. Transcranial Direct Current Stimulation and behavioral models of smoking addiction

    Directory of Open Access Journals (Sweden)

    Paige eFraser

    2012-08-01

    Full Text Available While few studies have applied transcranial direct current stimulation (tDCS to smoking addiction, existing work suggests that the intervention holds promise for altering the complex system by which environmental cues interact with cravings to drive behavior. Imaging and repetitive transcranial magnetic stimulation (rTMS studies suggest that increased dorsolateral prefrontal cortex (DLPFC activation and integrity may be associated with increased resistance to smoking cues. Anodal tDCS of the DLPFC, believed to boost activation, reduces cravings in response to these cues. The finding that noninvasive stimulation modifies cue induced cravings has profound implications for understanding the processes underlying addiction and relapse. TDCS can also be applied to probe mechanisms underlying and supporting nicotine addiction, as was done in a pharmacologic study that applied nicotine, tDCS, and TMS paired associative stimulation to find that stopping nicotine after chronic use induces a reduction in plasticity, causing difficulty in breaking free from association between cues and cravings. This mini-review will place studies that apply tDCS to smokers in the context of research involving the neural substrates of nicotine addiction.

  6. Direct Electrical Stimulation in the Human Brain Disrupts Melody Processing.

    Science.gov (United States)

    Garcea, Frank E; Chernoff, Benjamin L; Diamond, Bram; Lewis, Wesley; Sims, Maxwell H; Tomlinson, Samuel B; Teghipco, Alexander; Belkhir, Raouf; Gannon, Sarah B; Erickson, Steve; Smith, Susan O; Stone, Jonathan; Liu, Lynn; Tollefson, Trenton; Langfitt, John; Marvin, Elizabeth; Pilcher, Webster H; Mahon, Bradford Z

    2017-09-11

    Prior research using functional magnetic resonance imaging (fMRI) [1-4] and behavioral studies of patients with acquired or congenital amusia [5-8] suggest that the right posterior superior temporal gyrus (STG) in the human brain is specialized for aspects of music processing (for review, see [9-12]). Intracranial electrical brain stimulation in awake neurosurgery patients is a powerful means to determine the computations supported by specific brain regions and networks [13-21] because it provides reversible causal evidence with high spatial resolution (for review, see [22, 23]). Prior intracranial stimulation or cortical cooling studies have investigated musical abilities related to reading music scores [13, 14] and singing familiar songs [24, 25]. However, individuals with amusia (congenitally, or from a brain injury) have difficulty humming melodies but can be spared for singing familiar songs with familiar lyrics [26]. Here we report a detailed study of a musician with a low-grade tumor in the right temporal lobe. Functional MRI was used pre-operatively to localize music processing to the right STG, and the patient subsequently underwent awake intraoperative mapping using direct electrical stimulation during a melody repetition task. Stimulation of the right STG induced "music arrest" and errors in pitch but did not affect language processing. These findings provide causal evidence for the functional segregation of music and language processing in the human brain and confirm a specific role of the right STG in melody processing. VIDEO ABSTRACT. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Direct Intracochlear Acoustic Stimulation Using a PZT Microactuator

    Directory of Open Access Journals (Sweden)

    Chuan Luo

    2015-11-01

    Full Text Available Combined electric and acoustic stimulation has proven to be an effective strategy to improve hearing in some cochlear implant users. We describe an acoustic microactuator to directly deliver stimuli to the perilymph in the scala tympani. The 800 µm by 800 µm actuator has a silicon diaphragm driven by a piezoelectric thin film (e.g., lead-zirconium-titanium oxide or PZT. This device could also be used as a component of a bimodal acoustic-electric electrode array. In the current study, we established a guinea pig model to test the actuator for its ability to deliver auditory signals to the cochlea in vivo. The actuator was placed through the round window of the cochlea. Auditory brainstem response (ABR thresholds, peak latencies, and amplitude growth were calculated for an ear canal speaker versus the intracochlear actuator for tone burst stimuli at 4, 8, 16, and 24 kHz. An ABR was obtained after removal of the probe to assess loss of hearing related to the procedure. In some animals, the temporal bone was harvested for histologic analysis of cochlear damage. We show that the device is capable of stimulating ABRs in vivo with latencies and growth functions comparable to stimulation in the ear canal. Further experiments will be necessary to evaluate the efficiency and safety of this modality in long-term auditory stimulation and its ability to be integrated with conventional cochlear implant arrays.

  8. Identifying future directions for subsurface hydrocarbon migration research

    Science.gov (United States)

    Leifer, I.; Clark, J. F.; Luyendyk, B.; Valentine, D.

    Subsurface hydrocarbon migration is important for understanding the input and impacts of natural hydrocarbon seepage on the environment. Great uncertainties remain in most aspects of hydrocarbon migration, including some basic mechanisms of this four-phase flow of tar, oil, water, and gas through the complex fracture-network geometry particularly since the phases span a wide range of properties. Academic, government, and industry representatives recently attended a workshop to identify the areas of greatest need for future research in shallow hydrocarbon migration.Novel approaches such as studying temporal and spatial seepage variations and analogous geofluid systems (e.g., geysers and trickle beds) allow deductions of subsurface processes and structures that remain largely unclear. Unique complexities exist in hydrocarbon migration due to its multiphase flow and complex geometry, including in-situ biological weathering. Furthermore, many aspects of the role of hydrocarbons (positive and negative) in the environment are poorly understood, including how they enter the food chain (respiration, consumption, etc.) and “percolate” to higher trophic levels. But understanding these ecological impacts requires knowledge of the emissions' temporal and spatial variability and trajectories.

  9. Combined Dextroamphetamine and Transcranial Direct Current Stimulation in Poststroke Aphasia.

    Science.gov (United States)

    Keser, Zafer; Dehgan, Michelle Weber; Shadravan, Shaparak; Yozbatiran, Nuray; Maher, Lynn M; Francisco, Gerard E

    2017-10-01

    There is a growing need for various effective adjunctive treatment options for speech recovery after stroke. A pharmacological agent combined with noninvasive brain stimulation has not been previously reported for poststroke aphasia recovery. In this "proof of concept" study, we aimed to test the safety of a combined intervention consisting of dextroamphetamine, transcranial direct current stimulation, and speech and language therapy in subjects with nonfluent aphasia. Ten subjects with chronic nonfluent aphasia underwent two experiments where they received dextroamphetamine or placebo along with transcranial direct current stimulation and speech and language therapy on two separate days. The Western Aphasia Battery-Revised was used to monitor changes in speech performance. No serious adverse events were observed. There was no significant increase in blood pressure with amphetamine or deterioration in speech and language performance. Western Aphasia Battery-Revised aphasia quotient and language quotient showed a statistically significant increase in the active experiment. Comparison of proportional changes of aphasia quotient and language quotient in active experiment with those in placebo experiment showed significant difference. We showed that the triple combination therapy is safe and implementable and seems to induce positive changes in speech and language performance in the patients with chronic nonfluent aphasia due to stroke.

  10. Trajectory Analysis Unveils Reelin's Role in the Directed Migration of Granule Cells in the Dentate Gyrus.

    Science.gov (United States)

    Wang, Shaobo; Brunne, Bianka; Zhao, Shanting; Chai, Xuejun; Li, Jiawei; Lau, Jeremie; Failla, Antonio Virgilio; Zobiak, Bernd; Sibbe, Mirjam; Westbrook, Gary L; Lutz, David; Frotscher, Michael

    2018-01-03

    Reelin controls neuronal migration and layer formation. Previous studies in reeler mice deficient in Reelin focused on the result of the developmental process in fixed tissue sections. It has remained unclear whether Reelin affects the migratory process, migration directionality, or migrating neurons guided by the radial glial scaffold. Moreover, Reelin has been regarded as an attractive signal because newly generated neurons migrate toward the Reelin-containing marginal zone. Conversely, Reelin might be a stop signal because migrating neurons in reeler , but not in wild-type mice, invade the marginal zone. Here, we monitored the migration of newly generated proopiomelanocortin-EGFP -expressing dentate granule cells in slice cultures from reeler , reeler -like mutants and wild-type mice of either sex using real-time microscopy. We discovered that not the actual migratory process and migratory speed, but migration directionality of the granule cells is controlled by Reelin. While wild-type granule cells migrated toward the marginal zone of the dentate gyrus, neurons in cultures from reeler and reeler -like mutants migrated randomly in all directions as revealed by vector analyses of migratory trajectories. Moreover, live imaging of granule cells in reeler slices cocultured to wild-type dentate gyrus showed that the reeler neurons changed their directions and migrated toward the Reelin-containing marginal zone of the wild-type culture, thus forming a compact granule cell layer. In contrast, directed migration was not observed when Reelin was ubiquitously present in the medium of reeler slices. These results indicate that topographically administered Reelin controls the formation of a granule cell layer. SIGNIFICANCE STATEMENT Neuronal migration and the various factors controlling its onset, speed, directionality, and arrest are poorly understood. Slice cultures offer a unique model to study the migration of individual neurons in an almost natural environment. In the

  11. Enhanced motor learning with bilateral transcranial direct current stimulation: Impact of polarity or current flow direction?

    Science.gov (United States)

    Naros, Georgios; Geyer, Marc; Koch, Susanne; Mayr, Lena; Ellinger, Tabea; Grimm, Florian; Gharabaghi, Alireza

    2016-04-01

    Bilateral transcranial direct current stimulation (TDCS) is superior to unilateral TDCS when targeting motor learning. This effect could be related to either the current flow direction or additive polarity-specific effects on each hemisphere. This sham-controlled randomized study included fifty right-handed healthy subjects in a parallel-group design who performed an exoskeleton-based motor task of the proximal left arm on three consecutive days. Prior to training, we applied either sham, right anodal (a-TDCS), left cathodal (c-TDCS), concurrent a-TDCS and c-TDCS with two independent current sources and return electrodes (double source (ds)-TDCS) or classical bilateral stimulation (bi-TDCS). Motor performance improved over time for both unilateral (a-TDCS, c-TDCS) and bilateral (bi-TDCS, ds-TDCS) TDCS montages. However, only the two bilateral paradigms led to an improvement of the final motor performance at the end of the training period as compared to the sham condition. There was no difference between the two bilateral stimulation conditions (bi-TDCS, ds-TDCS). Bilateral TDCS is more effective than unilateral stimulation due to its polarity-specific effects on each hemisphere rather than due to its current flow direction. This study is the first systematic evaluation of stimulation polarity and current flow direction of bi-hemispheric motor cortex TDCS on motor learning of proximal upper limb muscles. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation

    Science.gov (United States)

    Kwon, Yong Hyun; Jang, Sung Ho

    2012-01-01

    We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions. Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation. These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation. PMID:25624815

  13. Outcomes in spasticity after repetitive transcranial magnetic and transcranial direct current stimulations

    OpenAIRE

    Gunduz, Aysegul; Kumru, Hatice; Pascual-Leone, Alvaro

    2014-01-01

    Non-invasive brain stimulations mainly consist of repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Repetitive transcranial magnetic stimulation exhibits satisfactory outcomes in improving multiple sclerosis, stroke, spinal cord injury and cerebral palsy-induced spasticity. By contrast, transcranial direct current stimulation has only been studied in post-stroke spasticity. To better validate the efficacy of non-invasive brain stimulations in improving ...

  14. Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells.

    Directory of Open Access Journals (Sweden)

    Prabhat S Kunwar

    2003-12-01

    Full Text Available In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR, Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells, and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently, the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target.

  15. Critical role of the FERM domain in Pyk2 stimulated glioma cell migration

    International Nuclear Information System (INIS)

    Lipinski, Christopher A.; Tran, Nhan L.; Dooley, Andrea; Pang, Yuan-Ping; Rohl, Carole; Kloss, Jean; Yang, Zhongbo; McDonough, Wendy; Craig, David; Berens, Michael E.; Loftus, Joseph C.

    2006-01-01

    The strong tendency of malignant glioma cells to invade locally into surrounding normal brain precludes effective surgical resection, reduces the efficacy of radiotherapy, and is associated with increased resistance to chemotherapy regimens. We report that the N-terminal FERM domain of Pyk2 regulates its promigratory function. A 3-dimensional model of the Pyk2 FERM domain was generated and mutagenesis studies identified residues essential for Pyk2 promigratory function. Model-based targeted mutations within the FERM domain decreased Pyk2 phosphorylation and reduced the capacity of Pyk2 to stimulate glioma cell migration but did not significantly alter the intracellular distribution of Pyk2. Expression of autonomous Pyk2 FERM domain fragments containing analogous mutations exhibited reduced capacity to inhibit glioma cell migration and Pyk2 phosphorylation relative to expression of an autonomous wild type FERM domain fragment. These results indicate that the FERM domain plays an important role in regulating the functional competency of Pyk2 as a promigratory factor in glioma

  16. Transcranial cerebellar direct current stimulation and transcutaneous spinal cord direct current stimulation as innovative tools for neuroscientists

    Science.gov (United States)

    Priori, Alberto; Ciocca, Matteo; Parazzini, Marta; Vergari, Maurizio; Ferrucci, Roberta

    2014-01-01

    Two neuromodulatory techniques based on applying direct current (DC) non-invasively through the skin, transcranial cerebellar direct current stimulation (tDCS) and transcutaneous spinal DCS, can induce prolonged functional changes consistent with a direct influence on the human cerebellum and spinal cord. In this article we review the major experimental works on cerebellar tDCS and on spinal tDCS, and their preliminary clinical applications. Cerebellar tDCS modulates cerebellar motor cortical inhibition, gait adaptation, motor behaviour, and cognition (learning, language, memory, attention). Spinal tDCS influences the ascending and descending spinal pathways, and spinal reflex excitability. In the anaesthetised mouse, DC stimulation applied under the skin along the entire spinal cord may affect GABAergic and glutamatergic systems. Preliminary clinical studies in patients with cerebellar disorders, and in animals and patients with spinal cord injuries, have reported beneficial effects. Overall the available data show that cerebellar tDCS and spinal tDCS are two novel approaches for inducing prolonged functional changes and neuroplasticity in the human cerebellum and spinal cord, and both are new tools for experimental and clinical neuroscientists. PMID:24907311

  17. Atractylodes macrocephala Koidz stimulates intestinal epithelial cell migration through a polyamine dependent mechanism.

    Science.gov (United States)

    Song, Hou-Pan; Li, Ru-Liu; Zhou, Chi; Cai, Xiong; Huang, Hui-Yong

    2015-01-15

    decrease of cellular polyamines levels, Rho mRNAs and proteins expression, non-muscle myosin II protein formation and distribution, thereby inhibiting IEC-6 cell migration. AMK not only reversed the inhibitory effects of DFMO on the polyamines content, Rho mRNAs and proteins expression, non-muscle myosin II protein formation and distribution, but also restored cell migration to control levels. The results obtained from this study revealed that AMK significantly stimulates the migration of IEC-6 cells through a polyamine dependent mechanism, which could accelerate the healing of intestinal injury. These findings suggest the potential value of AMK in curing intestinal diseases characterized by injury and ineffective repair of the intestinal mucosa in clinical practice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. In vitro effect of direct current electrical stimulation on rat mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Sahba Mobini

    2017-01-01

    Full Text Available Background Electrical stimulation (ES has been successfully used to treat bone defects clinically. Recently, both cellular and molecular approaches have demonstrated that ES can change cell behavior such as migration, proliferation and differentiation. Methods In the present study we exposed rat bone marrow- (BM- and adipose tissue- (AT- derived mesenchymal stem cells (MSCs to direct current electrical stimulation (DC ES and assessed temporal changes in osteogenic differentiation. We applied 100 mV/mm of DC ES for 1 h per day for three, seven and 14 days to cells cultivated in osteogenic differentiation medium and assessed viability and calcium deposition at the different time points. In addition, expression of osteogenic genes, Runx2, Osteopontin, and Col1A2 was assessed in BM- and AT-derived MSCs at the different time points. Results Results showed that ES changed osteogenic gene expression patterns in both BM- and AT-MSCs, and these changes differed between the two groups. In BM-MSCs, ES caused a significant increase in mRNA levels of Runx2, Osteopontin and Col1A2 at day 7, while in AT-MSCs, the increase in Runx2 and Osteopontin expression were observed after 14 days of ES. Discussion This study shows that rat bone marrow- and adipose tissue-derived stem cells react differently to electrical stimuli, an observation that could be important for application of electrical stimulation in tissue engineering.

  19. Effects of Transcranial Direct Current Stimulation on Expression of Immediate Early Genes (IEG’s)

    Science.gov (United States)

    2015-12-01

    TRANSCRANIAL DIRECT CURRENT STIMULATION OF EXPRESSION OF IMMEDIATE EARLY GENES (IEG’S) Jessica...AND SUBTITLE Effects of Transcranial Direct Current Stimulation on Expression of Immediate Early Genes (IEG’s) 5a. CONTRACT NUMBER In-House 5b...community in better understanding what is occurring biologically during tDCS. 15. SUBJECT TERMS Transcranial direct current stimulation

  20. Transcranial Direct Current Stimulation: Considerations for Research in Adolescent Depression

    Directory of Open Access Journals (Sweden)

    Jonathan C. Lee

    2017-06-01

    Full Text Available Adolescent depression is a prevalent disorder with substantial morbidity and mortality. Current treatment interventions do not target relevant pathophysiology and are frequently ineffective, thereby leading to a substantial burden for individuals, families, and society. During adolescence, the prefrontal cortex undergoes extensive structural and functional changes. Recent work suggests that frontolimbic development in depressed adolescents is delayed or aberrant. The judicious application of non-invasive brain stimulation techniques to the prefrontal cortex may present a promising opportunity for durable interventions in adolescent depression. Transcranial direct current stimulation (tDCS applies a low-intensity, continuous current that alters cortical excitability. While this modality does not elicit action potentials, it is thought to manipulate neuronal activity and neuroplasticity. Specifically, tDCS may modulate N-methyl-d-aspartate receptors and L-type voltage-gated calcium channels and effect changes through long-term potentiation or long-term depression-like mechanisms. This mini-review considers the neurobiological rationale for developing tDCS protocols in adolescent depression, reviews existing work in adult mood disorders, surveys the existing tDCS literature in adolescent populations, reviews safety studies, and discusses distinct ethical considerations in work with adolescents.

  1. Mechanisms and Effects of Transcranial Direct Current Stimulation

    Science.gov (United States)

    Giordano, James; Bikson, Marom; Kappenman, Emily S.; Clark, Vincent P.; Coslett, H. Branch; Hamblin, Michael R.; Hamilton, Roy; Jankord, Ryan; Kozumbo, Walter J.; McKinley, R. Andrew; Nitsche, Michael A.; Reilly, J. Patrick; Richardson, Jessica; Wurzman, Rachel

    2017-01-01

    The US Air Force Office of Scientific Research convened a meeting of researchers in the fields of neuroscience, psychology, engineering, and medicine to discuss most pressing issues facing ongoing research in the field of transcranial direct current stimulation (tDCS) and related techniques. In this study, we present opinions prepared by participants of the meeting, focusing on the most promising areas of research, immediate and future goals for the field, and the potential for hormesis theory to inform tDCS research. Scientific, medical, and ethical considerations support the ongoing testing of tDCS in healthy and clinical populations, provided best protocols are used to maximize safety. Notwithstanding the need for ongoing research, promising applications include enhancing vigilance/attention in healthy volunteers, which can accelerate training and support learning. Commonly, tDCS is used as an adjunct to training/rehabilitation tasks with the goal of leftward shift in the learning/treatment effect curves. Although trials are encouraging, elucidating the basic mechanisms of tDCS will accelerate validation and adoption. To this end, biomarkers (eg, clinical neuroimaging and findings from animal models) can support hypotheses linking neurobiological mechanisms and behavioral effects. Dosage can be optimized using computational models of current flow and understanding dose–response. Both biomarkers and dosimetry should guide individualized interventions with the goal of reducing variability. Insights from other applied energy domains, including ionizing radiation, transcranial magnetic stimulation, and low-level laser (light) therapy, can be prudently leveraged. PMID:28210202

  2. Cerebellar transcranial direct current stimulation modulates verbal working memory.

    Science.gov (United States)

    Boehringer, Andreas; Macher, Katja; Dukart, Juergen; Villringer, Arno; Pleger, Burkhard

    2013-07-01

    Neuroimaging studies show cerebellar activations in a wide range of cognitive tasks and patients with cerebellar lesions often present cognitive deficits suggesting a cerebellar role in higher-order cognition. We used cathodal transcranial direct current stimulation (tDCS), known to inhibit neuronal excitability, over the cerebellum to investigate if cathodal tDCS impairs verbal working memory, an important higher-order cognitive faculty. We tested verbal working memory as measured by forward and backward digit spans in 40 healthy young participants before and after applying cathodal tDCS (2 mA, stimulation duration 25 min) to the right cerebellum using a randomized, sham-controlled, double-blind, cross-over design. In addition, we tested the effect of cerebellar tDCS on word reading, finger tapping and a visually cued sensorimotor task. In line with lower digit spans in patients with cerebellar lesions, cerebellar tDCS reduced forward digit spans and blocked the practice dependent increase in backward digit spans. No effects of tDCS on word reading, finger tapping or the visually cued sensorimotor task were found. Our results support the view that the cerebellum contributes to verbal working memory as measured by forward and backward digit spans. Moreover, the induction of reversible "virtual cerebellar lesions" in healthy individuals by means of tDCS may improve our understanding of the mechanistic basis of verbal working memory deficits in patients with cerebellar lesions. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Characterization of monoclonal antibodies directed against human thyroid stimulating hormone

    International Nuclear Information System (INIS)

    Soos, M.; Siddle, K.

    1982-01-01

    Monoclonal antibodies directed against human thyroid stimulating hormone (TSH) were obtained from hybrid myelomas, following fusion of mouse NSI myeloma cells with mouse spleen cells. Ten different antibodies were obtained from 4 separate fusions. Eight antibodies were of the IgG 1 subclass. Affinities of antibodies for TSH were in the range 2 x 10 8 -5 x 10 10 M -1 . Five of the antibodies were specific for TSH and did not react with LH, FSH or hCG. The remaining antibodies reacted with all these hormones and were assumed to recognise their common (α) subunit. The 5 specific antibodies fell into 3 subgroups recognising distinct antigenic determinants, whereas the 5 non-specific antibodies recognised a single determinant or closely related set of sites. It is concluded that these antibodies should be valuable reagents for use in sensitive and specific two-site immunoradiometric assays. (Auth.)

  4. Transcranial direct current stimulation as a treatment for auditory hallucinations.

    Directory of Open Access Journals (Sweden)

    Sanne eKoops

    2015-03-01

    Full Text Available Auditory hallucinations (AH are a symptom of several psychiatric disorders, such as schizophrenia. In a significant minority of patients, AH are resistant to antipsychotic medication. Alternative treatment options for this medication-resistant group are scarce and most of them focus on coping with the hallucinations. Finding an alternative treatment that can diminish AH is of great importance.Transcranial direct current stimulation (tDCS is a safe and non-invasive technique that is able to directly influence cortical excitability through the application of very low electric currents. A 1-2 mA direct current is applied between two surface electrodes, one serving as the anode and the other as the cathode. Cortical excitability is increased in the vicinity of the anode and reduced near the cathode. The technique, which has only a few transient side effects and is cheap and portable, is increasingly explored as a treatment for neurological and psychiatric symptoms. It has shown efficacy on symptoms of depression, bipolar disorder, schizophrenia, Alzheimer’s disease, Parkinson’s disease, epilepsy and stroke. However, the application of tDCS as a treatment for AH is relatively new. This article provides an overview of the current knowledge in this field and provides guidelines for future research.

  5. Direct observations of American eels migrating across the continental shelf to the Sargasso Sea.

    Science.gov (United States)

    Béguer-Pon, Mélanie; Castonguay, Martin; Shan, Shiliang; Benchetrit, José; Dodson, Julian J

    2015-10-27

    Since inferring spawning areas from larval distributions in the Sargasso Sea a century ago, the oceanic migration of adult American eels has remained a mystery. No adult eel has ever been observed migrating in the open ocean or in the spawning area. Here, we track movements of maturing eels equipped with pop-up satellite archival tags from the Scotian Shelf (Canada) into the open ocean, with one individual migrating 2,400 km to the northern limit of the spawning site in the Sargasso Sea. The reconstructed routes suggest a migration in two phases: one over the continental shelf and along its edge in shallow waters; the second in deeper waters straight south towards the spawning area. This study is the first direct evidence of adult Anguilla migrating to the Sargasso Sea and represents an important step forward in the understanding of routes and migratory cues.

  6. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.

    Science.gov (United States)

    Bikson, Marom; Grossman, Pnina; Thomas, Chris; Zannou, Adantchede Louis; Jiang, Jimmy; Adnan, Tatheer; Mourdoukoutas, Antonios P; Kronberg, Greg; Truong, Dennis; Boggio, Paulo; Brunoni, André R; Charvet, Leigh; Fregni, Felipe; Fritsch, Brita; Gillick, Bernadette; Hamilton, Roy H; Hampstead, Benjamin M; Jankord, Ryan; Kirton, Adam; Knotkova, Helena; Liebetanz, David; Liu, Anli; Loo, Colleen; Nitsche, Michael A; Reis, Janine; Richardson, Jessica D; Rotenberg, Alexander; Turkeltaub, Peter E; Woods, Adam J

    2016-01-01

    This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Focal Hemodynamic Responses in the Stimulated Hemisphere During High-Definition Transcranial Direct Current Stimulation.

    Science.gov (United States)

    Muthalib, Makii; Besson, Pierre; Rothwell, John; Perrey, Stéphane

    2017-07-17

    High-definition transcranial direct current stimulation (HD-tDCS) using a 4 × 1 electrode montage has been previously shown using modeling and physiological studies to constrain the electric field within the spatial extent of the electrodes. The aim of this proof-of-concept study was to determine if functional near-infrared spectroscopy (fNIRS) neuroimaging can be used to determine a hemodynamic correlate of this 4 × 1 HD-tDCS electric field on the brain. In a three session cross-over study design, 13 healthy males received one sham (2 mA, 30 sec) and two real (HD-tDCS-1 and HD-tDCS-2, 2 mA, 10 min) anodal HD-tDCS targeting the left M1 via a 4 × 1 electrode montage (anode on C3 and 4 return electrodes 3.5 cm from anode). The two real HD-tDCS sessions afforded a within-subject replication of the findings. fNIRS was used to measure changes in brain hemodynamics (oxygenated hemoglobin integral-O 2 Hb int ) during each 10 min session from two regions of interest (ROIs) in the stimulated left hemisphere that corresponded to "within" (L in ) and "outside" (L out ) the spatial extent of the 4 × 1 electrode montage, and two corresponding ROIs (R in and R out ) in the right hemisphere. The ANOVA showed that both real anodal HD-tDCS compared to sham induced a significantly greater O 2 Hb int in the L in than L out ROIs of the stimulated left hemisphere; while there were no significant differences between the real and sham sessions for the right hemisphere ROIs. Intra-class correlation coefficients showed "fair-to-good" reproducibility for the left stimulated hemisphere ROIs. The greater O 2 Hb int "within" than "outside" the spatial extent of the 4 × 1 electrode montage represents a hemodynamic correlate of the electrical field distribution, and thus provides a prospective reliable method to determine the dose of stimulation that is necessary to optimize HD-tDCS parameters in various applications. © 2017 International Neuromodulation Society.

  8. Adrenaline stimulates the proliferation and migration of mesenchymal stem cells towards the LPS-induced lung injury.

    Science.gov (United States)

    Wu, Xiaodan; Wang, Zhiming; Qian, Mengjia; Wang, Lingyan; Bai, Chunxue; Wang, Xiangdong

    2014-08-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) could modulate inflammation in experimental lung injury. On the other hand, adrenergic receptor agonists could increase DNA synthesis of stem cells. Therefore, we investigated the therapeutic role of adrenaline-stimulated BMSCs on lipopolysaccharide (LPS)-induced lung injury. BMSCs were cultured with adrenergic receptor agonists or antagonists. Suspensions of lung cells or sliced lung tissue from animals with or without LPS-induced injury were co-cultured with BMSCs. LPS-stimulated alveolar macrophages were co-cultured with BMSCs (with adrenaline stimulation or not) in Transwell for 6 hrs. A preliminary animal experiment was conducted to validate the findings in ex vivo study. We found that adrenaline at 10 μM enhanced proliferation of BMSCs through both α- and β-adrenergic receptors. Adrenaline promoted the migration of BMSCs towards LPS-injured lung cells or lung tissue. Adrenaline-stimulated BMSCs decreased the inflammation of LPS-stimulated macrophages, probably through the expression and secretion of several paracrine factors. Adrenaline reduced the extent of injury in LPS-injured rats. Our data indicate that adrenaline-stimulated BMSCs might contribute to the prevention from acute lung injury through the activation of adrenergic receptors, promotion of proliferation and migration towards injured lung, and modulation of inflammation. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  9. Considering the influence of stimulation parameters on the effect of conventional and high-definition transcranial direct current stimulation.

    Science.gov (United States)

    To, Wing Ting; Hart, John; De Ridder, Dirk; Vanneste, Sven

    2016-01-01

    Recently, techniques to non-invasively modulate specific brain areas gained popularity in the form of transcranial direct current stimulation (tDCS) and high-definition transcranial direct current stimulation. These non-invasive techniques have already shown promising outcomes in various studies with healthy subjects as well as patient populations. Despite widespread dissemination of tDCS, there remain significant unknowns about the influence of a diverse number of tDCS parameters (e.g. polarity, size, position of electrodes & duration of stimulation) in inducing neurophysiological and behavioral effects. This article explores both techniques starting with the history of tDCS, to the differences between conventional tDCS and high-definition transcranial direct current stimulation, the underlying physiological mechanism, the (in)direct effects, the applications of tDCS with varying parameters, the efficacy, the safety issues and the opportunities for future research.

  10. Direct and crossed effects of somatosensory stimulation on neuronal excitability and motor performance in humans

    NARCIS (Netherlands)

    Veldman, M. P.; Maffiuletti, N. A.; Hallett, M.; Zijdewind, I.; Hortobagyi, T.

    2014-01-01

    This analytic review reports how prolonged periods of somatosensory electric stimulation (SES) with repetitive transcutaneous nerve stimulation can have 'direct' and 'crossed' effects on brain activation, corticospinal excitability, and motor performance. A review of 26 studies involving 315 healthy

  11. Is transcranial direct current stimulation a potential method for improving response inhibition?

    Science.gov (United States)

    Kwon, Yong Hyun; Kwon, Jung Won

    2013-04-15

    Inhibitory control of movement in motor learning requires the ability to suppress an inappropriate action, a skill needed to stop a planned or ongoing motor response in response to changes in a variety of environments. This study used a stop-signal task to determine whether transcranial direct-current stimulation over the pre-supplementary motor area alters the reaction time in motor inhibition. Forty healthy subjects were recruited for this study and were randomly assigned to either the transcranial direct-current stimulation condition or a sham-transcranial direct-current stimulation condition. All subjects consecutively performed the stop-signal task before, during, and after the delivery of anodal transcranial direct-current stimulation over the pre-supplementary motor area (pre-transcranial direct-current stimulation phase, transcranial direct-current stimulation phase, and post-transcranial direct-current stimulation phase). Compared to the sham condition, there were significant reductions in the stop-signal processing times during and after transcranial direct-current stimulation, and change times were significantly greater in the transcranial direct-current stimulation condition. There was no significant change in go processing-times during or after transcranial direct-current stimulation in either condition. Anodal transcranial direct-current stimulation was feasibly coupled to an interactive improvement in inhibitory control. This coupling led to a decrease in the stop-signal process time required for the appropriate responses between motor execution and inhibition. However, there was no transcranial direct-current stimulation effect on the no-signal reaction time during the stop-signal task. Transcranial direct-current stimulation can adjust certain behaviors, and it could be a useful clinical intervention for patients who have difficulties with response inhibition.

  12. Acute insulin resistance stimulates and insulin sensitization attenuates vascular smooth muscle cell migration and proliferation.

    Science.gov (United States)

    Cersosimo, Eugenio; Xu, Xiaojing; Upala, Sikarin; Triplitt, Curtis; Musi, Nicolas

    2014-08-01

    Differential activation/deactivation of insulin signaling, PI-3K and MAP-K pathways by high glucose and palmitate, with/out the insulin sensitizer pioglitazone (PIO), have been previously shown in vascular smooth muscle cells (VSMCs). To determine the biological impact of these molecular changes, we examined VSMC migration and proliferation ("M"&"P") patterns in similar conditions. VSMCs from healthy human coronary arteries were incubated in growth medium and "M"&"P" were analyzed after exposure to high glucose (25 mmol/L) ± palmitate (200 μmol/L) and ± PIO (8 μmol/L) for 5 h. "M"&"P" were assessed by: (1) polycarbonate membrane barrier with chemo-attractants and extended cell protrusions quantified by optical density (OD595 nm); (2) % change in radius area (2D Assay) using inverted microscopy images; and (3) cell viability assay expressed as cell absorbance (ABS) in media. "M" in 25 mmol/L glucose media increased by ~25% from baseline and % change in radius area rose from ~20% to ~30%. The addition of PIO was accompanied by a significant decrease in "M" from 0.25 ± 0.02 to 0.19 ± 0.02; a comparable decline from 0.25 ± 0.02 to 0.18 ± 0.02 was also seen with 25 mmol/L of glucose +200 μmol/L of palmitate. When PIO was coincubated with high glucose plus palmitate there was a 50% reduction in % change in radius. A ~10% increase in ABS, reflecting augmented "P" in media with 25 mmol/L glucose versus control was documented. The addition of PIO reduced ABS from 0.208 ± 0.03 to 0.183 ± 0.06. Both high glucose and palmitate showed ABS of ~0.140 ± 0.02, which decreased with PIO to ~0.120 ± 0.02, indicating "P" was reduced. These results confirm that high glucose and palmitate stimulate VSMCs migration and proliferation in vitro, which is attenuated by coincubation with the insulin sensitizer PIO. Although, we cannot ascertain whether these functional changes are coincident with the activation/deactivation of signal molecules, our findings are consistent with the

  13. Directed cell migration in the presence of obstacles

    Directory of Open Access Journals (Sweden)

    Grima Ramon

    2007-01-01

    Full Text Available Abstract Background Chemotactic movement is a common feature of many cells and microscopic organisms. In vivo, chemotactic cells have to follow a chemotactic gradient and simultaneously avoid the numerous obstacles present in their migratory path towards the chemotactic source. It is not clear how cells detect and avoid obstacles, in particular whether they need a specialized biological mechanism to do so. Results We propose that cells can sense the presence of obstacles and avoid them because obstacles interfere with the chemical field. We build a model to test this hypothesis and find that this naturally enables efficient at-a-distance sensing to be achieved with no need for a specific and active obstacle-sensing mechanism. We find that (i the efficiency of obstacle avoidance depends strongly on whether the chemotactic chemical reacts or remains unabsorbed at the obstacle surface. In particular, it is found that chemotactic cells generally avoid absorbing barriers much more easily than non-absorbing ones. (ii The typically low noise in a cell's motion hinders the ability to avoid obstacles. We also derive an expression estimating the typical distance traveled by chemotactic cells in a 3D random distribution of obstacles before capture; this is a measure of the distance over which chemotaxis is viable as a means of directing cells from one point to another in vivo. Conclusion Chemotactic cells, in many cases, can avoid obstacles by simply following the spatially perturbed chemical gradients around obstacles. It is thus unlikely that they have developed specialized mechanisms to cope with environments having low to moderate concentrations of obstacles.

  14. Transcranial direct current stimulation, implicit alcohol associations and craving

    NARCIS (Netherlands)

    den Uijl, T.E.; Gladwin, T.E.; Wiers, R.W.

    2015-01-01

    Previous research has shown that stimulation of the left dorsolateral prefrontal cortex (DLPFC) enhances working memory (e.g. in the n-back task), and reduces craving for cigarettes and alcohol. Stimulation of the right inferior frontal gyrus (IFG) improves response inhibition. The underlying

  15. Larval migration in PERL chambers as an in vitro model for percutaneous infection stimulates feeding in the canine hookworm Ancylostoma caninum

    Directory of Open Access Journals (Sweden)

    Welz Claudia

    2011-01-01

    Full Text Available Abstract Background Ancylostoma caninum third-stage larvae are the non-feeding infective stage of this parasite and are able to infect potential hosts via different infection routes. Since percutaneous infection is one of the most important routes and skin penetration is the first step into parasitic life, an existing in vitro model for percutaneous migration was modified and evaluated. The main parameter used to evaluate migration was the migration ratio (migrated larvae as a percentage of total number of larvae recovered. Additionally, the skin lag was calculated, expressing the percentage of larvae remaining in the skin and therefore not being recovered. Since initiation of feeding is proposed to be an important step in the transition from free-living to parasitic A. caninum larvae, feeding assays were performed with in vitro percutaneously migrated larvae. Additionally, infective larvae of A. caninum were activated via serum-stimulation and feeding behaviour was analysed and compared between percutaneously migrated and serum-stimulated larvae. Results Maximum skin migration levels of infective larvae were observed at temperatures above 32°C when larvae were placed on the epidermal side of skin for more than 12 hours. The medium beneath the skin had no effect on migration ratio, and no significant difference between the migration ratios through fresh and frozen/thawed skin was observed. Maximum feeding levels of 93.2% were observed for percutaneously migrated larvae after 48 h incubation, whereas serum-stimulated larvae reached the maximum of 91.0% feeding larvae after 24 h. Conclusions The PERL chamber system was optimised and standardised as an in vitro model for percutaneous migration. The larvae recovered after percutaneous migration showed characteristic signs of activation similar to that of serum-stimulated larvae. The observed difference in time course of resumption of feeding indicates that percutaneously migrated larvae are not

  16. Specific sizes of hyaluronan oligosaccharides stimulate fibroblast migration and excisional wound repair.

    Directory of Open Access Journals (Sweden)

    Cornelia Tolg

    Full Text Available The extracellular matrix polysaccharide hyaluronan (HA plays a key role in both fibrotic and regenerative tissue repair. Accumulation of high molecular weight HA is typical of regenerative repair, which is associated with minimal inflammation and fibrosis, while fragmentation of HA is typical of postnatal wounds, which heal in the presence of inflammation and transient fibrosis. It is generally considered that HA oligosaccharides and fragments of a wide size range support these processes of adult, fibrotic wound repair yet the consequences of sized HA fragments/oligosaccharides to each repair stage is not well characterized. Here, we compared the effects of native HA, HA oligosaccharide mixtures and individual sizes (4-10 mer oligosaccharides, 5 and, 40 kDa of HA oligosaccharides and fragments, on fibroblast migration in scratch wound assays and on excisional skin wound repair in vivo. We confirm that 4-10 mer mixtures significantly stimulated scratch wound repair and further report that only the 6 and 8 mer oligosaccharides in this mixture are responsible for this effect. The HA 6 mer promoted wound closure, accumulation of wound M1 and M2 macrophages and the M2 cytokine TGFβ1, but did not increase myofibroblast differentiation. The effect of 6 mer HA on wound closure required both RHAMM and CD44 expression. In contrast, The 40 kDa HA fragment inhibited wound closure, increased the number of wound macrophages but had no effect on TGFβ1 accumulation or subsequent fibrosis. These results show that specific sizes of HA polymer have unique effects on postnatal wound repair. The ability of 6 mer HA to promote wound closure and inflammation resolution without increased myofibroblast differentiation suggests that this HA oligosaccharide could be useful for treatment of delayed or inefficient wound repair where minimal fibrosis is advantageous.

  17. In vivo relative quantitative proteomics reveals HMGB1 as a downstream mediator of oestrogen-stimulated keratinocyte migration.

    Science.gov (United States)

    Shin, Jung U; Noh, Ji Yeon; Lee, Ju Hee; Lee, Won Jai; Yoo, Jong Shin; Kim, Jin Young; Kim, Hyeran; Jung, Inhee; Jin, Shan; Lee, Kwang Hoon

    2015-06-01

    It is known that oestrogen influences skin wound healing by modulating the inflammatory response, cytokine expression and extracellular matrix deposition; accelerating re-epithelialization; and stimulating angiogenesis. To identify novel proteins associated with effects of oestrogen on keratinocyte, stable isotope labelling by amino acids in cell culture (SILAC)-based mass spectrometry was performed. Using SILAC, quantification of 1085 proteins was achieved. Among these proteins, 60 proteins were upregulated and 32 proteins were downregulated. Among significantly upregulated proteins, high-mobility group protein B1 (HMGB1) has been further evaluated for its role in the effect of oestrogen on keratinocytes. HMGB1 expression was strongly induced in oestrogen-treated keratinocytes in dose- and time-dependent manner. Further, HMGB1 was able to significantly accelerate the rate of HaCaT cell migration. To determine whether HMGB1 is involved in E2-induced HaCaT cell migration, cells were transfected with HMGB1 siRNA. Knockdown of HMGB1 blocked oestrogen-induced keratinocyte migration. Collectively, these experiments demonstrate that HMGB1 is a novel downstream mediator of oestrogen-stimulated keratinocyte migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Novel methods to optimize the effects of transcranial direct current stimulation: a systematic review of transcranial direct current stimulation patents.

    Science.gov (United States)

    Malavera, Alejandra; Vasquez, Alejandra; Fregni, Felipe

    2015-01-01

    Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that has been extensively studied. While there have been initial positive results in some clinical trials, there is still variability in tDCS results. The aim of this article is to review and discuss patents assessing novel methods to optimize the use of tDCS. A systematic review was performed using Google patents database with tDCS as the main technique, with patents filling date between 2010 and 2015. Twenty-two patents met our inclusion criteria. These patents attempt to address current tDCS limitations. Only a few of them have been investigated in clinical trials (i.e., high-definition tDCS), and indeed most of them have not been tested before in human trials. Further clinical testing is required to assess which patents are more likely to optimize the effects of tDCS. We discuss the potential optimization of tDCS based on these patents and the current experience with standard tDCS.

  19. Cerebellar transcranial direct current stimulation improves adaptive postural control.

    Science.gov (United States)

    Poortvliet, Peter; Hsieh, Billie; Cresswell, Andrew; Au, Jacky; Meinzer, Marcus

    2018-01-01

    Rehabilitation interventions contribute to recovery of impaired postural control, but it remains a priority to optimize their effectiveness. A promising strategy may involve transcranial direct current stimulation (tDCS) of brain areas involved in fine-tuning of motor adaptation. This study explored the effects of cerebellar tDCS (ctDCS) on postural recovery from disturbance by Achilles tendon vibration. Twenty-eight healthy volunteers participated in this sham-ctDCS controlled study. Standing blindfolded on a force platform, four trials were completed: 60 s quiet standing followed by 20 min active (anodal-tDCS, 1 mA, 20 min, N = 14) or sham-ctDCS (40 s, N = 14) tDCS; three quiet standing trials with 15 s of Achilles tendon vibration and 25 s of postural recovery. Postural steadiness was quantified as displacement, standard deviation and path derived from the center of pressure (COP). Baseline demographics and quiet standing postural steadiness, and backwards displacement during vibration were comparable between groups. However, active-tDCS significantly improved postural steadiness during vibration and reduced forward displacement and variability in COP derivatives during recovery. We demonstrate that ctDCS results in short-term improvement of postural adaptation in healthy individuals. Future studies need to investigate if multisession ctDCS combined with training or rehabilitation interventions can induce prolonged improvement of postural balance. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  20. Transcranial direct current stimulation versus caffeine as a fatigue countermeasure.

    Science.gov (United States)

    McIntire, Lindsey K; McKinley, R Andy; Nelson, Justin M; Goodyear, Chuck

    To assess the efficacy of using transcranial direct current stimulation (tDCS) to remediate the deleterious effects of fatigue induced by sleep deprivation and compare these results to caffeine, a commonly used fatigue countermeasure. Based on previous research, tDCS of the dorsolateral prefrontal cortex (DLPFC) can modulate attention and arousal. The authors hypothesize that tDCS can be an effective fatigue countermeasure. Five groups of ten participants each received either active tDCS and placebo gum at 1800, caffeine gum with sham tDCS at 1800, active tDCS and placebo gum at 0400, caffeine gum with sham tDCS at 0400, or sham tDCS with placebo gum at 1800 and 0400 during 36-h of sustained wakefulness. Participants completed a vigilance task, working memory task, psychomotor vigilance task (PVT), and a procedural game beginning at 1800 h and continued every two hours throughout the night until 1900 the next day. tDCS dosed at 1800 provided 6 h of improved attentional accuracy and reaction times compared to the control group. Caffeine did not produce an effect. Both tDCS groups also had an improved effect on mood. Participants receiving tDCS reported feeling more vigor, less fatigue, and less bored throughout the night compared to the control and caffeine groups. We believe tDCS could be a powerful fatigue countermeasure. The effects appear to be comparable or possibly more beneficial than caffeine because they are longer lasting and mood remains more positive. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Randomized trial of transcranial direct current stimulation for poststroke dysphagia.

    Science.gov (United States)

    Suntrup-Krueger, Sonja; Ringmaier, Corinna; Muhle, Paul; Wollbrink, Andreas; Kemmling, Andre; Hanning, Uta; Claus, Inga; Warnecke, Tobias; Teismann, Inga; Pantev, Christo; Dziewas, Rainer

    2018-02-01

    We evaluated whether transcranial direct current stimulation (tDCS) is able to enhance dysphagia rehabilitation following stroke. Besides relating clinical effects with neuroplastic changes in cortical swallowing processing, we aimed to identify factors influencing treatment success. In this double-blind, randomized study, 60 acute dysphagic stroke patients received contralesional anodal (1mA, 20 minutes) or sham tDCS on 4 consecutive days. Swallowing function was thoroughly assessed before and after the intervention using the validated Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) and clinical assessment. In 10 patients, swallowing-related brain activation was recorded applying magnetoencephalography before and after the intervention. Voxel-based statistical lesion pattern analysis was also performed. Study groups did not differ according to demographic data, stroke characteristics, or baseline dysphagia severity. Patients treated with tDCS showed greater improvement in FEDSS than the sham group (1.3 vs 0.4 points, mean difference = 0.9, 95% confidence interval [CI] = 0.4-1.4, p < 0.0005). Functional recovery was accompanied by a significant increase of activation (p < 0.05) in the contralesional swallowing network after real but not sham tDCS. Regarding predictors of treatment success, for every hour earlier that treatment was initiated, there was greater improvement on the FEDSS (adjusted odds ratio = 0.99, 95% CI = 0.98-1.00, p < 0.05) in multivariate analysis. Stroke location in the right insula and operculum was indicative of worse response to tDCS (p < 0.05). Application of tDCS over the contralesional swallowing motor cortex supports swallowing network reorganization, thereby leading to faster rehabilitation of acute poststroke dysphagia. Early treatment initiation seems beneficial. tDCS may be less effective in right-hemispheric insulo-opercular stroke. Ann Neurol 2018;83:328-340. © 2018 American Neurological

  2. Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation

    OpenAIRE

    Kwon, Yong Hyun; Jang, Sung Ho

    2012-01-01

    We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel coun...

  3. The role of granulocyte macrophage colony stimulating factor (GM-CSF) in radiation-induced tumor cell migration.

    Science.gov (United States)

    Vilalta, Marta; Brune, Jourdan; Rafat, Marjan; Soto, Luis; Graves, Edward E

    2018-03-13

    Recently it has been observed in preclinical models that that radiation enhances the recruitment of circulating tumor cells to primary tumors, and results in tumor regrowth after treatment. This process may have implications for clinical radiotherapy, which improves control of a number of tumor types but which, despite continued dose escalation and aggressive fractionation, is unable to fully prevent local recurrences. By irradiating a single tumor within an animal bearing multiple lesions, we observed an increase in tumor cell migration to irradiated and unirradiated sites, suggesting a systemic component to this process. Previous work has identified the cytokine GM-CSF, produced by tumor cells following irradiation, as a key effector of this process. We evaluated the ability of systemic injections of a PEGylated form of GM-CSF to stimulate tumor cell migration. While increases in invasion and migration were observed for tumor cells in a transwell assay, we found that daily injections of PEG-GM-CSF to tumor-bearing animals did not increase migration of cells to tumors, despite the anticipated changes in circulating levels of granulocytes and monocytes produced by this treatment. Combination of PEG-GM-CSF treatment with radiation also did not increase tumor cell migration. These findings suggest that clinical use of GM-CSF to treat neutropenia in cancer patients will not have negative effects on the aggressiveness of residual cancer cells. However, further work is needed to characterize the mechanism by which GM-CSF facilitates systemic recruitment of trafficking tumor cells to tumors.

  4. Cathodal Transcranial Direct Current Stimulation of the Right Wernicke's Area Improves Comprehension in Subacute Stroke Patients

    Science.gov (United States)

    You, Dae Sang; Kim, Dae-Yul; Chun, Min Ho; Jung, Seung Eun; Park, Sung Jong

    2011-01-01

    Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and…

  5. Recruitment order of quadriceps motor units: femoral nerve vs. direct quadriceps stimulation.

    Science.gov (United States)

    Rodriguez-Falces, Javier; Place, Nicolas

    2013-12-01

    To investigate potential differences in the recruitment order of motor units (MUs) in the quadriceps femoris when electrical stimulation is applied over the quadriceps belly versus the femoral nerve. M-waves and mechanical twitches were evoked using femoral nerve stimulation and direct quadriceps stimulation of gradually increasing intensity from 20 young, healthy subjects. Recruitment order was investigated by analysing the time-to-peak twitch and the time interval from the stimulus artefact to the M-wave positive peak (M-wave latency) for the vastus medialis (VM) and vastus lateralis (VL) muscles. During femoral nerve stimulation, time-to-peak twitch and M-wave latency decreased consistently (P  0.05). For the VM muscle, M-wave latency decreased with increasing stimulation level for both femoral nerve and direct quadriceps stimulation, whereas, for the VL muscle, the variation of M-wave latency with stimulus intensity was different for the two stimulation geometries (P recruitment order during direct quadriceps stimulation was more complex, depending ultimately on the architecture of the peripheral nerve and its terminal branches below the stimulating electrodes for each muscle. For the VM, MUs were orderly recruited for both stimulation geometries, whereas, for the VL muscle, MUs were orderly recruited for femoral nerve stimulation, but followed no particular order for direct quadriceps stimulation.

  6. Nonmuscle myosin IIA and IIB differentially contribute to intrinsic and directed migration of human embryonic lung fibroblasts.

    Science.gov (United States)

    Kuragano, Masahiro; Murakami, Yota; Takahashi, Masayuki

    2018-03-25

    Nonmuscle myosin II (NMII) plays an essential role in directional cell migration. In this study, we investigated the roles of NMII isoforms (NMIIA and NMIIB) in the migration of human embryonic lung fibroblasts, which exhibit directionally persistent migration in an intrinsic manner. NMIIA-knockdown (KD) cells migrated unsteadily, but their direction of migration was approximately maintained. By contrast, NMIIB-KD cells occasionally reversed their direction of migration. Lamellipodium-like protrusions formed in the posterior region of NMIIB-KD cells prior to reversal of the migration direction. Moreover, NMIIB KD led to elongation of the posterior region in migrating cells, probably due to the lack of load-bearing stress fibers in this area. These results suggest that NMIIA plays a role in steering migration by maintaining stable protrusions in the anterior region, whereas NMIIB plays a role in maintenance of front-rear polarity by preventing aberrant protrusion formation in the posterior region. These distinct functions of NMIIA and NMIIB might promote intrinsic and directed migration of normal human fibroblasts. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Multiday Transcranial Direct Current Stimulation Causes Clinically Insignificant Changes in Childhood Dystonia: A Pilot Study.

    Science.gov (United States)

    Bhanpuri, Nasir H; Bertucco, Matteo; Young, Scott J; Lee, Annie A; Sanger, Terence D

    2015-10-01

    Abnormal motor cortex activity is common in dystonia. Cathodal transcranial direct current stimulation may alter cortical activity by decreasing excitability while anodal stimulation may increase motor learning. Previous results showed that a single session of cathodal transcranial direct current stimulation can improve symptoms in childhood dystonia. Here we performed a 5-day, sham-controlled, double-blind, crossover study, where we measured tracking and muscle overflow in a myocontrol-based task. We applied cathodal and anodal transcranial direct current stimulation (2 mA, 9 minutes per day). For cathodal transcranial direct current stimulation (7 participants), 3 subjects showed improvements whereas 2 showed worsening in overflow or tracking error. The effect size was small (about 1% of maximum voluntary contraction) and not clinically meaningful. For anodal transcranial direct current stimulation (6 participants), none showed improvement, whereas 5 showed worsening. Thus, multiday cathodal transcranial direct current stimulation reduced symptoms in some children but not to a clinically meaningful extent, whereas anodal transcranial direct current stimulation worsened symptoms. Our results do not support transcranial direct current stimulation as clinically viable for treating childhood dystonia. © The Author(s) 2015.

  8. Multitarget transcranial direct current stimulation for freezing of gait in Parkinson's disease.

    Science.gov (United States)

    Dagan, Moria; Herman, Talia; Harrison, Rachel; Zhou, Junhong; Giladi, Nir; Ruffini, Giulio; Manor, Brad; Hausdorff, Jeffrey M

    2018-04-01

    Recent findings suggest that transcranial direct current stimulation of the primary motor cortex may ameliorate freezing of gait. However, the effects of multitarget simultaneous stimulation of motor and cognitive networks are mostly unknown. The objective of this study was to evaluate the effects of multitarget transcranial direct current stimulation of the primary motor cortex and left dorsolateral prefrontal cortex on freezing of gait and related outcomes. Twenty patients with Parkinson's disease and freezing of gait received 20 minutes of transcranial direct current stimulation on 3 separate visits. Transcranial direct current stimulation targeted the primary motor cortex and left dorsolateral prefrontal cortex simultaneously, primary motor cortex only, or sham stimulation (order randomized and double-blinded assessments). Participants completed a freezing of gait-provoking test, the Timed Up and Go, and the Stroop test before and after each transcranial direct current stimulation session. Performance on the freezing of gait-provoking test (P = 0.010), Timed Up and Go (P = 0.006), and the Stroop test (P = 0.016) improved after simultaneous stimulation of the primary motor cortex and left dorsolateral prefrontal cortex, but not after primary motor cortex only or sham stimulation. Transcranial direct current stimulation designed to simultaneously target motor and cognitive regions apparently induces immediate aftereffects in the brain that translate into reduced freezing of gait and improvements in executive function and mobility. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

  9. Sensing of substratum rigidity and directional migration by fast-crawling cells

    Science.gov (United States)

    Okimura, Chika; Sakumura, Yuichi; Shimabukuro, Katsuya; Iwadate, Yoshiaki

    2018-05-01

    Living cells sense the mechanical properties of their surrounding environment and respond accordingly. Crawling cells detect the rigidity of their substratum and migrate in certain directions. They can be classified into two categories: slow-moving and fast-moving cell types. Slow-moving cell types, such as fibroblasts, smooth muscle cells, mesenchymal stem cells, etc., move toward rigid areas on the substratum in response to a rigidity gradient. However, there is not much information on rigidity sensing in fast-moving cell types whose size is ˜10 μ m and migration velocity is ˜10 μ m /min . In this study, we used both isotropic substrata with different rigidities and an anisotropic substratum that is rigid on the x axis but soft on the y axis to demonstrate rigidity sensing by fast-moving Dictyostelium cells and neutrophil-like differentiated HL-60 cells. Dictyostelium cells exerted larger traction forces on a more rigid isotropic substratum. Dictyostelium cells and HL-60 cells migrated in the "soft" direction on the anisotropic substratum, although myosin II-null Dictyostelium cells migrated in random directions, indicating that rigidity sensing of fast-moving cell types differs from that of slow types and is induced by a myosin II-related process.

  10. The role of lipolysis stimulated lipoprotein receptor in breast cancer and directing breast cancer cell behavior.

    Directory of Open Access Journals (Sweden)

    Denise K Reaves

    Full Text Available The claudin-low molecular subtype of breast cancer is of particular interest for clinically the majority of these tumors are poor prognosis, triple negative, invasive ductal carcinomas. Claudin-low tumors are characterized by cancer stem cell-like features and low expression of cell junction and adhesion proteins. Herein, we sought to define the role of lipolysis stimulated lipoprotein receptor (LSR in breast cancer and cancer cell behavior as LSR was recently correlated with tumor-initiating features. We show that LSR was expressed in epithelium, endothelium, and stromal cells within the healthy breast tissue, as well as in tumor epithelium. In primary breast tumor bioposies, LSR expression was significantly correlated with invasive ductal carcinomas compared to invasive lobular carcinomas, as well as ERα positive tumors and breast cancer cell lines. LSR levels were significantly reduced in claudin-low breast cancer cell lines and functional studies illustrated that re-introduction of LSR into a claudin-low cell line suppressed the EMT phenotype and reduced individual cell migration. However, our data suggest that LSR may promote collective cell migration. Re-introduction of LSR in claudin-low breast cancer cell lines reestablished tight junction protein expression and correlated with transepithelial electrical resistance, thereby reverting claudin-low lines to other intrinsic molecular subtypes. Moreover, overexpression of LSR altered gene expression of pathways involved in transformation and tumorigenesis as well as enhanced proliferation and survival in anchorage independent conditions, highlighting that reestablishment of LSR signaling promotes aggressive/tumor initiating cell behaviors. Collectively, these data highlight a direct role for LSR in driving aggressive breast cancer behavior.

  11. Investigation of in vitro bone cell adhesion and proliferation on Ti using direct current stimulation

    International Nuclear Information System (INIS)

    Bodhak, Subhadip; Bose, Susmita; Kinsel, William C.; Bandyopadhyay, Amit

    2012-01-01

    Our objective was to establish an in vitro cell culture protocol to improve bone cell attachment and proliferation on Ti substrate using direct current stimulation. For this purpose, a custom made electrical stimulator was developed and a varying range of direct currents, from 5 to 25 μA, was used to study the current stimulation effect on bone cells cultured on conducting Ti samples in vitro. Cell–material interaction was studied for a maximum of 5 days by culturing with human fetal osteoblast cells (hFOB). The direct current was applied in every 8 h time interval and the duration of electrical stimulation was kept constant at 15 min for all cases. In vitro results showed that direct current stimulation significantly favored bone cell attachment and proliferation in comparison to nonstimulated Ti surface. Immunochemistry and confocal microscopy results confirmed that the cell adhesion was most pronounced on 25 μA direct current stimulated Ti surfaces as hFOB cells expressed higher vinculin protein with increasing amount of direct current. Furthermore, MTT assay results established that cells grew 30% higher in number under 25 μA electrical stimulation as compared to nonstimulated Ti surface after 5 days of culture period. In this work we have successfully established a simple and cost effective in vitro protocol offering easy and rapid analysis of bone cell–material interaction which can be used in promotion of bone cell attachment and growth on Ti substrate using direct current electrical stimulation in an in vitro model. - Highlights: ► D.C. stimulation was used to enhance in vitro bone cell adhesion and proliferation. ► Cells cultured on Ti were stimulated by using a custom made electrical stimulator. ► Optimization was performed by using a varying range of direct currents ∼ 5 to 25 μA. ► 25 μA stimulation was found most beneficial for promotion of cell adhesion/growth.

  12. Lck/PLCγ control migration and proliferation of interleukin (IL)-2-stimulated T cells via the Rac1 GTPase/glycogen phosphorylase pathway.

    Science.gov (United States)

    Llavero, Francisco; Artaso, Alain; Lacerda, Hadriano M; Parada, Luis A; Zugaza, José L

    2016-11-01

    Recently, we have reported that the IL-2-stimulated T cells activate PKCθ in order to phosphorylate the serine residues of αPIX-RhoGEF, and to switch on the Rac1/PYGM pathway resulting in T cell migration and proliferation. However, the molecular mechanism connecting the activated IL-2-R with the PKCθ/αPIX/Rac1/PYGM pathway is still unknown. In this study, the use of a combined pharmacological and genetic approach identified Lck, a Src family member, as the tyrosine kinase phosphorylating PLCγ leading to Rac1 and PYGM activation in the IL-2-stimulated Kit 225 T cells via the PKCθ/αPIX pathway. The PLCγ tyrosine phosphorylation was required to activate first PKCθ, and then αPIX and Rac1/PYGM. The results presented here delineate a novel signalling pathway ranking equally in importance to the three major pathways controlled by the IL-2-R, i.e. PI3K, Ras/MAPK and JAK/STAT pathways. The overall evidence strongly indicates that the central biological role of the novel IL-2-R/Lck/PLCγ/PKCθ/αPIX/Rac1/PYGM signalling pathway is directly related to the control of fundamental cellular processes such as T cell migration and proliferation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Subcortical structures in humans can be facilitated by transcranial direct current stimulation

    NARCIS (Netherlands)

    Nonnekes, Johan Hendrik; Arrogi, Anass; Munneke, Moniek; van Asseldonk, Edwin H.F.; Oude Nijhuis, Lars; Geurts, Alexander; Weerdesteyn, Vivian

    2014-01-01

    BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that alters cortical excitability via application of a weak direct current. Interestingly, it was demonstrated in cats that tDCS can facilitate subcortical structures as well (Bolzonii et al., J

  14. Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells

    DEFF Research Database (Denmark)

    Czuchra, Aleksandra; Wu, Xunwei; Meyer, Hannelore

    2005-01-01

    of Cdc42 did not affect filopodium or lamellipodium formation and had no significant influence on the speed of directed migration nor on mitosis. Cdc42-deficient cells displayed a more elongated cell shape and had a reduced area. Furthermore, directionality during migration and reorientation of the Golgi...

  15. Control of directed cell migration in vivo by membrane-to-cortex attachment.

    Directory of Open Access Journals (Sweden)

    Alba Diz-Muñoz

    2010-11-01

    Full Text Available Cell shape and motility are primarily controlled by cellular mechanics. The attachment of the plasma membrane to the underlying actomyosin cortex has been proposed to be important for cellular processes involving membrane deformation. However, little is known about the actual function of membrane-to-cortex attachment (MCA in cell protrusion formation and migration, in particular in the context of the developing embryo. Here, we use a multidisciplinary approach to study MCA in zebrafish mesoderm and endoderm (mesendoderm germ layer progenitor cells, which migrate using a combination of different protrusion types, namely, lamellipodia, filopodia, and blebs, during zebrafish gastrulation. By interfering with the activity of molecules linking the cortex to the membrane and measuring resulting changes in MCA by atomic force microscopy, we show that reducing MCA in mesendoderm progenitors increases the proportion of cellular blebs and reduces the directionality of cell migration. We propose that MCA is a key parameter controlling the relative proportions of different cell protrusion types in mesendoderm progenitors, and thus is key in controlling directed migration during gastrulation.

  16. Validating computationally predicted TMS stimulation areas using direct electrical stimulation in patients with brain tumors near precentral regions.

    Science.gov (United States)

    Opitz, Alexander; Zafar, Noman; Bockermann, Volker; Rohde, Veit; Paulus, Walter

    2014-01-01

    The spatial extent of transcranial magnetic stimulation (TMS) is of paramount interest for all studies employing this method. It is generally assumed that the induced electric field is the crucial parameter to determine which cortical regions are excited. While it is difficult to directly measure the electric field, one usually relies on computational models to estimate the electric field distribution. Direct electrical stimulation (DES) is a local brain stimulation method generally considered the gold standard to map structure-function relationships in the brain. Its application is typically limited to patients undergoing brain surgery. In this study we compare the computationally predicted stimulation area in TMS with the DES area in six patients with tumors near precentral regions. We combine a motor evoked potential (MEP) mapping experiment for both TMS and DES with realistic individual finite element method (FEM) simulations of the electric field distribution during TMS and DES. On average, stimulation areas in TMS and DES show an overlap of up to 80%, thus validating our computational physiology approach to estimate TMS excitation volumes. Our results can help in understanding the spatial spread of TMS effects and in optimizing stimulation protocols to more specifically target certain cortical regions based on computational modeling.

  17. Human bone marrow mesenchymal stem cells secrete endocannabinoids that stimulate in vitro hematopoietic stem cell migration effectively comparable to beta-adrenergic stimulation.

    Science.gov (United States)

    Köse, Sevil; Aerts-Kaya, Fatima; Köprü, Çağla Zübeyde; Nemutlu, Emirhan; Kuşkonmaz, Barış; Karaosmanoğlu, Beren; Taşkıran, Ekim Zihni; Altun, Belgin; Uçkan Çetinkaya, Duygu; Korkusuz, Petek

    2018-01-01

    Granulocyte colony-stimulating factor (G-CSF) is a well-known hematopoietic stem cell (HSC)-mobilizing agent used in both allogeneic and autologous transplantation. However, a proportion of patients or healthy donors fail to mobilize a sufficient number of cells. New mobilization agents are therefore needed. Endocannabinoids (eCBs) are endogenous lipid mediators generated in the brain and peripheral tissues and activate the cannabinoid receptors CB1 and CB2. We suggest that eCBs may act as mobilizers of HSCs from the bone marrow (BM) under stress conditions as beta-adrenergic receptors (Adrβ). This study demonstrates that BM mesenchymal stem cells (MSCs) secrete anandamide (AEA) and 2-arachidonylglycerol (2-AG) and the peripheral blood (PB) and BM microenvironment contain AEA and 2-AG. 2-AG levels are significantly higher in PB of the G-CSF-treated group compared with BM plasma. BM mononuclear cells (MNCs) and CD34 + HSCs express CB1, CB2, and Adrβ subtypes. CD34 + HSCs had higher CB1 and CB2 receptor expression in G-CSF-untreated and G-CSF-treated groups compared with MSCs. MNCs but not MSCs expressed CB1 and CB2 receptors based on qRT-PCR and flow cytometry. AEA- and 2-AG-stimulated HSC migration was blocked by eCB receptor antagonists in an in vitro migration assay. In conclusion, components of the eCB system and their interaction with Adrβ subtypes were demonstrated on HSCs and MSCs of G-CSF-treated and G-CSF-untreated healthy donors in vitro, revealing that eCBs might be potential candidates to enhance or facilitate G-CSF-mediated HSC migration under stress conditions in a clinical setting. Copyright © 2018 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  18. Transcranial Magnetic Stimulation in Child Neurology: Current and Future Directions

    Science.gov (United States)

    Frye, Richard E.; Rotenberg, Alexander; Ousley, Molliann; Pascual-Leone, Alvaro

    2008-01-01

    Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation based on the principle of electromagnetic induction, where small intracranial electric currents are generated by a powerful, rapidly changing extracranial magnetic field. Over the past 2 decades TMS has shown promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disease in adults, but has been used on a more limited basis in children. We reviewed the literature to identify potential diagnostic and therapeutic applications of TMS in child neurology and also its safety in pediatrics. Although TMS has not been associated with any serious side effects in children and appears to be well tolerated, general safety guidelines should be established. The potential for applications of TMS in child neurology and psychiatry is significant. Given its excellent safety profile and possible therapeutic effect, this technique should develop as an important tool in pediatric neurology over the next decade. PMID:18056688

  19. Transcranial direct current stimulation for motor recovery of upper limb function after stroke.

    Science.gov (United States)

    Lüdemann-Podubecká, Jitka; Bösl, Kathrin; Rothhardt, Sandra; Verheyden, Geert; Nowak, Dennis Alexander

    2014-11-01

    Changes in neural processing after stroke have been postulated to impede recovery from stroke. Transcranial direct current stimulation has the potential to alter cortico-spinal excitability and thereby might be beneficial in stroke recovery. We review the pertinent literature prior to 30/09/2013 on transcranial direct current stimulation in promoting motor recovery of the affected upper limb after stroke. We found overall 23 trials (they included 523 participants). All stimulation protocols pride on interhemispheric imbalance model. In a comparative approach, methodology and effectiveness of (a) facilitation of the affected hemisphere, (b) inhibition of the unaffected hemisphere and (c) combined application of transcranial direct current stimulation over the affected and unaffected hemispheres to treat impaired hand function after stroke are presented. Transcranial direct current stimulation is associated with improvement of the affected upper limb after stroke, but current evidence does not support its routine use. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Migrated hydrocarbons in outcrop samples: revised petroleum exploration directions in the Tarim Basin

    Energy Technology Data Exchange (ETDEWEB)

    Li, Maowen; Snowdon, Lloyd [Geological Survey of Canada, Calgary, AB (Canada); Xiao, Zhongyao [CNPC Tarim Petroleum Exploration Bureau, Kuerle, Xinjiang (China); Lin, Renzi [Petroleum Univ., Changping, Beijing (China); Wang, Peirong; Hou, Dujie [Jianghan Petroleum Univ., Hubei (China); Zhang, Linye [SINOPEC Shengli Petroleum Bureau, Dongying, Shandong (China); Zhang, Shuichang; Liang, Digang [Research Inst. of Petroleum Exploration and Development, Beijing (China)

    2000-07-01

    The application of age-specific biomarker distributions established from mature exploration areas of the Tarim Basin, northwestern China, indicates that most Carboniferous-Permian outcrop samples in the eastern segment of the Southwest Depression, previously believed to have significant petroleum source potential, in fact contain migrated hydrocarbons derived from Cambrian-Lower Ordovician strata. New geochemical results have led to a major revision of petroleum exploration directions in this area. (Author)

  1. Are Participants Aware of the Type and Intensity of Transcranial Direct Current Stimulation?

    Directory of Open Access Journals (Sweden)

    Matthew F Tang

    Full Text Available Transcranial direct current stimulation (tDCS is commonly used to alter cortical excitability but no experimental study has yet determined whether human participants are able to distinguish between the different types (anodal, cathodal, and sham of stimulation. If they can then they are not blind to experimental conditions. We determined whether participants could identify different types of stimulation (anodal, cathodal, and sham and current strengths after experiencing the sensations of stimulation during current onset and offset (which are associated with the most intense sensations in Experiment 1 and also with a prolonged period of stimulation in Experiment 2. We first familiarized participants with anodal, cathodal, and sham stimulation at both 1 and 2 mA over either primary motor or visual cortex while their sensitivity to small changes in visual stimuli was assessed. The different stimulation types were then applied for a short (Experiment 1 or extended (Experiment 2 period with participants indicating the type and strength of the stimulation on the basis of the evoked sensations. Participants were able to identify the intensity of stimulation with shorter, but not longer periods, of stimulation at better than chance levels but identification of the different stimulation types was at chance levels. This result suggests that even after exposing participants to stimulation, and ensuring they are fully aware of the existence of a sham condition, they are unable to identify the type of stimulation from transient changes in stimulation intensity or from more prolonged stimulation. Thus participants are able to identify intensity of stimulation but not the type of stimulation.

  2. Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils.

    Science.gov (United States)

    Liu, L Y; Wang, H; Xenakis, J J; Spencer, L A

    2015-07-01

    Priming with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM-CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell-intrinsic cues. This study investigates the hypothesis that the priming-induced enhanced migration of human eosinophils requires the Notch signaling pathway. Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo. Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM-CSF priming impaired priming-enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK-MAPK activation was required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor. These data identify Notch signaling as an intrinsic pathway central to GM-CSF priming-induced eosinophil tissue migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Neuroprotective effect of cathodal transcranial direct current stimulation in a rat stroke model.

    Science.gov (United States)

    Notturno, Francesca; Pace, Marta; Zappasodi, Filippo; Cam, Etrugul; Bassetti, Claudio L; Uncini, Antonino

    2014-07-15

    Experimental focal brain ischemia generates in the penumbra recurrent depolarizations which spread across the injured cortex inducing infarct growth. Transcranial direct current stimulation can induce a lasting, polarity-specific, modulation of cortical excitability. To verify whether cathodal transcranial direct current stimulation could reduce the infarct size and the number of depolarizations, focal ischemia was induced in the rat by the 3 vessels occlusion technique. In the first experiment 12 ischemic rats received cathodal stimulation (alternating 15 min on and 15 min off) starting 45 min after middle cerebral artery occlusion and lasting 4 h. In the second experiment 12 ischemic rats received cathodal transcranial direct current stimulation with the same protocol but starting soon after middle cerebral artery occlusion and lasting 6 h. In both experiments controls were 12 ischemic rats not receiving stimulation. Cathodal stimulation reduced the infarct volume in the first experiment by 20% (p=0.002) and in the second by 30% (p=0.003). The area of cerebral infarction was smaller in animals receiving cathodal stimulation in both experiments (p=0.005). Cathodal stimulation reduced the number of depolarizations (p=0.023) and infarct volume correlated with the number of depolarizations (p=0.048). Our findings indicate that cathodal transcranial direct current stimulation exert a neuroprotective effect in the acute phase of stroke possibly decreasing the number of spreading depolarizations. These findings may have translational relevance and open a new avenue in neuroprotection of stroke in humans. Copyright © 2014. Published by Elsevier B.V.

  4. Migration-driven aggregation behaviors in job markets with direct foreign immigration

    International Nuclear Information System (INIS)

    Sun, Ruoyan

    2014-01-01

    This Letter introduces a new set of rate equations describing migration-driven aggregation behaviors in job markets with direct foreign immigration. We divide the job market into two groups: native and immigrant. A reversible migration of jobs exists in both groups. The interaction between two groups creates a birth and death rate for the native job market. We find out that regardless of initial conditions or the rates, the total number of cities with either job markets decreases. This indicates a more concentrated job markets for both groups in the future. On the other hand, jobs available for immigrants increase over time but the ones for natives are uncertain. The native job markets can either expand or shrink or remain constant due to combined effects of birth and death rates. Finally, we test our analytical results with the population data of all counties in the US from 2000 to 2011. - Highlights: • A rate equation model describing the migration of job market is proposed. • We study the migration-driven aggregation behaviors over the longer term. • An illustrative example is given to check the effectiveness of the model

  5. Migration-driven aggregation behaviors in job markets with direct foreign immigration

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Ruoyan

    2014-09-05

    This Letter introduces a new set of rate equations describing migration-driven aggregation behaviors in job markets with direct foreign immigration. We divide the job market into two groups: native and immigrant. A reversible migration of jobs exists in both groups. The interaction between two groups creates a birth and death rate for the native job market. We find out that regardless of initial conditions or the rates, the total number of cities with either job markets decreases. This indicates a more concentrated job markets for both groups in the future. On the other hand, jobs available for immigrants increase over time but the ones for natives are uncertain. The native job markets can either expand or shrink or remain constant due to combined effects of birth and death rates. Finally, we test our analytical results with the population data of all counties in the US from 2000 to 2011. - Highlights: • A rate equation model describing the migration of job market is proposed. • We study the migration-driven aggregation behaviors over the longer term. • An illustrative example is given to check the effectiveness of the model.

  6. Lactate stimulates migration of human cancer cells: possible consequences for the development of metastases

    International Nuclear Information System (INIS)

    Walenta, S.; Springborn, C.; Zilkens, S.; Groetzebach, B.; Mueller-Klieser, W.

    2003-01-01

    A high lactate production is a common feature of the majority of malignant tumors. In several independent series of clinical studies we could show that a high lactate content in primary human carcinomas was correlated with a higher incidence of metastases and a reduced patient survival, compared to tumors with a lower lactate content. Since one of the early events in metastasis is the active movement of cancer cells out of the primary tumor site, we have investigated the effect of exogenous lactate on the migratory activity of human cancer cells in vitro. - A 48 well micro chemotaxis chamber was used to quantify the migration of SQ20B and PCI13 cells which were derived from human head and neck squamous cell carcinomas. The chamber consists of bottom and a top Lucite slide, separated by a gelatin covered polycarbonate membrane with pores of 8 μm, where cells eventually migrate through. - In summary, there was a time and concentration dependent unidirectional enhancement of cell migration. For example, cells were incubated in growth medium supplemented with 20 mM L-lactate. On the average, the rate of cell migration was significantly enhanced (p < 0.001) to 139 % for SQ20 and 136 % for PCI cells, compared to untreated control cells (100 %). No effects on cell migration were detected for culture media containing 20 mM D-lactate or 20 mM sodium chloride. These results suggest that an elevated lactate production may not only be an accompanying phenomenon of malignant transformation, but may also play an active part in tumor progression by enhancing cell migration and dissemination of potentially metastatic cells from primary lesions

  7. Clinical Research with Transcranial Direct Current Stimulation (tDCS): Challenges and Future Directions

    Science.gov (United States)

    Brunoni, Andre Russowsky; Nitsche, Michael A.; Bolognini, Nadia; Bikson, Marom; Wagner, Tim; Merabet, Lotfi; Edwards, Dylan J.; Valero-Cabre, Antoni; Rotenberg, Alexander; Pascual-Leone, Alvaro; Ferrucci, Roberta; Priori, Alberto; Boggio, Paulo; Fregni, Felipe

    2011-01-01

    Background Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past ten years, tDCS physiological mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodological, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. Methods We convened a workgroup of researchers in the field to review, discuss and provide updates and key challenges of neuromodulation use for clinical research. Main Findings/Discussion We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (i) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (ii) methodological aspects related to the clinical research of tDCS as divided according to study phase (i.e., preclinical, phase I, phase II and phase III studies); (iii) ethical and regulatory concerns; (iv) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS. PMID:22037126

  8. Combined motor point associative stimulation (MPAS) and transcranial direct current stimulation (tDCS) improves plateaued manual dexterity performance.

    Science.gov (United States)

    Hoseini, Najmeh; Munoz-Rubke, Felipe; Wan, Hsuan-Yu; Block, Hannah J

    2016-10-28

    Motor point associative stimulation (MPAS) in hand muscles is known to modify motor cortex excitability and improve learning rate, but not plateau of performance, in manual dexterity tasks. Central stimulation of motor cortex, such as transcranial direct current stimulation (tDCS), can have similar effects if accompanied by motor practice, which can be difficult and tiring for patients. Here we asked whether adding tDCS to MPAS could improve manual dexterity in healthy individuals who are already performing at their plateau, with no motor practice during stimulation. We hypothesized that MPAS could provide enough coordinated muscle activity to make motor practice unnecessary, and that this combination of stimulation techniques could yield improvements even in subjects at or near their peak. If so, this approach could have a substantial effect on patients with impaired dexterity, who are far from their peak. MPAS was applied for 30min to two right hand muscles important for manual dexterity. tDCS was simultaneously applied over left sensorimotor cortex. The motor cortex input/output (I/O) curve was assessed with transcranial magnetic stimulation (TMS), and manual dexterity was assessed with the Purdue Pegboard Test. Compared to sham or cathodal tDCS combined with MPAS, anodal tDCS combined with MPAS significantly increased the plateau of manual dexterity. This result suggests that MPAS has the potential to substitute for motor practice in mediating a beneficial effect of tDCS on manual dexterity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Onsite-effects of dual-hemisphere versus conventional single-hemisphere transcranial direct current stimulation: A functional MRI study.

    Science.gov (United States)

    Kwon, Yong Hyun; Jang, Sung Ho

    2012-08-25

    We performed functional MRI examinations in six right-handed healthy subjects. During functional MRI scanning, transcranial direct current stimulation was delivered with the anode over the right primary sensorimotor cortex and the cathode over the left primary sensorimotor cortex using dual-hemispheric transcranial direct current stimulation. This was compared to a cathode over the left supraorbital area using conventional single-hemispheric transcranial direct current stimulation. Voxel counts and blood oxygenation level-dependent signal intensities in the right primary sensorimotor cortex regions were estimated and compared between the two transcranial direct current stimulation conditions. Our results showed that dual-hemispheric transcranial direct current stimulation induced greater cortical activities than single-hemispheric transcranial direct current stimulation. These findings suggest that dual-hemispheric transcranial direct current stimulation may provide more effective cortical stimulation than single-hemispheric transcranial direct current stimulation.

  10. Point defects in lines in single crystalline phosphorene: directional migration and tunable band gaps.

    Science.gov (United States)

    Li, Xiuling; Ma, Liang; Wang, Dayong; Zeng, Xiao Cheng; Wu, Xiaojun; Yang, Jinlong

    2016-10-20

    Extended line defects in two-dimensional (2D) materials can play an important role in modulating their electronic properties. During the experimental synthesis of 2D materials, line defects are commonly generated at grain boundaries between domains of different orientations. In this work, twelve types of line-defect structures in single crystalline phosphorene are examined by using first-principles calculations. These line defects are typically formed via migration and aggregation of intrinsic point defects, including the Stone-Wales (SW), single or double vacancy (SV or DV) defects. Our calculated results demonstrate that the migration of point defects in phosphorene is anisotropic, for instance, the lowest migration energy barriers are 1.39 (or 0.40) and 2.58 (or 0.49) eV for SW (or SV) defects in zigzag and armchair directions, respectively. The aggregation of point defects into lines is energetically favorable compared with the separated point defects in phosphorene. In particular, the axis of line defects in phosphorene is direction-selective, depending on the composed point defects. The presence of line defects effectively modulates the electronic properties of phosphorene, rendering the defect-containing phosphorene either metallic or semiconducting with a tunable band gap. Of particular interest is the fact that the SV-based line defect can behave as a metallic wire, suggesting a possibility to fabricate a circuit with subnanometer widths in the semiconducting phosphorene for nanoscale electronic application.

  11. Impact of transcranial direct current stimulation (tDCS) on neuronal functions

    NARCIS (Netherlands)

    Das, S. (Suman); P.J. Holland (Peter); M.A. Frens (Maarten); O. Donchin (Opher)

    2016-01-01

    textabstractTranscranial direct current stimulation (tDCS), a non-invasive brain stimulation technique, modulates neuronal excitability by the application of a small electrical current. The low cost and ease of the technique has driven interest in potential clinical applications. However, outcomes

  12. Effects of Transcranial Direct Current Stimulation (tDCS) on Behaviour and Electrophysiology of Language Production

    Science.gov (United States)

    Wirth, Miranka; Rahman, Rasha Abdel; Kuenecke, Janina; Koenig, Thomas; Horn, Helge; Sommer, Werner; Dierks, Thomas

    2011-01-01

    Excitatory anodal transcranial direct current stimulation (A-tDCS) over the left dorsal prefrontal cortex (DPFC) has been shown to improve language production. The present study examined neurophysiological underpinnings of this effect. In a single-blinded within-subject design, we traced effects of A-tDCS compared to sham stimulation over the left…

  13. Subcortical structures in humans can be facilitated by transcranial direct current stimulation

    NARCIS (Netherlands)

    Nonnekes, J.H.; Arrogi, A.; Munneke, M.A.M.; Asseldonk, E.H. van; Nijhuis, L.B.; Geurts, A.C.H.; Weerdesteyn, V.G.M.

    2014-01-01

    Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that alters cortical excitability. Interestingly, in recent animal studies facilitatory effects of tDCS have also been observed on subcortical structures. Here, we sought to provide evidence for the potential

  14. Subcortical Structures in Humans Can Be Facilitated by Transcranial Direct Current Stimulation

    NARCIS (Netherlands)

    Nonnekes, Johan Hendrik; Arrogi, A.; Munneke, M.A.M.; van Asseldonk, Edwin H.F.; Oude Nijhuis, L.B.; Geurts, A.C.; Weerdesteyn, V.

    2014-01-01

    Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that alters cortical excitability. Interestingly, in recent animal studies facilitatory effects of tDCS have also been observed on subcortical structures. Here, we sought to provide evidence for the potential

  15. Simulating Transcranial Direct Current Stimulation With a Detailed Anisotropic Human Head Model

    NARCIS (Netherlands)

    Rampersad, S.; Janssen, A.J.E.M.; Lucka, F.; Aydin, U.; Lanfer, B.; Lew, S.; Wolters, C.H.; Stegeman, D.F.; Oostendorp, T.F.

    2014-01-01

    Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique able to induce long-lasting changes in cortical excitability that can benefit cognitive functioning and clinical treatment. In order to both better understand the mechanisms behind tDCS and possibly improve

  16. Simulating transcranial direct current stimulation with a detailed anisotropic human head model

    NARCIS (Netherlands)

    Rampersad, S.M.; Janssen, A.M.; Lucka, F.; Aydin, U.; Lanfer, B.; Lew, S.; Wolters, C.H.; Stegeman, D.F.; Oostendorp, T.F.

    2014-01-01

    Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique able to induce long-lasting changes in cortical excitability that can benefit cognitive functioning and clinical treatment. In order to both better understand the mechanisms behind tDCS and possibly improve

  17. SERCA directs cell migration and branching across species and germ layers

    Directory of Open Access Journals (Sweden)

    Danielle V. Bower

    2017-10-01

    Full Text Available Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca2+ reuptake pump (SERCA directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in Drosophila air sac budding. Live imaging of Drosophila tracheogenesis revealed elevated Ca2+ levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca2+ differential, aborting both cell migration and new branching. Activating protein kinase C (PKC rescued Ca2+ in tip cells and restored cell migration and branching. Likewise, inhibiting SERCA abolished mammalian epithelial budding, PKC activation rescued budding, while morphogens did not. Mesoderm (zebrafish angiogenesis and ectoderm (Drosophila nervous system behaved similarly, suggesting a conserved requirement for cell-autonomous Ca2+ signaling, established by SERCA, in iterative budding.

  18. Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans.

    Science.gov (United States)

    Batsikadze, G; Moliadze, V; Paulus, W; Kuo, M-F; Nitsche, M A

    2013-04-01

    Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI

  19. Pressure pain thresholds increase after preconditioning 1 Hz repetitive transcranial magnetic stimulation with transcranial direct current stimulation.

    Science.gov (United States)

    Moloney, Tonya M; Witney, Alice G

    2014-01-01

    The primary motor cortex (M1) is an effective target of non-invasive cortical stimulation (NICS) for pain threshold modulation. It has been suggested that the initial level of cortical excitability of M1 plays a key role in the plastic effects of NICS. Here we investigate whether transcranial direct current stimulation (tDCS) primed 1 Hz repetitive transcranial magnetic stimulation (rTMS) modulates experimental pressure pain thresholds and if this is related to observed alterations in cortical excitability. 15 healthy, male participants received 10 min 1 mA anodal, cathodal and sham tDCS to the left M1 before 15 min 1 Hz rTMS in separate sessions over a period of 3 weeks. Motor cortical excitability was recorded at baseline, post-tDCS priming and post-rTMS through recording motor evoked potentials (MEPs) from right FDI muscle. Pressure pain thresholds were determined by quantitative sensory testing (QST) through a computerized algometer, on the palmar thenar of the right hand pre- and post-stimulation. Cathodal tDCS-primed 1 Hz-rTMS was found to reverse the expected suppressive effect of 1 Hz rTMS on cortical excitability; leading to an overall increase in activity (ppain thresholds (ppain. This study demonstrates that priming the M1 before stimulation of 1 Hz-rTMS modulates experimental pressure pain thresholds in a safe and controlled manner, producing a form of analgesia.

  20. Comments on: “Transcranial Direct Current Stimulation for Obsessive-Compulsive Disorder: A Systematic Review”

    Directory of Open Access Journals (Sweden)

    Mohammad Alwardat

    2018-03-01

    Full Text Available Dear Editor, Brunelin et al. [1] recently conducted a systematic review that evaluated the effect of applied transcranial direct current stimulation (tDCS on patients with obsessive compulsive disorder (OCD.[...

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

    Science.gov (United States)

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

    2016-06-01

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

  2. Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord

    Science.gov (United States)

    Xia, Peng; Pan, Su; Cheng, Jieping; Yang, Maoguang; Qi, Zhiping; Hou, Tingting; Yang, Xiaoyu

    2014-01-01

    Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtubule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of microtubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord. PMID:25374590

  3. Safety Parameter Considerations of Anodal Transcranial Direct Current Stimulation in Rats

    Science.gov (United States)

    2017-10-01

    Richardson, J.D., Baker, J.M., Rorden, C., 2011. Transcranial direct current stimulation improves naming reaction time in fluent aphasia: a...AFRL-RH-WP-TR-2017-0069 Safety parameter considerations of anodal transcranial Direct Current Stimulation in rats R. Andy McKinley...response, including the time for reviewing instructions, searching existing data sources, searching existing data sources, gathering and maintaining the

  4. Transcranial direct-current stimulation induced in stroke patients with aphasia: a prospective experimental cohort study

    OpenAIRE

    Santos,Michele Devido; Gagliardi,Rubens José; Mac-Kay,Ana Paula Machado Goyano; Boggio,Paulo Sergio; Lianza,Roberta; Fregni,Felipe

    2013-01-01

    CONTEXT AND OBJECTIVE: Previous animal and human studies have shown that transcranial direct current stimulation can induce significant and lasting neuroplasticity and may improve language recovery in patients with aphasia. The objective of the study was to describe a cohort of patients with aphasia after stroke who were treated with transcranial direct current stimulation. DESIGN AND SETTING: Prospective cohort study developed in a public university hospital. METHODS: Nineteen patients with ...

  5. Direct electrical stimulation of human cortex evokes high gamma activity that predicts conscious somatosensory perception

    Science.gov (United States)

    Muller, Leah; Rolston, John D.; Fox, Neal P.; Knowlton, Robert; Rao, Vikram R.; Chang, Edward F.

    2018-04-01

    Objective. Direct electrical stimulation (DES) is a clinical gold standard for human brain mapping and readily evokes conscious percepts, yet the neurophysiological changes underlying these percepts are not well understood. Approach. To determine the neural correlates of DES, we stimulated the somatosensory cortex of ten human participants at frequency-amplitude combinations that both elicited and failed to elicit conscious percepts, meanwhile recording neural activity directly surrounding the stimulation site. We then compared the neural activity of perceived trials to that of non-perceived trials. Main results. We found that stimulation evokes distributed high gamma activity, which correlates with conscious perception better than stimulation parameters themselves. Significance. Our findings suggest that high gamma activity is a reliable biomarker for perception evoked by both natural and electrical stimuli.

  6. Mechanosensitivity of Embryonic Neurites Promotes Their Directional Extension and Schwann Cells Progenitors Migration

    Directory of Open Access Journals (Sweden)

    Gonzalo Rosso

    2017-11-01

    Full Text Available Background/Aims: Migration of Schwann cells (SCs progenitors and neurite outgrowth from embryonic dorsal root ganglions (DRGs are two central events during the development of the peripheral nervous system (PNS. How these two enthralling events preceding myelination are promoted is of great relevance from basic research and clinical aspects alike. Recent evidence demonstrates that biophysical cues (extracellular matrix stiffness and biochemical signaling act in concert to regulate PNS myelination. Microenvironment stiffness of SCs progenitors and embryonic neurites dynamically changes during development. Methods: DRG explants were isolated from day 12.5 to 13.5 mice embryos and plated on laminin-coated substrates with varied stiffness values. After 4 days in culture and immunostaining with specific markers, neurite outgrowth pattern, SCs progenitors migration, and growth cone shape and advance were analyzed with confocal fluorescence microscopy. Results: We found out that growing substrate stiffness promotes directional neurite outgrowth, SCs progenitors migration, growth cone advance and presumably axons fasciculation. Conclusions: DRG explants are in vitro models for the research of PNS development, myelination and regeneration. Consequently, we conclude the following: Our observations point out the importance of mechanosensitivity for the PNS. At the same time, they prompt the investigation of the important yet unclear links between PNS biomechanics and inherited neuropathies with myelination disorders such as Charcot-Marie-Tooth 1A and hereditary neuropathy with liability to pressure palsies. Finally, they encourage the consideration of mechanosensitivity in bioengineering of scaffolds to aid nerve regeneration after injury.

  7. Mertk deficiency affects macrophage directional migration via disruption of cytoskeletal organization.

    Directory of Open Access Journals (Sweden)

    Yong Tang

    Full Text Available Mertk belongs to the Tyro3, Axl and Mertk (TAM family of receptor tyrosine kinases, and plays a pivotal role in regulation of cytoskeletal rearrangement during phagocytosis. Phagocytosis by either professional or non-professional phagocytes is impaired in the Mertk deficient individual. In the present study, we further investigated the effects of Mertk mutation on peritoneal macrophage morphology, attachment, spreading and movement. Mertk-mutated macrophages exhibited decreased attachment, weak spreading, loss of spindle-like body shape and lack of clear leading and trailing edges within the first few hours of culture, as observed by environmental scanning electron microscopy. Time-lapse video photography recording showed that macrophage without Mertk conducted mainly random movement with oscillating swing around the cell body, and lost the directional migration action seen on the WT cells. Western blotting showed a decreased phosphorylation of focal adhesion kinase (FAK. Immunocytochemistry revealed that actin filaments and dynamic protein myosin II failed to concentrate in the leading edge of migrating cells. Microtubules were localized mainly in one side of mutant cell body, with no clear MTOC and associated radially-distributed microtubule bundles, which were clearly evident in the WT cells. Our results suggest that Mertk deficiency affects not only phagocytosis but also cell shape and migration, likely through a common regulatory mechanism on cytoskeletons.

  8. Iduronic acid in chondroitin/dermatan sulfate affects directional migration of aortic smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Barbara Bartolini

    Full Text Available Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS proteoglycans that regulate extracellular matrix organization and cell behavior in normal and pathological conditions. A unique feature of CS/DS proteoglycans is the presence of iduronic acid (IdoA, catalyzed by two DS epimerases. Functional ablation of DS-epi1, the main epimerase in these cells, resulted in a major reduction of IdoA both on cell surface and in secreted CS/DS proteoglycans. Downregulation of IdoA led to delayed ability to re-populate wounded areas due to loss of directional persistence of migration. DS-epi1-/- aortic smooth muscle cells, however, had not lost the general property of migration showing even increased speed of movement compared to wild type cells. Where the cell membrane adheres to the substratum, stress fibers were denser whereas focal adhesion sites were fewer. Total cellular expression of focal adhesion kinase (FAK and phospho-FAK (pFAK was decreased in mutant cells compared to control cells. As many pathological conditions are dependent on migration, modulation of IdoA content may point to therapeutic strategies for diseases such as cancer and atherosclerosis.

  9. Interleukin-6 stimulates Akt and p38 MAPK phosphorylation and fibroblast migration in non-diabetic but not diabetic mice.

    Directory of Open Access Journals (Sweden)

    Tsubame Nishikai-Yan Shen

    Full Text Available Persistent inflammatory environment and abnormal macrophage activation are characteristics of chronic diabetic wounds. Here, we attempted to characterize the differences in macrophage activation and temporal variations in cytokine expression in diabetic and non-diabetic wounds, with a focus on interleukin (IL-6 mRNA expression and the p38 MAPK and PI3K/Akt signaling pathways. Cutaneous wound closure, CD68- and arginase-1 (Arg-1-expressing macrophages, and cytokine mRNA expression were examined in non-diabetic and streptozotocin-induced type 1 diabetic mice at different time points after injury. The effect of IL-6 on p38 MAPK and Akt phosphorylation was investigated, and an in vitro scratch assay was performed to determine the role of IL-6 in primary skin fibroblast migration. Before injury, mRNA expression levels of the inflammatory markers iNOS, IL-6, and TNF-α were higher in diabetic mice; however, IL-6 expression was significantly lower 6 h post injury in diabetic wounds than that in non-diabetic wounds. Non-diabetic wounds exhibited increased p38 MAPK and Akt phosphorylation; however, no such increase was found in diabetic wounds. In fibroblasts from non-diabetic mice, IL-6 increased the phosphorylation of p38 MAPK and levels of its downstream factor CREB, and also significantly increased Akt phosphorylation and levels of its upstream factor P13K. These effects of IL-6 were not detected in fibroblasts derived from the diabetic mice. In scratch assays, IL-6 stimulated the migration of primary cultured skin fibroblasts from the non-diabetic mice, and the inhibition of p38 MAPK was found to markedly suppress IL-6-stimulated fibroblast migration. These findings underscore the critical differences between diabetic and non-diabetic wounds in terms of macrophage activation, cytokine mRNA expression profile, and involvement of the IL-6-stimulated p38 MAPK-Akt signaling pathway. Aberrant macrophage activation and abnormalities in the cytokine m

  10. Feasibility of transcranial direct current stimulation use in children aged 5 to 12 years.

    Science.gov (United States)

    Andrade, Agnes Carvalho; Magnavita, Guilherme Moreira; Allegro, Juleilda Valéria Brasil Nunes; Neto, Carlos Eduardo Borges Passos; Lucena, Rita de Cássia Saldanha; Fregni, Felipe

    2014-10-01

    Transcranial direct current stimulation is a noninvasive brain stimulation technique that has been studied for the treatment of neuropsychiatric disorders in adults, with minimal side effects. The objective of this study is to report the feasibility, tolerability, and the short-term adverse effects of transcranial direct current stimulation in children from 5 to 12 years of age. It is a naturalistic study of 14 children who underwent 10 sessions of transcranial direct current stimulation as an alternative, off-label, and open-label treatment for various languages disorders. Frequency, intensity, adverse effects, and perception of improvement reported by parents were collected. The main side effects detected were tingling (28.6%) and itching (28.6%), acute mood changes (42.9%), and irritability (35.7%). Transcranial direct current stimulation is a feasible and tolerable technique in children, although studies regarding plastic and cognitive changes in children are needed to confirm its safety. In conclusion, this is a naturalistic report in which we considered transcranial direct current stimulation as feasible in children. © The Author(s) 2013.

  11. Matrine inhibits the adhesion and migration of BCG823 gastric cancer cells by affecting the structure and function of the vasodilator-stimulated phosphoprotein (VASP).

    Science.gov (United States)

    Zhang, Jing-wei; Su, Ke; Shi, Wen-tao; Wang, Ying; Hu, Peng-chao; Wang, Yang; Wei, Lei; Xiang, Jin; Yang, Fang

    2013-08-01

    Vasodilator-stimulated phosphoprotein (VASP) expression is upregulated in human cancers and correlates with more invasive advanced tumor stages. The aim of this study was to elucidate the mechanisms by which matrine, an alkaloid derived from Sophora species plants, acted on the VASP protein in human gastric cancer cells in vitro. VASP was expressed and purified. Intrinsic fluorescence spectroscopy was used to study the binding of matrine to VASP. CD spectroscopy was used to examine the changes in the VASP protein secondary structure. Human gastric carcinoma cell line BGC823 was tested. Scratch wound and cell adhesion assays were used to detect the cell migration and adhesion, respectively. Real-time PCR and Western blotting assays were used to measure mRNA and protein expression of VASP. In the fluorescence assay, the dissociation constant for binding of matrine to VASP protein was 0.86 mmol/L, thus the direct binding between the two molecules was weak. However, matrine (50 μg/mL) caused obvious change in the secondary structure of VASP protein shown in CD spectrum. Treatments of BGC823 cells with matrine (50 μg/mL) significantly inhibited the cell migration and adhesion. The alkaloid changed the subcellular distribution of VASP and formation of actin stress fibers in BGC823 cells. The alkaloid caused small but statistically significant decreases in VASP protein expression and phosphorylation, but had no significant effect on VASP mRNA expression. Matrine modulates the structure, subcellular distribution, expression and phosphorylation of VASP in human gastric cancer cells, thus inhibiting the cancer cell adhesion and migration.

  12. Autocrine stimulation of VEGFR-2 activates human leukemic cell growth and migration

    Science.gov (United States)

    Dias, Sergio; Hattori, Koichi; Zhu, Zhenping; Heissig, Beate; Choy, Margaret; Lane, William; Wu, Yan; Chadburn, Amy; Hyjek, Elizabeth; Gill, Muhammad; Hicklin, Daniel J.; Witte, Larry; Moore, M.A.S.; Rafii, Shahin

    2000-01-01

    Emerging data suggest that VEGF receptors are expressed by endothelial cells as well as hematopoietic stem cells. Therefore, we hypothesized that functional VEGF receptors may also be expressed in malignant counterparts of hematopoietic stem cells such as leukemias. We demonstrate that certain leukemias not only produce VEGF but also express functional VEGFR-2 in vivo and in vitro, resulting in the generation of an autocrine loop that may support leukemic cell survival and proliferation. Approximately 50% of freshly isolated leukemias expressed mRNA and protein for VEGFR-2. VEGF165 induced phosphorylation of VEGFR-2 and increased proliferation of leukemic cells, demonstrating these receptors were functional. VEGF165 also induced the expression of MMP-9 by leukemic cells and promoted their migration through reconstituted basement membrane. The neutralizing mAb IMC-1C11, specific to human VEGFR-2, inhibited leukemic cell survival in vitro and blocked VEGF165-mediated proliferation of leukemic cells and VEGF-induced leukemic cell migration. Xenotransplantation of primary leukemias and leukemic cell lines into immunocompromised nonobese diabetic mice resulted in significant elevation of human, but not murine, VEGF in plasma and death of inoculated mice within 3 weeks. Injection of IMC-1C11 inhibited proliferation of xenotransplanted human leukemias and significantly increased the survival of inoculated mice. Interruption of signaling by VEGFRs, particularly VEGFR-2, may provide a novel strategy for inhibiting leukemic cell proliferation. PMID:10953026

  13. Enhanced motor learning following task-concurrent dual transcranial direct current stimulation.

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    Sophia Karok

    Full Text Available OBJECTIVE: Transcranial direct current stimulation (tDCS of the primary motor cortex (M1 has beneficial effects on motor performance and motor learning in healthy subjects and is emerging as a promising tool for motor neurorehabilitation. Applying tDCS concurrently with a motor task has recently been found to be more effective than applying stimulation before the motor task. This study extends this finding to examine whether such task-concurrent stimulation further enhances motor learning on a dual M1 montage. METHOD: Twenty healthy, right-handed subjects received anodal tDCS to the right M1, dual tDCS (anodal current over right M1 and cathodal over left M1 and sham tDCS in a repeated-measures design. Stimulation was applied for 10 mins at 1.5 mA during an explicit motor learning task. Response times (RT and accuracy were measured at baseline, during, directly after and 15 mins after stimulation. Motor cortical excitability was recorded from both hemispheres before and after stimulation using single-pulse transcranial magnetic stimulation. RESULTS: Task-concurrent stimulation with a dual M1 montage significantly reduced RTs by 23% as early as with the onset of stimulation (p<0.01 with this effect increasing to 30% at the final measurement. Polarity-specific changes in cortical excitability were observed with MEPs significantly reduced by 12% in the left M1 and increased by 69% in the right M1. CONCLUSION: Performance improvement occurred earliest in the dual M1 condition with a stable and lasting effect. Unilateral anodal stimulation resulted only in trendwise improvement when compared to sham. Therefore, task-concurrent dual M1 stimulation is most suited for obtaining the desired neuromodulatory effects of tDCS in explicit motor learning.

  14. Unilateral prefrontal direct current stimulation effects are modulated by working memory load and gender.

    Science.gov (United States)

    Meiron, Oded; Lavidor, Michal

    2013-05-01

    Recent studies revealed that anodal transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (DLPFC) may improve verbal working memory (WM) performance in humans. In the present study, we evaluated executive attention, which is the core of WM capacity, considered to be significantly involved in tasks that require active maintenance of memory representations in interference-rich conditions, and is highly dependent on DLPFC function. We investigated verbal WM accuracy using a WM task that is highly sensitive to executive attention function. We were interested in how verbal WM accuracy may be affected by WM load, unilateral DLPFC stimulation, and gender, as previous studies showed gender-dependent brain activation during verbal WM tasks. We utilized a modified verbal n-Back task hypothesized to increase demands on executive attention. We examined "online" WM performance while participants received transcranial direct current stimulation (tDCS), and implicit learning performance in a post-stimulation WM task. Significant lateralized "online" stimulation effects were found only in the highest WM load condition revealing that males benefit from left DLPFC stimulation, while females benefit from right DLPFC stimulation. High WM load performance in the left DLPFC stimulation was significantly related to post-stimulation recall performance. Our findings support the idea that lateralized stimulation effects in high verbal WM load may be gender-dependent. Further, our post-stimulation results support the idea that increased left hemisphere activity may be important for encoding verbal information into episodic memory as well as for facilitating retrieval of context-specific targets from semantic memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Effect of Cathodal Transcranial Direct Current Stimulation on a Child with Involuntary Movement after Hypoxic Encephalopathy

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    Mayumi Nagai

    2018-01-01

    Full Text Available The aim of the study was to investigate the effect of cathodal transcranial direct current stimulation to the supplementary motor area to inhibit involuntary movements of a child. An 8-year-old boy who developed hypoxic encephalopathy after asphyxia at the age of 2 had difficulty in remaining standing without support because of involuntary movements. He was instructed to remain standing with his plastic ankle-foot orthosis for 10 s at three time points by leaning forward with his forearms on a desk. He received cathodal or sham transcranial direct current stimulation to the supplementary motor area at 1 mA for 10 min. Involuntary movements during standing were measured using an accelerometer attached to his forehead. The low-frequency power of involuntary movements during cathodal transcranial direct current stimulation significantly decreased compared with that during sham stimulation. No adverse effects were observed. Involuntary movement reduction by cathodal stimulation to supplementary motor areas suggests that stimulations modulated the corticobasal ganglia motor circuit. Cathodal stimulation to supplementary motor areas may be effective for reducing involuntary movements and may be safely applied to children with movement disorders.

  16. Main directions and priorities of Ukraine state migration policy in the context of its european integration changes

    Directory of Open Access Journals (Sweden)

    К.V. Shymanska

    2016-09-01

    Full Text Available The exceptional socio-economic importance of migration and its significant impact on the living standards and welfare of the population, labor market, ethnic and religious profile of Ukrainians, cultural and educational environment and migration activation social context cause the raising of the relevance of the research issues on international migration. This article is devoted to the study of existing approaches to identification of main directions and priorities of state migration policy for eliminating of external migration negative effects in Ukraine, ensuring an adequate level of social and economic protection of people and national security of Ukraine. The article considers the current problems of Ukraine's migration policy formation, characterizes the main priorities of Ukraine's migration policy according to its basic component, and describes the tendencies of migration processes in Ukraine and over the world. It is determined that the cooperation between Ukraine and the EU in the case of migratory flow regulating will have a number of advantages including the reduction of illegal migration, preservation of the professional level of Ukrainian migrants and receiving work experience abroad, strengthening their social protection and reduction of illegal employed migrants.

  17. Transcranial direct current stimulation for depression in Alzheimer's disease: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Narita, Zui; Yokoi, Yuma

    2017-06-19

    Patients with Alzheimer's disease frequently elicit neuropsychiatric symptoms as well as cognitive deficits. Above all, depression is one of the most common neuropsychiatric symptoms in Alzheimer's disease but antidepressant drugs have not shown significant beneficial effects on it. Moreover, electroconvulsive therapy has not ensured its safety for potential severe adverse events although it does show beneficial clinical effect. Transcranial direct current stimulation can be the safe alternative of neuromodulation, which applies weak direct electrical current to the brain. Although transcranial direct current stimulation has plausible evidence for its effect on depression in young adult patients, no study has explored it in older subjects with depression in Alzheimer's disease. Therefore, we present a study protocol designed to evaluate the safety and clinical effect of transcranial direct current stimulation on depression in Alzheimer's disease in subjects aged over 65 years. This is a two-arm, parallel-design, randomized controlled trial, in which patients and assessors will be blinded. Subjects will be randomized to either an active or a sham transcranial direct current stimulation group. Participants in both groups will be evaluated at baseline, immediately, and 2 weeks after the intervention. This study investigates the safety and effect of transcranial direct current stimulation that may bring a significant impact on both depression and cognition in patients with Alzheimer's disease, and may be useful to enhance their quality of life. ClinicalTrials.gov, NCT02351388 . Registered on 27 January 2015. Last updated on 30 May 2016.

  18. Transcranial direct-current stimulation induced in stroke patients with aphasia: a prospective experimental cohort study

    Directory of Open Access Journals (Sweden)

    Michele Devido Santos

    Full Text Available CONTEXT AND OBJECTIVE: Previous animal and human studies have shown that transcranial direct current stimulation can induce significant and lasting neuroplasticity and may improve language recovery in patients with aphasia. The objective of the study was to describe a cohort of patients with aphasia after stroke who were treated with transcranial direct current stimulation. DESIGN AND SETTING: Prospective cohort study developed in a public university hospital. METHODS: Nineteen patients with chronic aphasia received 10 transcranial direct current stimulation sessions lasting 20 minutes each on consecutive days, using a current of 2 mA. The anode was positioned over the supraorbital area and the cathode over the contralateral motor cortex. The following variables were analyzed before and after the 10 neuromodulation sessions: oral language comprehension, copying, dictation, reading, writing, naming and verbal fluency. RESULTS: There were no adverse effects in the study. We found statistically significant differences from before to after stimulation in relation to simple sentence comprehension (P = 0.034, naming (P = 0.041 and verbal fluency for names of animals (P = 0.038. Improved scores for performing these three tasks were seen after stimulation. CONCLUSIONS: We observed that excitability of the primary motor cortex through transcranial direct current stimulation was associated with effects on different aspects of language. This can contribute towards future testing in randomized controlled trials.

  19. Transcranial direct-current stimulation induced in stroke patients with aphasia: a prospective experimental cohort study.

    Science.gov (United States)

    Santos, Michele Devido; Gagliardi, Rubens José; Mac-Kay, Ana Paula Machado Goyano; Boggio, Paulo Sergio; Lianza, Roberta; Fregni, Felipe

    2013-01-01

    Previous animal and human studies have shown that transcranial direct current stimulation can induce significant and lasting neuroplasticity and may improve language recovery in patients with aphasia. The objective of the study was to describe a cohort of patients with aphasia after stroke who were treated with transcranial direct current stimulation. Prospective cohort study developed in a public university hospital. Nineteen patients with chronic aphasia received 10 transcranial direct current stimulation sessions lasting 20 minutes each on consecutive days, using a current of 2 mA. The anode was positioned over the supraorbital area and the cathode over the contralateral motor cortex. The following variables were analyzed before and after the 10 neuromodulation sessions: oral language comprehension, copying, dictation, reading, writing, naming and verbal fluency. There were no adverse effects in the study. We found statistically significant differences from before to after stimulation in relation to simple sentence comprehension (P = 0.034), naming (P = 0.041) and verbal fluency for names of animals (P = 0.038). Improved scores for performing these three tasks were seen after stimulation. We observed that excitability of the primary motor cortex through transcranial direct current stimulation was associated with effects on different aspects of language. This can contribute towards future testing in randomized controlled trials.

  20. Pressure pain thresholds increase after preconditioning 1 Hz repetitive transcranial magnetic stimulation with transcranial direct current stimulation.

    Directory of Open Access Journals (Sweden)

    Tonya M Moloney

    Full Text Available BACKGROUND: The primary motor cortex (M1 is an effective target of non-invasive cortical stimulation (NICS for pain threshold modulation. It has been suggested that the initial level of cortical excitability of M1 plays a key role in the plastic effects of NICS. OBJECTIVE: Here we investigate whether transcranial direct current stimulation (tDCS primed 1 Hz repetitive transcranial magnetic stimulation (rTMS modulates experimental pressure pain thresholds and if this is related to observed alterations in cortical excitability. METHOD: 15 healthy, male participants received 10 min 1 mA anodal, cathodal and sham tDCS to the left M1 before 15 min 1 Hz rTMS in separate sessions over a period of 3 weeks. Motor cortical excitability was recorded at baseline, post-tDCS priming and post-rTMS through recording motor evoked potentials (MEPs from right FDI muscle. Pressure pain thresholds were determined by quantitative sensory testing (QST through a computerized algometer, on the palmar thenar of the right hand pre- and post-stimulation. RESULTS: Cathodal tDCS-primed 1 Hz-rTMS was found to reverse the expected suppressive effect of 1 Hz rTMS on cortical excitability; leading to an overall increase in activity (p<0.001 with a parallel increase in pressure pain thresholds (p<0.01. In contrast, anodal tDCS-primed 1 Hz-rTMS resulted in a corresponding decrease in cortical excitability (p<0.05, with no significant effect on pressure pain. CONCLUSION: This study demonstrates that priming the M1 before stimulation of 1 Hz-rTMS modulates experimental pressure pain thresholds in a safe and controlled manner, producing a form of analgesia.

  1. Direct stimulation of angiotensin II type 2 receptor enhances spatial memory

    DEFF Research Database (Denmark)

    Jing, Fei; Mogi, Masaki; Sakata, Akiko

    2012-01-01

    We examined the possibility that direct stimulation of the angiotensin II type 2 (AT(2)) receptor by a newly generated direct AT(2) receptor agonist, Compound 21 (C21), enhances cognitive function. Treatment with C21 intraperitoneal injection for 2 weeks significantly enhanced cognitive function...

  2. Transcranial direct current stimulation over left inferior frontal cortex improves speech fluency in adults who stutter.

    Science.gov (United States)

    Chesters, Jennifer; Möttönen, Riikka; Watkins, Kate E

    2018-04-01

    See Crinion (doi:10.1093/brain/awy075) for a scientific commentary on this article.Stuttering is a neurodevelopmental condition affecting 5% of children, and persisting in 1% of adults. Promoting lasting fluency improvement in adults who stutter is a particular challenge. Novel interventions to improve outcomes are of value, therefore. Previous work in patients with acquired motor and language disorders reported enhanced benefits of behavioural therapies when paired with transcranial direct current stimulation. Here, we report the results of the first trial investigating whether transcranial direct current stimulation can improve speech fluency in adults who stutter. We predicted that applying anodal stimulation to the left inferior frontal cortex during speech production with temporary fluency inducers would result in longer-lasting fluency improvements. Thirty male adults who stutter completed a randomized, double-blind, controlled trial of anodal transcranial direct current stimulation over left inferior frontal cortex. Fifteen participants received 20 min of 1-mA stimulation on five consecutive days while speech fluency was temporarily induced using choral and metronome-timed speech. The other 15 participants received the same speech fluency intervention with sham stimulation. Speech fluency during reading and conversation was assessed at baseline, before and after the stimulation on each day of the 5-day intervention, and at 1 and 6 weeks after the end of the intervention. Anodal stimulation combined with speech fluency training significantly reduced the percentage of disfluent speech measured 1 week after the intervention compared with fluency intervention alone. At 6 weeks after the intervention, this improvement was maintained during reading but not during conversation. Outcome scores at both post-intervention time points on a clinical assessment tool (the Stuttering Severity Instrument, version 4) also showed significant improvement in the group receiving

  3. CXCR3 Directs Antigen-Specific Effector CD4+ T Cell Migration to the Lung During Parainfluenza Virus Infection

    DEFF Research Database (Denmark)

    Kohlmeier, Jacob E; Cookenham, Tres; Miller, Shannon C

    2009-01-01

    effector CD4(+) T cell migration to the lungs. To assess the role of CCR5 and CXCR3 in vivo, we directly compared the migration of Ag-specific wild-type and chemokine receptor-deficient effector T cells in mixed bone marrow chimeric mice during a parainfluenza virus infection. CXCR3-deficient effector CD4......(+) T cells were 5- to 10-fold less efficient at migrating to the lung compared with wild-type cells, whereas CCR5-deficient effector T cells were not impaired in their migration to the lung. In contrast to its role in trafficking, CXCR3 had no impact on effector CD4(+) T cell proliferation, phenotype......, or function in any of the tissues examined. These findings demonstrate that CXCR3 controls virus-specific effector CD4(+) T cell migration in vivo, and suggest that blocking CXCR3-mediated recruitment may limit T cell-induced immunopathology during respiratory virus infections....

  4. Transcranial direct current stimulation in refractory continuous spikes and waves during slow sleep: a controlled study

    DEFF Research Database (Denmark)

    Varga, Edina T; Terney, Daniella; Atkins, Mary D

    2011-01-01

    Cathodal transcranial direct current stimulation (tDCS) decreases cortical excitability. The purpose of the study was to investigate whether cathodal tDCS could interrupt the continuous epileptiform activity. Five patients with focal, refractory continuous spikes and waves during slow sleep were...... recruited. Cathodal tDCS and sham stimulation were applied to the epileptic focus, before sleep (1 mA; 20 min). Cathodal tDCS did not reduce the spike-index in any of the patients....

  5. Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder

    OpenAIRE

    van?t Wout, Mascha; Longo, Sharon M.; Reddy, Madhavi K.; Philip, Noah S.; Bowker, Marguerite T.; Greenberg, Benjamin D.

    2017-01-01

    Abstract Background Abnormalities in fear extinction and recall are core components of posttraumatic stress disorder (PTSD). Data from animal and human studies point to a role of the ventromedial prefrontal cortex (vmPFC) in extinction learning and subsequent retention of extinction memories. Given the increasing interest in developing noninvasive brain stimulation protocols for psychopathology treatment, we piloted whether transcranial direct current stimulation (tDCS) during extinction lear...

  6. Modulation of amplitude and latency of motor evoked potential by direction of transcranial magnetic stimulation

    Science.gov (United States)

    Sato, Aya; Torii, Tetsuya; Iwahashi, Masakuni; Itoh, Yuji; Iramina, Keiji

    2014-05-01

    The present study analyzed the effects of monophasic magnetic stimulation to the motor cortex. The effects of magnetic stimulation were evaluated by analyzing the motor evoked potentials (MEPs). The amplitude and latency of MEPs on the abductor pollicis brevis muscle were used to evaluate the effects of repetitive magnetic stimulation. A figure eight-shaped flat coil was used to stimulate the region over the primary motor cortex. The intensity of magnetic stimulation was 120% of the resting motor threshold, and the frequency of magnetic stimulation was 0.1 Hz. In addition, the direction of the current in the brain was posterior-anterior (PA) or anterior-posterior (AP). The latency of MEP was compared with PA and AP on initial magnetic stimulation. The results demonstrated that a stimulus in the AP direction increased the latency of the MEP by approximately 2.5 ms. MEP amplitude was also compared with PA and AP during 60 magnetic stimulations. The results showed that a stimulus in the PA direction gradually increased the amplitude of the MEP. However, a stimulus in the AP direction did not modulate the MEP amplitude. The average MEP amplitude induced from every 10 magnetic pulses was normalized by the average amplitude of the first 10 stimuli. These results demonstrated that the normalized MEP amplitude increased up to approximately 150%. In terms of pyramidal neuron indirect waves (I waves), magnetic stimulation inducing current flowing backward to the anterior preferentially elicited an I1 wave, and current flowing forward to the posterior elicited an I3 wave. It has been reported that the latency of the I3 wave is approximately 2.5 ms longer than the I1 wave elicitation, so the resulting difference in latency may be caused by this phenomenon. It has also been reported that there is no alteration of MEP amplitude at a frequency of 0.1 Hz. However, this study suggested that the modulation of MEP amplitude depends on stimulation strength and stimulation direction.

  7. Modulation of Total Sleep Time by Transcranial Direct Current Stimulation (tDCS).

    Science.gov (United States)

    Frase, Lukas; Piosczyk, Hannah; Zittel, Sulamith; Jahn, Friederike; Selhausen, Peter; Krone, Lukas; Feige, Bernd; Mainberger, Florian; Maier, Jonathan G; Kuhn, Marion; Klöppel, Stefan; Normann, Claus; Sterr, Annette; Spiegelhalder, Kai; Riemann, Dieter; Nitsche, Michael A; Nissen, Christoph

    2016-09-01

    Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a 'top-down' cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal 'activation', cathodal 'deactivation', and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the 'top-down' pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep.

  8. Effects of Transcranial Direct Current Stimulation (tDCS) on Pain Distress Tolerance: A Preliminary Study.

    Science.gov (United States)

    Mariano, Timothy Y; van't Wout, Mascha; Jacobson, Benjamin L; Garnaat, Sarah L; Kirschner, Jason L; Rasmussen, Steven A; Greenberg, Benjamin D

    2015-08-01

    Pain remains a critical medical challenge. Current treatments target nociception without addressing affective symptoms. Medically intractable pain is sometimes treated with cingulotomy or deep brain stimulation to increase tolerance of pain-related distress. Transcranial direct current stimulation (tDCS) may noninvasively modulate cortical areas related to sensation and pain representations. The present study aimed to test the hypothesis that cathodal ("inhibitory") stimulation targeting left dorsal anterior cingulate cortex (dACC) would increase tolerance to distress from acute painful stimuli vs anodal stimulation. Forty healthy volunteers received both anodal and cathodal stimulation. During stimulation, we measured pain distress tolerance with three tasks: pressure algometer, cold pressor, and breath holding. We measured pain intensity with a visual-analog scale before and after each task. Mixed ANOVA revealed that mean cold pressor tolerance tended to be higher with cathodal vs anodal stimulation (P = 0.055) for participants self-completing the task. Pressure algometer (P = 0.81) and breath holding tolerance (P = 0.19) did not significantly differ. The pressure algometer exhibited a statistically significant order effect irrespective of stimulation polarity (all P tDCS (P = 0.072). Although our primary results were nonsignificant, there is a preliminary suggestion that cathodal tDCS targeting left dACC may increase pain distress tolerance to cold pressor. Pressure algometer results are consistent with task-related sensitization. Future studies are needed to refine this novel approach for pain neuromodulation. Wiley Periodicals, Inc.

  9. Neural mechanisms underlying transcranial direct current stimulation in aphasia: A feasibility study.

    Directory of Open Access Journals (Sweden)

    Lena eUlm

    2015-10-01

    Full Text Available Little is known about the neural mechanisms by which transcranial direct current stimulation (tDCS impacts on language processing in post-stroke aphasia. This was addressed in a proof-of-principle study that explored the effects of tDCS application in aphasia during simultaneous functional magnetic resonance imaging (fMRI. We employed a single subject, cross-over, sham-tDCS controlled design and the stimulation was administered to an individualized perilesional stimulation site that was identified by a baseline fMRI scan and a picture naming task. Peak activity during the baseline scan was located in the spared left inferior frontal gyrus (IFG and this area was stimulated during a subsequent cross-over phase. tDCS was successfully administered to the target region and anodal- vs. sham-tDCS resulted in selectively increased activity at the stimulation site. Our results thus demonstrate that it is feasible to precisely target an individualized stimulation site in aphasia patients during simultaneous fMRI which allows assessing the neural mechanisms underlying tDCS application. The functional imaging results of this case report highlight one possible mechanism that may have contributed to beneficial behavioural stimulation effects in previous clinical tDCS trials in aphasia. In the future, this approach will allow identifying distinct patterns of stimulation effects on neural processing in larger cohorts of patients. This may ultimately yield information about the variability of tDCS-effects on brain functions in aphasia.

  10. Multi-session transcranial direct current stimulation (tDCS elicits inflammatory and regenerative processes in the rat brain.

    Directory of Open Access Journals (Sweden)

    Maria Adele Rueger

    Full Text Available Transcranial direct current stimulation (tDCS is increasingly being used in human studies as an adjuvant tool to promote recovery of function after stroke. However, its neurobiological effects are still largely unknown. Electric fields are known to influence the migration of various cell types in vitro, but effects in vivo remain to be shown. Hypothesizing that tDCS might elicit the recruitment of cells to the cortex, we here studied the effects of tDCS in the rat brain in vivo. Adult Wistar rats (n = 16 were randomized to either anodal or cathodal stimulation for either 5 or 10 consecutive days (500 µA, 15 min. Bromodeoxyuridine (BrdU was given systemically to label dividing cells throughout the experiment. Immunohistochemical analyses ex vivo included stainings for activated microglia and endogenous neural stem cells (NSC. Multi-session tDCS with the chosen parameters did not cause a cortical lesion. An innate immune response with early upregulation of Iba1-positive activated microglia occurred after both cathodal and anodal tDCS. The involvement of adaptive immunity as assessed by ICAM1-immunoreactivity was less pronounced. Most interestingly, only cathodal tDCS increased the number of endogenous NSC in the stimulated cortex. After 10 days of cathodal stimulation, proliferating NSC increased by ∼60%, with a significant effect of both polarity and number of tDCS sessions on the recruitment of NSC. We demonstrate a pro-inflammatory effect of both cathodal and anodal tDCS, and a polarity-specific migratory effect on endogenous NSC in vivo. Our data suggest that tDCS in human stroke patients might also elicit NSC activation and modulate neuroinflammation.

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

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    Fan, Denggui; Wang, Zhihui; Wang, Qingyun

    2016-07-01

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

  12. Differential effects of bifrontal and occipital nerve stimulation on pain and fatigue using transcranial direct current stimulation in fibromyalgia patients.

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    To, Wing Ting; James, Evan; Ost, Jan; Hart, John; De Ridder, Dirk; Vanneste, Sven

    2017-07-01

    Fibromyalgia is a disorder characterized by widespread musculoskeletal pain frequently accompanied by other symptoms such as fatigue. Moderate improvement from pharmacological and non-pharmacological treatments have proposed non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) to the occipital nerve (more specifically the C2 area) or to the dorsolateral prefrontal cortex (DLPFC) as potential treatments. We aimed to explore the effectiveness of repeated sessions of tDCS (eight sessions) targeting the C2 area and DLPFC in reducing fibromyalgia symptoms, more specifically pain and fatigue. Forty-two fibromyalgia patients received either C2 tDCS, DLPFC tDCS or sham procedure (15 C2 tDCS-11 DLPFC tDCS-16 sham). All groups were treated with eight sessions (two times a week for 4 weeks). Our results show that repeated sessions of C2 tDCS significantly improved pain, but not fatigue, in fibromyalgia patients, whereas repeated sessions of DLPFC tDCS significantly improved pain as well as fatigue. This study shows that eight sessions of tDCS targeting the DLPFC have a more general relief in fibromyalgia patients than when targeting the C2 area, suggesting that stimulating different targets with eight sessions of tDCS can lead to benefits on different symptom dimensions of fibromyalgia.

  13. Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation.

    Science.gov (United States)

    Ille, Sebastian; Sollmann, Nico; Hauck, Theresa; Maurer, Stefanie; Tanigawa, Noriko; Obermueller, Thomas; Negwer, Chiara; Droese, Doris; Zimmer, Claus; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

    2015-07-01

    Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS's specificity and positive predictive value, the authors aim to provide thresholds for rTMS's positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods. The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery. The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%. In comparison with fMRI, rTMS is a more sensitive but less specific

  14. Hypoxia stimulates migration of breast cancer cells via the PERK/ATF4/LAMP3-arm of the unfolded protein response

    NARCIS (Netherlands)

    Nagelkerke, A.; Bussink, J.; Mujcic, H.; Wouters, B.G.; Lehmann, S.A.; Sweep, F.C.; Span, P.N.

    2013-01-01

    ABSTRACT: INTRODUCTION: The hypoxia-inducible factor (HIF)-1 pathway can stimulate tumor cell migration and metastasis. Furthermore, hypoxic tumors are associated with a poor prognosis. Besides the HIF-1 pathway, the unfolded protein response (UPR) is also induced by hypoxic conditions. The PKR-like

  15. Is Transcranial Direct Current Stimulation an Effective Predictor for Invasive Occipital Nerve Stimulation Treatment Success in Fibromyalgia Patients?

    Science.gov (United States)

    Plazier, Mark; Tchen, Stephanie; Ost, Jan; Joos, Kathleen; De Ridder, Dirk; Vanneste, Sven

    2015-10-01

    Fibromyalgia is a disorder distinguished by pervasive musculoskeletal pain that has pervasive effects on affected individuals magnifying the importance of finding a safe and viable treatment option. The goal of this study is to investigate if transcranial direct current stimulation (tDCS) treatment can predict the outcome of occipital nerve field stimulation (ONFS) via a subcutaneous electrode. Nine patients with fibromyalgia were selected fulfilling the American College of Rheumatology-90 criteria. The patients were implanted with a subcutaneous trial-lead in the C2 dermatome innervated by the occipital nerve. After the treatment phase of ONFS using a C2 implant, each patient participated in three sessions of tDCS. Stimulation outcomes for pain suppression were examined between the two methods to determine possible correlations. Positive correlation of stimulation effect was noted between the numeric rating scale changes for pain obtained by tDCS treatments and short-term measures of ONFS, but no correlation was noted between tDCS and long-term ONFS outcomes. A correlation also was noted between short-term ONS C2 implant pain suppression and long-term ONS C2 implant treatment success. This pilot study suggests that tDCS is a predictive measure for success of OFNS in short-term but cannot be used as a predictive measure for success of long-term OFNS. Our data confirm previous findings that ONFS via an implanted electrode can improve fibromyalgia pain in a placebo-controlled way and exert a long-term pain suppression effect for ONFS via an implanted electrode. © 2015 International Neuromodulation Society.

  16. Transcranial magnetic stimulation and transcranial direct current stimulation: treatments for cognitive and neuropsychiatric symptoms in the neurodegenerative dementias?

    Science.gov (United States)

    2014-01-01

    Introduction Two methods of non-invasive brain stimulation, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), have demonstrable positive effects on cognition and can ameliorate neuropsychiatric symptoms such as depression. Less is known about the efficacy of these approaches in common neurodegenerative diseases. In this review, we evaluate the effects of TMS and tDCS upon cognitive and neuropsychiatric symptoms in the major dementias, including Alzheimer’s disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson’s disease with dementia (PDD), and frontotemporal dementia (FTD), as well as the potential pre-dementia states of Mild Cognitive Impairment (MCI) and Parkinson’s disease (PD). Methods PubMed (until 7 February 2014) and PsycINFO (from 1967 to January Week 3 2014) databases were searched in a semi-systematic manner in order to identify relevant treatment studies. A total of 762 studies were identified and 32 studies (18 in the dementias and 14 in PD populations) were included. Results No studies were identified in patients with PDD, FTD or VaD. Of the dementias, 13 studies were conducted in patients with AD, one in DLB, and four in MCI. A total of 16 of the 18 studies showed improvements in at least one cognitive or neuropsychiatric outcome measure. Cognitive or neuropsychiatric improvements were observed in 12 of the 14 studies conducted in patients with PD. Conclusions Both TMS and tDCS may have potential as interventions for the treatment of symptoms associated with dementia and PD. These results are promising; however, available data were limited, particularly within VaD, PDD and FTD, and major challenges exist in order to maximise the efficacy and clinical utility of both techniques. In particular, stimulation parameters vary considerably between studies and are likely to subsequently impact upon treatment efficacy. PMID:25478032

  17. Shaping pseudoneglect with transcranial cerebellar direct current stimulation and music listening

    Directory of Open Access Journals (Sweden)

    Silvia ePicazio

    2015-03-01

    Full Text Available Non-invasive brain stimulation modulates cortical excitability depending on the initial activation state of the structure being stimulated. Combination of cognitive with neurophysiological stimulations has been successfully employed to modulate responses of specific brain regions. The present research combined a neurophysiological pre-conditioning with a cognitive conditioning stimulation to modulate behavior. We applied this new state-dependency approach to investigate the cerebellar role in musical and spatial information processing, given that a link between musical perception and visuo-spatial abilities and a clear cerebellar involvement in music perception and visuo-spatial tasks have been reported. Cathodal, anodal or sham transcranial cerebellar Direct Current Stimulation (tcDCS pre-conditioning was applied on the left cerebellar hemisphere followed by conditioning stimulation through music or white noise listening in a sample of healthy subjects performing a Line Bisection Task (LBT. The combination of the cathodal stimulation with music listening resulted in a marked attentional shift toward the right hemispace, compensating thus the natural leftward bias of the baseline condition (pseudoneglect. Conversely, the anodal or sham pre-conditioning stimulations combined with either music and white noise conditioning listening did not modulate spatial attention. The efficacy of the combined stimulation (cathodal pre-conditioning and music conditioning and the absence of any effect of the single stimulations provide a strong support to the state-dependency theory. They propose that tcDCS in combination with music listening could act as a rehabilitative tool to improve cognitive functions in the presence of neglect or other spatial disorders.

  18. Direct current stimulation of the left temporoparietal junction modulates dynamic humor appreciation.

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    Slaby, Isabella; Holmes, Amanda; Moran, Joseph M; Eddy, Marianna D; Mahoney, Caroline R; Taylor, Holly A; Brunyé, Tad T

    2015-11-11

    The aim of this study was to evaluate the influence of transcranial direct current stimulation targeting the left temporoparietal junction (TPJ) on humor appreciation during a dynamic video rating task. In a within-participants design, we targeted the left TPJ with anodal, cathodal, or no transcranial direct current stimulation, centered at electrode site C3 using a 4×1 targeted stimulation montage. During stimulation, participants dynamically rated a series of six stand-up comedy videos for perceived humor. We measured event-related (time-locked to crowd laughter) modulation of humor ratings as a function of stimulation condition. Results showed decreases in rated humor during anodal (vs. cathodal or none) stimulation; this pattern was evident for the majority of videos and was only partially predicted by individual differences in humor style. We discuss the possibility that upregulation of neural circuits involved in the theory of mind and empathizing with others may reduce appreciation of aggressive humor. In conclusion, the present data show that neuromodulation of the TPJ can alter the mental processes underlying humor appreciation, suggesting critical involvement of this cortical region in detecting, comprehending, and appreciating humor.

  19. Evaluation of the effectiveness of transcranial direct current stimulation (tDCS) and psychosensory stimulation through DOCS scale in a minimally conscious subject.

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    Dimitri, Danilo; De Filippis, Daniela; Galetto, Valentina; Zettin, Marina

    2017-04-01

    The aim of our study was to assess the effectiveness of transcranial direct current stimulation (tDCS) on alertness improvement in a patient in a minimally conscious state (MCS) by means of disorders of consciousness scale combined with psycho-sensory stimulation. The effects of tDCS on muscle hypertonia through the Ashworth scale were also examined. tDCS was performed through a two-channel intra-cephalic stimulator. After stimulation, the patient followed a psychosensory stimulation training. Results pointed out an increase in DOCunit score, as well as an increase in alertness maintenance and an improvement in muscle hypertonia, although a MCS state persisted.

  20. Clinical effectiveness of primary and secondary headache treatment by transcranial direct current stimulation

    Directory of Open Access Journals (Sweden)

    Dmitry ePinchuk

    2013-03-01

    Full Text Available The clinical effectiveness of headache treatment by transcranial direct current stimulation with various locations of stimulating electrodes on the scalp was analyzed retrospectively. The results of the treatment were analyzed in 90 patients aged from 19 to 54 years (48 patients had migraine without aura, 32 – frequent episodic tension-type headaches, 10 – chronic tension-type headaches and in 44 adolescents aged 11 – 16 years with chronic posttraumatic headaches after a mild head injury. Clinical effectiveness of tDCS with 70 – 150 µA current for 30 – 45 minutes via 6.25 cm2 stimulating electrodes is comparable to that of modern pharmacological drugs, with no negative side effects. The obtained result has been maintained on average from 5 to 9 months. It has been demonstrated that effectiveness depends on localization of stimulating electrodes used for different types of headaches.

  1. Facilitation of Function and Manipulation Knowledge of Tools Using Transcranial Direct Current Stimulation (tDCS

    Directory of Open Access Journals (Sweden)

    Ryo Ishibashi

    2018-01-01

    Full Text Available Using a variety of tools is a common and essential component of modern human life. Patients with brain damage or neurological disorders frequently have cognitive deficits in their recognition and manipulation of tools. In this study, we focused on improving tool-related cognition using transcranial direct current stimulation (tDCS. Converging evidence from neuropsychology, neuroimaging and non- invasive brain stimulation has identified the anterior temporal lobe (ATL and inferior parietal lobule (IPL as brain regions supporting action semantics. We observed enhanced performance in tool cognition with anodal tDCS over ATL and IPL in two cognitive tasks that require rapid access to semantic knowledge about the function or manipulation of common tools. ATL stimulation improved access to both function and manipulation knowledge of tools. The effect of IPL stimulation showed a trend toward better manipulation judgments. Our findings support previous studies of tool semantics and provide a novel approach for manipulation of underlying circuits.

  2. Enhanced Working Memory Binding by Direct Electrical Stimulation of the Parietal Cortex

    Directory of Open Access Journals (Sweden)

    Agustina Birba

    2017-06-01

    Full Text Available Recent works evince the critical role of visual short-term memory (STM binding deficits as a clinical and preclinical marker of Alzheimer’s disease (AD. These studies suggest a potential role of posterior brain regions in both the neurocognitive deficits of Alzheimer’s patients and STM binding in general. Thereupon, we surmised that stimulation of the posterior parietal cortex (PPC might be a successful approach to tackle working memory deficits in this condition, especially at early stages. To date, no causal evidence exists of the role of the parietal cortex in STM binding. A unique approach to assess this issue is afforded by single-subject direct intracranial electrical stimulation of specific brain regions during a relevant cognitive task. Electrical stimulation has been used both for clinical purposes and to causally probe brain mechanisms. Previous evidence of electrical currents spreading through white matter along well defined functional circuits indicates that visual working memory mechanisms are subserved by a specific widely distributed network. Here, we stimulated the parietal cortex of a subject with intracranial electrodes as he performed the visual STM task. We compared the ensuing results to those from a non-stimulated condition and to the performance of a matched control group. In brief, direct stimulation of the parietal cortex induced a selective improvement in STM. These results, together with previous studies, provide very preliminary but promising ground to examine behavioral changes upon parietal stimulation in AD. We discuss our results regarding: (a the usefulness of the task to target prodromal stages of AD; (b the role of a posterior network in STM binding and in AD; and (c the potential opportunity to improve STM binding through brain stimulation.

  3. Online effects of transcranial direct current stimulation on prefrontal metabolites in gambling disorder.

    Science.gov (United States)

    Dickler, Maya; Lenglos, Christophe; Renauld, Emmanuelle; Ferland, Francine; Edden, Richard A; Leblond, Jean; Fecteau, Shirley

    2018-03-15

    Gambling disorder is characterized by persistent maladaptive gambling behaviors and is now considered among substance-related and addictive disorders. There is still unmet therapeutic need for these clinical populations, however recent advances indicate that interventions targeting the Glutamatergic/GABAergic system hold promise in reducing symptoms in substance-related and addictive disorders, including gambling disorder. There is some data indicating that transcranial direct current stimulation may hold clinical benefits in substance use disorders and modulate levels of brain metabolites including glutamate and GABA. The goal of the present work was to test whether this non-invasive neurostimulation method modulates key metabolites in gambling disorder. We conducted a sham-controlled, crossover, randomized study, blinded at two levels in order to characterize the effects of transcranial direct current stimulation over the dorsolateral prefrontal cortex on neural metabolites levels in sixteen patients with gambling disorder. Metabolite levels were measured with magnetic resonance spectroscopy from the right dorsolateral prefrontal cortex and the right striatum during active and sham stimulation. Active as compared to sham stimulation elevated prefrontal GABA levels. There were no significant changes between stimulation conditions in prefrontal glutamate + glutamine and N-acetyl Aspartate, or in striatal metabolite levels. Results also indicated positive correlations between metabolite levels during active, but not sham, stimulation and levels of risk taking, impulsivity and craving. Our findings suggest that transcranial direct current stimulation can modulate GABA levels in patients with gambling disorder which may represent an interesting future therapeutic avenue. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Effect of transcranial direct current stimulation on vestibular-ocular and vestibulo-perceptual thresholds.

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    Kyriakareli, Artemis; Cousins, Sian; Pettorossi, Vito E; Bronstein, Adolfo M

    2013-10-02

    Transcranial direct current stimulation (tDCS) was used in 17 normal individuals to modulate vestibulo-ocular reflex (VOR) and self-motion perception rotational thresholds. The electrodes were applied over the temporoparietal junction bilaterally. Both vestibular nystagmic and perceptual thresholds were increased during as well as after tDCS stimulation. Body rotation was labeled as ipsilateral or contralateral to the anode side, but no difference was observed depending on the direction of rotation or hemisphere polarity. Threshold increase during tDCS was greater for VOR than for motion perception. 'Sham' stimulation had no effect on thresholds. We conclude that tDCS produces an immediate and sustained depression of cortical regions controlling VOR and movement perception. Temporoparietal areas appear to be involved in vestibular threshold modulation but the differential effects observed between VOR and perception suggest a partial dissociation between cortical processing of reflexive and perceptual responses.

  5. Intraoperative direct electrical stimulations of central nervous system during surgery of gliomas near eloquent areas

    Directory of Open Access Journals (Sweden)

    WANG Wei-min

    2012-12-01

    Full Text Available Objective To report our experiences of direct cortical stimulation in surgery of gliomas located in eloquent areas. Methods Clinical data of 157 patients with gliomas underwent awake craniotomy with the direct electrical stimulation for functional mapping of the eloquent areas were analysed retrospectively. Results Negative cortical stimulation was found in 4 patients, and positive cortical stimulation was achieved in 153 patients (97.45% . Four hundred and ninty -six cortical sites in 139 patients were detected for motor response by direct electrical stimulation, 70 sites in 21 patients for sensory, 112 sites in 91 patients for language (such as counting and naming. The positive areas of counting disturbance were mainly seen at the lower part of left precentral gyri operculum of left inferior frontal gyri, triangular part of left inferior frontal gyri, posterior part of left middle frontal gyri, and posterior part of left superior frontal gyri. Postoperative MRI showed 92 patients (58.60% achieved total resection, 55 cases (35.03% subtotal and 10 cases (6.37% partial. One hundred and ten patients (70.06% were diagnosed as having low grade glimas, including 71 cases of astrocytoma, 26 cases of oligodendroglioma, and 13 cases of mixed astro ? oligodendroglioma, 47 patients (29.94% were high grade gliomas, including 19 cases of glioblastoma, 15 cases of anaplastic astrocytoma, and 13 cases of anaplastic oligodendroglioma. After operation 53 patients (33.76% occurred transient postoperative paralysis, 39 patients (24.84% transient language disturbance and 4 patients (2.55% permanent neurological deficits. Conclusion Intraoperative direct electrical stimulation is a reliable, precise and safety method for functional mapping of the eloquent areas. This technique allows us to achieve 'maximal safety resection' in glioma surgery.

  6. Boosting Cognition : Effects of Multiple-Session Transcranial Direct Current Stimulation on Working Memory

    NARCIS (Netherlands)

    Talsma, L.J.; Kroese, H.A.; Slagter, H.A.

    Transcranial direct current stimulation (tDCS) is a promising tool for neurocognitive enhancement. Several studies have shown that just a single session of tDCS over the left dorsolateral pFC (lDLPFC) can improve the core cognitive function of working memory (WM) in healthy adults. Yet, recent

  7. A clinical trial with combined transcranial direct current stimulation and alcohol approach bias retraining

    NARCIS (Netherlands)

    den Uyl, T.E.; Gladwin, T.E.; Rinck, M.; Lindenmeyer, J.; Wiers, R.W.

    2017-01-01

    Two studies showed an improvement in clinical outcomes after alcohol approach bias retraining, a form of Cognitive Bias Modification (CBM). We investigated whether transcranial direct current stimulation (tDCS) could enhance effects of CBM. TDCS is a neuromodulation technique that can increase

  8. Transcranial Direct Current Stimulation Does Not Improve Language Outcome in Subacute Poststroke Aphasia.

    Science.gov (United States)

    Spielmann, Kerstin; van de Sandt-Koenderman, W Mieke E; Heijenbrok-Kal, Majanka H; Ribbers, Gerard M

    2018-04-01

    The aim of the present study is to investigate the effect of transcranial direct current stimulation on word-finding treatment outcome in subacute poststroke aphasia. In this multi-center, double-blind, randomized controlled trial with 6-month follow-up, we included 58 patients with subacute aphasia (transcranial direct current stimulation (1 mA, 20 minutes; experimental group) or sham transcranial direct current stimulation (control group) over the left inferior frontal gyrus. The primary outcome measure was the Boston Naming Test. Secondary outcome measures included naming performance for trained/untrained picture items and verbal communication. Both the experimental (n=26) and the control group (n=32) improved on the Boston Naming Test over the intervention period and 6-month follow-up; however, there were no significant differences between groups. Also for the secondary outcome measures, no significant differences were found. The results of the present study do not support an effect of transcranial direct current stimulation as an adjuvant treatment in subacute poststroke aphasia. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp. Unique identifier: NTR4364. © 2018 American Heart Association, Inc.

  9. Improving Naming Abilities among Healthy Young-Old Adults Using Transcranial Direct Current Stimulation

    Science.gov (United States)

    Lifshitz-Ben-Basat, Adi; Mashal, Nira

    2018-01-01

    Transcranial direct current stimulation (tDCS) is a noninvasive tool to facilitate brain plasticity and enhance language abilities. Our study aims to search for a potential beneficial influence of tDCS on a cognitive linguistic task of naming which found to decline during aging. A group of fifteen healthy old adults (M = 64.93 ± 5.09 years) were…

  10. Single-layer skull approximations perform well in transcranial direct current stimulation modeling

    NARCIS (Netherlands)

    Rampersad, S.M.; Stegeman, D.F.; Oostendorp, T.F.

    2013-01-01

    In modeling the effect of transcranial direct current stimulation, the representation of the skull is an important factor. In a spherical model, we compared a realistic skull modeling approach, in which the skull consisted of three isotropic layers, to anisotropic and isotropic single-layer

  11. Trans-spinal direct current stimulation for the modulation of the lumbar spinal motor networks

    NARCIS (Netherlands)

    Kuck, Alexander

    2018-01-01

    Trans-spinal Direct Current Stimulation (tsDCS) is a noninvasive neuromodulatory tool for the modulation of the spinal neurocircuitry. Initial studies have shown that tsDCS is able to induce a significant and lasting change in spinal-reflex- and corticospinal information processing. It is therefore

  12. Counteracting fatigue in multiple sclerosis with right parietal anodal transcranial direct current stimulation

    NARCIS (Netherlands)

    Hanken, K.; Bosse, M.; Möhrke, K.; Eling, P.A.T.M.; Kastrup, A.; Antal, A.; Hildebrandt, H.

    2016-01-01

    Background: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation

  13. Fibroblasts are in a position to provide directional information to migrating neutrophils during pneumonia in rabbit lungs.

    Science.gov (United States)

    Behzad, A R; Chu, F; Walker, D C

    1996-05-01

    Previous findings have shown that pulmonary fibroblasts are associated with preexisting holes in the endothelial and epithelial basal laminae through which neutrophils appear to enter and leave the interstitium as they migrate from capillaries to alveoli. To determine their role in neutrophil migration, fibroblast organization within the interstitium was assessed by transmission electron microscope observations of serial-sectioned rabbit lung tissue. Interstitial fibroblasts were found to physically interconnect the endothelial basal lamina holes to epithelial basal lamina holes. Morphometric assessment of rabbit lung tissue instilled with Streptococcus pneumoniae revealed that approximately 70% of the surface area density of migrating neutrophils is in close contact (15 nm or less) with interstitial fibroblasts and extracellular matrix elements (30 and 40%, respectively). Although migrating neutrophils were close enough to adhere to both fibroblasts and extracellular elements, the interstitial fibroblasts are organized in a manner that would allow them to provide directional information to the neutrophils. A model illustrating this process is proposed.

  14. Combined effects of cerebellar transcranial direct current stimulation and transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic brain stroke: A pilot, single blind, randomized controlled trial.

    Science.gov (United States)

    Picelli, Alessandro; Chemello, Elena; Castellazzi, Paola; Filippetti, Mirko; Brugnera, Annalisa; Gandolfi, Marialuisa; Waldner, Andreas; Saltuari, Leopold; Smania, Nicola

    2018-01-01

    Preliminary evidence showed additional effects of anodal transcranial direct current stimulation over the damaged cerebral hemisphere combined with cathodal transcutaneous spinal direct current stimulation during robot-assisted gait training in chronic stroke patients. This is consistent with the neural organization of locomotion involving cortical and spinal control. The cerebellum is crucial for locomotor control, in particular for avoidance of obstacles, and adaptation to novel conditions during walking. Despite its key role in gait control, to date the effects of transcranial direct current stimulation of the cerebellum have not been investigated on brain stroke patients treated with robot-assisted gait training. To evaluate the effects of cerebellar transcranial direct current stimulation combined with transcutaneous spinal direct current stimulation on robot-assisted gait training in patients with chronic brain stroke. After balanced randomization, 20 chronic stroke patients received ten, 20-minute robot-assisted gait training sessions (five days a week, for two consecutive weeks) combined with central nervous system stimulation. Group 1 underwent on-line cathodal transcranial direct current stimulation over the contralesional cerebellar hemisphere + cathodal transcutaneous spinal direct current stimulation. Group 2 received on-line anodal transcranial direct current stimulation over the damaged cerebral hemisphere + cathodal transcutaneous spinal direct current stimulation. The primary outcome was the 6-minute walk test performed before, after, and at follow-up at 2 and 4 weeks post-treatment. The significant differences in the 6-minute walk test noted between groups at the first post-treatment evaluation (p = 0.041) were not maintained at either the 2-week (P = 0.650) or the 4-week (P = 0.545) follow-up evaluations. Our preliminary findings support the hypothesis that cathodal transcranial direct current stimulation over the contralesional

  15. Plasma rich in growth factors (PRGF-Endoret) stimulates tendon and synovial fibroblasts migration and improves the biological properties of hyaluronic acid.

    Science.gov (United States)

    Anitua, E; Sanchez, M; De la Fuente, M; Zalduendo, M M; Orive, G

    2012-09-01

    Cell migration plays an essential role in development, wound healing, and tissue regeneration. Plasma rich in growth factors (PRGF-Endoret) technology offers a potential source of growth factors involved in tissue regeneration. Here, we evaluate the potential of PRGF-Endoret over tendon cells and synovial fibroblasts migration and study whether the combination of this autologous technology with hyaluronic acid (HA) improves the effect and potential of the biomaterials over the motility of both types of fibroblasts. Migration of primary tendon cells and synovial fibroblasts after culturing with either PRGF or PPGF (plasma poor in growth factors) at different doses was evaluated. Furthermore, the migratory capacity induced by the combination of PPGF and PRGF with HA was tested. PPGF stimulated migration of both types of cells but this effect was significantly higher when PRGF was used. Tendon cells showed an increase of 212% in migratory ability when HA was combined with PPGF and of 335% in the case of HA + PRGF treatment compared with HA alone. PRGF-Endoret stimulates migration of tendon cells and synovial fibroblasts and improves the biological properties of HA.

  16. Electrified emotions: Modulatory effects of transcranial direct stimulation on negative emotional reactions to social exclusion.

    Science.gov (United States)

    Riva, Paolo; Romero Lauro, Leonor J; Vergallito, Alessandra; DeWall, C Nathan; Bushman, Brad J

    2015-01-01

    Social exclusion, ostracism, and rejection can be emotionally painful because they thwart the need to belong. Building on studies suggesting that the right ventrolateral prefrontal cortex (rVLPFC) is associated with regulation of negative emotions, the present experiment tests the hypothesis that decreasing the cortical excitability of the rVLPFC may increase negative emotional reactions to social exclusion. Specifically, we applied cathodal transcranial direct current stimulation (tDCS) over the rVLPFC and predicted an increment of negative emotional reactions to social exclusion. In Study 1, participants were either socially excluded or included, while cathodal tDCS or sham stimulation was applied over the rVLPFC. Cathodal stimulation of rVLPFC boosted the typical negative emotional reaction caused by social exclusion. No effects emerged from participants in the inclusion condition. To test the specificity of tDCS effects over rVLPFC, in Study 2, participants were socially excluded and received cathodal tDCS or sham stimulation over a control region (i.e., the right posterior parietal cortex). No effects of tDCS stimulation were found. Our results showed that the rVLPFC is specifically involved in emotion regulation and suggest that cathodal stimulation can increase negative emotional responses to social exclusion.

  17. Effects of transcranial direct current stimulation for treating depression: A modeling study

    DEFF Research Database (Denmark)

    Csifcsák, Gábor; Boayue, Nya Mehnwolo; Puonti, Oula

    2018-01-01

    Background: Transcranial direct current stimulation (tDCS) above the left dorsolateral prefrontal cortex (lDLPFC) has been widely used to improve symptoms of major depressive disorder (MDD). However, the effects of different stimulation protocols in the entire frontal lobe have not been investiga......Background: Transcranial direct current stimulation (tDCS) above the left dorsolateral prefrontal cortex (lDLPFC) has been widely used to improve symptoms of major depressive disorder (MDD). However, the effects of different stimulation protocols in the entire frontal lobe have not been...... regions. We evaluated effects of seven bipolar and two multi-electrode 4 × 1 tDCS protocols. Results: For bipolar montages, EFs were of comparable strength in the lDLPFC and in the medial prefrontal cortex (MPFC). Depending on stimulation parameters, EF cortical maps varied to a considerable degree......, but were found to be similar in controls and patients. 4 × 1 montages produced more localized, albeit weaker effects. Limitations: White matter anisotropy was not modeled. The relationship between EF strength and clinical response to tDCS could not be evaluated. Conclusions: In addition to l...

  18. Directed migration of cancer cells by the graded texture of the underlying matrix

    Science.gov (United States)

    Park, JinSeok; Kim, Deok-Ho; Kim, Hong-Nam; Wang, Chiaochun Joanne; Kwak, Moon Kyu; Hur, Eunmi; Suh, Kahp-Yang; An, Steven S.; Levchenko, Andre

    2016-01-01

    Living cells and the extracellular matrix (ECM) can display complex interactions that define key developmental, physiological and pathological processes. Here, we report a new type of directed migration — which we term ‘topotaxis’ — by which cell movement is guided by the gradient of the nanoscale topographic features in the cells’ ECM environment. We show that the direction of topotaxis is reflective of the effective cell stiffness, and that it depends on the balance of the ECM-triggered signalling pathways PI3K-Akt and ROCK-MLCK. In melanoma cancer cells, this balance can be altered by different ECM inputs, pharmacological perturbations or genetic alterations, particularly a loss of PTEN in aggressive melanoma cells. We conclude that topotaxis is a product of the material properties of cells and the surrounding ECM, and propose that the invasive capacity of many cancers may depend broadly on topotactic responses, providing a potentially attractive mechanism for controlling invasive and metastatic behaviour. PMID:26974411

  19. Radionuclide Migration at the Rio Blanco Site, A Nuclear-stimulated Low-permeability Natural Gas Reservoir

    Energy Technology Data Exchange (ETDEWEB)

    Clay A. Cooper; Ming Ye; Jenny Chapman; Craig Shirley

    2005-10-01

    The U.S. Department of Energy and its predecessor agencies conducted a program in the 1960s and 1970s that evaluated technology for the nuclear stimulation of low-permeability gas reservoirs. The third and final project in the program, Project Rio Blanco, was conducted in Rio Blanco County, in northwestern Colorado. In this experiment, three 33-kiloton nuclear explosives were simultaneously detonated in a single emplacement well in the Mesaverde Group and Fort Union Formation, at depths of 1,780, 1,899, and 2,039 m below land surface on May 17, 1973. The objective of this work is to estimate lateral distances that tritium released from the detonations may have traveled in the subsurface and evaluate the possible effect of postulated natural-gas development on radionuclide migration. Other radionuclides were considered in the analysis, but the majority occur in relatively immobile forms (such as nuclear melt glass). Of the radionuclides present in the gas phase, tritium dominates in terms of quantity of radioactivity in the long term and contribution to possible whole body exposure. One simulation is performed for {sup 85}Kr, the second most abundant gaseous radionuclide produced after tritium.

  20. Effects of an NMDA antagonist on the auditory mismatch negativity response to transcranial direct current stimulation.

    Science.gov (United States)

    Impey, Danielle; de la Salle, Sara; Baddeley, Ashley; Knott, Verner

    2017-05-01

    Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a weak constant current to alter cortical excitability and activity temporarily. tDCS-induced increases in neuronal excitability and performance improvements have been observed following anodal stimulation of brain regions associated with visual and motor functions, but relatively little research has been conducted with respect to auditory processing. Recently, pilot study results indicate that anodal tDCS can increase auditory deviance detection, whereas cathodal tDCS decreases auditory processing, as measured by a brain-based event-related potential (ERP), mismatch negativity (MMN). As evidence has shown that tDCS lasting effects may be dependent on N-methyl-D-aspartate (NMDA) receptor activity, the current study investigated the use of dextromethorphan (DMO), an NMDA antagonist, to assess possible modulation of tDCS's effects on both MMN and working memory performance. The study, conducted in 12 healthy volunteers, involved four laboratory test sessions within a randomised, placebo and sham-controlled crossover design that compared pre- and post-anodal tDCS over the auditory cortex (2 mA for 20 minutes to excite cortical activity temporarily and locally) and sham stimulation (i.e. device is turned off) during both DMO (50 mL) and placebo administration. Anodal tDCS increased MMN amplitudes with placebo administration. Significant increases were not seen with sham stimulation or with anodal stimulation during DMO administration. With sham stimulation (i.e. no stimulation), DMO decreased MMN amplitudes. Findings from this study contribute to the understanding of underlying neurobiological mechanisms mediating tDCS sensory and memory improvements.

  1. Effects of transcranial direct current stimulation (tDCS) on pain distress tolerance: a preliminary study

    Science.gov (United States)

    Mariano, Timothy Y.; Wout, Mascha van’t; Jacobson, Benjamin L.; Garnaat, Sarah L.; Kirschner, Jason L.; Rasmussen, Steven A.; Greenberg, Benjamin D.

    2015-01-01

    Objective Pain remains a critical medical challenge. Current treatments target nociception without addressing affective symptoms. Medically intractable pain is sometimes treated with cingulotomy or deep brain stimulation to increase tolerance of pain-related distress. Transcranial direct current stimulation (tDCS) may noninvasively modulate cortical areas related to sensation and pain representations. The present study aimed to test the hypothesis that cathodal (“inhibitory”) stimulation targeting left dorsal anterior cingulate cortex (dACC) would increase tolerance to distress from acute painful stimuli versus anodal stimulation. Methods Forty healthy volunteers received both anodal and cathodal stimulation. During stimulation, we measured pain distress tolerance with three tasks: pressure algometer, cold pressor, and breath holding. We measured pain intensity with a visual-analog scale before and after each task. Results Mixed ANOVA revealed that mean cold pressor tolerance tended to be higher with cathodal versus anodal stimulation (p = 0.055) for participants self-completing the task. Pressure algometer (p = 0.81) and breath holding tolerance (p = 0.19) did not significantly differ. The pressure algometer exhibited a statistically significant order effect irrespective of stimulation polarity (all p Pain intensity ratings increased acutely after cold pressor and pressure algometer tasks (both p pain ratings tended to rise less after cathodal versus anodal tDCS (p = 0.072). Conclusions Although our primary results were nonsignificant, there is a preliminary suggestion that cathodal tDCS targeting left dACC may increase pain distress tolerance to cold pressor. Pressure algometer results are consistent with task-related sensitization. Future studies are needed to refine this novel approach for pain neuromodulation. PMID:26115372

  2. Modelling the effect of electrode displacement on transcranial direct current stimulation (tDCS)

    Science.gov (United States)

    Ramaraju, Sriharsha; Roula, Mohammed A.; McCarthy, Peter W.

    2018-02-01

    Objective. Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers a low-intensity, direct current to cortical areas with the purpose of modulating underlying brain activity. Recent studies have reported inconsistencies in tDCS outcomes. The underlying assumption of many tDCS studies has been that replication of electrode montage equates to replicating stimulation conditions. It is possible however that anatomical difference between subjects, as well as inherent inaccuracies in montage placement, could affect current flow to targeted areas. The hypothesis that stimulation of a defined brain region will be stable under small displacements was tested. Approach. Initially, we compared the total simulated current flowing through ten specific brain areas for four commonly used tDCS montages: F3-Fp2, C3-Fp2, Fp1-F4, and P3-P4 using the software tool COMETS. The effect of a slight (~1 cm in each of four directions) anode displacement on the simulated regional current density for each of the four tDCS montages was then determined. Current flow was calculated and compared through ten segmented brain areas to determine the effect of montage type and displacement. The regional currents, as well as the localised current densities, were compared with the original electrode location, for each of these new positions. Main results. Recommendations for montages that maximise stimulation current for the ten brain regions are considered. We noted that the extent to which stimulation is affected by electrode displacement varies depending on both area and montage type. The F3-Fp2 montage was found to be the least stable with up to 38% change in average current density in the left frontal lobe while the Fp1-F4 montage was found to the most stable exhibiting only 1% change when electrodes were displaced. Significance. These results indicate that even relatively small changes in stimulation electrode placement appear to result in surprisingly large

  3. Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

    International Nuclear Information System (INIS)

    An, Caiyan; Sato, Koichi; Wu, Taoya; Bao, Muqiri; Bao, Liang; Tobo, Masayuki; Damirin, Alatangaole

    2015-01-01

    The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement of cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the

  4. Extracellular acidification synergizes with PDGF to stimulate migration of mouse embryo fibroblasts through activation of p38MAPK with a PTX-sensitive manner

    Energy Technology Data Exchange (ETDEWEB)

    An, Caiyan [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China); Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Clinical Medicine Research Center of the Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia (China); Sato, Koichi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Wu, Taoya; Bao, Muqiri; Bao, Liang [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China); Tobo, Masayuki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi (Japan); Damirin, Alatangaole, E-mail: bigaole@imu.edu.cn [Department of Biochemistry and Molecular Biology, College of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia (China)

    2015-05-01

    The elucidation of the functional mechanisms of extracellular acidification stimulating intracellular signaling pathway is of great importance for developing new targets of treatment for solid tumors, and inflammatory disorders characterized by extracellular acidification. In the present study, we focus on the regulation of extracellular acidification on intracellular signaling pathways in mouse embryo fibroblasts (MEFs). We found extracellular acidification was at least partly involved in stimulating p38MAPK pathway through PTX-sensitive behavior to enhance cell migration in the presence or absence of platelet-derived growth factor (PDGF). Statistical analysis showed that the actions of extracellular acidic pH and PDGF on inducing enhancement of cell migration were not an additive effect. However, we also found extracellular acidic pH did inhibit the viability and proliferation of MEFs, suggesting that extracellular acidification stimulates cell migration probably through proton-sensing mechanisms within MEFs. Using OGR1-, GPR4-, and TDAG8-gene knock out technology, and real-time qPCR, we found known proton-sensing G protein-coupled receptors (GPCRs), transient receptor potential vanilloid subtype 1 (TRPV1), and acid-sensing ion channels (ASICs) were unlikely to be involved in the regulation of acidification on cell migration. In conclusion, our present study validates that extracellular acidification stimulates chemotactic migration of MEFs through activation of p38MAPK with a PTX-sensitive mechanism either by itself, or synergistically with PDGF, which was not regulated by the known proton-sensing GPCRs, TRPV1, or ASICs. Our results suggested that others proton-sensing GPCRs or ion channels might exist in MEFs, which mediates cell migration induced by extracellular acidification in the presence or absence of PDGF. - Highlights: • Acidic pH and PDGF synergize to stimulate MEFs migration via Gi/p38MAPK pathway. • Extracellular acidification inhibits the

  5. High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression

    Directory of Open Access Journals (Sweden)

    Ji Young Oh

    2018-04-01

    Full Text Available Background/Aims: Glucose plays an important role in stem cell fate determination and behaviors. However, it is still not known how glucose contributes to the precise molecular mechanisms responsible for stem cell migration. Thus, we investigate the effect of glucose on the regulation of the human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC migration, and analyze the mechanism accompanied by this effect. Methods: Western blot analysis, wound healing migration assays, immunoprecipitation, and chromatin immunoprecipitation assay were performed to investigate the effect of high glucose on hUCB-MSC migration. Additionally, hUCB-MSC transplantation was performed in the mouse excisional wound splinting model. Results: High concentration glucose (25 mM elicits hUCB-MSC migration compared to normal glucose and high glucose-pretreated hUCB-MSC transplantation into the wound sites in mice also accelerates skin wound repair. We therefore elucidated the detailed mechanisms how high glucose induces hUCB-MSC migration. We showed that high glucose regulates E-cadherin repression through increased Snail and EZH2 expressions. And, we found high glucose-induced reactive oxygen species (ROS promotes two signaling; JNK which regulates γ–secretase leading to the cleavage of Notch proteins and PI3K/Akt signaling which enhances GSK-3β phosphorylation. High glucose-mediated JNK/Notch pathway regulates the expression of EZH2, and PI3K/Akt/GSK-3β pathway stimulates Snail stabilization, respectively. High glucose enhances the formation of EZH2/Snail/HDAC1 complex in the nucleus, which in turn causes E-cadherin repression. Conclusion: This study reveals that high glucose-induced ROS stimulates the migration of hUCB-MSC through E-cadherin repression via Snail and EZH2 signaling pathways.

  6. Combining physical training with transcranial direct current stimulation to improve gait in Parkinson's disease: a pilot randomized controlled study.

    Science.gov (United States)

    Kaski, D; Dominguez, R O; Allum, J H; Islam, A F; Bronstein, A M

    2014-11-01

    To improve gait and balance in patients with Parkinson's disease by combining anodal transcranial direct current stimulation with physical training. In a double-blind design, one group (physical training; n = 8) underwent gait and balance training during transcranial direct current stimulation (tDCS; real/sham). Real stimulation consisted of 15 minutes of 2 mA transcranial direct current stimulation over primary motor and premotor cortex. For sham, the current was switched off after 30 seconds. Patients received the opposite stimulation (sham/real) with physical training one week later; the second group (No physical training; n = 8) received stimulation (real/sham) but no training, and also repeated a sequential transcranial direct current stimulation session one week later (sham/real). Hospital Srio Libanes, Buenos Aires, Argentina. Sixteen community-dwelling patients with Parkinson's disease. Transcranial direct current stimulation with and without concomitant physical training. Gait velocity (primary gait outcome), stride length, timed 6-minute walk test, Timed Up and Go Test (secondary outcomes), and performance on the pull test (primary balance outcome). Transcranial direct current stimulation with physical training increased gait velocity (mean = 29.5%, SD = 13; p transcranial direct current stimulation alone. There was no isolated benefit of transcranial direct current stimulation alone. Although physical training improved gait velocity (mean = 15.5%, SD = 12.3; p = 0.03), these effects were comparatively less than with combined tDCS + physical therapy (p stimulation-related improvements were seen in patients with more advanced disease. Anodal transcranial direct current stimulation during physical training improves gait and balance in patients with Parkinson's disease. Power calculations revealed that 14 patients per treatment arm (α = 0.05; power = 0.8) are required for a definitive trial. © The Author(s) 2014.

  7. Effect of transcranial direct current stimulation on neuroplasticity in corticomotor pathways of the tongue muscles

    DEFF Research Database (Denmark)

    Kothari, Mohit; Stubbs, Peter William; Figlewski, Krystian

    2017-01-01

    To investigate effects of transcranial direct current stimulation (tDCS) on neuroplasticity in corticomotor pathways related to tongue muscles evoked by a training task using the Tongue Drive System (TDS). Using a cross-over design, 13 healthy participants completed two sessions of tDCS while...... performing 30 min of TDS training. Sessions were spaced at least 2 weeks apart and participants randomly received anodal and sham tDCS stimulation in the first session and the other condition in the second session. Single and paired pulse transcranial magnetic stimulation was used to elicit motor evoked...... potentials (MEPs) of the tongue at three time-points; before, immediately after and 30 min after training. Participant-based reports of fun, pain, fatigue and motivation, level of difficulty and effort were evaluated on numerical rating scales. There was no consistent significant effect of anodal and sham...

  8. Acute changes in motor cortical excitability during slow oscillatory and constant anodal transcranial direct current stimulation

    DEFF Research Database (Denmark)

    Bergmann, Til Ole; Groppa, Sergiu; Seeger, Markus

    2009-01-01

    Transcranial oscillatory current stimulation has recently emerged as a noninvasive technique that can interact with ongoing endogenous rhythms of the human brain. Yet, there is still little knowledge on how time-varied exogenous currents acutely modulate cortical excitability. In ten healthy...... individuals we used on-line single-pulse transcranial magnetic stimulation (TMS) to search for systematic shifts in corticospinal excitability during anodal sleeplike 0.8-Hz slow oscillatory transcranial direct current stimulation (so-tDCS). In separate sessions, we repeatedly applied 30-s trials (two blocks...... at 20 min) of either anodal so-tDCS or constant tDCS (c-tDCS) to the primary motor hand area during quiet wakefulness. Simultaneously and time-locked to different phase angles of the slow oscillation, motor-evoked potentials (MEPs) as an index of corticospinal excitability were obtained...

  9. Transcranial Direct Current Stimulation (tDCS: A Beginner's Guide for Design and Implementation

    Directory of Open Access Journals (Sweden)

    Hayley Thair

    2017-11-01

    Full Text Available Transcranial direct current stimulation (tDCS is a popular brain stimulation method that is used to modulate cortical excitability, producing facilitatory or inhibitory effects upon a variety of behaviors. There is, however, a current lack of consensus between studies, with many results suggesting that polarity-specific effects are difficult to obtain. This article explores some of these differences and highlights the experimental parameters that may underlie their occurrence. We provide a general, practical snapshot of tDCS methodology, including what it is used for, how to use it, and considerations for designing an effective and safe experiment. Our aim is to equip researchers who are new to tDCS with the essential knowledge so that they can make informed and well-rounded decisions when designing and running successful experiments. By summarizing the varied approaches, stimulation parameters, and outcomes, this article should help inform future tDCS research in a variety of fields.

  10. Transcranial Direct Current Stimulation (tDCS): A Beginner's Guide for Design and Implementation

    Science.gov (United States)

    Thair, Hayley; Holloway, Amy L.; Newport, Roger; Smith, Alastair D.

    2017-01-01

    Transcranial direct current stimulation (tDCS) is a popular brain stimulation method that is used to modulate cortical excitability, producing facilitatory or inhibitory effects upon a variety of behaviors. There is, however, a current lack of consensus between studies, with many results suggesting that polarity-specific effects are difficult to obtain. This article explores some of these differences and highlights the experimental parameters that may underlie their occurrence. We provide a general, practical snapshot of tDCS methodology, including what it is used for, how to use it, and considerations for designing an effective and safe experiment. Our aim is to equip researchers who are new to tDCS with the essential knowledge so that they can make informed and well-rounded decisions when designing and running successful experiments. By summarizing the varied approaches, stimulation parameters, and outcomes, this article should help inform future tDCS research in a variety of fields. PMID:29213226

  11. Impairments of motor-cortex responses to unilateral and bilateral direct current stimulation in schizophrenia

    Directory of Open Access Journals (Sweden)

    Alkomiet eHasan

    2013-10-01

    Full Text Available Transcranial direct current stimulation (tDCS is a non-invasive stimulation technique that can be applied to modulate cortical activity through induction of cortical plasticity. Since various neuropsychiatric disorders are characterised by fluctuations in cortical activity levels (e.g. schizophrenia, tDCS is increasingly investigated as a treatment tool. Several studies have shown that the induction of cortical plasticity following classical, unilateral tDCS is reduced or impaired in the stimulated and non-stimulated primary motor cortices (M1 of schizophrenia patients. Moreover, an alternative, bilateral tDCS setup has recently been shown to modulate cortical plasticity in both hemispheres in healthy subjects, highlighting another potential treatment approach. Here we present the first study comparing the efficacy of unilateral tDCS (cathode left M1, anode right supraorbital with simultaneous bilateral tDCS (cathode left M1, anode right M1 in schizophrenia patients. tDCS-induced cortical plasticity was monitored by investigating motor-evoked potentials induced by single-pulse transcranial magnetic stimulation applied to both hemispheres. Healthy subjects showed a reduction of left M1 excitability following unilateral tDCS on the stimulated left hemisphere and an increase in right M1 excitability following bilateral tDCS. In schizophrenia, no plasticity was induced following both stimulation paradigms. The pattern of these results indicates a complex interplay between plasticity and connectivity that is impaired in schizophrenia patients. Further studies are needed to clarify the biological underpinnings and clinical impact of these findings.

  12. Adult subependymal neural precursors, but not differentiated cells, undergo rapid cathodal migration in the presence of direct current electric fields.

    Directory of Open Access Journals (Sweden)

    Robart Babona-Pilipos

    Full Text Available BACKGROUND: The existence of neural stem and progenitor cells (together termed neural precursor cells in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke. METHODS AND FINDINGS: With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour. CONCLUSIONS: These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma.

  13. Operant conditioning of rat navigation using electrical stimulation for directional cues and rewards.

    Science.gov (United States)

    Lee, Maan-Gee; Jun, Gayoung; Choi, Hyo-Soon; Jang, Hwan Soo; Bae, Yong Chul; Suk, Kyoungho; Jang, Il-Sung; Choi, Byung-Ju

    2010-07-01

    Operant conditioning is often used to train a desired behavior in an animal. The contingency between a specific behavior and a reward is required for successful training. Here, we compared the effectiveness of two different mazes for training turning behaviors in response to directional cues in Sprague-Dawley rats. Forty-three rats were implanted with electrodes into the medial forebrain bundle and the left and right somatosensory cortices for reward and cues. Among them, thirteen rats discriminated between the left and right somatosensory stimulations to obtain rewards. They were trained to learn ipsilateral turning response to the stimulation of the left or right somatosensory cortex in either the T-maze (Group T) or the E| maze (Group W). Performance was measured by the navigation speed in the mazes. Performances of rats in Group T were enhanced faster than those in Group W. A significant correlation between performances during training and performance in final testing was observed in Group T starting with the fifth training session while such a correlation was not observed in Group W until the tenth training session. The training mazes did not however affect the performances in the final test. These results suggest that a simple maze is better than a complicated maze for training animals to learn directions and direct cortical stimulation can be used as a cue for direction training. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  14. Anodal transcranial direct current stimulation of right temporoparietal area inhibits self-recognition.

    Science.gov (United States)

    Payne, Sophie; Tsakiris, Manos

    2017-02-01

    Self-other discrimination is a crucial mechanism for social cognition. Neuroimaging and neurostimulation research has pointed to the involvement of the right temporoparietal region in a variety of self-other discrimination tasks. Although repetitive transcranial magnetic stimulation over the right temporoparietal area has been shown to disrupt self-other discrimination in face-recognition tasks, no research has investigated the effect of increasing the cortical excitability in this region on self-other face discrimination. Here we used transcranial direct current stimulation (tDCS) to investigate changes in self-other discrimination with a video-morphing task in which the participant's face morphed into, or out of, a familiar other's face. The task was performed before and after 20 min of tDCS targeting the right temporoparietal area (anodal, cathodal, or sham stimulation). Differences in task performance following stimulation were taken to indicate a change in self-other discrimination. Following anodal stimulation only, we observed a significant increase in the amount of self-face needed to distinguish between self and other. The findings are discussed in relation to the control of self and other representations and to domain-general theories of social cognition.

  15. Direct electrical stimulation as an input gate into brain functional networks: principles, advantages and limitations.

    Science.gov (United States)

    Mandonnet, Emmanuel; Winkler, Peter A; Duffau, Hugues

    2010-02-01

    While the fundamental and clinical contribution of direct electrical stimulation (DES) of the brain is now well acknowledged, its advantages and limitations have not been re-evaluated for a long time. Here, we critically review exactly what DES can tell us about cerebral function. First, we show that DES is highly sensitive for detecting the cortical and axonal eloquent structures. Moreover, DES also provides a unique opportunity to study brain connectivity, since each area responsive to stimulation is in fact an input gate into a large-scale network rather than an isolated discrete functional site. DES, however, also has a limitation: its specificity is suboptimal. Indeed, DES may lead to interpretations that a structure is crucial because of the induction of a transient functional response when stimulated, whereas (1) this effect is caused by the backward spreading of the electro-stimulation along the network to an essential area and/or (2) the stimulated region can be functionally compensated owing to long-term brain plasticity mechanisms. In brief, although DES is still the gold standard for brain mapping, its combination with new methods such as perioperative neurofunctional imaging and biomathematical modeling is now mandatory, in order to clearly differentiate those networks that are actually indispensable to function from those that can be compensated.

  16. Modulation of mu rhythm desynchronization during motor imagery by transcranial direct current stimulation

    Directory of Open Access Journals (Sweden)

    Kimura Akio

    2010-06-01

    Full Text Available Abstract Background The mu event-related desynchronization (ERD is supposed to reflect motor preparation and appear during motor imagery. The aim of this study is to examine the modulation of ERD with transcranial direct current stimulation (tDCS. Methods Six healthy subjects were asked to imagine their right hand grasping something after receiving a visual cue. Electroencephalograms (EEGs were recorded near the left M1. ERD of the mu rhythm (mu ERD by right hand motor imagery was measured. tDCS (10 min, 1 mA was used to modulate the cortical excitability of M1. Anodal, cathodal, and sham tDCS were tested in each subject with a randomized sequence on different days. Each condition was separated from the preceding one by more than 1 week in the same subject. Before and after tDCS, mu ERD was assessed. The motor thresholds (MT of the left M1 were also measured with transcranial magnetic stimulation. Results Mu ERD significantly increased after anodal stimulation, whereas it significantly decreased after cathodal stimulation. There was a significant correlation between mu ERD and MT. Conclusions Opposing effects on mu ERD based on the orientation of the stimulation suggest that mu ERD is affected by cortical excitability.

  17. Improved reading measures in adults with dyslexia following transcranial direct current stimulation treatment.

    Science.gov (United States)

    Heth, Inbahl; Lavidor, Michal

    2015-04-01

    To better understand the contribution of the dorsal system to word reading, we explored transcranial direct current stimulation (tDCS) effects when adults with developmental dyslexia received active stimulation over the visual extrastriate area MT/V5, which is dominated by magnocellular input. Stimulation was administered in 5 sessions spread over two weeks, and reading speed and accuracy as well as reading fluency were assessed before, immediately after, and a week after the end of the treatment. A control group of adults with developmental dyslexia matched for age, gender, reading level, vocabulary and block-design WAIS-III sub-tests and reading level was exposed to the same protocol but with sham stimulation. The results revealed that active, but not sham stimulation, significantly improved reading speed and fluency. This finding suggests that the dorsal stream may play a role in efficient retrieval from the orthographic input lexicon in the lexical route. It also underscores the potential of tDCS as an intervention tool for improving reading speed, at least in adults with developmental dyslexia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Polarity Specific Suppression Effects of Transcranial Direct Current Stimulation for Tinnitus

    Directory of Open Access Journals (Sweden)

    Kathleen Joos

    2014-01-01

    Full Text Available Tinnitus is the perception of a sound in the absence of an external auditory stimulus and affects 10–15% of the Western population. Previous studies have demonstrated the therapeutic effect of anodal transcranial direct current stimulation (tDCS over the left auditory cortex on tinnitus loudness, but the effect of this presumed excitatory stimulation contradicts with the underlying pathophysiological model of tinnitus. Therefore, we included 175 patients with chronic tinnitus to study polarity specific effects of a single tDCS session over the auditory cortex (39 anodal, 136 cathodal. To assess the effect of treatment, we used the numeric rating scale for tinnitus loudness and annoyance. Statistical analysis demonstrated a significant main effect for tinnitus loudness and annoyance, but for tinnitus annoyance anodal stimulation has a significantly more pronounced effect than cathodal stimulation. We hypothesize that the suppressive effect of tDCS on tinnitus loudness may be attributed to a disrupting effect of ongoing neural hyperactivity, independent of the inhibitory or excitatory effects and that the reduction of annoyance may be induced by influencing adjacent or functionally connected brain areas involved in the tinnitus related distress network. Further research is required to explain why only anodal stimulation has a suppressive effect on tinnitus annoyance.

  19. Acylated and unacylated ghrelin do not directly stimulate glucose transport in isolated rodent skeletal muscle.

    Science.gov (United States)

    Cervone, Daniel T; Dyck, David J

    2017-07-01

    Emerging evidence implicates ghrelin, a gut-derived, orexigenic hormone, as a potential mediator of insulin-responsive peripheral tissue metabolism. However, in vitro and in vivo studies assessing ghrelin's direct influence on metabolism have been controversial, particularly due to confounding factors such as the secondary rise in growth hormone (GH) after ghrelin injection. Skeletal muscle is important in the insulin-stimulated clearance of glucose, and ghrelin's exponential rise prior to a meal could potentially facilitate this. This study was aimed at elucidating any direct stimulatory action that ghrelin may have on glucose transport and insulin signaling in isolated rat skeletal muscle, in the absence of confounding secondary factors. Oxidative soleus and glycolytic extensor digitorum longus skeletal muscles were isolated from male Sprague Dawley rats in the fed state and incubated with various concentrations of acylated and unacylated ghrelin in the presence or absence of insulin. Ghrelin did not stimulate glucose transport in either muscle type, with or without insulin. Moreover, GH had no acute, direct stimulatory effect on either basal or insulin-stimulated muscle glucose transport. In agreement with the lack of observed effect on glucose transport, ghrelin and GH also had no stimulatory effect on Ser 473 AKT or Thr 172 AMPK phosphorylation, two key signaling proteins involved in glucose transport. Furthermore, to our knowledge, we are among the first to show that ghrelin can act independent of its receptor and cause an increase in calmodulin-dependent protein kinase 2 (CaMKII) phosphorylation in glycolytic muscle, although this was not associated with an increase in glucose transport. We conclude that both acylated and unacylated ghrelin have no direct, acute influence on skeletal muscle glucose transport. Furthermore, the immediate rise in GH in response to ghrelin also does not appear to directly stimulate glucose transport in muscle. © 2017 The

  20. Chemistry of ice: Migration of ions and gases by directional freezing of water

    Directory of Open Access Journals (Sweden)

    Umer Shafique

    2016-09-01

    Full Text Available Redistribution of anions and cations creates an electrical imbalance in ice grown from electrolyte solutions. Movement of acidic and basic ions in cooling solutions can permanently change the pH of frozen and unfrozen parts of the system, largely. The extent of pH change associated with freezing is determined by solute concentration and the extent of cooling. In the present work, redistribution of hydrogen, hydroxyl, carbonate, and bicarbonate ions was studied during directional freezing in batch aqueous systems. Controlled freezing was employed vertically as well as radially in acidic and basic solutions. In each case, the ions substantially migrated along with moving freezing front. Conductometry and pH-metry were employed to monitor the moving ions. Besides, some other experiments were carried out with molecular gases, such as oxygen, carbon dioxide, and chlorine and an azeotropic mixture like water–ethanol. Findings can be used to understand possible changes that can occur in preserving materials by freezing.

  1. Direct detection of near-surface faults by migration of back-scattered surface waves

    KAUST Repository

    Yu, Han

    2014-08-05

    We show that diffraction stack migration can be used to estimate the distribution of near-surface faults. The assumption is that near-surface faults generate detectable back-scattered surface waves from impinging surface waves. The processing steps are to isolate the back-scattered surface waves, and then migrate them by diffraction migration using the surface wave velocity as the migration velocity. Instead of summing events along trial quasi-hyperbolas, surface wave migration sums events along trial quasi-linear trajectories that correspond to the moveout of back-scattered surface waves. A deconvolution filter derived from the data can be used to collapse a dispersive arrival into a non-dispersive event. Results with synthetic data and field records validate the feasibility of this method. Applying this method to USArray data or passively recorded exploration data might open new opportunities in mapping tectonic features over the extent of the array.

  2. ANODAL TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) INCREASES ISOMETRIC STRENGTH OF SHOULDER ROTATORS MUSCLES IN HANDBALL PLAYERS.

    Science.gov (United States)

    Hazime, Fuad Ahmad; da Cunha, Ronaldo Alves; Soliaman, Renato Rozenblit; Romancini, Ana Clara Bezerra; Pochini, Alberto de Castro; Ejnisman, Benno; Baptista, Abrahão Fontes

    2017-06-01

    Weakness of the rotator cuff muscles can lead to imbalances in the strength of shoulder external and internal rotators, change the biomechanics of the glenohumeral joint and predispose an athlete to injury. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has demonstrated promising results in a variety of health conditions. However few studies addressed its potential approach in the realm of athletics. The purpose of this study was to investigate if transcranial direct current stimulation (tDCS) technique increases the isometric muscle strength of shoulder external and internal rotators in handball athletes. Randomized, double-blind, placebo-controlled, crossover study. Eight female handball players aged between 17 and 21 years (Mean=19.65; SD=2.55) with 7.1 ± 4.8 years of experience in training, participating in regional and national competitions were recruited. Maximal voluntary isometric contraction (MVIC) of shoulder external and internal rotator muscles was evaluated during and after 30 and 60 minutes post one session of anodal and sham current (2mA; 0.057mA/cm 2 ) with a one-week interval between stimulations. Compared to baseline, MVIC of shoulder external and internal rotators significantly increased after real but not sham tDCS. Between-group differences were observed for external and internal rotator muscles. Maximal voluntary isometric contraction of external rotation increased significantly during tDCS, and 30 and 60 minutes post-tDCS for real tDCS compared to that for sham tDCS. For internal rotation MVIC increased significantly during and 60 minutes post-tDCS. The results indicate that transcranial direct current stimulation temporarily increases maximal isometric contractions of the internal and external rotators of the shoulder in handball players. 2.

  3. The ectodomain of cadherin-11 binds to erbB2 and stimulates Akt phosphorylation to promote cranial neural crest cell migration.

    Directory of Open Access Journals (Sweden)

    Ketan Mathavan

    Full Text Available During development, a multi-potent group of cells known as the cranial neural crest (CNC migrate to form craniofacial structures. Proper migration of these cells requires proteolysis of cell adhesion molecules, such as cadherins. In Xenopus laevis, preventing extracellular cleavage of cadherin-11 impairs CNC migration. However, overexpression of the soluble cleavage product (EC1-3 is capable of rescuing this phenotype. The mechanism by which EC1-3 promotes CNC migration has not been investigated until now. Here we show that EC1-3 stimulates phosphorylation of Akt, a target of PI3K, in X.laevis CNC. Through immunoprecipitation experiments, we determined that EC1-3 interacts with all ErbB receptors, PDGFRα, and FGFR1. Of these receptors, only ErbB2 was able to produce an increase in Akt phosphorylation upon treatment with a recombinant EC1-3. This increase was abrogated by mubritinib, an inhibitor of ErbB2. We were able to recapitulate this decrease in Akt phosphorylation in vivo by knocking down ErbB2 in CNC cells. Knockdown of the receptor also significantly reduced CNC migration in vivo. We confirmed the importance of ErbB2 and ErbB receptor signaling in CNC migration using mubritinib and canertinib, respectively. Mubritinib and the PI3K inhibitor LY294002 significantly decreased cell migration while canertinib nearly prevented it altogether. These data show that ErbB2 and Akt are important for CNC migration and implicate other ErbB receptors and Akt-independent signaling pathways. Our findings provide the first example of a functional interaction between the extracellular domain of a type II classical cadherin and growth factor receptors.

  4. Is transcranial direct current stimulation a potential method for improving response inhibition?☆

    OpenAIRE

    Kwon, Yong Hyun; Kwon, Jung Won

    2013-01-01

    Inhibitory control of movement in motor learning requires the ability to suppress an inappropriate action, a skill needed to stop a planned or ongoing motor response in response to changes in a variety of environments. This study used a stop-signal task to determine whether transcranial direct-current stimulation over the pre-supplementary motor area alters the reaction time in motor inhibition. Forty healthy subjects were recruited for this study and were randomly assigned to either the tran...

  5. Counteracting fatigue in multiple sclerosis with right parietal anodal transcranial direct current stimulation

    OpenAIRE

    Katrin Hanken; Katrin Hanken; Mona Bosse; Kim Möhrke; Paul Eling; Andreas Kastrup; Andrea Antal; Helmut Hildebrandt; Helmut Hildebrandt

    2016-01-01

    Background: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. Methods: In study I, a randomized double-blind placebo-controlled study, anoda...

  6. Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation

    OpenAIRE

    Hanken, Katrin; Bosse, Mona; M?hrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

    2016-01-01

    BACKGROUND: Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. OBJECTIVES: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. METHODS: In study I, a randomized double-blind placebo-controll...

  7. Landbird migration in the American West: Recent progress and future research directions

    Science.gov (United States)

    Carlisle, J.D.; Skagen, S.K.; Kus, B.E.; van Riper, Charles; Paxton, K.L.; Kelly, J.F.

    2009-01-01

    Our knowledge of avian behaviors during the nonbreeding period still lags behind that of the breeding season, but the last decade has witnessed a proliferation in research that has yielded significant progress in understanding migration patterns of North American birds. And, although historically the great majority of migration research has been conducted in the eastern half of the continent, there has been much recent progress on aspects of avian migration in the West. In particular, expanded use of techniques such as radar, plasma metabolites, mist-netting, count surveys, stable isotopes, genetic data, and animal tracking, coupled with an increase in multi-investigator collaborations, have all contributed to this growth of knowledge. There is increasing recognition that migration is likely the most limiting time of year for migratory birds, increasing the importance of continuing to decipher patterns of stopover ecology, identifying critical stopover habitats, and documenting migration routes in the diverse and changing landscapes of the American West. Here, we review and briefly synthesize the latest findings and advances in avian migration and consider research needs to guide future research on migration in the West. ?? 2009 by The Cooper Ornithological Society. All rights reserved.

  8. Transcranial direct current stimulation of the posterior parietal cortex modulates arithmetic learning.

    Science.gov (United States)

    Grabner, Roland H; Rütsche, Bruno; Ruff, Christian C; Hauser, Tobias U

    2015-07-01

    The successful acquisition of arithmetic skills is an essential step in the development of mathematical competencies and has been associated with neural activity in the left posterior parietal cortex (PPC). It is unclear, however, whether this brain region plays a causal role in arithmetic skill acquisition and whether arithmetic learning can be modulated by means of non-invasive brain stimulation of this key region. In the present study we addressed these questions by applying transcranial direct current stimulation (tDCS) over the left PPC during a short-term training that simulates the typical path of arithmetic skill acquisition (specifically the transition from effortful procedural to memory-based problem-solving strategies). Sixty participants received either anodal, cathodal or sham tDCS while practising complex multiplication and subtraction problems. The stability of the stimulation-induced learning effects was assessed in a follow-up test 24 h after the training. Learning progress was modulated by tDCS. Cathodal tDCS (compared with sham) decreased learning rates during training and resulted in poorer performance which lasted over 24 h after stimulation. Anodal tDCS showed an operation-specific improvement for subtraction learning. Our findings extend previous studies by demonstrating that the left PPC is causally involved in arithmetic learning (and not only in arithmetic performance) and that even a short-term tDCS application can modulate the success of arithmetic knowledge acquisition. Moreover, our finding of operation-specific anodal stimulation effects suggests that the enhancing effects of tDCS on learning can selectively affect just one of several cognitive processes mediated by the stimulated area. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. Counteracting fatigue in multiple sclerosis with right parietal anodal transcranial direct current stimulation

    Directory of Open Access Journals (Sweden)

    Katrin Hanken

    2016-09-01

    Full Text Available Background: Fatigue in multiple sclerosis (MS patients appears to correlate with vigilance decrement as reflected in an increase in reaction time and errors with prolonged time-on-task. Objectives: The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. Methods: In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1,5mA was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20min of a 40min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5mA over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. TDCS was delivered for 20min before patients performed a 20min lasting visual vigilance task.Results: Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in reaction time associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation.Conclusions: Anodal tDCS over the right parietal cortex can counteract the increase in reaction times during vigilance performance but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

  10. Counteracting Fatigue in Multiple Sclerosis with Right Parietal Anodal Transcranial Direct Current Stimulation.

    Science.gov (United States)

    Hanken, Katrin; Bosse, Mona; Möhrke, Kim; Eling, Paul; Kastrup, Andreas; Antal, Andrea; Hildebrandt, Helmut

    2016-01-01

    Fatigue in multiple sclerosis (MS) patients appears to correlate with vigilance decrement as reflected in an increase in reaction time (RT) and errors with prolonged time-on-task. The aim of this study was to investigate whether anodal transcranial direct current stimulation (tDCS) over the right parietal or frontal cortex counteracts fatigue-associated vigilance decrement and subjective fatigue. In study I, a randomized double-blind placebo-controlled study, anodal tDCS (1.5 mA) was delivered to the right parietal cortex or the right frontal cortex of 52 healthy participants during the first 20 min of a 40-min lasting visual vigilance task. Study II, also a randomized double-blind placebo-controlled study, investigated the effect of anodal tDCS (1.5 mA) over the right parietal cortex in 46 MS patients experiencing cognitive fatigue. tDCS was delivered for 20 min before patients performed a 20-min lasting visual vigilance task. Study I showed that right parietal stimulation, but not right frontal stimulation, counteracts the increase in RT associated with vigilance decrement. Hence, only right parietal stimulation was applied to the MS patients in study II. Stimulation had a significant effect on vigilance decrement in mildly to moderately cognitively fatigued MS patients. Vigilance testing significantly increased the feeling of fatigue independent of stimulation. Anodal tDCS over the right parietal cortex can counteract the increase in RTs during vigilance performance, but not the increase in subjective fatigue. This finding is compatible with our model of fatigue in MS, suggesting a dissociation between the feeling and the behavioral characteristics of fatigue.

  11. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

    Science.gov (United States)

    Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

    2003-11-15

    Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

  12. Understanding effects of matrix protease and matrix organization on directional persistence and translational speed in three-dimensional cell migration.

    Science.gov (United States)

    Zaman, Muhammad H; Matsudaira, Paul; Lauffenburger, Douglas A

    2007-01-01

    Recent studies have shown significant differences in migration mechanisms between two- and three-dimensional environments. While experiments have suggested a strong dependence of in vivo migration on both structure and proteolytic activity, the underlying biophysics of such dependence has not been studied adequately. In addition, the existing models of persistent random walk migration are primarily based on two-dimensional movement and do not account for the effect of proteolysis or matrix inhomogeneity. Using lattice Monte Carlo methods, we present a model to study the role of matrix metallo-proteases (MMPs) on directional persistence and speed. The simulations account for a given cell's ability to deform as well as to digest the matrix as the cell moves in three dimensions. Our results show a bimodal dependence of speed and persistence on matrix pore size and suggest high sensitivity on MMP activity, which is in very good agreement with experimental studies carried out in 3D matrices.

  13. The morphological and molecular changes of brain cells exposed to direct current electric field stimulation.

    Science.gov (United States)

    Pelletier, Simon J; Lagacé, Marie; St-Amour, Isabelle; Arsenault, Dany; Cisbani, Giulia; Chabrat, Audrey; Fecteau, Shirley; Lévesque, Martin; Cicchetti, Francesca

    2014-12-07

    The application of low-intensity direct current electric fields has been experimentally used in the clinic to treat a number of brain disorders, predominantly using transcranial direct current stimulation approaches. However, the cellular and molecular changes induced by such treatment remain largely unknown. Here, we tested various intensities of direct current electric fields (0, 25, 50, and 100V/m) in a well-controlled in vitro environment in order to investigate the responses of neurons, microglia, and astrocytes to this type of stimulation. This included morphological assessments of the cells, viability, as well as shape and fiber outgrowth relative to the orientation of the direct current electric field. We also undertook enzyme-linked immunosorbent assays and western immunoblotting to identify which molecular pathways were affected by direct current electric fields. In response to direct current electric field, neurons developed an elongated cell body shape with neurite outgrowth that was associated with a significant increase in growth associated protein-43. Fetal midbrain dopaminergic explants grown in a collagen gel matrix also showed a reorientation of their neurites towards the cathode. BV2 microglial cells adopted distinct morphological changes with an increase in cyclooxygenase-2 expression, but these were dependent on whether they had already been activated with lipopolysaccharide. Finally, astrocytes displayed elongated cell bodies with cellular filopodia that were oriented perpendicularly to the direct current electric field. We show that cells of the central nervous system can respond to direct current electric fields both in terms of their morphological shape and molecular expression of certain proteins, and this in turn can help us to begin understand the mechanisms underlying the clinical benefits of direct current electric field. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  14. Direct detection of near-surface faults by migration of back-scattered surface waves

    KAUST Repository

    Yu, Han; Guo, Bowen; Hanafy, Sherif; Lin, Fan-Chi; Schuster, Gerard T.

    2014-01-01

    We show that diffraction stack migration can be used to estimate the distribution of near-surface faults. The assumption is that near-surface faults generate detectable back-scattered surface waves from impinging surface waves. The processing steps

  15. ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells

    International Nuclear Information System (INIS)

    Sun, Qing; Liang, Ying; Zhang, Tianli; Wang, Kun; Yang, Xingsheng

    2017-01-01

    Objective: Estrogen receptor alpha 36 (ER-α36), a truncated variant of ER-α, is different from other nuclear receptors of the ER-α family. Previous findings indicate that ER-α36 might be involved in cell growth, proliferation, and differentiation in carcinomas and primarily mediates non-genomic estrogen signaling. However, studies on ER-α36 and cervical cancer are rare. This study aimed to detect the expression of ER-α36 in cervical cancer; the role of ER-α36 in 17-β-estradiol (E2)-induced invasion, migration and proliferation of cervical cancer; and their probable molecular mechanisms. Methods: Immunohistochemistry and immunofluorescence were used to determine the location of ER-α36 in cervical cancer tissues and cervical cell lines. CaSki and HeLa cell lines were transfected with lentiviruses to establish stable cell lines with knockdown and overexpression of ER-α36. Wound healing assay, transwell invasion assay, and EdU incorporation proliferation assay were performed to evaluate the migration, invasion, and proliferation ability. The phosphorylation levels of mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling molecules were examined with western blot analysis. Results: ER-α36 expression was detected in both cervical cell lines and cervical cancer tissues. Downregulation of ER-α36 significantly inhibited cell invasion, migration, and proliferation. Moreover, upregulation of ER-α36 increased the invasion, migration, and proliferation ability of CaSki and HeLa cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation. Conclusion: ER-α36 is localized on the plasma membrane and cytoplasm in both cervical cancer tissues and cell lines. ER-α36 mediates estrogen-stimulated MAPK/ERK activation and regulates migration, invasion, proliferation in cervical cancer cells. - Highlights: • ER-α36 is expressed on both cervical cell lines and cervical cancer tissues. • ER-α36 mediates estrogen-stimulated

  16. Directional migration in the Hindu castes: inferences from mitochondrial, autosomal and Y-chromosomal data.

    Science.gov (United States)

    Wooding, Stephen; Ostler, Christopher; Prasad, B V Ravi; Watkins, W Scott; Sung, Sandy; Bamshad, Mike; Jorde, Lynn B

    2004-08-01

    Genetic, ethnographic, and historical evidence suggests that the Hindu castes have been highly endogamous for several thousand years and that, when movement between castes does occur, it typically consists of females joining castes of higher social status. However, little is known about migration rates in these populations or the extent to which migration occurs between caste groups of low, middle, and high social status. To investigate these aspects of migration, we analyzed the largest collection of genetic markers collected to date in Hindu caste populations. These data included 45 newly typed autosomal short tandem repeat polymorphisms (STRPs), 411 bp of mitochondrial DNA sequence, and 43 Y-chromosomal single-nucleotide polymorphisms that were assayed in more than 200 individuals of known caste status sampled in Andrah Pradesh, in South India. Application of recently developed likelihood-based analyses to this dataset enabled us to obtain genetically derived estimates of intercaste migration rates. STRPs indicated migration rates of 1-2% per generation between high-, middle-, and low-status caste groups. We also found support for the hypothesis that rates of gene flow differ between maternally and paternally inherited genes. Migration rates were substantially higher in maternally than in paternally inherited markers. In addition, while prevailing patterns of migration involved movement between castes of similar rank, paternally inherited markers in the low-status castes were most likely to move into high-status castes. Our findings support earlier evidence that the caste system has been a significant, long-term source of population structuring in South Indian Hindu populations, and that patterns of migration differ between males and females. Copyright 2004 Springer-Verlag

  17. Notes on Human Trials of Transcranial Direct Current Stimulation between 1960 and 1998

    Science.gov (United States)

    Esmaeilpour, Zeinab; Schestatsky, Pedro; Bikson, Marom; Brunoni, André R.; Pellegrinelli, Ada; Piovesan, Fernanda X.; Santos, Mariana M. S. A.; Menezes, Renata B.; Fregni, Felipe

    2017-01-01

    Background: Transcranial direct current stimulation (tDCS) is investigated to modulate neuronal function including cognitive neuroscience and neuropsychiatric therapies. While cases of human stimulation with rudimentary batteries date back more than 200 years, clinical trials with current controlled stimulation were published intermittently since the 1960s. The modern era of tDCS only started after 1998. Objectives: To review methods and outcomes of tDCS studies from old literature (between 1960 and 1998) with intention of providing new insight for ongoing tDCS trials and development of tDCS protocols especially for the purpose of treatment. Methods: Articles were identified through a search in PubMed and through the reference list from its selected articles. We included only non-invasive human studies that provided controlled direct current and were written in English, French, Spanish or Portuguese before the year of 1998, the date in which modern stimulation paradigms were implemented. Results: Fifteen articles met our criteria. The majority were small-randomized controlled clinical trials that enrolled a mean of approximately 26 subjects (Phase II studies). Most of the studies (around 83%) assessed the role of tDCS in the treatment of psychiatric conditions, in which the main outcomes were measured by means of behavioral scales and clinical observation, but the diagnostic precision and the quality of outcome monitoring, including adverse events, were deficient by modern standards. Compared to modern tDCS dose, the stimulation intensities used (0.1–1 mA) were lower, however as the electrodes were typically smaller (e.g., 1.26 cm2), the average electrode current density (0.2 mA/cm2) was approximately 4× higher. The number of sessions ranged from one to 120 (median 14). Notably, the stimulation session durations of several minutes to 11 h (median 4.5 h) could markedly exceed modern tDCS protocols. Twelve studies out of 15 showed positive results. Only mild side

  18. Influence of Concurrent Finger Movements on Transcranial Direct Current Stimulation (tDCS)-Induced Aftereffects.

    Science.gov (United States)

    Shirota, Yuichiro; Terney, Daniella; Antal, Andrea; Paulus, Walter

    2017-01-01

    Transcranial direct current stimulation (tDCS) has been reported to have bidirectional influence on the amplitude of motor-evoked potentials (MEPs) in resting participants in a polarity-specific manner: anodal tDCS increased and cathodal tDCS decreased them. More recently, the effects of tDCS have been shown to depend on a number of additional factors. We investigated whether a small variety of movements involving target and non-target muscles could differentially modify the efficacy of tDCS. MEPs were elicited from the right first dorsal interosseous muscle, defined as the target muscle, by single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1). During M1 tDCS, which lasted for 10 min applying anodal, cathodal, or sham condition, the participants were instructed to squeeze a ball with their right hand (Task 1), to move their right index finger only in the medial (Task 2), in the lateral direction (Task 3), or in medial and lateral direction alternatively (Task 4). Anodal tDCS reduced MEP amplitudes measured in Task 1 and Task 2, but to a lesser extent in the latter. In Task 3, anodal tDCS led to greater MEP amplitudes than cathodal stimulation. Alternating movements resulted in no effect of tDCS on MEP amplitude (Task 4). The results are congruent with the current notion that the aftereffects of tDCS are highly variable relying on a number of factors including the type of movements executed during stimulation.

  19. Direct Acoustic Stimulation at the Lateral Canal: An Alternative Route to the Inner Ear?

    Directory of Open Access Journals (Sweden)

    Nicolas Verhaert

    Full Text Available Severe to profound mixed hearing loss is associated with hearing rehabilitation difficulties. Recently, promising results for speech understanding were obtained with a direct acoustic cochlear implant (DACI. The surgical implantation of a DACI with standard coupling through a stapedotomy can however be regarded as challenging. Therefore, in this experimental study, the feasibility of direct acoustic stimulation was investigated at an anatomically and surgically more accessible inner ear site. DACI stimulation of the intact, blue-lined and opened lateral semicircular canal (LC was investigated and compared with standard oval window (OW coupling. Additionally, stapes footplate fixation was induced. Round window (RW velocity, as a measure of the performance of the device and its coupling efficiency, was determined in fresh-frozen human cadaver heads. Using single point laser Doppler vibrometry, RW velocity could reliably be measured in low and middle frequency range, and equivalent sound pressure level (LE output was calculated. Results for the different conditions obtained in five heads were analyzed in subsequent frequency ranges. Comparing the difference in RW membrane velocity showed higher LE in the LC opened condition [mean: 103 equivalent dB SPL], than in LC intact or blue-lined conditions [63 and 74 equivalent dB SPL, respectively]. No difference was observed between the LC opened and the standard OW condition. Inducing stapes fixation, however, led to a difference in the low frequency range of LE compared to LC opened. In conclusion, this feasibility study showed promising results for direct acoustic stimulation at this specific anatomically and surgically more accessible inner ear site. Future studies are needed to address the impact of LC stimulation on cochlear micromechanics and on the vestibular system like dizziness and risks of hearing loss.

  20. The Modulation of Error Processing in the Medial Frontal Cortex by Transcranial Direct Current Stimulation

    Directory of Open Access Journals (Sweden)

    Lisa Bellaïche

    2013-01-01

    Full Text Available Background. In order to prevent future errors, we constantly control our behavior for discrepancies between the expected (i.e., intended and the real action outcome and continuously adjust our behavior accordingly. Neurophysiological correlates of this action-monitoring process can be studied with event-related potentials (error-related negativity (ERN and error positivity (Pe originating from the medial prefrontal cortex (mPFC. Patients with neuropsychiatric diseases often show performance monitoring dysfunctions potentially caused by pathological changes of cortical excitability; therefore, a modulation of the underlying neuronal activity might be a valuable therapeutic tool. One technique which allows us to explore cortical modulation of neural networks is transcranial direct current stimulation (tDCS. Therefore, we tested the effect of medial-prefrontal tDCS on error-monitoring potentials in 48 healthy subjects randomly assigned to anodal, cathodal, or sham stimulation. Results. We found that cathodal stimulation attenuated Pe amplitudes compared to both anodal and sham stimulation, but no effect for the ERN. Conclusions. Our results indicate that cathodal tDCS over the mPFC results in an attenuated cortical excitability leading to decreased Pe amplitudes. We therefore conclude that tDCS has a neuromodulatory effect on error-monitoring systems suggesting a future approach to modify the sensitivity of corresponding neural networks in patients with action-monitoring deficits.

  1. Monitoring transcranial direct current stimulation induced changes in cortical excitability during the serial reaction time task.

    Science.gov (United States)

    Ambrus, Géza Gergely; Chaieb, Leila; Stilling, Roman; Rothkegel, Holger; Antal, Andrea; Paulus, Walter

    2016-03-11

    The measurement of the motor evoked potential (MEP) amplitudes using single pulse transcranial magnetic stimulation (TMS) is a common method to observe changes in motor cortical excitability. The level of cortical excitability has been shown to change during motor learning. Conversely, motor learning can be improved by using anodal transcranial direct current stimulation (tDCS). In the present study, we aimed to monitor cortical excitability changes during an implicit motor learning paradigm, a version of the serial reaction time task (SRTT). Responses from the first dorsal interosseous (FDI) and forearm flexor (FLEX) muscles were recorded before, during and after the performance of the SRTT. Online measurements were combined with anodal, cathodal or sham tDCS for the duration of the SRTT. Negative correlations between the amplitude of online FDI MEPs and SRTT reaction times (RTs) were observed across the learning blocks in the cathodal condition (higher average MEP amplitudes associated with lower RTs) but no significant differences in the anodal and sham conditions. tDCS did not have an impact on SRTT performance, as would be predicted based on previous studies. The offline before-after SRTT MEP amplitudes showed an increase after anodal and a tendency to decrease after cathodal stimulation, but these changes were not significant. The combination of different interventions during tDCS might result in reduced efficacy of the stimulation that in future studies need further attention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Anodal transcranial direct current stimulation reduces psychophysically measured surround suppression in the human visual cortex.

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    Daniel P Spiegel

    Full Text Available Transcranial direct current stimulation (tDCS is a safe, non-invasive technique for transiently modulating the balance of excitation and inhibition within the human brain. It has been reported that anodal tDCS can reduce both GABA mediated inhibition and GABA concentration within the human motor cortex. As GABA mediated inhibition is thought to be a key modulator of plasticity within the adult brain, these findings have broad implications for the future use of tDCS. It is important, therefore, to establish whether tDCS can exert similar effects within non-motor brain areas. The aim of this study was to assess whether anodal tDCS could reduce inhibitory interactions within the human visual cortex. Psychophysical measures of surround suppression were used as an index of inhibition within V1. Overlay suppression, which is thought to originate within the lateral geniculate nucleus (LGN, was also measured as a control. Anodal stimulation of the occipital poles significantly reduced psychophysical surround suppression, but had no effect on overlay suppression. This effect was specific to anodal stimulation as cathodal stimulation had no effect on either measure. These psychophysical results provide the first evidence for tDCS-induced reductions of intracortical inhibition within the human visual cortex.

  3. Modulation of electric brain responses evoked by pitch deviants through transcranial direct current stimulation.

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    Royal, Isabelle; Zendel, Benjamin Rich; Desjardins, Marie-Ève; Robitaille, Nicolas; Peretz, Isabelle

    2018-01-31

    Congenital amusia is a neurodevelopmental disorder, characterized by a difficulty detecting pitch deviation that is related to abnormal electrical brain responses. Abnormalities found along the right fronto-temporal pathway between the inferior frontal gyrus (IFG) and the auditory cortex (AC) are the likely neural mechanism responsible for amusia. To investigate the causal role of these regions during the detection of pitch deviants, we applied cathodal (inhibitory) transcranial direct current stimulation (tDCS) over right frontal and right temporal regions during separate testing sessions. We recorded participants' electrical brain activity (EEG) before and after tDCS stimulation while they performed a pitch change detection task. Relative to a sham condition, there was a decrease in P3 amplitude after cathodal stimulation over both frontal and temporal regions compared to pre-stimulation baseline. This decrease was associated with small pitch deviations (6.25 cents), but not large pitch deviations (200 cents). Overall, this demonstrates that using tDCS to disrupt regions around the IFG and AC can induce temporary changes in evoked brain activity when processing pitch deviants. These electrophysiological changes are similar to those observed in amusia and provide causal support for the connection between P3 and fronto-temporal brain regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Transcranial direct current stimulation of the left dorsolateral prefrontal cortex shifts preference of moral judgments.

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    Maria Kuehne

    Full Text Available Attitude to morality, reflecting cultural norms and values, is considered unique to human social behavior. Resulting moral behavior in a social environment is controlled by a widespread neural network including the dorsolateral prefrontal cortex (DLPFC, which plays an important role in decision making. In the present study we investigate the influence of neurophysiological modulation of DLPFC reactivity by means of transcranial direct current stimulation (tDCS on moral reasoning. For that purpose we administered anodal, cathodal, and sham stimulation of the left DLPFC while subjects judged the appropriateness of hard moral personal dilemmas. In contrast to sham and cathodal stimulation, anodal stimulation induced a shift in judgment of personal moral dilemmas towards more non-utilitarian actions. Our results demonstrate that alterations of left DLPFC activity can change moral judgments and, in consequence, provide a causal link between left DLPFC activity and moral reasoning. Most important, the observed shift towards non-utilitarian actions suggests that moral decision making is not a permanent individual trait but can be manipulated; consequently individuals with boundless, uncontrollable, and maladaptive moral behavior, such as found in psychopathy, might benefit from neuromodulation-based approaches.

  5. Categorization is modulated by transcranial direct current stimulation over left prefrontal cortex.

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    Lupyan, Gary; Mirman, Daniel; Hamilton, Roy; Thompson-Schill, Sharon L

    2012-07-01

    Humans have an unparalleled ability to represent objects as members of multiple categories. A given object, such as a pillow may be-depending on current task demands-represented as an instance of something that is soft, as something that contains feathers, as something that is found in bedrooms, or something that is larger than a toaster. This type of processing requires the individual to dynamically highlight task-relevant properties and abstract over or suppress object properties that, although salient, are not relevant to the task at hand. Neuroimaging and neuropsychological evidence suggests that this ability may depend on cognitive control processes associated with the left inferior prefrontal gyrus. Here, we show that stimulating the left inferior frontal cortex using transcranial direct current stimulation alters performance of healthy subjects on a simple categorization task. Our task required subjects to select pictures matching a description, e.g., "click on all the round things." Cathodal stimulation led to poorer performance on classification trials requiring attention to specific dimensions such as color or shape as opposed to trials that required selecting items belonging to a more thematic category such as objects that hold water. A polarity reversal (anodal stimulation) lowered the threshold for selecting items that were more weakly associated with the target category. These results illustrate the role of frontally-mediated control processes in categorization and suggest potential interactions between categorization, cognitive control, and language. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Categorization is modulated by transcranical direct current stimulation over left prefrontal cortex

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    Lupyan, Gary; Mirman, Daniel; Hamilton, Roy; Thompson-Schill, Sharon L.

    2013-01-01

    Humans have an unparalleled ability to represent objects as members of multiple categories. A given object, such as a pillow may be—depending on current task demands—represented as an instance of something that is soft, as something that contains feathers, as something that is found in bedrooms, or something that is larger than a toaster. This type of processing requires the individual to dynamically highlight task-relevant properties and abstract over or suppress object properties that, although salient, are not relevant to the task at hand. Neuroimaging and neuropsychological evidence suggests that this ability may depend on cognitive control processes associated with the left inferior prefrontal gyrus. Here, we show that stimulating the left inferior frontal cortex using transcranial direct current stimulation alters performance of healthy subjects on a simple categorization task. Our task required subjects to select pictures matching a description, e.g., “click on all the round things.“ Cathodal stimulation led to poorer performance on classification trials requiring attention to specific dimensions such as color or shape as opposed to trials that required selecting items belonging to a more thematic category such as objects that hold water. A polarity reversal (anodal stimulation) lowered the threshold for selecting items that were more weakly associated with the target category. These results illustrate the role of frontally-mediated control processes in categorization and suggest potential interactions between categorization, cognitive control, and language. PMID:22578885

  7. The Joint Effects of Spatial Cueing and Transcranial Direct Current Stimulation on Visual Acuity

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    Taly Bonder

    2018-02-01

    Full Text Available The present study examined the mutual influence of cortical neuroenhancement and allocation of spatial attention on perception. Specifically, it explored the effects of transcranial Direct Current Stimulation (tDCS on visual acuity measured with a Landolt gap task and attentional precues. The exogenous cues were used to draw attention either to the location of the target or away from it, generating significant performance benefits and costs. Anodal tDCS applied to posterior occipital area for 15 min improved performance during stimulation, reflecting heightened visual acuity. Reaction times were lower, and accuracy was higher in the tDCS group, compared to a sham control group. Additionally, in post-stimulation trials tDCS significantly interacted with the effect of precuing. Reaction times were lower in valid cued trials (benefit and higher in invalid trials (cost compared to neutrally cued trials, the effect which was pronounced stronger in tDCS group than in sham control group. The increase of cost and benefit effects in the tDCS group was of a similar magnitude, suggesting that anodal tDCS influenced the overall process of attention orienting. The observed interaction between the stimulation of the visual cortex and precueing indicates a magnification of attention modulation.

  8. Intensity, Duration, and Location of High-Definition Transcranial Direct Current Stimulation for Tinnitus Relief.

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    Shekhawat, Giriraj Singh; Sundram, Frederick; Bikson, Marom; Truong, Dennis; De Ridder, Dirk; Stinear, Cathy M; Welch, David; Searchfield, Grant D

    2016-05-01

    Tinnitus is the perception of a phantom sound. The aim of this study was to compare current intensity (center anode 1 mA and 2 mA), duration (10 minutes and 20 minutes), and location (left temporoparietal area [LTA] and dorsolateral prefrontal cortex [DLPFC]) using 4 × 1 high-definition transcranial direct current stimulation (HD-tDCS) for tinnitus reduction. Twenty-seven participants with chronic tinnitus (>2 years) and mean age of 53.5 years underwent 2 sessions of HD-tDCS of the LTA and DLPFC in a randomized order with a 1 week gap between site of stimulation. During each session, a combination of 4 different settings were used in increasing dose (1 mA, 10 minutes; 1 mA, 20 minutes; 2 mA, 10 minutes; and 2 mA, 20 minutes). The impact of different settings on tinnitus loudness and annoyance was documented. Twenty-one participants (77.78%) reported a minimum of 1 point reduction on tinnitus loudness or annoyance scales. There were significant changes in loudness and annoyance for duration of stimulation,F(1, 26) = 10.08,Ptinnitus relief. The stimulation of the LTA and DLPFC were equally effective for suppressing tinnitus loudness and annoyance. © The Author(s) 2015.

  9. Is effect of transcranial direct current stimulation on visuomotor coordination dependent on task difficulty?

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    Yong Hyun Kwon

    2015-01-01

    Full Text Available Transcranial direct current stimulation (tDCS, an emerging technique for non-invasive brain stimulation, is increasingly used to induce changes in cortical excitability and modulate motor behavior, especially for upper limbs. The purpose of this study was to investigate the effects of tDCS of the primary motor cortex on visuomotor coordination based on three levels of task difficulty in healthy subjects. Thirty-eight healthy participants underwent real tDCS or sham tDCS. Using a single-blind, sham-controlled crossover design, tDCS was applied to the primary motor cortex. For real tDCS conditions, tDCS intensity was 1 mA while stimulation was applied for 15 minutes. For the sham tDCS, electrodes were placed in the same position, but the stimulator was turned off after 5 seconds. Visuomotor tracking task, consisting of three levels (levels 1, 2, 3 of difficulty with higher level indicating greater difficulty, was performed before and after tDCS application. At level 2, real tDCS of the primary motor cortex improved the accurate index compared to the sham tDCS. However, at levels 1 and 3, the accurate index was not significantly increased after real tDCS compared to the sham tDCS. These findings suggest that tasks of moderate difficulty may improve visuomotor coordination in healthy subjects when tDCS is applied compared with easier or more difficult tasks.

  10. The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

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    Blom, Magdalena; Reis, Katarina [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Heldin, Johan [Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala SE-751 22 Uppsala (Sweden); Kreuger, Johan [Department of Medical Cell Biology, Science for Life Laboratory, Uppsala University, SE-751 23 Uppsala (Sweden); Aspenström, Pontus, E-mail: pontus.aspenstrom@ki.se [Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden)

    2017-03-15

    RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

  11. The atypical Rho GTPase RhoD is a regulator of actin cytoskeleton dynamics and directed cell migration

    International Nuclear Information System (INIS)

    Blom, Magdalena; Reis, Katarina; Heldin, Johan; Kreuger, Johan; Aspenström, Pontus

    2017-01-01

    RhoD belongs to the Rho GTPases, a protein family responsible for the regulation and organization of the actin cytoskeleton, and, consequently, many cellular processes like cell migration, cell division and vesicle trafficking. Here, we demonstrate that the actin cytoskeleton is dynamically regulated by increased or decreased protein levels of RhoD. Ectopic expression of RhoD has previously been shown to give an intertwined weave of actin filaments. We show that this RhoD-dependent effect is detected in several cell types and results in a less dynamic actin filament system. In contrast, RhoD depletion leads to increased actin filament-containing structures, such as cortical actin, stress fibers and edge ruffles. Moreover, vital cellular functions such as cell migration and proliferation are defective when RhoD is silenced. Taken together, we present data suggesting that RhoD is an important component in the control of actin dynamics and directed cell migration. - Highlights: • Increased RhoD expression leads to loss of actin structures, e.g. stress fibers and gives rise to decreased actin dynamics. • RhoD knockdown induces various actin-containing structures such as edge ruffles, stress fibers and cortical actin, in a cell-type specific manner. • RhoD induces specific actin rearrangements depending on its subcellular localization. • RhoD knockdown has effects on cellular processes, such as directed cell migration and proliferation.

  12. Effects of transcranial direct current stimulation on motor learning in healthy individuals: a systematic review

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    Águida Foerster

    Full Text Available Introduction Transcranial direct current stimulation (tDCS has been used to modify cortical excitability and promote motor learning. Objective To systematically review published data to investigate the effects of transcranial direct current stimulation on motor learning in healthy individuals. Methods Randomized or quasi-randomized studies that evaluated the tDCS effects on motor learning were included and the risk of bias was examined by Cochrane Collaboration’s tool. The following electronic databases were used: PubMed, Scopus, Web of Science, LILACS, CINAHL with no language restriction. Results It was found 160 studies; after reading the title and abstract, 17 of those were selected, but just 4 were included. All studies involved healthy, right-handed adults. All studies assessed motor learning by the Jebsen Taylor Test or by the Serial Finger Tapping Task (SFTT. Almost all studies were randomized and all were blinding for participants. Some studies presented differences at SFTT protocol. Conclusion The result is insufficient to draw conclusions if tDCS influences the motor learning. Furthermore, there was significant heterogeneity of the stimulation parameters used. Further researches are needed to investigate the parameters that are more important for motor learning improvement and measure whether the effects are long-lasting or limited in time.

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

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    Sotiropoulos, Stamatios N.; Steinmetz, Peter N.

    2007-06-01

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

  14. Augmentation of Fear Extinction by Transcranial Direct Current Stimulation (tDCS

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    Natalie Dittert

    2018-04-01

    Full Text Available Although posttraumatic stress disorder (PTSD; DSM-V 309.82 and anxiety disorders (DSM-V 300.xx are widely spread mental disorders, the effectiveness of their therapy is still unsatisfying. Non-invasive brain-stimulation techniques like transcranial direct current stimulation (tDCS might be an option to improve extinction learning, which is a main functional factor of exposure-based therapy for anxiety disorders. To examine this hypothesis, we used a fear conditioning paradigm with female faces as conditioned stimuli (CS and a 95-dB female scream as unconditioned stimulus (UCS. We aimed to perform a tDCS of the ventromedial prefrontal cortex (vmPFC, which is mainly involved in the control of extinction-processes. Therefore, we applied two 4 × 4 cm electrodes approximately at the EEG-positions F7 and F8 and used a direct current of 1.5 mA. The 20-min stimulation was started during a 10-min break between acquisition and extinction and went on overall extinction-trials. The healthy participants were randomly assigned in two double-blinded process into two sham stimulation and two verum stimulation groups with opposite current flow directions. To measure the fear reactions, we used skin conductance responses (SCR and subjective ratings. We performed a generalized estimating equations model for the SCR to assess the impact of tDCS and current flow direction on extinction processes for all subjects that showed a successful conditioning (N = 84. The results indicate that tDCS accelerates early extinction processes with a significantly faster loss of CS+/CS– discrimination. The discrimination loss was driven by a significant decrease in reaction toward the CS+ as well as an increase in reaction toward the CS– in the tDCS verum groups, whereas the sham groups showed no significant reaction changes during this period. Therefore, we assume that tDCS of the vmPFC can be used to enhance early extinction processes successfully. But before it should be

  15. Effect of excitation direction on cochlear macro-mechanics during bone conduction stimulation

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    Kamieniecki, Konrad; Tudruj, Sylwester; Piechna, Janusz; Borkowski, Paweł

    2018-05-01

    In many instances of hearing loss, audiological improvement can be made via direct excitation of a temporal bone (i.e., bone conduction). In order to design better and more efficient devices, the macro-mechanics of the bone conduction hearing pathway must be better understood. Based on previous empirical work, numerical models are useful. In this work, we present results of a time-domain Fluid Structure Interaction model that describes stimulation of the bone conduction pathway. The cochlea was modelled as uncoiled and consisted of an oval window, a round window, a basilar membrane and a helicotrema. In order to monitor pressure waves in the perilymph, the fluid was considered compressible. The excitation, in form of sinusoidal velocity, was applied to the cochlea bony walls. The system was excited in three perpendicular directions: along the basilar membrane, perpendicularly to the membrane and transversely to the membrane. The numerical simulation examined which stimulation direction maximally excited the basilar membrane, the pressure distributions for each excitation direction, and the associated mechanics.

  16. Specific Intensity Direct Current (DC) Electric Field Improves Neural Stem Cell Migration and Enhances Differentiation towards βIII-Tubulin+ Neurons

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    Zhao, Huiping; Steiger, Amanda; Nohner, Mitch; Ye, Hui

    2015-01-01

    Control of stem cell migration and differentiation is vital for efficient stem cell therapy. Literature reporting electric field–guided migration and differentiation is emerging. However, it is unknown if a field that causes cell migration is also capable of guiding cell differentiation—and the mechanisms for these processes remain unclear. Here, we report that a 115 V/m direct current (DC) electric field can induce directional migration of neural precursor cells (NPCs). Whole cell patching revealed that the cell membrane depolarized in the electric field, and buffering of extracellular calcium via EGTA prevented cell migration under these conditions. Immunocytochemical staining indicated that the same electric intensity could also be used to enhance differentiation and increase the percentage of cell differentiation into neurons, but not astrocytes and oligodendrocytes. The results indicate that DC electric field of this specific intensity is capable of promoting cell directional migration and orchestrating functional differentiation, suggestively mediated by calcium influx during DC field exposure. PMID:26068466

  17. Transcranial direct current stimulation over the parietal cortex alters bias in item and source memory tasks.

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    Pergolizzi, Denise; Chua, Elizabeth F

    2016-10-01

    Neuroimaging data have shown that activity in the lateral posterior parietal cortex (PPC) correlates with item recognition and source recollection, but there is considerable debate about its specific contributions. Performance on both item and source memory tasks were compared between participants who were given bilateral transcranial direct current stimulation (tDCS) over the parietal cortex to those given prefrontal or sham tDCS. The parietal tDCS group, but not the prefrontal group, showed decreased false recognition, and less bias in item and source discrimination tasks compared to sham stimulation. These results are consistent with a causal role of the PPC in item and source memory retrieval, likely based on attentional and decision-making biases. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Transcranial Direct Current Stimulation (tDCS): A Promising Treatment for Major Depressive Disorder?

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    Bennabi, Djamila; Haffen, Emmanuel

    2018-01-01

    Background: Transcranial direct current stimulation (tDCS) opens new perspectives in the treatment of major depressive disorder (MDD), because of its ability to modulate cortical excitability and induce long-lasting effects. The aim of this review is to summarize the current status of knowledge regarding tDCS application in MDD. Methods: In this review, we searched for articles published in PubMed/MEDLINE from the earliest available date to February 2018 that explored clinical and cognitive effects of tDCS in MDD. Results: Despite differences in design and stimulation parameters, the examined studies indicated beneficial effects of tDCS for MDD. These preliminary results, the non-invasiveness of tDCS, and its good tolerability support the need for further research on this technique. Conclusions: tDCS constitutes a promising therapeutic alternative for patients with MDD, but its place in the therapeutic armamentarium remains to be determined. PMID:29734768

  19. Transcranial direct current stimulation in patients with Alzheimer’s disease: Challenges and responses

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    Hong Yuan

    2015-09-01

    Full Text Available The use of transcranial direct current stimulation (tDCS as a noninvasive therapeutic approach for Alzheimer’s disease (AD has gained increasing attention. Research regarding the utility of tDCS in AD is inconsistent. In this study, we reviewed the importance of individual diversity among AD patients, starting from the uninformative mean results. We also demonstrated variation among AD patients. Highly educated patients seem to benefit more; education also seems to modulate baseline measurements and the results. Individual cortical morphology also affects the current distribution, which influences the effectiveness of stimulation. We suggest the use of structural MRI to distinguish inter-individual variability; high-resolution modeling can also be used to predict current distributions and should be combined with cognitive training (CT along with tDCS.

  20. Effects of Anodal Transcranial Direct Current Stimulation on Visually Guided Learning of Grip Force Control

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    Tamas Minarik

    2015-03-01

    Full Text Available Anodal transcranial Direct Current Stimulation (tDCS has been shown to be an effective non-invasive brain stimulation method for improving cognitive and motor functioning in patients with neurological deficits. tDCS over motor cortex (M1, for instance, facilitates motor learning in stroke patients. However, the literature on anodal tDCS effects on motor learning in healthy participants is inconclusive, and the effects of tDCS on visuo-motor integration are not well understood. In the present study we examined whether tDCS over the contralateral motor cortex enhances learning of grip-force output in a visually guided feedback task in young and neurologically healthy volunteers. Twenty minutes of 1 mA anodal tDCS were applied over the primary motor cortex (M1 contralateral to the dominant (right hand, during the first half of a 40 min power-grip task. This task required the control of a visual signal by modulating the strength of the power-grip for six seconds per trial. Each participant completed a two-session sham-controlled crossover protocol. The stimulation conditions were counterbalanced across participants and the sessions were one week apart. Performance measures comprised time-on-target and target-deviation, and were calculated for the periods of stimulation (or sham and during the afterphase respectively. Statistical analyses revealed significant performance improvements over the stimulation and the afterphase, but this learning effect was not modulated by tDCS condition. This suggests that the form of visuomotor learning taking place in the present task was not sensitive to neurostimulation. These null effects, together with similar reports for other types of motor tasks, lead to the proposition that tDCS facilitation of motor learning might be restricted to cases or situations where the motor system is challenged, such as motor deficits, advanced age, or very high task demand.

  1. Effects of transcranial direct current stimulation for treating depression: A modeling study.

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    Csifcsák, Gábor; Boayue, Nya Mehnwolo; Puonti, Oula; Thielscher, Axel; Mittner, Matthias

    2018-07-01

    Transcranial direct current stimulation (tDCS) above the left dorsolateral prefrontal cortex (lDLPFC) has been widely used to improve symptoms of major depressive disorder (MDD). However, the effects of different stimulation protocols in the entire frontal lobe have not been investigated in a large sample including patient data. We used 38 head models created from structural magnetic resonance imaging data of 19 healthy adults and 19 MDD patients and applied computational modeling to simulate the spatial distribution of tDCS-induced electric fields (EFs) in 20 frontal regions. We evaluated effects of seven bipolar and two multi-electrode 4 × 1 tDCS protocols. For bipolar montages, EFs were of comparable strength in the lDLPFC and in the medial prefrontal cortex (MPFC). Depending on stimulation parameters, EF cortical maps varied to a considerable degree, but were found to be similar in controls and patients. 4 × 1 montages produced more localized, albeit weaker effects. White matter anisotropy was not modeled. The relationship between EF strength and clinical response to tDCS could not be evaluated. In addition to lDLPFC stimulation, excitability changes in the MPFC should also be considered as a potential mechanism underlying clinical efficacy of bipolar montages. MDD-associated anatomical variations are not likely to substantially influence current flow. Individual modeling of tDCS protocols can substantially improve cortical targeting. We make recommendations for future research to explicitly test the contribution of lDLPFC vs. MPFC stimulation to therapeutic outcomes of tDCS in this disorder. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Influence of Transcranial Direct Current Stimulation to the Cerebellum on Standing Posture Control

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    Yasuto Inukai

    2016-07-01

    Full Text Available Damage to the vestibular cerebellum results in dysfunctional standing posture control. Patients with cerebellum dysfunction have a larger sway in the center of gravity while standing compared with healthy subjects. Transcranial direct current stimulation (tDCS is a noninvasive technique for selectively exciting or inhibiting specific neural structures with potential applications in functional assessment and treatment of neural disorders. However, the specific stimulation parameters for influencing postural control have not been assessed. In this study, we investigated the influence of tDCS when applied over the cerebellum on standing posture control. Sixteen healthy subjects received tDCS (20 min, 2 mA over the scalp 2 cm below the inion. In experiment 1, all 16 subjects received tDCS under three stimulus conditions, Sham, Cathodal, and Anodal, in a random order with the second electrode placed on the forehead. In experiment 2, five subjects received cathodal stimulation only with the second electrode placed over the right buccinator muscle. Center of gravity sway was measured twice for 60 s before and after tDCS in a standing posture with eyes open and legs closed, and average total locus length, locus length per second, rectangular area, and enveloped area were calculated. In experiment 1, total locus length and locus length per second decreased significantly after cathodal stimulation but not after anodal or sham stimulation, while no tDCS condition influenced rectangular or enveloped areas. In experiment 2, cathodal tDCS again significantly reduced total locus length and locus length per second but not rectangular and enveloped areas. The effects of tDCS on postural control are polarity-dependent, likely reflecting the selective excitation or inhibition of cerebellar Purkinje cells. Cathodal tDCS to the cerebellum of healthy subjects can alter body sway (velocity.

  3. Potential directions of the 'town-to-town' migration in Vojvodina

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    Savić Mirko

    2008-01-01

    Full Text Available Population of Vojvodina is showing the characteristics of late demographic transition. The main characteristics of that phase are low mortality rate, slow decrease of fertility rate, increased number of older people etc. This phase is connected to fourth development phase of migrations with significant migrations from one city to another and inside the city area. The purpose of this paper is to define the basic characteristics of potential internal migrations in the region of Vojvodina between cities, most of all towards Novi Sad as economic, political and cultural center. The sample of 2.000 respondents was formed and survey was conducted in the 15 largest cities in the region. The data were analyzed with methods of descriptive and multivariate statistical analysis (rank correlation and MDS analysis. Basic conclusions are that theory of transitional migration is confirmed in Vojvodina, the size of the city is not the only factor for potential migration movements and Novi Sad is by far the most desired destination for significant portion of population in the region, especially of population aged between 20 and 40 years because around 40% of that cohort wish to move to Novi Sad. That will cause significant urban, economic and social problems, not only in the city of Novi Sad but also in the cities where immigrants are coming from. .

  4. Anodal transcranial direct current stimulation of parietal cortex enhances action naming in Corticobasal Syndrome

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    Rosa eManenti

    2015-04-01

    Full Text Available Background: Corticobasal Syndrome (CBS is a neurodegenerative disorder that overlaps both clinically and neuropathologically with Frontotemporal dementia and is characterized by apraxia, alien limb phenomena, cortical sensory loss, cognitive impairment, behavioural changes and aphasia. It has been recently demonstrated that transcranial direct current stimulation (tDCS improves naming in healthy subjects and in subjects with language deficits.Objective: The aim of the present study was to explore the extent to which anodal transcranial direct current stimulation (anodal tDCS over the parietal cortex (PARC could facilitate naming performance in CBS subjects. Methods: Anodal tDCS was applied to the left and right PARC during object and action naming in seventeen patients with a diagnosis of possible CBS. Participants underwent two sessions of anodal tDCS (left and right and one session of placebo tDCS. Vocal responses were recorded and analyzed for accuracy and vocal Reaction Times (vRTs. Results: A shortening of naming latency for actions was observed only after active anodal stimulation over the left PARC, as compared to placebo and right stimulations. No effects have been reported for accuracy.Conclusions: Our preliminary finding demonstrated that tDCS decreased vocal reaction time during action naming in a sample of patients with CBS. A possible explanation of our results is that anodal tDCS over the left PARC effects the brain network implicated in action observation and representation. Further studies, based on larger patient samples, should be conducted to investigate the usefulness of tDCS as an additional treatment of linguistic deficits in CBS patients.

  5. Top-Down Effect of Direct Current Stimulation on the Nociceptive Response of Rats.

    Directory of Open Access Journals (Sweden)

    Luiz Fabio Dimov

    Full Text Available Transcranial direct current stimulation (tDCS is an emerging, noninvasive technique of neurostimulation for treating pain. However, the mechanisms and pathways involved in its analgesic effects are poorly understood. Therefore, we investigated the effects of direct current stimulation (DCS on thermal and mechanical nociceptive thresholds and on the activation of the midbrain periaqueductal gray (PAG and the dorsal horn of the spinal cord (DHSC in rats; these central nervous system areas are associated with pain processing. Male Wistar rats underwent cathodal DCS of the motor cortex and, while still under stimulation, were evaluated using tail-flick and paw pressure nociceptive tests. Sham stimulation and naive rats were used as controls. We used a randomized design; the assays were not blinded to the experimenter. Immunoreactivity of the early growth response gene 1 (Egr-1, which is a marker of neuronal activation, was evaluated in the PAG and DHSC, and enkephalin immunoreactivity was evaluated in the DHSC. DCS did not change the thermal nociceptive threshold; however, it increased the mechanical nociceptive threshold of both hind paws compared with that of controls, characterizing a topographical effect. DCS decreased the Egr-1 labeling in the PAG and DHSC as well as the immunoreactivity of spinal enkephalin. Altogether, the data suggest that DCS disinhibits the midbrain descending analgesic pathway, consequently inhibiting spinal nociceptive neurons and causing an increase in the nociceptive threshold. This study reinforces the idea that the motor cortex participates in the neurocircuitry that is involved in analgesia and further clarifies the mechanisms of action of tDCS in pain treatment.

  6. Intensity dependent effects of transcranial direct current stimulation on corticospinal excitability in chronic spinal cord injury.

    Science.gov (United States)

    Murray, Lynda M; Edwards, Dylan J; Ruffini, Giulio; Labar, Douglas; Stampas, Argyrios; Pascual-Leone, Alvaro; Cortes, Mar

    2015-04-01

    To investigate the effects of anodal transcranial direct current stimulation (a-tDCS) intensity on corticospinal excitability and affected muscle activation in individuals with chronic spinal cord injury (SCI). Single-blind, randomized, sham-controlled, crossover study. Medical research institute and rehabilitation hospital. Volunteers (N = 9) with chronic SCI and motor dysfunction in wrist extensor muscles. Three single session exposures to 20 minutes of a-tDCS (anode over the extensor carpi radialis [ECR] muscle representation on the left primary motor cortex, cathode over the right supraorbital area) using 1 mA, 2 mA, or sham stimulation, delivered at rest, with at least 1 week between sessions. Corticospinal excitability was assessed with motor-evoked potentials (MEPs) from the ECR muscle using surface electromyography after transcranial magnetic stimulation. Changes in spinal excitability, sensory threshold, and muscle strength were also investigated. Mean MEP amplitude significantly increased by approximately 40% immediately after 2mA a-tDCS (pre: 0.36 ± 0.1 mV; post: 0.47 ± 0.11 mV; P = .001), but not with 1 mA or sham. Maximal voluntary contraction measures remained unaltered across all conditions. Sensory threshold significantly decreased over time after 1mA (P = .002) and 2mA (P = .039) a-tDCS and did not change with sham. F-wave persistence showed a nonsignificant trend for increase (pre: 32% ± 12%; post: 41% ± 10%; follow-up: 46% ± 12%) after 2 mA stimulation. No adverse effects were reported with any of the experimental conditions. The a-tDCS can transiently raise corticospinal excitability to affected muscles in patients with chronic SCI after 2 mA stimulation. Sensory perception can improve with both 1 and 2 mA stimulation. This study gives support to the safe and effective use of a-tDCS using small electrodes in patients with SCI and highlights the importance of stimulation intensity. Copyright © 2015 American Congress of Rehabilitation

  7. Noninvasive brain stimulation with transcranial magnetic or direct current stimulation (TMS/tDCS)-From insights into human memory to therapy of its dysfunction.

    Science.gov (United States)

    Sparing, Roland; Mottaghy, Felix M

    2008-04-01

    Noninvasive stimulation of the brain by means of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) has driven important discoveries in the field of human memory functions. Stand-alone or in combination with other brain mapping techniques noninvasive brain stimulation can assess issues such as location and timing of brain activity, connectivity and plasticity of neural circuits and functional relevance of a circumscribed brain area to a given cognitive task. In this emerging field, major advances in technology have been made in a relatively short period. New stimulation protocols and, especially, the progress in the application of tDCS have made it possible to obtain longer and much clearer inhibitory or facilitatory effects even after the stimulation has ceased. In this introductory review, we outline the basic principles, discuss technical limitations and describe how noninvasive brain stimulation can be used to study human memory functions in vivo. Though improvement of cognitive functions through noninvasive brain stimulation is promising, it still remains an exciting challenge to extend the use of TMS and tDCS from research tools in neuroscience to the treatment of neurological and psychiatric patients.

  8. High-performance, polymer-based direct cellular interfaces for electrical stimulation and recording

    Science.gov (United States)

    Kim, Seong-Min; Kim, Nara; Kim, Youngseok; Baik, Min-Seo; Yoo, Minsu; Kim, Dongyoon; Lee, Won-June; Kang, Dong-Hee; Kim, Sohee; Lee, Kwanghee; Yoon, Myung-Han

    2018-04-01

    Due to the trade-off between their electrical/electrochemical performance and underwater stability, realizing polymer-based, high-performance direct cellular interfaces for electrical stimulation and recording has been very challenging. Herein, we developed transparent and conductive direct cellular interfaces based on a water-stable, high-performance poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) film via solvent-assisted crystallization. The crystallized PEDOT:PSS on a polyethylene terephthalate (PET) substrate exhibited excellent electrical/electrochemical/optical characteristics, long-term underwater stability without film dissolution/delamination, and good viability for primarily cultured cardiomyocytes and neurons over several weeks. Furthermore, the highly crystallized, nanofibrillar PEDOT:PSS networks enabled dramatically enlarged surface areas and electrochemical activities, which were successfully employed to modulate cardiomyocyte beating via direct electrical stimulation. Finally, the high-performance PEDOT:PSS layer was seamlessly incorporated into transparent microelectrode arrays for efficient, real-time recording of cardiomyocyte action potentials with a high signal fidelity. All these results demonstrate the strong potential of crystallized PEDOT:PSS as a crucial component for a variety of versatile bioelectronic interfaces.

  9. Transcranial direct current stimulation transiently increases the blood-brain barrier solute permeability in vivo

    Science.gov (United States)

    Shin, Da Wi; Khadka, Niranjan; Fan, Jie; Bikson, Marom; Fu, Bingmei M.

    2016-03-01

    Transcranial Direct Current Stimulation (tDCS) is a non-invasive electrical stimulation technique investigated for a broad range of medical and performance indications. Whereas prior studies have focused exclusively on direct neuron polarization, our hypothesis is that tDCS directly modulates endothelial cells leading to transient changes in blood-brain-barrier (BBB) permeability (P) that are highly meaningful for neuronal activity. For this, we developed state-of-the-art imaging and animal models to quantify P to various sized solutes after tDCS treatment. tDCS was administered using a constant current stimulator to deliver a 1mA current to the right frontal cortex of rat (approximately 2 mm posterior to bregma and 2 mm right to sagittal suture) to obtain similar physiological outcome as that in the human tDCS application studies. Sodium fluorescein (MW=376), or FITC-dextrans (20K and 70K), in 1% BSA mammalian Ringer was injected into the rat (SD, 250-300g) cerebral circulation via the ipsilateral carotid artery by a syringe pump at a constant rate of ~3 ml/min. To determine P, multiphoton microscopy with 800-850 nm wavelength laser was applied to take the images from the region of interest (ROI) with proper microvessels, which are 100-200 micron below the pia mater. It shows that the relative increase in P is about 8-fold for small solute, sodium fluorescein, ~35-fold for both intermediate sized (Dex-20k) and large (Dex-70k) solutes, 10 min after 20 min tDCS pretreatment. All of the increased permeability returns to the control after 20 min post treatment. The results confirmed our hypothesis.

  10. Effects of Dual Transcranial Direct Current Stimulation for Aphasia in Chronic Stroke Patients

    OpenAIRE

    Lee, Seung Yeol; Cheon, Hee-Jung; Yoon, Kyoung Jae; Chang, Won Hyuk; Kim, Yun-Hee

    2013-01-01

    Objective To investigate any additional effect of dual transcranial direct current stimulation (tDCS) compared with single tDCS in chronic stroke patients with aphasia. Methods Eleven chronic stroke patients (aged 52.6?13.4 years, nine men) with aphasia were enrolled. Single anodal tDCS was applied over the left inferior frontal gyrus (IFG) and a cathodal electrode was placed over the left buccinator muscle. Dual tDCS was applied as follows: 1) anodal tDCS over the left IFG and cathodal tDCS ...

  11. Determination of optimal electrode positions for transcranial direct current stimulation (tDCS)

    International Nuclear Information System (INIS)

    Im, Chang-Hwan; Jung, Hui-Hun; Choi, Jung-Do; Lee, Soo Yeol; Jung, Ki-Young

    2008-01-01

    The present study introduces a new approach to determining optimal electrode positions in transcranial direct current stimulation (tDCS). Electric field and 3D conduction current density were analyzed using 3D finite element method (FEM) formulated for a dc conduction problem. The electrode positions for minimal current injection were optimized by changing the Cartesian coordinate system into the spherical coordinate system and applying the (2+6) evolution strategy (ES) algorithm. Preliminary simulation studies applied to a standard three-layer head model demonstrated that the proposed approach is promising in enhancing the performance of tDCS. (note)

  12. Determination of optimal electrode positions for transcranial direct current stimulation (tDCS)

    Energy Technology Data Exchange (ETDEWEB)

    Im, Chang-Hwan; Jung, Hui-Hun; Choi, Jung-Do [Department of Biomedical Engineering, Yonsei University, Wonju, 220-710 (Korea, Republic of); Lee, Soo Yeol [Department of Biomedical Engineering, Kyung Hee University, Suwon (Korea, Republic of); Jung, Ki-Young [Korea University Medical Center, Korea University College of Medicine, Seoul (Korea, Republic of)], E-mail: ich@yonsei.ac.kr

    2008-06-07

    The present study introduces a new approach to determining optimal electrode positions in transcranial direct current stimulation (tDCS). Electric field and 3D conduction current density were analyzed using 3D finite element method (FEM) formulated for a dc conduction problem. The electrode positions for minimal current injection were optimized by changing the Cartesian coordinate system into the spherical coordinate system and applying the (2+6) evolution strategy (ES) algorithm. Preliminary simulation studies applied to a standard three-layer head model demonstrated that the proposed approach is promising in enhancing the performance of tDCS. (note)

  13. Effects of frontal transcranial direct current stimulation on emotional processing and mood in healthy humans

    Directory of Open Access Journals (Sweden)

    Michael A. Nitsche

    2012-06-01

    Full Text Available The prefrontal cortex is involved in mood and emotional processing. In patients suffering from depression, the left dorsolateral prefrontal cortex is hypoactive, while activity of the right dorsolateral prefrontal cortex is enhanced. Counterbalancing these pathological excitability alterations by repetitive transcranial magnetic stimulation (rTMS or transcranial direct current stimulation (tDCS improves mood in these patients. In healthy subjects, however, rTMS of the same areas has no major effect, and the effects of tDCS are mixed. We aimed to evaluate the effects of prefrontal tDCS on mood and mood-related cognitive processing in healthy humans. In a first study, we administered excitability-enhancing anodal, excitability-diminishing cathodal and placebo tDCS to the left dorsolateral prefrontal cortex, combined with antagonistic stimulation of the right frontopolar cortex, and tested acute mood changes by an adjective checklist. Subjective mood was not influenced by tDCS. Emotional face identification, however, which was explored in a second experiment, was subtly improved by a tDCS-driven excitability modulation of the prefrontal cortex, markedly by anodal tDCS of the left dorsolateral prefrontal cortex for positive emotional content. We conclude that tDCS of the prefrontal cortex improves mood processing in healthy subjects, but does not influence subjective mood state.

  14. Using transcranial direct-current stimulation (tDCS) to understand cognitive processing.

    Science.gov (United States)

    Reinhart, Robert M G; Cosman, Josh D; Fukuda, Keisuke; Woodman, Geoffrey F

    2017-01-01

    Noninvasive brain stimulation methods are becoming increasingly common tools in the kit of the cognitive scientist. In particular, transcranial direct-current stimulation (tDCS) is showing great promise as a tool to causally manipulate the brain and understand how information is processed. The popularity of this method of brain stimulation is based on the fact that it is safe, inexpensive, its effects are long lasting, and you can increase the likelihood that neurons will fire near one electrode and decrease the likelihood that neurons will fire near another. However, this method of manipulating the brain to draw causal inferences is not without complication. Because tDCS methods continue to be refined and are not yet standardized, there are reports in the literature that show some striking inconsistencies. Primary among the complications of the technique is that the tDCS method uses two or more electrodes to pass current and all of these electrodes will have effects on the tissue underneath them. In this tutorial, we will share what we have learned about using tDCS to manipulate how the brain perceives, attends, remembers, and responds to information from our environment. Our goal is to provide a starting point for new users of tDCS and spur discussion of the standardization of methods to enhance replicability.

  15. Transcranial Direct Current Stimulation in Stroke Rehabilitation: A Review of Recent Advancements

    Science.gov (United States)

    Gomez Palacio Schjetnan, Andrea; Faraji, Jamshid; Metz, Gerlinde A.; Tatsuno, Masami; Luczak, Artur

    2013-01-01

    Transcranial direct current stimulation (tDCS) is a promising technique to treat a wide range of neurological conditions including stroke. The pathological processes following stroke may provide an exemplary system to investigate how tDCS promotes neuronal plasticity and functional recovery. Changes in synaptic function after stroke, such as reduced excitability, formation of aberrant connections, and deregulated plastic modifications, have been postulated to impede recovery from stroke. However, if tDCS could counteract these negative changes by influencing the system's neurophysiology, it would contribute to the formation of functionally meaningful connections and the maintenance of existing pathways. This paper is aimed at providing a review of underlying mechanisms of tDCS and its application to stroke. In addition, to maximize the effectiveness of tDCS in stroke rehabilitation, future research needs to determine the optimal stimulation protocols and parameters. We discuss how stimulation parameters could be optimized based on electrophysiological activity. In particular, we propose that cortical synchrony may represent a biomarker of tDCS efficacy to indicate communication between affected areas. Understanding the mechanisms by which tDCS affects the neural substrate after stroke and finding ways to optimize tDCS for each patient are key to effective rehabilitation approaches. PMID:23533955

  16. Transcranial direct current stimulation over prefrontal cortex diminishes degree of risk aversion.

    Science.gov (United States)

    Ye, Hang; Chen, Shu; Huang, Daqiang; Wang, Siqi; Jia, Yongmin; Luo, Jun

    2015-06-26

    Previous studies have established that transcranial direct current stimulation (tDCS) is a powerful technique for manipulating the activity of the human cerebral cortex. Many studies have found that weighing the risks and benefits in decision-making involves a complex neural network that includes the dorsolateral prefrontal cortex (DLPFC). We studied whether participants change the balance of risky and safe responses after receiving tDCS applied over the right and left prefrontal cortex. A total of 60 healthy volunteers performed a risk task while they received either anodal tDCS over the right prefrontal cortex, with cathodal over the left; anodal tDCS over the left prefrontal cortex, with cathodal over the right; or sham stimulation. The participants tended to choose less risky options after receiving sham stimulation, demonstrating that the task might be highly influenced by the "wealth effect". There was no statistically significant change after either right anodal/left cathodal or left anodal/right cathodal tDCS, indicating that both types of tDCS impact the participants' degrees of risk aversion, and therefore, counteract the wealth effect. We also found gender differences in the participants' choices. These findings extend the notion that DLPFC activity is critical for risk decision-making. Application of tDCS to the right/left DLPFC may impact a person's attitude to taking risks. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Can Transcranial Direct Current Stimulation Improve Cognitive Functioning in Adults with Schizophrenia?

    Science.gov (United States)

    Schretlen, David J; van Steenburgh, Joseph J; Varvaris, Mark; Vannorsdall, Tracy D; Andrejczuk, Megan A; Gordon, Barry

    Cognitive impairment is nearly ubiquitous in schizophrenia. First-degree relatives of persons with schizophrenia often show similar but milder deficits. Current methods for the treatment of schizophrenia are often ineffective in cognitive remediation. Since transcranial direct current stimulation (tDCS) can enhance cognitive functioning in healthy adults, it might provide a viable option to enhance cognition in schizophrenia. We sought to explore whether tDCS can be tolerated by persons with schizophrenia and potentially improve their cognitive functioning. We examined the effects of anodal versus cathodal tDCS on working memory and other cognitive tasks in five outpatients with schizophrenia and six first-degree relatives of persons with schizophrenia. Each participant completed tasks thought to be mediated by the prefrontal cortex during two 30-minute sessions of tDCS to the left and right dorsolateral prefrontal cortex (DLPFC). Anodal stimulation over the left DLPFC improved performance relative to cathodal stimulation on measures of working memory and aspects of verbal fluency relevant to word retrieval. The patient group showed differential changes in novel design production without alteration of overall productivity, suggesting that tDCS might be capable of altering self-monitoring and executive control. All participants tolerated tDCS well. None withdrew from the study or experienced any adverse reaction. We conclude that adults with schizophrenia can tolerate tDCS while engaging in cognitive tasks and that tDCS can alter their performance.

  18. Transcranial Direct Current Stimulation in Substance Use Disorders: A Systematic Review of Scientific Literature.

    Science.gov (United States)

    Lupi, Matteo; Martinotti, Giovanni; Santacroce, Rita; Cinosi, Eduardo; Carlucci, Maria; Marini, Stefano; Acciavatti, Tiziano; di Giannantonio, Massimo

    2017-09-01

    New treatment options such as noninvasive brain stimulation have been recently explored in the field of substance use disorders (SUDs), including transcranial direct current stimulation (tDCS). In light of this, we have performed a review of the scientific literature to assess efficacy and technical and methodological issues resulting from applying tDCS to the field of SUDs. Our analysis highlighted the following selection criteria: clinical studies on tDCS and SUDs (alcohol, caffeine, cannabis, cocaine, heroin, methamphetamine, and nicotine). Study selection, data analysis, and reporting were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Exclusion criteria were as follows: clinical studies about tDCS among behavioral addiction; review and didactic articles; physiopathological studies; and case reports. Eighteen scientific papers were selected out of 48 articles. Among these, 16 studied the efficacy of tDCS applied to the dorsolateral prefrontal cortex, and 8 suggested the efficacy of tDCS in reducing substance craving. In light of these data, it is premature to conclude that tDCS over the dorsolateral prefrontal cortex is a very efficient technique in reducing craving. Small sample size, different stimulation protocols, and study duration were the main limitations. However, the efficacy of tDCS in treating SUDs requires further investigation.

  19. Sex Mediates the Effects of High-Definition Transcranial Direct Current Stimulation on "Mind-Reading".

    Science.gov (United States)

    Martin, A K; Huang, J; Hunold, A; Meinzer, M

    2017-12-16

    Sex differences in social cognitive ability are well established, including measures of Theory of Mind (ToM). The aim of this study was to investigate if sex mediates the effects of high-definition transcranial direct current stimulation (HD-tDCS) administered to a key hub of the social brain (i.e., the dorsomedial prefrontal cortex, dmPFC) on the Reading the Mind in the Eyes Test (RMET). Forty healthy young adults (18-35 years) were randomly allocated to receive either anodal or cathodal HD-tDCS in sham HD-tDCS controlled, double blind designs. In each of the two sessions, subjects completed the RMET. Anodal stimulation to the dmPFC increased accuracy on the RMET in females only. To assure regional specificity we performed a follow-up study stimulating the right temporoparietal junction and found no effect in either sex. The current study is the first to show improved performance on the RMET after tDCS to the dmPFC in females only. The polarity-specific effects and use of focal HD-tDCS provide evidence for sex-dependent differences in dmPFC function in relation to the RMET. Future studies using tDCS to study or improve ToM, need to consider sex. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  20. Action mechanisms of transcranial direct current stimulation in Alzheimer´s disease and memory loss

    Directory of Open Access Journals (Sweden)

    Niels eHansen

    2012-05-01

    Full Text Available The pharmacological treatment of Alzheimer´s disease (AD is often limited and accompanied by drug side effects. Thus alternative therapeutic strategies such as non-invasive brain stimulation are needed. Few studies have demonstrated that transcranial direct current stimulation (tDCS, a method of neuromodulation with consecutive robust excitability changes within the stimulated cortex area, is beneficial in AD. There is also evidence that tDCS enhances memory function in cognitive rehabilitation in depressive patients, Parkinson´s disease and stroke. TDCS improves working and visual recognition memory in humans and object-recognition learning in the elderly. Neurobiological mechanisms of AD comprise changes in neuronal activity and the cerebral blood flow caused by altered microvasculature, synaptic dysregulation from ß-amyloid peptide accumulation, altered neuromodulation by degeneration of modulatory amine transmitter systems, altered brain oscillations, and changes in network connectivity. tDCS alters (i neuronal activity and (ii human cerebral blood flow, (iii has synaptic and non-synaptic after-effects (iv, can modify neurotransmitters polarity-dependently, (v and alter oscillatory brain activity and (vi functional connectivity patterns in the brain. It thus is reasonable to use tDCS as a therapeutic instrument in AD as it improves cognitive function in manner based on a disease mechanism. Moreover, it might prove valuable in other types of dementia. Future large-scale clinical and mechanism-oriented studies may enable to identify its therapeutic validity in other types of demential disorders.

  1. Action mechanisms of transcranial direct current stimulation in Alzheimer's disease and memory loss.

    Science.gov (United States)

    Hansen, Niels

    2012-01-01

    The pharmacological treatment of Alzheimer's disease (AD) is often limited and accompanied by drug side effects. Thus alternative therapeutic strategies such as non-invasive brain stimulation are needed. Few studies have demonstrated that transcranial direct current stimulation (tDCS), a method of neuromodulation with consecutive robust excitability changes within the stimulated cortex area, is beneficial in AD. There is also evidence that tDCS enhances memory function in cognitive rehabilitation in depressive patients, Parkinson's disease, and stroke. tDCS improves working and visual recognition memory in humans and object-recognition learning in the elderly. AD's neurobiological mechanisms comprise changes in neuronal activity and the cerebral blood flow (CBF) caused by altered microvasculature, synaptic dysregulation from ß-amyloid peptide accumulation, altered neuromodulation via degenerated modulatory amine transmitter systems, altered brain oscillations, and changes in network connectivity. tDCS alters (i) neuronal activity and (ii) human CBF, (iii) has synaptic and non-synaptic after-effects (iv), can modify neurotransmitters polarity-dependently, (v) and alter oscillatory brain activity and (vi) functional connectivity patterns in the brain. It thus is reasonable to use tDCS as a therapeutic instrument in AD as it improves cognitive function in manner based on a disease mechanism. Moreover, it could prove valuable in other types of dementia. Future large-scale clinical and mechanism-oriented studies may enable us to identify its therapeutic validity in other types of demential disorders.

  2. Simultaneous recording of electroretinogram and visual evoked response. Focal stimulation under direct observation.

    Science.gov (United States)

    Hirose, T; Miyake, Y; Hara, A

    1977-07-01

    A system has been tested that allows simultaneous recording of the retinal response (electroretinogram [ERG]) and the occipital response (visual evoked response [VER]) with focal photic stimulation of the retina under direct observation of the fundus. A helium-neon gas laser is used as a stimulus source. The laser is chopped either by a pen motor or a rotating disc. The laser is attached to a biomicroscope through which the examiner can observe the fundus of the subject during the entire recording session. The optically clear contact lens is made with a flat surface that neutralizes refraction due to the cornea, thereby allowing fundus observation by microscope. Two metal wires mounted inside and outside of the lens serve as the electrode for the ERG. Graticules consisting of concentric circles and radial lines are projected onto the subject's fundus, providing a pattern that the examiner can use to determine the exact location to be stimulated in the fundus. With proper adjustment of stimulus and background illumination, local ERG and VER can be recorded simultaneously by stimulating the macula.

  3. Electrical stimulation directs engineered cardiac tissue to an age-matched native phenotype

    Directory of Open Access Journals (Sweden)

    Richard A Lasher

    2012-12-01

    Full Text Available Quantifying structural features of native myocardium in engineered tissue is essential for creating functional tissue that can serve as a surrogate for in vitro testing or the eventual replacement of diseased or injured myocardium. We applied three-dimensional confocal imaging and image analysis to quantitatively describe the features of native and engineered cardiac tissue. Quantitative analysis methods were developed and applied to test the hypothesis that environmental cues direct engineered tissue toward a phenotype resembling that of age-matched native myocardium. The analytical approach was applied to engineered cardiac tissue with and without the application of electrical stimulation as well as to age-matched and adult native tissue. Individual myocytes were segmented from confocal image stacks and assigned a coordinate system from which measures of cell geometry and connexin-43 spatial distribution were calculated. The data were collected from 9 nonstimulated and 12 electrically stimulated engineered tissue constructs and 5 postnatal day 12 and 7 adult hearts. The myocyte volume fraction was nearly double in stimulated engineered tissue compared to nonstimulated engineered tissue (0.34 ± 0.14 vs 0.18 ± 0.06 but less than half of the native postnatal day 12 (0.90 ± 0.06 and adult (0.91 ± 0.04 myocardium. The myocytes under electrical stimulation were more elongated compared to nonstimulated myocytes and exhibited similar lengths, widths, and heights as in age-matched myocardium. Furthermore, the percentage of connexin-43-positive membrane staining was similar in the electrically stimulated, postnatal day 12, and adult myocytes, whereas it was significantly lower in the nonstimulated myocytes. Connexin-43 was found to be primarily located at cell ends for adult myocytes and irregularly but densely clustered over the membranes of nonstimulated, stimulated, and postnatal day 12 myocytes. These findings support our hypothesis and reveal

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

    Science.gov (United States)

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

    2018-04-01

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

  5. The effects of transcranial direct current stimulation in patients with neuropathic pain from spinal cord injury.

    Science.gov (United States)

    Ngernyam, Niran; Jensen, Mark P; Arayawichanon, Preeda; Auvichayapat, Narong; Tiamkao, Somsak; Janjarasjitt, Suparerk; Punjaruk, Wiyada; Amatachaya, Anuwat; Aree-uea, Benchaporn; Auvichayapat, Paradee

    2015-02-01

    Transcranial direct current stimulation (tDCS) has demonstrated efficacy for reducing neuropathic pain, but the respective mechanisms remain largely unknown. The current study tested the hypothesis that pain reduction with tDCS is associated with an increase in the peak frequency spectrum density in the theta-alpha range. Twenty patients with spinal cord injury and bilateral neuropathic pain received single sessions of both sham and anodal tDCS (2 mA) over the left primary motor area (M1) for 20 min. Treatment order was randomly assigned. Pre- to post-procedure changes in pain intensity and peak frequency of electroencephalogram spectral analysis were compared between treatment conditions. The active treatment condition (anodal tDCS over M1) but not sham treatment resulted in significant decreases in pain intensity. In addition, consistent with the study hypothesis, peak theta-alpha frequency (PTAF) assessed from an electrode placed over the site of stimulation increased more from pre- to post-session among participants in the active tDCS condition, relative to those in the sham tDCS condition. Moreover, we found a significant association between a decrease in pain intensity and an increase in PTAF at the stimulation site. The findings are consistent with the possibility that anodal tDCS over the left M1 may be effective, at least in part, because it results in an increase in M1 cortical excitability, perhaps due to a pain inhibitory effect of motor cortex stimulation that may influence the descending pain modulation system. Future research is needed to determine if there is a causal association between increased left anterior activity and pain reduction. The results provide new findings regarding the effects of tDCS on neuropathic pain and brain oscillation changes. Copyright © 2014 International Federation of Clinical Neurophysiology. All rights reserved.

  6. In situ Probe Microphone Measurement for Testing the Direct Acoustical Cochlear Stimulator

    Directory of Open Access Journals (Sweden)

    Christof Stieger

    2017-08-01

    Full Text Available Hypothesis: Acoustical measurements can be used for functional control of a direct acoustic cochlear stimulator (DACS.Background: The DACS is a recently released active hearing implant that works on the principle of a conventional piston prosthesis driven by the rod of an electromagnetic actuator. An inherent part of the DACS actuator is a thin titanium diaphragm that allows for movement of the stimulation rod while hermetically sealing the housing. In addition to mechanical stimulation, the actuator emits sound into the mastoid cavity because of the motion of the diaphragm.Methods: We investigated the use of the sound emission of a DACS for intra-operative testing. We measured sound emission in the external auditory canal (PEAC and velocity of the actuators stimulation rod (Vact in five implanted ears of whole-head specimens. We tested the influence various positions of the loudspeaker and a probe microphone on PEAC and simulated implant malfunction in one example.Results: Sound emission of the DACS with a signal-to-noise ratio >10 dB was observed between 0.5 and 5 kHz. Simulated implant misplacement or malfunction could be detected by the absence or shift in the characteristic resonance frequency of the actuator. PEAC changed by <6 dB for variations of the microphone and loudspeaker position.Conclusion: Our data support the feasibility of acoustical measurements for in situ testing of the DACS implant in the mastoid cavity as well as for post-operative monitoring of actuator function.

  7. Modulation of Perception or Emotion? A Scoping Review of Tinnitus Neuromodulation Using Transcranial Direct Current Stimulation.

    Science.gov (United States)

    Shekhawat, Giriraj Singh; Stinear, Cathy M; Searchfield, Grant D

    2015-10-01

    Tinnitus is the phantom perception of sound and can have negative effect on the quality of life. Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique, which can increase or decrease the cortical excitability in the brain region to which it is applied. tDCS has been used for tinnitus research since 2006. To investigate whether tDCS affects tinnitus perception, related emotion, or both, and the potential implications for tinnitus management. A scoping review was undertaken using the methods proposed by Arksey and O'Malley. After initial consideration of title relevance and reading abstracts, 15 studies were included in this review. The data from these studies were charted to investigate the impact of tDCS on tinnitus perception and emotions. tDCS results in transient suppression of tinnitus loudness and annoyance; however, it does not lead to long-term impact on tinnitus related emotion. Local stimulation of different sites of stimulation (left temporoparietal area, dorsolateral prefrontal cortex, and auditory cortex) might modulate tinnitus perception (loudness) and emotions differently; however, further research is needed to explore this hypothesis. This review has identified aspects of methodologies that require attention in upcoming tinnitus and tDCS trials to offer better insights. tDCS is an effective research tool for transient tinnitus neuromodulation. However, efforts should be invested in designing clinical trials using local and multiple sites of stimulation, optimized parameters, and objective outcome measures before it can be translated in to a clinical tool for tinnitus management. © The Author(s) 2015.

  8. Transcranial Direct Current Stimulation of Frontal Cortex Decreases Performance on the WAIS-IV Intelligence Test

    Science.gov (United States)

    Sellers, Kristin K.; Mellin, Juliann M.; Lustenberger, Caroline M.; Boyle, Michael R.; Lee, Won Hee; Peterchev, Angel V.; Frohlich, Flavio

    2015-01-01

    Transcranial direct current stimulation (tDCS) modulates excitability of motor cortex. However, there is conflicting evidence about the efficacy of this non-invasive brain stimulation modality to modulate performance on cognitive tasks. Previous work has tested the effect of tDCS on specific facets of cognition and executive processing. However, no randomized, double-blind, sham-controlled study has looked at the effects of tDCS on a comprehensive battery of cognitive processes. The objective of this study was to test if tDCS had an effect on performance on a comprehensive assay of cognitive processes, a standardized intelligence quotient (IQ) test. The study consisted of two substudies and followed a double-blind, between-subjects, sham-controlled design. In total, 41 healthy adult participants completed the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) as a baseline measure. At least one week later, participants in substudy 1 received either bilateral tDCS (anodes over both F4 and F3, cathode over Cz, 2mA at each anode for 20 minutes) or active sham tDCS (2mA for 40 seconds), and participants in substudy 2 received either right or left tDCS (anode over either F4 or F3, cathode over Cz, 2mA for 20 minutes). In both studies, the WAIS-IV was immediately administered following stimulation to assess for performance differences induced by bilateral and unilateral tDCS. Compared to sham stimulation, right, left, and bilateral tDCS reduced improvement between sessions on Full Scale IQ and the Perceptual Reasoning Index. This demonstration that frontal tDCS selectively degraded improvement on specific metrics of the WAIS-IV raises important questions about the often proposed role of tDCS in cognitive enhancement. PMID:25934490

  9. Imaging transcranial direct current stimulation (tDCS) of the prefrontal cortex-correlation or causality in stimulation-mediated effects?

    Science.gov (United States)

    Wörsching, Jana; Padberg, Frank; Ertl-Wagner, Birgit; Kumpf, Ulrike; Kirsch, Beatrice; Keeser, Daniel

    2016-10-01

    Transcranial current stimulation approaches include neurophysiologically distinct non-invasive brain stimulation techniques widely applied in basic, translational and clinical research: transcranial direct current stimulation (tDCS), oscillating transcranial direct current stimulation (otDCS), transcranial alternating current stimulation (tACS) and transcranial random noise stimulation (tRNS). Prefrontal tDCS seems to be an especially promising tool for clinical practice. In order to effectively modulate relevant neural circuits, systematic research on prefrontal tDCS is needed that uses neuroimaging and neurophysiology measures to specifically target and adjust this method to physiological requirements. This review therefore analyses the various neuroimaging methods used in combination with prefrontal tDCS in healthy and psychiatric populations. First, we provide a systematic overview on applications, computational models and studies combining neuroimaging or neurophysiological measures with tDCS. Second, we categorise these studies in terms of their experimental designs and show that many studies do not vary the experimental conditions to the extent required to demonstrate specific relations between tDCS and its behavioural or neurophysiological effects. Finally, to support best-practice tDCS research we provide a methodological framework for orientation among experimental designs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Direct interaction between caffeic acid phenethyl ester and human neutrophil elastase inhibits the growth and migration of PANC-1 cells.

    Science.gov (United States)

    Duan, Jianhui; Xiaokaiti, Yilixiati; Fan, Shengjun; Pan, Yan; Li, Xin; Li, Xuejun

    2017-05-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumors of the digestive system, but the mechanisms of its development and progression are unclear. Inflammation is thought to be fundamental to pancreatic cancer development and caffeic acid phenethyl ester (CAPE) is an active component of honey bee resin or propolis with anti-inflammatory and anticancer activities. We investigated the inhibitory effects of CAPE on cell growth and migration induced by human neutrophil elastase (HNE) and report that HNE induced cancer cell migration at low doses and growth at higher doses. In contrast, lower CAPE doses inhibited migration and higher doses of CAPE inhibited the growth induced by HNE. HNE activity was significantly inhibited by CAPE (7.5-120 µM). Using quantitative real-time PCR and western blotting, we observed that CAPE (18-60 µM) did not affect transcription and translation of α1-antitrypsin (α1-AT), an endogenous HNE inhibitor. However, in an in silico drug target docking model, we found that CAPE directly bound to the binding pocket of HNE (25.66 kcal/mol) according to CDOCKER, and the residue of the catalytic site stabilized the interaction between CAPE and HNE as evidenced by molecular dynamic simulation. Response unit (RU) values of surface plasmon resonance (SPR) significantly increased with incremental CAPE doses (7.5-120 µM), indicating that CAPE could directly bind to HNE in a concentration-dependent manner. Thus, CAPE is an effective inhibitor of HNE via direct interaction whereby it inhibits the migration and growth of PANC-1 cells in a dose-dependent manner.

  11. Self-Rated Attentiveness Interacts with Transcranial Direct Current Stimulation and Noise Stimulation in Reaction Time in a Go/No-Go Task.

    Science.gov (United States)

    Sikström, Sverker; Jürgensen, Anna-Maria; Haghighi, Maryam; Månsson, Daniel; Smidelik, David; Habekost, Thomas

    2016-01-01

    Previous research has found that stimulating inattentive people with auditory white noise induces enhancement in cognitive performance. This enhancement is believed to occur due to a statistical phenomenon called stochastic resonance, where noise increases the probability of a signal passing the firing threshold in the neural cells. Here we investigate whether people with low attentiveness benefit to a larger extent than attentive people from stimulation by auditory white noise and transcranial direct current stimulation (tDCS). The results show, for both auditory noise and tDCS stimulation, that the changes in performance relative to nonstimulation correlate with the degree of attentiveness in a Go/No-Go task, but not in a N-back task. These results suggest that the benefit of tDCS may interact with inattentiveness.

  12. Transcranial direct current stimulation of the primary motor cortex improves word-retrieval in older adults.

    Directory of Open Access Journals (Sweden)

    Marcus eMeinzer

    2014-09-01

    Full Text Available Language facilitation by transcranial direct current stimulation (tDCS in healthy individuals has generated hope that tDCS may also allow improving language impairment after stroke (aphasia. However, current stimulation protocols have yielded variable results and may require identification of residual language cortex using functional magnetic resonance imaging (fMRI, which complicates incorporation into clinical practice. Based on previous behavioral studies that demonstrated improved language processing by motor system pre-activation, the present study assessed whether tDCS administered to the primary motor cortex (M1 can enhance language functions.This proof-of-concept study employed a sham-tDCS controlled, cross-over, within-subject design and assessed the impact of unilateral excitatory (anodal and bihemispheric (dual tDCS in eighteen healthy older adults during semantic word-retrieval and motor speech tasks. Simultaneous fMRI scrutinized the neural mechanisms underlying tDCS effects.Both active tDCS conditions significantly improved word-retrieval compared to sham-tDCS. The direct comparison of activity elicited by word-retrieval vs. motor-speech trials revealed bilateral frontal activity increases during both anodal- and dual-tDCS compared to sham-tDCS. This effect was driven by more pronounced deactivation of frontal regions during the motor-speech task, while activity during word-retrieval trials was unaffected by the stimulation. No effects were found in M1 and secondary motor regions.Our results show that tDCS administered to M1 can improve word-retrieval in healthy individuals, thereby providing a rationale to explore whether M1-tDCS may offer a novel approach to improve language functions in aphasia. fMRI revealed neural facilitation specifically during motor speech trials, which may have reduced switching costs between the overlapping neural systems for lexical retrieval and speech processing, thereby resulting in improved

  13. Adaptive threshold hunting for the effects of transcranial direct current stimulation on primary motor cortex inhibition.

    Science.gov (United States)

    Mooney, Ronan A; Cirillo, John; Byblow, Winston D

    2018-06-01

    Primary motor cortex excitability can be modulated by anodal and cathodal transcranial direct current stimulation (tDCS). These neuromodulatory effects may, in part, be dependent on modulation within gamma-aminobutyric acid (GABA)-mediated inhibitory networks. GABAergic function can be quantified non-invasively using adaptive threshold hunting paired-pulse transcranial magnetic stimulation (TMS). The previous studies have used TMS with posterior-anterior (PA) induced current to assess tDCS effects on inhibition. However, TMS with anterior-posterior (AP) induced current in the brain provides a more robust measure of GABA-mediated inhibition. The aim of the present study was to assess the modulation of corticomotor excitability and inhibition after anodal and cathodal tDCS using TMS with PA- and AP-induced current. In 16 young adults (26 ± 1 years), we investigated the response to anodal, cathodal, and sham tDCS in a repeated-measures double-blinded crossover design. Adaptive threshold hunting paired-pulse TMS with PA- and AP-induced current was used to examine separate interneuronal populations within M1 and their influence on corticomotor excitability and short- and long-interval inhibition (SICI and LICI) for up to 60 min after tDCS. Unexpectedly, cathodal tDCS increased corticomotor excitability assessed with AP (P = 0.047) but not PA stimulation (P = 0.74). SICI AP was reduced after anodal tDCS compared with sham (P = 0.040). Pearson's correlations indicated that SICI AP and LICI AP modulation was associated with corticomotor excitability after anodal (P = 0.027) and cathodal tDCS (P = 0.042). The after-effects of tDCS on corticomotor excitability may depend on the direction of the TMS-induced current used to make assessments, and on modulation within GABA-mediated inhibitory circuits.

  14. Modulation of Isometric Quadriceps Strength in Soccer Players With Transcranial Direct Current Stimulation: A Crossover Study.

    Science.gov (United States)

    Vargas, Valentine Z; Baptista, Abrahão F; Pereira, Guilherme O C; Pochini, Alberto C; Ejnisman, Benno; Santos, Marcelo B; João, Silvia M A; Hazime, Fuad A

    2018-05-01

    Vargas, VZ, Baptista, AF, Pereira, GOC, Pochini, AC, Ejnisman, B, Santos, MB, João, SMA, and Hazime, FA. Modulation of isometric quadriceps strength in soccer players with transcranial direct current stimulation: a crossover study. J Strength Cond Res 32(5): 1336-1341, 2018-The aim of this study was to evaluate the effect of transcranial direct current stimulation (tDCS) on the maximum isometric muscle contraction (MVIC) of the knee extensors in soccer players at the preprofessional level. Twenty female soccer players aged 15-17 years (mean = 16.1; SD = 0.9) with 5.2 ± 2.6 years of training were randomly divided into 2 groups to receive either active or sham tDCS in a single session (2 mA; 0.057 mA·cm). The MVIC of the knee extensors was evaluated in both lower limbs by manual dynamometry in 5 sets of contractions divided into 4 blocks: (a) prestimulation, (b) during tDCS, (c) 30 minutes after tDCS, and (d) 60 minutes after tDCS. After an interval of 7 days, the groups were evaluated again, and the type of initial stimulation was inverted between participants. The MVIC of the knee extensors increased significantly during active tDCS (dominant limb (DL) = 0.4; IC = 0.1-0.8 N·Kg), 30 minutes after active tDCS (DL = 0.9; IC 0.4-1.4 N·Kg), and 60 minutes after active tDCS (DL = 1.0; IC 0.3-1.6 N·Kg) but not for sham tDCS. Our conclusion was that tDCS temporarily increases isometric quadriceps strength in adolescent female soccer players, which may be useful for both strength training and rehabilitation.

  15. Transcranial direct current stimulation over the right DLPFC selectively modulates subprocesses in working memory

    Directory of Open Access Journals (Sweden)

    Jiarui Wang

    2018-05-01

    Full Text Available Background Working memory, as a complex system, consists of two independent components: manipulation and maintenance process, which are defined as executive control and storage process. Previous studies mainly focused on the overall effect of transcranial direct current stimulation (tDCS on working memory. However, little has been known about the segregative effects of tDCS on the sub-processes within working memory. Method Transcranial direct current stimulation, as one of the non-invasive brain stimulation techniques, is being widely used to modulate the cortical activation of local brain areas. This study modified a spatial n-back experiment with anodal and cathodal tDCS exertion on the right dorsolateral prefrontal cortex (DLPFC, aiming to investigate the effects of tDCS on the two sub-processes of working memory: manipulation (updating and maintenance. Meanwhile, considering the separability of tDCS effects, we further reconfirmed the causal relationship between the right DLPFC and the sub-processes of working memory with different tDCS conditions. Results The present study showed that cathodal tDCS on the right DLPFC selectively improved the performance of the modified 2-back task in the difficult condition, whereas anodal tDCS significantly reduced the performance of subjects and showed an speeding-up tendency of response time. More precisely, the results of discriminability index and criterion showed that only cathodal tDCS enhanced the performance of maintenance in the difficult condition. Neither of the two tDCS conditions affected the performance of manipulation (updating. Conclusion These findings provide evidence that cathodal tDCS of the right DLPFC selectively affects maintenance capacity. Besides, cathodal tDCS also serves as an interference suppressor to reduce the irrelevant interference, thereby indirectly improving the working memory capacity. Moreover, the right DLPFC is not the unique brain regions for working memory

  16. Transcranial direct current stimulation of the primary motor cortex improves word-retrieval in older adults.

    Science.gov (United States)

    Meinzer, Marcus; Lindenberg, Robert; Sieg, Mira M; Nachtigall, Laura; Ulm, Lena; Flöel, Agnes

    2014-01-01

    Language facilitation by transcranial direct current stimulation (tDCS) in healthy individuals has generated hope that tDCS may also allow improving language impairment after stroke (aphasia). However, current stimulation protocols have yielded variable results and may require identification of residual language cortex using functional magnetic resonance imaging (fMRI), which complicates incorporation into clinical practice. Based on previous behavioral studies that demonstrated improved language processing by motor system pre-activation, the present study assessed whether tDCS administered to the primary motor cortex (M1) can enhance language functions. This proof-of-concept study employed a sham-tDCS controlled, cross-over, within-subject design and assessed the impact of unilateral excitatory (anodal) and bihemispheric (dual) tDCS in 18 healthy older adults during semantic word-retrieval and motor speech tasks. Simultaneous fMRI scrutinized the neural mechanisms underlying tDCS effects. Both active tDCS conditions significantly improved word-retrieval compared to sham-tDCS. The direct comparison of activity elicited by word-retrieval vs. motor-speech trials revealed bilateral frontal activity increases during both anodal- and dual-tDCS compared to sham-tDCS. This effect was driven by more pronounced deactivation of frontal regions during the motor-speech task, while activity during word-retrieval trials was unaffected by the stimulation. No effects were found in M1 and secondary motor regions. Our results show that tDCS administered to M1 can improve word-retrieval in healthy individuals, thereby providing a rationale to explore whether M1-tDCS may offer a novel approach to improve language functions in aphasia. Functional magnetic resonance imaging revealed neural facilitation specifically during motor speech trials, which may have reduced switching costs between the overlapping neural systems for lexical retrieval and speech processing, thereby resulting in

  17. Transcutaneous spinal direct current stimulation induces lasting fatigue resistance and enhances explosive vertical jump performance

    Science.gov (United States)

    Tate, Rothwelle J.; Conway, Bernard A.

    2017-01-01

    Transcutaneous spinal direct current stimulation (tsDCS) is a non-invasive neuromodulatory intervention that has been shown to modify excitability in spinal and supraspinal circuits in animals and humans. Our objective in this study was to explore the functional neuromodulatory potential of tsDCS by examining its immediate and lasting effects over the repeated performance of a whole body maximal exercise in healthy volunteers. Using a double-blind, randomized, crossover, sham-controlled design we investigated the effects of 15 min of anodal tsDCS on repeated vertical countermovement jump (VCJ) performance at 0, 20, 60, and 180 minutes post-stimulation. Measurements of peak and take-off velocity, vertical displacement, peak power and work done during countermovement and push-off VCJ phases were derived from changes in vertical ground reaction force (12 performance parameters) in 12 healthy participants. The magnitude and direction of change in VCJ performance from pre- to post-stimulation differed significantly between sham and active tsDCS for 7 of the 12 VCJ performance measures (P 0.05). Our original findings demonstrate that one single session of anodal tsDCS in healthy subjects can prevent fatigue and maintain or enhance different aspects of whole body explosive motor power over repeated sets of VCJs performed over a period of three hours. The observed effects are discussed in relation to alterations in central fatigue mechanisms, muscle contraction mode during jump execution and changes in spinal cord excitability. These findings have important implications for power endurance sport performance and for neuromotor rehabilitation. PMID:28379980

  18. Transcutaneous spinal direct current stimulation induces lasting fatigue resistance and enhances explosive vertical jump performance.

    Directory of Open Access Journals (Sweden)

    Helen R Berry

    Full Text Available Transcutaneous spinal direct current stimulation (tsDCS is a non-invasive neuromodulatory intervention that has been shown to modify excitability in spinal and supraspinal circuits in animals and humans. Our objective in this study was to explore the functional neuromodulatory potential of tsDCS by examining its immediate and lasting effects over the repeated performance of a whole body maximal exercise in healthy volunteers. Using a double-blind, randomized, crossover, sham-controlled design we investigated the effects of 15 min of anodal tsDCS on repeated vertical countermovement jump (VCJ performance at 0, 20, 60, and 180 minutes post-stimulation. Measurements of peak and take-off velocity, vertical displacement, peak power and work done during countermovement and push-off VCJ phases were derived from changes in vertical ground reaction force (12 performance parameters in 12 healthy participants. The magnitude and direction of change in VCJ performance from pre- to post-stimulation differed significantly between sham and active tsDCS for 7 of the 12 VCJ performance measures (P 0.05. Our original findings demonstrate that one single session of anodal tsDCS in healthy subjects can prevent fatigue and maintain or enhance different aspects of whole body explosive motor power over repeated sets of VCJs performed over a period of three hours. The observed effects are discussed in relation to alterations in central fatigue mechanisms, muscle contraction mode during jump execution and changes in spinal cord excitability. These findings have important implications for power endurance sport performance and for neuromotor rehabilitation.

  19. The Effects of Transcranial Direct Current Stimulation (tDCS on Multitasking Throughput Capacity

    Directory of Open Access Journals (Sweden)

    Justin Nelson

    2016-11-01

    Full Text Available Background: Multitasking has become an integral attribute associated with military operations within the past several decades. As the amount of information that needs to be processed during these high level multitasking environments exceeds the human operators’ capabilities, the information throughput capacity reaches an asymptotic limit. At this point, the human operator can no longer effectively process and respond to the incoming information resulting in a plateau or decline in performance. The objective of the study was to evaluate the efficacy of a non-invasive brain stimulation technique known as transcranial direct current stimulation (tDCS applied to a scalp location over the left dorsolateral prefrontal cortex (lDLPFC to improve information processing capabilities during a multitasking environment. Methods: The study consisted of 20 participants from Wright-Patterson Air Force Base (16 male and 4 female with an average age of 31.1 (SD = 4.5. Participants were randomly assigned into two groups, each consisting of eight males and two females. Group one received 2mA of anodal tDCS and group two received sham tDCS over the lDLPFC on their testing day. Results: The findings indicate that anodal tDCS significantly improves the participants’ information processing capability resulting in improved performance compared to sham tDCS. For example, the multitasking throughput capacity for the sham tDCS group plateaued near 1.0 bits/s at the higher baud input (2.0 bits/s whereas the anodal tDCS group plateaued near 1.3 bits/s. Conclusion: The findings provided new evidence that tDCS has the ability to augment and enhance multitasking capability in a human operator. Future research should be conducted to determine the longevity of the enhancement of transcranial direct current stimulation on multitasking performance, which has yet to be accomplished.

  20. The Effects of Transcranial Direct Current Stimulation (tDCS) on Multitasking Throughput Capacity.

    Science.gov (United States)

    Nelson, Justin; McKinley, Richard A; Phillips, Chandler; McIntire, Lindsey; Goodyear, Chuck; Kreiner, Aerial; Monforton, Lanie

    2016-01-01

    Background: Multitasking has become an integral attribute associated with military operations within the past several decades. As the amount of information that needs to be processed during these high level multitasking environments exceeds the human operators' capabilities, the information throughput capacity reaches an asymptotic limit. At this point, the human operator can no longer effectively process and respond to the incoming information resulting in a plateau or decline in performance. The objective of the study was to evaluate the efficacy of a non-invasive brain stimulation technique known as transcranial direct current stimulation (tDCS) applied to a scalp location over the left dorsolateral prefrontal cortex (lDLPFC) to improve information processing capabilities during a multitasking environment. Methods: The study consisted of 20 participants from Wright-Patterson Air Force Base (16 male and 4 female) with an average age of 31.1 (SD = 4.5). Participants were randomly assigned into two groups, each consisting of eight males and two females. Group one received 2 mA of anodal tDCS and group two received sham tDCS over the lDLPFC on their testing day. Results: The findings indicate that anodal tDCS significantly improves the participants' information processing capability resulting in improved performance compared to sham tDCS. For example, the multitasking throughput capacity for the sham tDCS group plateaued near 1.0 bits/s at the higher baud input (2.0 bits/s) whereas the anodal tDCS group plateaued near 1.3 bits/s. Conclusion: The findings provided new evidence that tDCS has the ability to augment and enhance multitasking capability in a human operator. Future research should be conducted to determine the longevity of the enhancement of transcranial direct current stimulation on multitasking performance, which has yet to be accomplished.

  1. Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study.

    Science.gov (United States)

    Benussi, Alberto; Koch, Giacomo; Cotelli, Maria; Padovani, Alessandro; Borroni, Barbara

    2015-10-01

    Numerous studies have highlighted the possibility of modulating the excitability of cerebellar circuits using transcranial direct current stimulation. The present study investigated whether a single session of cerebellar anodal transcranial direct current stimulation could improve symptoms in patients with ataxia. Nineteen patients with ataxia underwent a clinical and functional evaluation pre- and post-double-blind, randomized, sham, or anodal transcranial direct current stimulation. There was a significant interaction between treatment and time on the Scale for the Assessment and Rating of Ataxia, on the International Cooperative Ataxia Rating Scale, on the 9-Hole Peg Test, and on the 8-Meter Walking Time (P transcranial direct current stimulation can transiently improve symptoms in patients with ataxia and might represent a promising tool for future rehabilitative approaches. © 2015 International Parkinson and Movement Disorder Society.

  2. Slow-oscillatory transcranial direct current stimulation can induce bidirectional shifts in motor cortical excitability in awake humans

    DEFF Research Database (Denmark)

    Groppa, S; Bergmann, T O; Siems, C

    2010-01-01

    Constant transcranial direct stimulation (c-tDCS) of the primary motor hand area (M1(HAND)) can induce bidirectional shifts in motor cortical excitability depending on the polarity of tDCS. Recently, anodal slow oscillation stimulation at a frequency of 0.75 Hz has been shown to augment intrinsic...... slow oscillations during sleep and theta oscillations during wakefulness. To embed this new type of stimulation into the existing tDCS literature, we aimed to characterize the after effects of slowly oscillating stimulation (so-tDCS) on M1(HAND) excitability and to compare them to those of c-tDCS. Here...

  3. Surface EEG-Transcranial Direct Current Stimulation (tDCS) Closed-Loop System.

    Science.gov (United States)

    Leite, Jorge; Morales-Quezada, Leon; Carvalho, Sandra; Thibaut, Aurore; Doruk, Deniz; Chen, Chiun-Fan; Schachter, Steven C; Rotenberg, Alexander; Fregni, Felipe

    2017-09-01

    Conventional transcranial direct current stimulation (tDCS) protocols rely on applying electrical current at a fixed intensity and duration without using surrogate markers to direct the interventions. This has led to some mixed results; especially because tDCS induced effects may vary depending on the ongoing level of brain activity. Therefore, the objective of this preliminary study was to assess the feasibility of an EEG-triggered tDCS system based on EEG online analysis of its frequency bands. Six healthy volunteers were randomized to participate in a double-blind sham-controlled crossover design to receive a single session of 10[Formula: see text]min 2[Formula: see text]mA cathodal and sham tDCS. tDCS trigger controller was based upon an algorithm designed to detect an increase in the relative beta power of more than 200%, accompanied by a decrease of 50% or more in the relative alpha power, based on baseline EEG recordings. EEG-tDCS closed-loop-system was able to detect the predefined EEG magnitude deviation and successfully triggered the stimulation in all participants. This preliminary study represents a proof-of-concept for the development of an EEG-tDCS closed-loop system in humans. We discuss and review here different methods of closed loop system that can be considered and potential clinical applications of such system.

  4. Directional migration of leading-edge mesoderm generates physical forces: Implication in Xenopus notochord formation during gastrulation.

    Science.gov (United States)

    Hara, Yusuke; Nagayama, Kazuaki; Yamamoto, Takamasa S; Matsumoto, Takeo; Suzuki, Makoto; Ueno, Naoto

    2013-10-15

    Gastrulation is a dynamic tissue-remodeling process occurring during early development and fundamental to the later organogenesis. It involves both chemical signals and physical factors. Although much is known about the molecular pathways involved, the roles of physical forces in regulating cellular behavior and tissue remodeling during gastrulation have just begun to be explored. Here, we characterized the force generated by the leading edge mesoderm (LEM) that migrates preceding axial mesoderm (AM), and investigated the contribution of LEM during Xenopus gastrulation. First, we constructed an assay system using micro-needle which could measure physical forces generated by the anterior migration of LEM, and estimated the absolute magnitude of the force to be 20-80nN. Second, laser ablation experiments showed that LEM could affect the force distribution in the AM (i.e. LEM adds stretch force on axial mesoderm along anterior-posterior axis). Third, migrating LEM was found to be necessary for the proper gastrulation cell movements and the establishment of organized notochord structure; a reduction of LEM migratory activity resulted in the disruption of mediolateral cell orientation and convergence in AM. Finally, we found that LEM migration cooperates with Wnt/PCP to form proper notochord. These results suggest that the force generated by the directional migration of LEM is transmitted to AM and assists the tissue organization of notochord in vivo independently of the regulation by Wnt/PCP. We propose that the LEM may have a mechanical role in aiding the AM elongation through the rearrangement of force distribution in the dorsal marginal zone. © 2013 Elsevier Inc. All rights reserved.

  5. The effect of current flow direction on motor hot spot allocation by transcranial magnetic stimulation.

    Science.gov (United States)

    Stephani, Caspar; Paulus, Walter; Sommer, Martin

    2016-01-01

    The objective of this study was to investigate the significance of pulse configurations and current direction for corticospinal activation using transcranial magnetic stimulation (TMS). In 11 healthy subjects (8 female), a motor map for the motor evoked potentials (MEPs) recorded from the first dorsal interosseus (FDI), abductor digiti minimi (ADM), extensor carpi radialis, and biceps brachii (BB) muscles of the dominant side was established. Starting from a manually determined hot spot of the FDI representation, we measured MEPs at equal oriented points on an hexagonal grid, with 7 MEPs recorded at each point, using the following pulse configurations: posteriorly directed monophasic (Mo-P), anteriorly directed monophasic (Mo-A), biphasic with the more relevant second cycle oriented posteriorly (Bi-P) as well as a reversed biphasic condition (Bi-A). For each pulse configuration, a hot spot was determined and a center of gravity (CoG) was calculated. We found that the factor current direction had an effect on location of the CoG-adjusted hot spot in the cranio-caudal axis but not in the latero-medial direction with anteriorly directed pulses locating the CoG more anteriorly and vice versa. In addition, the CoG for the FDI was more laterally than the cortical representations for the abductor digiti minimi (ADM) and extensor carpi radialis (ECR) which were registered as well. The results indicate that direction of the current pulse should be taken into account for determination of the motor representation of a muscle by TMS. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  6. Stimulating the addicted brain : The effects of transcranial direct current stimulation and cognitive bias modification in alcohol users

    NARCIS (Netherlands)

    den Uyl, T.E.

    2017-01-01

    In this PhD project we investigated a new intervention in which we combined brain stimulation with cognitive training. We used a form of training called cognitive bias modification (CBM) aimed at retraining dysfunctional automatic reactions towards alcohol. We investigated whether transcranial

  7. Simulation study ε-Caprolactam monomer and metallic elements migration from irradiated polymeric packaging into food stimulants

    International Nuclear Information System (INIS)

    Rosa, Faena Machado Leite

    2008-01-01

    For decades migration study of chemical compounds from packaging into food, such as metals, residual monomers and additives, is a very important issue, concerning public health and minimize chemical contamination. In this work, it was done irradiations of packagings taken in contact with food simulant, and it was studied this migration through a mathematical model of the diffusion process, compiled in a computational simulation method in order to study the microscopic behavior of migration of metallic elements cadmium, chromium, antimony and cobalt, present in metallic plastics from dairy product packagings, and also the migration of - caprolactam monomer, present in nylon polymeric plastics used for package meat stuffs, to the food simulant acetic acid 3%. The results from simulations of the migration of -caprolactam monomer were compared with experimental results obtained from high resolution gas chromatography (HRGC) measurements, and the simulation of metallic elements migration were compared with the neutron activation analysis measurements (NAA). These experimental results were performed and kindly informed by another research groups, partners in this project. The food packaging system was discretized in one-dimension space and in time and the partial differential equation that defines the diffusive process, the second 'Fick's law', together with an equation of Arrhenius type dealing with the thermal influence, were solved using finite differences. The final step of the resolution was a tridiagonal linear system, solved using the Thomas algorithm. It was studied, and in some cases even foreseen, experimental quantities, like the diffusion coefficient, activation energy and concentration profile of migrant compounds, allowing the understanding of the diffusion process and the quantitative estimate of the migration of such compounds under ionizing radiation influence. Variation on the initial concentration levels (C 0 ) of the monomer inside the packaging

  8. Transcranial direct current stimulation improves word retrieval in healthy and nonfluent aphasic subjects.

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    Fiori, Valentina; Coccia, Michela; Marinelli, Chiara V; Vecchi, Veronica; Bonifazi, Silvia; Ceravolo, M Gabriella; Provinciali, Leandro; Tomaiuolo, Francesco; Marangolo, Paola

    2011-09-01

    A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects performances of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS to enhance associative verbal learning in 10 healthy individuals and to improve word retrieval deficits in three patients with stroke-induced aphasia. In healthy individuals, tDCS (20 min, 1 mA) was applied over Wernicke's area (position CP5 of the International 10-20 EEG System) while they learned 20 new "words" (legal nonwords arbitrarily assigned to 20 different pictures). The healthy subjects participated in a randomized counterbalanced double-blind procedure in which they were subjected to one session of anodic tDCS over left Wernicke's area, one sham session over this location and one session of anodic tDCS stimulating the right occipito-parietal area. Each experimental session was performed during a different week (over three consecutive weeks) with 6 days of intersession interval. Over 2 weeks, three aphasic subjects participated in a randomized double-blind experiment involving intensive language training for their anomic difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over Wernicke's area while they performed a picture-naming task. By the end of each week, anodic tDCS had significantly improved their accuracy on the picture-naming task. Both normal subjects and aphasic patients also had shorter naming latencies during anodic tDCS than during sham condition. At two follow-ups (1 and 3 weeks after the end of treatment), performed only in two aphasic subjects, response accuracy and reaction times were still significantly better in the anodic than in the sham condition, suggesting a long-term effect on recovery of their anomic disturbances.

  9. Transcranial Direct Current Stimulation: Five Important Issues We Aren’t Discussing (But Probably Should Be

    Directory of Open Access Journals (Sweden)

    Jared Cooney Horvath

    2014-01-01

    Full Text Available Transcranial Direct Current Stimulation (tDCS is a neuromodulatory device often publicized for its ability to enhance cognitive and behavioral performance. These enhancement claims, however, are predicated upon electrophysiological evidence and descriptions which are far from conclusive. In fact, a review of the literature reveals a number of important experimental and technical issues inherent with this device that are simply not being discussed in any meaningful manner. In this paper, we will consider five of these topics. The first, inter-subject variability, explores the extensive between- and within-group differences found within the tDCS literature and highlights the need to properly examine stimulatory response at the individual level. The second, intra-subject reliability, reviews the lack of data concerning tDCS response reliability over time and emphasizes the importance of this knowledge for appropriate stimulatory application. The third, sham stimulation and blinding, draws attention to the importance (yet relative lack of proper control and blinding practices in the tDCS literature. The fourth, motor and cognitive interference, highlights the often overlooked body of research that suggests typical behaviors and cognitions undertaken during or following tDCS can impair or abolish the effects of stimulation. Finally, the fifth, electric current influences, underscores several largely ignored variables (such as hair thickness and electrode attachments methods influential to tDCS electric current density and flow.Through this paper, we hope to increase awareness and start an ongoing dialogue of these important issues which speak to the efficacy, reliability, and mechanistic foundations of tDCS.

  10. Does anodal transcranial direct current stimulation modulate sensory perception and pain? A meta-analysis study.

    Science.gov (United States)

    Vaseghi, B; Zoghi, M; Jaberzadeh, S

    2014-09-01

    The primary aim of this systematic review was to evaluate the effects of anodal transcranial direct current stimulation (a-tDCS) on sensory (STh) and pain thresholds (PTh) in healthy individuals and pain levels (PL) in patients with chronic pain. Electronic databases were searched for a-tDCS studies. Methodological quality was examined using the PEDro and Downs and Black (D&B) assessment tools. a-tDCS of the primary motor cortex (M1) increases both STh (Psensory cortex (S1) (P<0.05 with an effect size of 4.34). Likewise, PL decreased significantly in the patient group following application of a-tDCS to both the M1 and dorsolateral prefrontal cortex (DLPFC). The average decrease in visual analogue score was 14.9% and 19.3% after applying a-tDCS on the M1 and DLPFC. Moreover, meta-analysis showed that in all subgroups (except a-tDCS of S1) active a-tDCS and sham stimulation produced significant differences. This review provides evidence for the effectiveness of a-tDCS in increasing STh/PTh in healthy group and decreasing PL in patients. However, due to small sample sizes in the included studies, our results should be interpreted cautiously. Given the level of blinding did not considered in inclusion criteria, the result of current study should be interpreted with caution. Site of stimulation should have a differential effect over pain relief. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  11. Electrophysiological and behavioral effects of frontal transcranial direct current stimulation on cognitive fatigue in multiple sclerosis.

    Science.gov (United States)

    Fiene, Marina; Rufener, Katharina S; Kuehne, Maria; Matzke, Mike; Heinze, Hans-Jochen; Zaehle, Tino

    2018-03-01

    Fatigue is one of the most common and debilitating symptoms affecting patients with multiple sclerosis (MS). Sustained cognitive effort induces cognitive fatigue, operationalized as subjective exhaustion and fatigue-related objective alertness decrements with time-on-task. During prolonged cognitive testing, MS patients show increased simple reaction times (RT) accompanied by lower amplitudes and prolonged latencies of the P300 event-related potential. Previous studies suggested a major role of structural and functional abnormalities in the frontal cortex including a frontal hypo-activation in fatigue pathogenesis. In the present study we investigated the neuromodulatory effect of transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) on objective measures of fatigue-related decrements in cognitive performance in MS patients. P300 during an auditory oddball task and simple reaction times in an alertness test were recorded at baseline, during and after stimulation. Compared to sham, anodal tDCS caused an increase in P300 amplitude that persisted after the end of stimulation and eliminated the fatigue-related increase in RT over the course of a testing session. Our findings demonstrate that anodal tDCS over the left DLPFC can counteract performance decrements associated with fatigue thereby leading to an improvement in the patient's ability to cope with sustained cognitive demands. This provides causal evidence for the functional relevance of the left DLPFC in fatigue pathophysiology. The results indicate that tDCS-induced modulations of frontal activity can be an effective therapeutic option for the treatment of fatigue-related declines in cognitive performance in MS patients.

  12. Effect of transcranial direct current stimulation on swallowing apraxia and cortical excitability in stroke patients.

    Science.gov (United States)

    Yuan, Ying; Wang, Jie; Wu, Dongyu; Huang, Xiaobo; Song, Weiqun

    2017-10-01

    Swallowing apraxia is characterized by impaired volitional swallowing but relatively preserved reflexive swallowing. Few studies are available on the effectiveness of behavioral therapy and management of the condition. This study aimed to investigate the effect of transcranial direct current stimulation (tDCS) on swallowing apraxia and cortical activation in stroke patients. The study included three inpatients (age 48-70 years; 1 male, 2 females; duration of stroke, 35-55 d) with post-stroke swallowing apraxia and six age-matched healthy subjects (age 45-65 years; 3 males, 3 females). Treatments were divided into two phases: Phase A and Phase B. During Phase A, the inpatients received three weeks of sham tDCS and conventional treatments. During Phase B, these patients received three weeks of anodal tDCS over the bilateral primary sensorimotor cortex (S 1 M 1 ) of swallowing and conventional treatments. Swallowing apraxia assessments were measured in three inpatients before Phase A, before Phase B, and after Phase B. The electroencephalography (EEG) nonlinear index of approximate entropy (ApEn) was calculated for three patients and six healthy subjects. After tDCS, scores of swallowing apraxia assessments increased, and ApEn indices increased in both stimulated and non-stimulated areas. Anodal tDCS might provide a useful means for recovering swallowing apraxia, and the recovery could be related to increased excitability of the swallowing cortex. Further investigations should explore the relationship between lesion size and/or lesion site and the prognosis of swallowing apraxia. Clinical trial registry: http://www.chictr.org Registration Number: ChiCTR-TRC-14004955.

  13. Transcranial direct current stimulation to lessen neuropathic pain after spinal cord injury: a mechanistic PET study.

    Science.gov (United States)

    Yoon, Eun Jin; Kim, Yu Kyeong; Kim, Hye-Ri; Kim, Sang Eun; Lee, Youngjo; Shin, Hyung Ik

    2014-01-01

    It is suggested that transcranial direct current stimulation (tDCS) can produce lasting changes in corticospinal excitability and can potentially be used for the treatment of neuropathic pain. However, the detailed mechanisms underlying the effects of tDCS are unknown. We investigated the underlying neural mechanisms of tDCS for chronic pain relief using [(18)F]-fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET). Sixteen patients with neuropathic pain (mean age 44.1 ± 8.6 years, 4 females) due to traumatic spinal cord injury received sham or active anodal stimulation of the motor cortex using tDCS for 10 days (20 minutes, 2 mA, twice a day). The effect of tDCS on regional cerebral glucose metabolism was evaluated by [(18)F]FDG-PET before and after tDCS sessions. There was a significant decrease in the numeric rating scale scores for pain, from 7.6 ± 0.5 at baseline to 5.9 ± 1.8 after active tDCS (P = .016). We found increased metabolism in the medulla and decreased metabolism in the left dorsolateral prefrontal cortex after active tDCS treatment compared with the changes induced by sham tDCS. Additionally, an increase in metabolism after active tDCS was observed in the subgenual anterior cingulate cortex and insula. The results of this study suggest that anodal stimulation of the motor cortex using tDCS can modulate emotional and cognitive components of pain and normalize excessive attention to pain and pain-related information.

  14. The effect of transcranial direct current stimulation on experimentally induced heat pain.

    Science.gov (United States)

    Aslaksen, Per M; Vasylenko, Olena; Fagerlund, Asbjørn J

    2014-06-01

    Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique that can affect human pain perception. Placebo effects are present in most treatments and could therefore also interact with treatment effects in tDCS. The present study investigated whether short-term tDCS reduced heat pain intensity, stress, blood pressure and increased heat pain thresholds in healthy volunteers when controlling for placebo effects. Seventy-five (37 females) participants were randomized into three groups: (1) active tDCS group receiving anodal tDCS (2 mA) for 7 min to the primary motor cortex (M1), (2) placebo group receiving the tDCS electrode montage but only active tDCS stimulation for 30 s and (3) natural history group that got no tDCS montage but the same pain stimulation as the active tDCS and the placebo group. Heat pain was induced by a PC-controlled thermode attached to the left forearm. Pain intensity was significantly lower in the active tDCS group when examining change scores (pretest-posttest) for the 47 °C condition. The placebo group displayed lower pain compared with the natural history group, displaying a significant placebo effect. In the 43 and 45 °C conditions, the effect of tDCS could not be separated from placebo effects. The results revealed no effects on pain thresholds. There was a tendency that active tDCS reduced stress and systolic blood pressure, however, not significant. In sum, tDCS had an analgesic effect on high-intensity pain, but the effect of tDCS could not be separated from placebo effects for medium and low pain.

  15. Enhanced Motor Skill Acquisition in the Non-dominant Upper Extremity using Intermittent Theta Burst Stimulation and Transcranial Direct Current Stimulation

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    Ray eButts

    2014-06-01

    Full Text Available Individuals suffering from motor impairments often require physical therapy (PT to help improve their level of function. Previous investigations suggest that both intermittent theta burst stimulation (iTBS and bihemispheric transcranial direct current stimulation may increase the speed and extent of motor learning/relearning and that this increase may be related to brain derived neurotrophic factor (BDNF. The purpose of the current study was to explore the feasibility and effectiveness of a novel, non-invasive brain stimulation approach that combined an iTBS primer, and bihemispheric stimulation coupled with motor training. We hypothesized that individuals exposed to this novel treatment would make greater functional improvements than individuals undergoing sham stimulation when tested immediately following, 24-hours, and 7-days post-training. A total of 26 right-handed, healthy young adults were randomly assigned to either a treatment (n = 15 or control group (n = 12. iTBS (20 trains of 10 pulse triplets each delivered at 80% AMT / 50Hz over 191.84 seconds and bihemispheric tDCS (1.0 ma for 20 minutes were used as a primer to, and in conjunction with, 20 minutes of motor training, respectively. Our primary outcome measure was performance on the Jebsen-Taylor Hand Function Test. Participants tolerated the combined iTBS/bihemispheric stimulation treatment without complaint. While performance gains in the sham and stimulation group were not significant immediately after training, they were nearly significant 24-hours post training (p = 0.055, and were significant at 7-days post training (p < 0.05. These results suggest that the combined iTBS/bihemispheric stimulation protocol is both feasible and effective. Future research should examine the mechanistic explanation of this approach as well as the potential of using this approach in clinical populations.

  16. Enhanced motor skill acquisition in the non-dominant upper extremity using intermittent theta burst stimulation and transcranial direct current stimulation.

    Science.gov (United States)

    Butts, Raymond J; Kolar, Melissa B; Newman-Norlund, Roger D

    2014-01-01

    Individuals suffering from motor impairments often require physical therapy (PT) to help improve their level of function. Previous investigations suggest that both intermittent theta burst stimulation (iTBS) and bihemispheric transcranial direct current stimulation (tDCS) may increase the speed and extent of motor learning/relearning. The purpose of the current study was to explore the feasibility and effectiveness of a novel, non-invasive brain stimulation approach that combined an iTBS primer, and bihemispheric stimulation coupled with motor training. We hypothesized that individuals exposed to this novel treatment would make greater functional improvements than individuals undergoing sham stimulation when tested immediately following, 24-h, and 7-days post-training. A total of 26 right-handed, healthy young adults were randomly assigned to either a treatment (n = 15) or control group (n = 12). iTBS (20 trains of 10 pulse triplets each delivered at 80% active motor threshold (AMT) / 50 Hz over 191.84 s) and bihemispheric tDCS (1.0 ma for 20 min) were used as a primer to, and in conjunction with, 20 min of motor training, respectively. Our primary outcome measure was performance on the Jebsen-Taylor Hand Function (JTHF) test. Participants tolerated the combined iTBS/bihemispheric stimulation treatment without complaint. While performance gains in the sham and stimulation group were not significant immediately after training, they were nearly significant 24-h post training (p = 0.055), and were significant at 7-days post training (p iTBS/bihemispheric stimulation protocol is both feasible and effective. Future research should examine the mechanistic explanation of this approach as well as the potential of using this approach in clinical populations.

  17. Derivatives of Dictyostelium differentiation-inducing factors inhibit lysophosphatidic acid–stimulated migration of murine osteosarcoma LM8 cells

    Energy Technology Data Exchange (ETDEWEB)

    Kubohara, Yuzuru, E-mail: ykuboha@juntendo.ac.jp [Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi 371-8512 (Japan); Department of Health Science, Juntendo University Graduate School of Health and Sports Science, Inzai 270-1695 (Japan); Komachi, Mayumi [Department of Molecular and Cellular Biology, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi 371-8512 (Japan); Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Homma, Yoshimi [Department of Biomolecular Science, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295 (Japan); Kikuchi, Haruhisa; Oshima, Yoshiteru [Laboratory of Natural Product Chemistry, Tohoku University Graduate School of Pharmaceutical Sciences, Aoba-yama, Aoba-ku, Sendai 980-8578 (Japan)

    2015-08-07

    Osteosarcoma is a common metastatic bone cancer that predominantly develops in children and adolescents. Metastatic osteosarcoma remains associated with a poor prognosis; therefore, more effective anti-metastatic drugs are needed. Differentiation-inducing factor-1 (DIF-1), −2, and −3 are novel lead anti-tumor agents that were originally isolated from the cellular slime mold Dictyostelium discoideum. Here we investigated the effects of a panel of DIF derivatives on lysophosphatidic acid (LPA)-induced migration of mouse osteosarcoma LM8 cells by using a Boyden chamber assay. Some DIF derivatives such as Br-DIF-1, DIF-3(+2), and Bu-DIF-3 (5–20 μM) dose-dependently suppressed LPA-induced cell migration with associated IC{sub 50} values of 5.5, 4.6, and 4.2 μM, respectively. On the other hand, the IC{sub 50} values of Br-DIF-1, DIF-3(+2), and Bu-DIF-3 versus cell proliferation were 18.5, 7.2, and 2.0 μM, respectively, in LM8 cells, and >20, 14.8, and 4.3 μM, respectively, in mouse 3T3-L1 fibroblasts (non-transformed). Together, our results demonstrate that Br-DIF-1 in particular may be a valuable tool for the analysis of cancer cell migration, and that DIF derivatives such as DIF-3(+2) and Bu-DIF-3 are promising lead anti-tumor agents for the development of therapies that suppress osteosarcoma cell proliferation, migration, and metastasis. - Highlights: • LPA induces cell migration (invasion) in murine osteosarcoma LM8 cells. • DIFs are novel lead anti-tumor agents found in Dictyostelium discoideum. • We examined the effects of DIF derivatives on LPA-induced LM8 cell migration in vitro. • Some of the DIF derivatives inhibited LPA-induced LM8 cell migration.

  18. Directional migration of recirculating lymphocytes through lymph nodes via random walks.

    Directory of Open Access Journals (Sweden)

    Niclas Thomas

    Full Text Available Naive T lymphocytes exhibit extensive antigen-independent recirculation between blood and lymph nodes, where they may encounter dendritic cells carrying cognate antigen. We examine how long different T cells may spend in an individual lymph node by examining data from long term cannulation of blood and efferent lymphatics of a single lymph node in the sheep. We determine empirically the distribution of transit times of migrating T cells by applying the Least Absolute Shrinkage & Selection Operator (LASSO or regularised S-LASSO to fit experimental data describing the proportion of labelled infused cells in blood and efferent lymphatics over time. The optimal inferred solution reveals a distribution with high variance and strong skew. The mode transit time is typically between 10 and 20 hours, but a significant number of cells spend more than 70 hours before exiting. We complement the empirical machine learning based approach by modelling lymphocyte passage through the lymph node insilico. On the basis of previous two photon analysis of lymphocyte movement, we optimised distributions which describe the transit times (first passage times of discrete one dimensional and continuous (Brownian three dimensional random walks with drift. The optimal fit is obtained when drift is small, i.e. the ratio of probabilities of migrating forward and backward within the node is close to one. These distributions are qualitatively similar to the inferred empirical distribution, with high variance and strong skew. In contrast, an optimised normal distribution of transit times (symmetrical around mean fitted the data poorly. The results demonstrate that the rapid recirculation of lymphocytes observed at a macro level is compatible with predominantly randomised movement within lymph nodes, and significant probabilities of long transit times. We discuss how this pattern of migration may contribute to facilitating interactions between low frequency T cells and antigen

  19. Modulation of motor performance and motor learning by transcranial direct current stimulation.

    Science.gov (United States)

    Reis, Janine; Fritsch, Brita

    2011-12-01

    Transcranial direct current stimulation (tDCS) has shown preliminary success in improving motor performance and motor learning in healthy individuals, and restitution of motor deficits in stroke patients. This brief review highlights some recent work. Within the past years, behavioural studies have confirmed and specified the timing and polarity specific effects of tDCS on motor skill learning and motor adaptation. There is strong evidence that timely co-application of (hand/arm) training and anodal tDCS to the contralateral M1 can improve motor learning. Improvements in motor function as measured by clinical scores have been described for combined tDCS and training in stroke patients. For this purpose, electrode montages have been modified with respect to interhemispheric imbalance after brain injury. Cathodal tDCS applied to the unlesioned M1 or bihemispheric M1 stimulation appears to be well tolerated and useful to induce improvements in motor function. Mechanistic studies in humans and animals are discussed with regard to physiological motor learning. tDCS is well tolerated, easy to use and capable of inducing lasting improvements in motor function. This method holds promise for the rehabilitation of motor disabilities, although acute studies in patients with brain injury are so far lacking.

  20. Effects of transcranial direct current stimulation (tDCS) on binge eating disorder.

    Science.gov (United States)

    Burgess, Emilee E; Sylvester, Maria D; Morse, Kathryn E; Amthor, Frank R; Mrug, Sylvie; Lokken, Kristine L; Osborn, Mary K; Soleymani, Taraneh; Boggiano, Mary M

    2016-10-01

    To investigate the effect of transcranial direct current stimulation (tDCS) on food craving, intake, binge eating desire, and binge eating frequency in individuals with binge eating disorder (BED). N = 30 adults with BED or subthreshold BED received a 20-min 2 milliampere (mA) session of tDCS targeting the dorsolateral prefrontal cortex (DLPFC; anode right/cathode left) and a sham session. Food image ratings assessed food craving, a laboratory eating test assessed food intake, and an electronic diary recorded binge variables. tDCS versus sham decreased craving for sweets, savory proteins, and an all-foods category, with strongest reductions in men (p tDCS also decreased total and preferred food intake by 11 and 17.5%, regardless of sex (p tDCS administration (p tDCS in BED. Stimulation of the right DLPFC suggests that enhanced cognitive control and/or decreased need for reward may be possible functional mechanisms. The results support investigation of repeated tDCS as a safe and noninvasive treatment adjunct for BED. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:930-936). © 2016 Wiley Periodicals, Inc.

  1. An image-guided transcranial direct current stimulation system: a pilot phantom study

    International Nuclear Information System (INIS)

    Jung, Young-Jin; Kim, Jung-Hoon; Kim, Daejeong; Im, Chang-Hwan

    2013-01-01

    In this study, an image-guided transcranial direct current stimulation (IG-tDCS) system that can deliver an increased stimulation current to a target brain area without the need to adjust the location of an active electrode was implemented. This IG-tDCS system was based on the array-type tDCS concept, which was validated through computer simulations in a previous study. Unlike a previous study, the present IG-tDCS system adopts a single reference electrode and an active electrode array consisting of 16 (4 × 4) sub-electrodes. The proposed IG-tDCS system is capable of shaping current flow inside the human head by controlling the input currents of the arrayed electrodes. Once a target brain area has been selected, the optimal injection current of each arrayed sub-electrode is evaluated automatically using a genetic algorithm in order to deliver the maximum available current to the target area. The operation of our pilot system was confirmed through a simple phantom experiment. (paper)

  2. Semantic Feature Training in Combination with Transcranial Direct Current Stimulation (tDCS for Progressive Anomia

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    Jinyi Hung

    2017-05-01

    Full Text Available We examined the effectiveness of a 2-week regimen of a semantic feature training in combination with transcranial direct current stimulation (tDCS for progressive naming impairment associated with primary progressive aphasia (N = 4 or early onset Alzheimer’s Disease (N = 1. Patients received a 2-week regimen (10 sessions of anodal tDCS delivered over the left temporoparietal cortex while completing a language therapy that consisted of repeated naming and semantic feature generation. Therapy targets consisted of familiar people, household items, clothes, foods, places, hygiene implements, and activities. Untrained items from each semantic category provided item level controls. We analyzed naming accuracies at multiple timepoints (i.e., pre-, post-, 6-month follow-up via a mixed effects logistic regression and individual differences in treatment responsiveness using a series of non-parametric McNemar tests. Patients showed advantages for naming trained over untrained items. These gains were evident immediately post tDCS. Trained items also showed a shallower rate of decline over 6-months relative to untrained items that showed continued progressive decline. Patients tolerated stimulation well, and sustained improvements in naming accuracy suggest that the current intervention approach is viable. Future implementation of a sham control condition will be crucial toward ascertaining whether neurostimulation and behavioral treatment act synergistically or alternatively whether treatment gains are exclusively attributable to either tDCS or the behavioral intervention.

  3. Task-specific effect of transcranial direct current stimulation on motor learning

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    Cinthia Maria Saucedo Marquez

    2013-07-01

    Full Text Available Transcranial direct current stimulation (tDCS is a relatively new non-invasive brain stimulation technique that modulates neural processes. When applied to the human primary motor cortex (M1, tDCS has beneficial effects on motor skill learning and consolidation in healthy controls and in patients. However, it remains unclear whether tDCS improves motor learning in a general manner or whether these effects depend on which motor task is acquired. Here we compare whether the effect of tDCS differs when the same individual acquires (1 a Sequential Finger Tapping Task (SEQTAP and (2 a Visual Isometric Pinch Force Task (FORCE. Both tasks have been shown to be sensitive to tDCS applied over M1, however, the underlying processes mediating learning and memory formation might benefit differently from anodal-tDCS. Thirty healthy subjects were randomly assigned to an anodal-tDCS group or sham-group. Using a double-blind, sham-controlled cross-over design, tDCS was applied over M1 while subjects acquired each of the motor tasks over 3 consecutive days, with the order being randomized across subjects. We found that anodal-tDCS affected each task differently: The SEQTAP task benefited from anodal-tDCS during learning, whereas the FORCE task showed improvements only at retention. These findings suggest that anodal tDCS applied over M1 appears to have a task-dependent effect on learning and memory formation.

  4. No Effect of Cathodal Transcranial Direct Current Stimulation on Fear Memory in Healthy Human Subjects

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    Aditya Mungee

    2016-11-01

    Full Text Available Background: Studies have demonstrated that fear memories can be modified using non-invasive methods. Recently, we demonstrated that anodal transcranial direct current stimulation (tDCS of the right dorsolateral prefrontal cortex is capable of enhancing fear memories. Here, we examined the effects of cathodal tDCS of the right dorsolateral prefrontal cortex during fear reconsolidation in humans. Methods: Seventeen young, healthy subjects were randomly assigned to two groups, which underwent fear conditioning with mild electric stimuli paired with a visual stimulus. Twenty-four hours later, both groups were shown a reminder of the conditioned fearful stimulus. Shortly thereafter, they received either tDCS (right prefrontal—cathodal, left supraorbital—anodal for 20 min at 1 mA, or sham stimulation. A day later, fear responses of both groups were compared. Results: On Day 3, during fear response assessment, there were no significant differences between the tDCS and sham group (p > 0.05. Conclusion: We conclude that cathodal tDCS of the right dorsolateral prefrontal cortex (right prefrontal—cathodal, left supraorbital—anodal did not influence fear memories.

  5. Cerebellar direct current stimulation enhances on-line motor skill acquisition through an effect on accuracy.

    Science.gov (United States)

    Cantarero, Gabriela; Spampinato, Danny; Reis, Janine; Ajagbe, Loni; Thompson, Tziporah; Kulkarni, Kopal; Celnik, Pablo

    2015-02-18

    The cerebellum is involved in the update of motor commands during error-dependent learning. Transcranial direct current stimulation (tDCS), a form of noninvasive brain stimulation, has been shown to increase cerebellar excitability and improve learning in motor adaptation tasks. Although cerebellar involvement has been clearly demonstrated in adaptation paradigms, a type of task that heavily relies on error-dependent motor learning mechanisms, its role during motor skill learning, a behavior that likely involves error-dependent as well as reinforcement and strategic mechanisms, is not completely understood. Here, in humans, we delivered cerebellar tDCS to modulate its activity during novel motor skill training over the course of 3 d and assessed gains during training (on-line effects), between days (off-line effects), and overall improvement. We found that excitatory anodal tDCS applied over the cerebellum increased skill learning relative to sham and cathodal tDCS specifically by increasing on-line rather than off-line learning. Moreover, the larger skill improvement in the anodal group was predominantly mediated by reductions in error rate rather than changes in movement time. These results have important implications for using cerebellar tDCS as an intervention to speed up motor skill acquisition and to improve motor skill accuracy, as well as to further our understanding of cerebellar function. Copyright © 2015 the authors 0270-6474/15/353285-06$15.00/0.

  6. Noninvasive transcranial direct current stimulation (tDCS) for the treatment of orofacial pain.

    Science.gov (United States)

    Fricova, Jitka; Englerova, Katerina; Rokyta, Richard

    2016-10-01

    tDCS is a promising method for the treatment of chronic pain. Electrode placement locations must be chosen in accordance with the density and the time course of the current in order to prevent pathological changes in the underlying tissue. In order to reduce current spatial variability, more electrodes of the same polarity are placed in a circle around the second electrode of the opposite polarity. The applied current produced the greatest changes directly beneath the electrodes: the cathode reduces the excitability of cortical neurons, while the anode has the opposite effect. Based on inclusion criteria, 10 patients with chronic orofacial pain, secondary trigeminal neuralgia after oral surgery, were enrolled and underwent both anode and cathode stimulation. Before the first session we measured pain intensity on a numeric pain rating scale and tactile and thermal stimulation were used to assess somatosensory status. tDCS was applied for five consecutive days. At the end of tDCS application, somatosensory status was assessed again. From our results we can conclude that the application of tDCS improves the perception of some types of pain. When we increase our sample size, we would expect confirmation not only on our positive results, but also some additional findings for explaining the pathophysiology of orofacial pain. These pathophysiological findings and explanations are very important for the application of tDCS in the treatment of orofacial pain and also for other types of neuropathic pain.

  7. Transcranial Direct Current Stimulation in Tinnitus Patients: A Systemic Review and Meta-Analysis

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    Jae-Jin Song

    2012-01-01

    Full Text Available Although transcranial direct current stimulation (tDCS has already been used to manage tinnitus patients, paucity of reports and variations in protocols preclude a comprehensive understanding. Hence, we conducted a meta-analysis based on systemic review to assess effectiveness of tDCS in tinnitus management and to compare stimulation parameters. PubMed was searched for tDCS studies in tinnitus. For randomized controlled trials (RCTs, a meta-analysis was performed. A total of 17 studies were identified and 6 of them were included in the systemic review and 2 RCTs were included in the meta-analysis. Overall 39.5% responded to active tDCS with a mean tinnitus intensity reduction of 13.5%. Additionally, left temporal area (LTA and bifrontal tDCS indicated comparable results. Active tDCS was found to be more effective than sham tDCS for tinnitus intensity reduction (Hedges' g=.77, 95% confidence interval 0.23–1.31. The efficacy of tDCS in tinnitus could not be fully confirmed by the current study because of the limited number of studies, but all studies included in the current systemic review and meta-analysis demonstrated significant tinnitus intensity improvement. Therefore, tDCS may be a promising tool for tinnitus management. Future RCTs in a large series regarding the efficacy as well as the comparison between LTA- and bifrontal tDCS are recommended.

  8. Angiotensin II type 2 receptor stimulation increases the rate of NG108-15 cell migration via actin depolymerization.

    Science.gov (United States)

    Kilian, Peter; Campbell, Shirley; Bilodeau, Lyne; Guimond, Marie-Odile; Roberge, Claude; Gallo-Payet, Nicole; Payet, Marcel Daniel

    2008-06-01

    Angiotensin II (Ang II) has been reported to induce migration in neuronal cell types. Using time-lapse microscopy, we show here that Ang II induces acceleration in NG108-15 cell migration. This effect was antagonized by PD123319, a selective AT2 receptor antagonist, but not by DUP753, a selective AT1 receptor antagonist, and was mimicked by the specific AT2 receptor agonist CGP42112. This Ang II-induced acceleration was not sensitive to the inhibition of previously described signaling pathways of the AT2 receptor, guanylyl cyclase/cyclic GMP or p42/p44 mapk cascades, but was abolished by pertussis toxin treatment and involved PP2A activation. Immunofluorescence studies indicate that Ang II or CGP42112 decreased the amount of filamentous actin at the leading edge of the cells. This decrease was accompanied by a concomitant increase in globular actin levels. Regulation of actin turnover in actin-based motile systems is known to be mainly under the control of the actin depolymerizing factor and cofilin. Basal migration speed decreased by 77.2% in cofilin-1 small interfering RNA-transfected NG108-15 cells, along with suppression of the effect of Ang II. In addition, the Ang II-induced increase in cell velocity was abrogated in serum-free medium as well as by genistein or okadaic acid treatment in a serum-containing medium. Such results indicate that the AT2 receptor increases the migration speed of NG108-15 cells and involves a tyrosine kinase activity, followed by phosphatase activation, which may be of the PP2A type. Therefore, the present study identifies actin depolymerization and cofilin as new targets of AT2 receptor action, in the context of cellular migration.

  9. In-chip fabrication of free-form 3D constructs for directed cell migration analysis

    DEFF Research Database (Denmark)

    Olsen, Mark Holm; Hjortø, Gertrud Malene; Hansen, Morten

    2013-01-01

    with a range of pore sizes from 5 × 5 μm to 15 × 15 μm and prefilled with fibrillar collagen. Dendritic cells seeded into the polymer chip in a concentration gradient of the chemoattractant CCL21 efficiently negotiated the microporous maze structure for pore sizes of 8 × 8 μm or larger. The cells migrating...... through smaller pore sizes made significantly more turns than those through larger pores. The introduction of additional defined barriers in the microporous structure resulted in dendritic cells making more turns while still being able to follow the chemoattractant concentration gradient....

  10. Direct Observation of Halide Migration and its Effect on the Photoluminescence of Methylammonium Lead Bromide Perovskite Single Crystals.

    Science.gov (United States)

    Luo, Yanqi; Khoram, Parisa; Brittman, Sarah; Zhu, Zhuoying; Lai, Barry; Ong, Shyue Ping; Garnett, Erik C; Fenning, David P

    2017-11-01

    Optoelectronic devices based on hybrid perovskites have demonstrated outstanding performance within a few years of intense study. However, commercialization of these devices requires barriers to their development to be overcome, such as their chemical instability under operating conditions. To investigate this instability and its consequences, the electric field applied to single crystals of methylammonium lead bromide (CH 3 NH 3 PbBr 3 ) is varied, and changes are mapped in both their elemental composition and photoluminescence. Synchrotron-based nanoprobe X-ray fluorescence (nano-XRF) with 250 nm resolution reveals quasi-reversible field-assisted halide migration, with corresponding changes in photoluminescence. It is observed that higher local bromide concentration is correlated to superior optoelectronic performance in CH 3 NH 3 PbBr 3 . A lower limit on the electromigration rate is calculated from these experiments and the motion is interpreted as vacancy-mediated migration based on nudged elastic band density functional theory (DFT) simulations. The XRF mapping data provide direct evidence of field-assisted ionic migration in a model hybrid-perovskite thin single crystal, while the link with photoluminescence proves that the halide stoichiometry plays a key role in the optoelectronic properties of the perovskite. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Transcranial Direct Current Stimulation combined with treadmill training in the subacute phase following stroke: case series

    DEFF Research Database (Denmark)

    Figlewski, Krystian; Nielsen, Jørgen Feldbæk; Blicher, Jakob

    such as transcranial Direct Current Stimulation (tDCS). In neurophysiologic studies an imbalance of interhemispheric interactions has been demonstrated which is believed to interfere with the recovery process. This imbalance can be ameliorated by upregulation of the excitability in the lesioned hemisphere applying...... anodal tDCS. Aims: to evaluate the feasibility of anodal tDCS with body weight support treadmill training (BWSTT) in the subacute stroke patients. Methods Four subjects (Table 1.) participated in BWSTT coupled with anodal tDCS thrice per week for 4 weeks. Subjects were included within 14 days from stroke...... onset. Anodal tDCS was delivered to excite the cortical leg motor area using 35 cm2 saline soaked electrodes. During BWSTT a 2 mA current was applied for 20 minutes. Evaluations conducted at baseline and after the intervention included 10-meters walking test (10 MWT), isokinetic muscle strength of knee...

  12. Enhancing transcranial direct current stimulation via motor imagery and kinesthetic illusion: crossing internal and external tools.

    Science.gov (United States)

    Bodranghien, Florian; Manto, Mario; Lebon, Florent

    2016-06-01

    Transcranial direct current stimulation is a safe technique which is now part of the therapeutic armamentarium for the neuromodulation of motor functions and cognitive operations. It is currently considered that tDCS is an intervention that might promote functional recovery after a lesion in the central nervous system, thus reducing long-term disability and associated socio-economic burden. A recent study shows that kinesthetic illusion and motor imagery prolong the effects of tDCS on corticospinal excitability, overcoming one of the limitations of this intervention. Because changes in excitability anticipate changes in structural plasticity in the CNS, this interesting multi-modal approach might very soon find applications in neurorehabilitation.

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

    Science.gov (United States)

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

    2012-12-06

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

  14. Individual differences in learning correlate with modulation of brain activity induced by transcranial direct current stimulation

    Science.gov (United States)

    Falcone, Brian; Wada, Atsushi; Parasuraman, Raja

    2018-01-01

    Transcranial direct current stimulation (tDCS) has been shown to enhance cognitive performance on a variety of tasks. It is hypothesized that tDCS enhances performance by affecting task related cortical excitability changes in networks underlying or connected to the site of stimulation facilitating long term potentiation. However, many recent studies have called into question the reliability and efficacy of tDCS to induce modulatory changes in brain activity. In this study, our goal is to investigate the individual differences in tDCS induced modulatory effects on brain activity related to the degree of enhancement in performance, providing insight into this lack of reliability. In accomplishing this goal, we used functional magnetic resonance imaging (fMRI) concurrently with tDCS stimulation (1 mA, 30 minutes duration) using a visual search task simulating real world conditions. The experiment consisted of three fMRI sessions: pre-training (no performance feedback), training (performance feedback which included response accuracy and target location and either real tDCS or sham stimulation given), and post-training (no performance feedback). The right posterior parietal cortex was selected as the site of anodal tDCS based on its known role in visual search and spatial attention processing. Our results identified a region in the right precentral gyrus, known to be involved with visual spatial attention and orienting, that showed tDCS induced task related changes in cortical excitability that were associated with individual differences in improved performance. This same region showed greater activity during the training session for target feedback of incorrect (target-error feedback) over correct trials for the tDCS stim over sham group indicating greater attention to target features during training feedback when trials were incorrect. These results give important insight into the nature of neural excitability induced by tDCS as it relates to variability in

  15. TGF-β1 stimulates migration of type II endometrial cancer cells by down-regulating PTEN via activation of SMAD and ERK1/2 signaling pathways.

    Science.gov (United States)

    Xiong, Siyuan; Cheng, Jung-Chien; Klausen, Christian; Zhao, Jianfang; Leung, Peter C K

    2016-09-20

    PTEN acts as a tumor suppressor primarily by antagonizing the PI3K/AKT signaling pathway. PTEN is frequently mutated in human cancers; however, in type II endometrial cancers its mutation rate is very low. Overexpression of TGF-β1 and its receptors has been reported to correlate with metastasis of human cancers and reduced survival rates. Although TGF-β1 has been shown to regulate PTEN expression through various mechanisms, it is not yet known if the same is true in type II endometrial cancer. In the present study, we show that treatment with TGF-β1 stimulates the migration of two type II endometrial cancer cell lines, KLE and HEC-50. In addition, TGF-β1 treatment down-regulates both mRNA and protein levels of PTEN. Overexpression of PTEN or inhibition of PI3K abolishes TGF-β1-stimulated cell migration. TGF-β1 induces SMAD2/3 phosphorylation and knockdown of common SMAD4 inhibits the suppressive effects of TGF-β1 on PTEN mRNA and protein. Interestingly, TGF-β1 induces ERK1/2 phosphorylation and pre-treatment with a MEK inhibitor attenuates the suppression of PTEN protein, but not mRNA, by TGF-β1. This study provides important insights into the molecular mechanisms mediating TGF-β1-induced down-regulation of PTEN and demonstrates an important role of PTEN in the regulation of type II endometrial cancer cell migration.

  16. Mild cognitive impairment in Parkinson's disease is improved by transcranial direct current stimulation combined with physical therapy.

    Science.gov (United States)

    Manenti, Rosa; Brambilla, Michela; Benussi, Alberto; Rosini, Sandra; Cobelli, Chiara; Ferrari, Clarissa; Petesi, Michela; Orizio, Italo; Padovani, Alessandro; Borroni, Barbara; Cotelli, Maria

    2016-05-01

    Parkinson's disease (PD) is characterized by both motor and cognitive deficits. In PD, physical exercise has been found to improve physical functioning. Recent studies demonstrated that repeated sessions of transcranial direct current stimulation led to an increased performance in cognitive and motor tasks in patients with PD. The present study investigated the effects of anodal transcranial direct current stimulation applied over the dorsolateral prefrontal cortex and combined with physical therapy in PD patients. A total of 20 patients with PD were assigned to 1 of 2 study groups: group 1, anodal transcranial direct current stimulation plus physical therapy (n = 10) or group 2, placebo transcranial direct current stimulation plus physical therapy (n = 10). The 2 weeks of treatment consisted of daily direct current stimulation application for 25 minutes during physical therapy. Long-term effects of treatment were evaluated on clinical, neuropsychological, and motor task performance at 3-month follow-up. An improvement in motor abilities and a reduction of depressive symptoms were observed in both groups after the end of treatment and at 3-month follow-up. The Parkinson's Disease Cognitive Rating Scale and verbal fluency test performances increased only in the anodal direct current stimulation group with a stable effect at follow-up. The application of anodal transcranial direct current stimulation may be a relevant tool to improve cognitive abilities in PD and might be a novel therapeutic strategy for PD patients with mild cognitive impairment. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  17. High density lipoprotein stimulated migration of macrophages depends on the scavenger receptor class B, type I, PDZK1 and Akt1 and is blocked by sphingosine 1 phosphate receptor antagonists.

    Directory of Open Access Journals (Sweden)

    Aishah Al-Jarallah

    Full Text Available HDL carries biologically active lipids such as sphingosine-1-phosphate (S1P and stimulates a variety of cell signaling pathways in diverse cell types, which may contribute to its ability to protect against atherosclerosis. HDL and sphingosine-1-phosphate receptor agonists, FTY720 and SEW2871 triggered macrophage migration. HDL-, but not FTY720-stimulated migration was inhibited by an antibody against the HDL receptor, SR-BI, and an inhibitor of SR-BI mediated lipid transfer. HDL and FTY720-stimulated migration was also inhibited in macrophages lacking either SR-BI or PDZK1, an adaptor protein that binds to SR-BI's C-terminal cytoplasmic tail. Migration in response to HDL and S1P receptor agonists was inhibited by treatment of macrophages with sphingosine-1-phosphate receptor type 1 (S1PR1 antagonists and by pertussis toxin. S1PR1 activates signaling pathways including PI3K-Akt, PKC, p38 MAPK, ERK1/2 and Rho kinases. Using selective inhibitors or macrophages from gene targeted mice, we demonstrated the involvement of each of these pathways in HDL-dependent macrophage migration. These data suggest that HDL stimulates the migration of macrophages in a manner that requires the activities of the HDL receptor SR-BI as well as S1PR1 activity.

  18. Directional Migration in Esophageal Squamous Cell Carcinoma (ESCC) is Epigenetically Regulated by SET Nuclear Oncogene, a Member of the Inhibitor of Histone Acetyltransferase Complex

    OpenAIRE

    Xiang Yuan; Xinshuai Wang; Bianli Gu; Yingjian Ma; Yiwen Liu; Man Sun; Jinyu Kong; Wei Sun; Huizhi Wang; Fuyou Zhou; Shegan Gao

    2017-01-01

    Directional cell migration is of fundamental importance to a variety of biological events, including metastasis of malignant cells. Herein, we specifically investigated SET oncoprotein, a subunit of the recently identified inhibitor of acetyltransferases (INHAT) complex and identified its role in the establishment of front–rear cell polarity and directional migration in Esophageal Squamous Cell Carcinoma (ESCC). We further define the molecular circuits that govern these processes by showing t...

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

    Science.gov (United States)

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

    2014-01-01

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

  20. Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton.

    Directory of Open Access Journals (Sweden)

    Cheng Cui

    2013-11-01

    Full Text Available Planar cell polarity (PCP regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin

  1. The Effects of Compensatory Auditory Stimulation and High-Definition Transcranial Direct Current Stimulation (HD-tDCS) on Tinnitus Perception - A Randomized Pilot Study.

    Science.gov (United States)

    Henin, Simon; Fein, Dovid; Smouha, Eric; Parra, Lucas C

    2016-01-01

    Tinnitus correlates with elevated hearing thresholds and reduced cochlear compression. We hypothesized that reduced peripheral input leads to elevated neuronal gain resulting in the perception of a phantom sound. The purpose of this pilot study was to test whether compensating for this peripheral deficit could reduce the tinnitus percept acutely using customized auditory stimulation. To further enhance the effects of auditory stimulation, this intervention was paired with high-definition transcranial direct current stimulation (HD-tDCS). A randomized sham-controlled, single blind study was conducted in a clinical setting on adult participants with chronic tinnitus (n = 14). Compensatory auditory stimulation (CAS) and HD-tDCS were administered either individually or in combination in order to access the effects of both interventions on tinnitus perception. CAS consisted of sound exposure typical to daily living (20-minute sound-track of a TV show), which was adapted with compressive gain to compensate for deficits in each subject's individual audiograms. Minimum masking levels and the visual analog scale were used to assess the strength of the tinnitus percept immediately before and after the treatment intervention. CAS reduced minimum masking levels, and visual analog scale trended towards improvement. Effects of HD-tDCS could not be resolved with the current sample size. The results of this pilot study suggest that providing tailored auditory stimulation with frequency-specific gain and compression may alleviate tinnitus in a clinical population. Further experimentation with longer interventions is warranted in order to optimize effect sizes.

  2. Repetitive transcranial magnetic stimulation and transcranial direct-current stimulation in neuropathic pain due to radiculopathy: a randomized sham-controlled comparative study.

    Science.gov (United States)

    Attal, Nadine; Ayache, Samar S; Ciampi De Andrade, Daniel; Mhalla, Alaa; Baudic, Sophie; Jazat, Frédérique; Ahdab, Rechdi; Neves, Danusa O; Sorel, Marc; Lefaucheur, Jean-Pascal; Bouhassira, Didier

    2016-06-01

    No study has directly compared the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in neuropathic pain (NP). In this 2-centre randomised double-blind sham-controlled study, we compared the efficacy of 10-Hz rTMS and anodal 2-mA tDCS of the motor cortex and sham stimulation contralateral to the painful area (3 daily sessions) in patients with NP due to lumbosacral radiculopathy. Average pain intensity (primary outcome) was evaluated after each session and 5 days later. Secondary outcomes included neuropathic symptoms and thermal pain thresholds for the upper limbs. We used an innovative design that minimised bias by randomly assigning patients to 1 of 2 groups: active rTMS and tDCS or sham rTMS and tDCS. For each treatment group (active or sham), the order of the sessions was again randomised according to a crossover design. In total, 51 patients were screened and 35 (51% women) were randomized. Active rTMS was superior to tDCS and sham in pain intensity (F = 2.89 and P = 0.023). Transcranial direct-current stimulation was not superior to sham, but its analgesic effects were correlated to that of rTMS (P = 0.046), suggesting common mechanisms of action. Repetitive transcranial magnetic stimulation lowered cold pain thresholds (P = 0.04) and its effect on cold pain was correlated with its analgesic efficacy (P = 0.006). However, rTMS had no impact on individual neuropathic symptoms. Thus, rTMS is more effective than tDCS and sham in patients with NP due to lumbosacral radiculopathy and may modulate the sensory and affective dimensions of pain.

  3. Aligned fibers direct collective cell migration to engineer closing and nonclosing wound gaps.

    Science.gov (United States)

    Sharma, Puja; Ng, Colin; Jana, Aniket; Padhi, Abinash; Szymanski, Paige; Lee, Jerry S H; Behkam, Bahareh; Nain, Amrinder S

    2017-09-15

    Cell emergence onto damaged or organized fibrous extracellular matrix (ECM) is a crucial precursor to collective cell migration in wound closure and cancer metastasis, respectively. However, there is a fundamental gap in our quantitative understanding of the role of local ECM size and arrangement in cell emergence-based migration and local gap closure. Here, using ECM-mimicking nanofibers bridging cell monolayers, we describe a method to recapitulate and quantitatively describe these in vivo behaviors over multispatial (single cell to cell sheets) and temporal (minutes to weeks) scales. On fiber arrays with large interfiber spacing, cells emerge (invade) either singularly by breaking cell-cell junctions analogous to release of a stretched rubber band (recoil), or in groups of few cells (chains), whereas on closely spaced fibers, multiple chains emerge collectively. Advancing cells on fibers form cell streams, which support suspended cell sheets (SCS) of various sizes and curvatures. SCS converge to form local gaps that close based on both the gap size and shape. We document that cell stream spacing of 375 µm and larger hinders SCS advancement, thus providing abilities to engineer closing and nonclosing gaps. Altogether we highlight the importance of studying cell-fiber interactions and matrix structural remodeling in fundamental and translational cell biology. © 2017 Sharma et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  4. Transcranial Direct Current Stimulation in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD): A Pilot Study.

    Science.gov (United States)

    Bandeira, Igor Dórea; Guimarães, Rachel Silvany Quadros; Jagersbacher, João Gabriel; Barretto, Thiago Lima; de Jesus-Silva, Jéssica Regina; Santos, Samantha Nunes; Argollo, Nayara; Lucena, Rita

    2016-06-01

    Studies investigating the possible benefits of transcranial direct current stimulation on left dorsolateral prefrontal cortex in children and adolescents with attention-deficit hyperactivity disorder (ADHD) have not been performed. This study assesses the effect of transcranial direct current stimulation in children and adolescents with ADHD on neuropsychological tests of visual attention, visual and verbal working memory, and inhibitory control. An auto-matched clinical trial was performed involving transcranial direct current stimulation in children and adolescents with ADHD, using SNAP-IV and subtests Vocabulary and Cubes of the Wechsler Intelligence Scale for Children III (WISC-III). Subjects were assessed before and after transcranial direct current stimulation sessions with the Digit Span subtest of the WISC-III, inhibitory control subtest of the NEPSY-II, Corsi cubes, and the Visual Attention Test (TAVIS-3). There were 9 individuals with ADHD according to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria. There was statistically significant difference in some aspects of TAVIS-3 tests and the inhibitory control subtest of NEPSY-II. Transcranial direct current stimulation can be related to a more efficient processing speed, improved detection of stimuli, and improved ability to switch between an ongoing activity and a new one. © The Author(s) 2016.

  5. RhoA is dispensable for skin development, but crucial for contraction and directed migration of keratinocytes

    DEFF Research Database (Denmark)

    Jackson, Ben; Peyrollier, Karine; Pedersen, Esben

    2011-01-01

    RhoA is a small guanosine-5'-triphosphatase (GTPase) suggested to be essential for cytokinesis, stress fiber formation, and epithelial cell-cell contacts. In skin, loss of RhoA was suggested to underlie pemphigus skin blistering. To analyze RhoA function in vivo, we generated mice with a keratino......RhoA is a small guanosine-5'-triphosphatase (GTPase) suggested to be essential for cytokinesis, stress fiber formation, and epithelial cell-cell contacts. In skin, loss of RhoA was suggested to underlie pemphigus skin blistering. To analyze RhoA function in vivo, we generated mice......-cell contacts. Furthermore we observed increased cell spreading due to impaired RhoA-ROCK (Rho-associated protein kinase)-MLC phosphatase-MLC-mediated cell contraction, independent of Rac1. Rho-inhibiting toxins further increased multinucleation of RhoA-null cells but had no significant effect on spreading......, suggesting that RhoB and RhoC have partially overlapping functions with RhoA. Loss of RhoA decreased directed cell migration in vitro caused by reduced migration speed and directional persistence. These defects were not related to the decreased cell contraction and were independent of ROCK, as ROCK...

  6. Impact of uncertain head tissue conductivity in the optimization of transcranial direct current stimulation for an auditory target

    Science.gov (United States)

    Schmidt, Christian; Wagner, Sven; Burger, Martin; van Rienen, Ursula; Wolters, Carsten H.

    2015-08-01

    Objective. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique to modify neural excitability. Using multi-array tDCS, we investigate the influence of inter-individually varying head tissue conductivity profiles on optimal electrode configurations for an auditory cortex stimulation. Approach. In order to quantify the uncertainty of the optimal electrode configurations, multi-variate generalized polynomial chaos expansions of the model solutions are used based on uncertain conductivity profiles of the compartments skin, skull, gray matter, and white matter. Stochastic measures, probability density functions, and sensitivity of the quantities of interest are investigated for each electrode and the current density at the target with the resulting stimulation protocols visualized on the head surface. Main results. We demonstrate that the optimized stimulation protocols are only comprised of a few active electrodes, with tolerable deviations in the stimulation amplitude of the anode. However, large deviations in the order of the uncertainty in the conductivity profiles could be noted in the stimulation protocol of the compensating cathodes. Regarding these main stimulation electrodes, the stimulation protocol was most sensitive to uncertainty in skull conductivity. Finally, the probability that the current density amplitude in the auditory cortex target region is supra-threshold was below 50%. Significance. The results suggest that an uncertain conductivity profile in computational models of tDCS can have a substantial influence on the prediction of optimal stimulation protocols for stimulation of the auditory cortex. The investigations carried out in this study present a possibility to predict the probability of providing a therapeutic effect with an optimized electrode system for future auditory clinical and experimental procedures of tDCS applications.

  7. What is the optimal anodal electrode position for inducing corticomotor excitability changes in transcranial direct current stimulation?

    Science.gov (United States)

    Lee, Minji; Kim, Yun-Hee; Im, Chang-Hwan; Kim, Jung-Hoon; Park, Chang-hyun; Chang, Won Hyuk; Lee, Ahee

    2015-01-01

    Transcranial direct current stimulation (tDCS) non-invasively modulates brain function by inducing neuronal excitability. The conventional hot spot for inducing the highest current density in the hand motor area may not be the optimal site for effective stimulation. In this study, we investigated the influence of the center position of the anodal electrode on changes in motor cortical excitability. We considered three tDCS conditions in 16 healthy subjects: (i) real stimulation with the anodal electrode located at the conventional hand motor hot spot determined by motor evoked potentials (MEPs); (ii) real stimulation with the anodal electrode located at the point with the highest current density in the hand motor area as determined by electric current simulation; and (iii) sham stimulation. Motor cortical excitability as measured by MEP amplitude increased after both real stimulation conditions, but not after sham stimulation. Stimulation using the simulation-derived anodal electrode position, which was found to be posterior to the MEP hot spot for all subjects, induced higher motor cortical excitability. Individual positioning of the anodal electrode, based on the consideration of anatomical differences between subjects, appears to be important for maximizing the effects of tDCS. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. Clinical predictors of acute response to transcranial direct current stimulation (tDCS) in major depression.

    Science.gov (United States)

    D'Urso, Giordano; Dell'Osso, Bernardo; Rossi, Rodolfo; Brunoni, Andre Russowsky; Bortolomasi, Marco; Ferrucci, Roberta; Priori, Alberto; de Bartolomeis, Andrea; Altamura, Alfredo Carlo

    2017-09-01

    Transcranial direct current stimulation (tDCS) is a promising neuromodulation intervention for poor-responding or refractory depressed patients. However, little is known about predictors of response to this therapy. The present study aimed to analyze clinical predictors of response to tDCS in depressed patients. Clinical data from 3 independent tDCS trials on 171 depressed patients (including unipolar and bipolar depression), were pooled and analyzed to assess predictors of response. Depression severity and the underlying clinical dimensions were measured using the Hamilton Depression Rating Scale (HDRS) at baseline and after the tDCS treatment. Age, gender and diagnosis (bipolar/unipolar depression) were also investigated as predictors of response. Linear mixed models were fitted in order to ascertain which HDRS factors were associated with response to tDCS. Age, gender and diagnosis did not show any association with response to treatment. The reduction in HDRS scores after tDCS was strongly associated with the baseline values of "Cognitive Disturbances" and "Retardation" factors, whilst the "Anxiety/Somatization" factor showed a mild association with the response. Open-label design, the lack of control group, and minor differences in stimulation protocols. No differences in response to tDCS were found between unipolar and bipolar patients, suggesting that tDCS is effective for both conditions. "Cognitive disturbance", "Retardation", and "Anxiety/Somatization", were identified as potential clinical predictors of response to tDCS. These findings point to the pre-selection of the potential responders to tDCS, therefore optimizing the clinical use of this technique and the overall cost-effectiveness of the psychiatric intervention for depressed patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Response variability of different anodal transcranial direct current stimulation intensities across multiple sessions.

    Science.gov (United States)

    Ammann, Claudia; Lindquist, Martin A; Celnik, Pablo A

    It is well known that transcranial direct current stimulation (tDCS) is capable of modulating corticomotor excitability. However, a source of growing concern has been the observed inter- and intra-individual variability of tDCS-responses. Recent studies have assessed whether individuals respond in a predictable manner across repeated sessions of anodal tDCS (atDCS). The findings of these investigations have been inconsistent, and their methods have some limitations (i.e. lack of sham condition or testing only one tDCS intensity). To study inter- and intra-individual variability of atDCS effects at two different intensities on primary motor cortex (M1) excitability. Twelve subjects participated in a crossover study testing 7-min atDCS over M1 in three separate conditions (2 mA, 1 mA, sham) each repeated three times separated by 48 h. Motor evoked potentials were recorded before and after stimulation (up to 30min). Time of testing was maintained consistent within participants. To estimate the reliability of tDCS effects across sessions, we calculated the Intra-class Correlation Coefficient (ICC). AtDCS at 2 mA, but not 1 mA, significantly increased cortical excitability at the group level in all sessions. The overall ICC revealed fair to high reliability of tDCS effects for multiple sessions. Given that the distribution of responses showed important variability in the sham condition, we established a Sham Variability-Based Threshold to classify responses and to track individual changes across sessions. Using this threshold an intra-individual consistent response pattern was then observed only for the 2 mA condition. 2 mA anodal tDCS results in consistent intra- and inter-individual increases of M1 excitability. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Polarity-Specific Transcranial Direct Current Stimulation Disrupts Auditory Pitch Learning

    Directory of Open Access Journals (Sweden)

    Reiko eMatsushita

    2015-05-01

    Full Text Available Transcranial direct current stimulation (tDCS is attracting increasing interest because of its potential for therapeutic use. While its effects have been investigated mainly with motor and visual tasks, less is known in the auditory domain. Past tDCS studies with auditory tasks demonstrated various behavioural outcomes, possibly due to differences in stimulation parameters or task measurements used in each study. Further research using well-validated tasks are therefore required for clarification of behavioural effects of tDCS on the auditory system. Here, we took advantage of findings from a prior functional magnetic resonance imaging study, which demonstrated that the right auditory cortex is modulated during fine-grained pitch learning of microtonal melodic patterns. Targeting the right auditory cortex with tDCS using this same task thus allowed us to test the hypothesis that this region is causally involved in pitch learning. Participants in the current study were trained for three days while we measured pitch discrimination thresholds using microtonal melodies on each day using a psychophysical staircase procedure. We administered anodal, cathodal, or sham tDCS to three groups of participants over the right auditory cortex on the second day of training during performance of the task. Both the sham and the cathodal groups showed the expected significant learning effect (decreased pitch threshold over the three days of training; in contrast we observed a blocking effect of anodal tDCS on auditory pitch learning, such that this group showed no significant change in thresholds over the three days. The results support a causal role for the right auditory cortex in pitch discrimination learning.

  11. Chronic Enhancement of Serotonin Facilitates Excitatory Transcranial Direct Current Stimulation-Induced Neuroplasticity.

    Science.gov (United States)

    Kuo, Hsiao-I; Paulus, Walter; Batsikadze, Giorgi; Jamil, Asif; Kuo, Min-Fang; Nitsche, Michael A

    2016-04-01

    Serotonin affects memory formation via modulating long-term potentiation (LTP) and depression (LTD). Accordingly, acute selective serotonin reuptake inhibitor (SSRI) administration enhanced LTP-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. However, it usually takes some time for SSRI to reduce clinical symptoms such as anxiety, negative mood, and related symptoms of depression and anxiety disorders. This might be related to an at least partially different effect of chronic serotonergic enhancement on plasticity, as compared with single-dose medication. Here we explored the impact of chronic application of the SSRI citalopram (CIT) on plasticity induced by tDCS in healthy humans in a partially double-blinded, placebo (PLC)-controlled, randomized crossover study. Furthermore, we explored the dependency of plasticity induction from the glutamatergic system via N-methyl-D-aspartate receptor antagonism. Twelve healthy subjects received PLC medication, combined with anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took CIT (20 mg/day) consecutively for 35 days. During this period, four additional interventions were performed (CIT and PLC medication with anodal/cathodal tDCS, CIT and dextromethorphan (150 mg) with anodal/cathodal tDCS). Plasticity was monitored by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic application of CIT increased and prolonged the LTP-like plasticity induced by anodal tDCS for over 24 h, and converted cathodal tDCS-induced LTD-like plasticity into facilitation. These effects were abolished by dextromethorphan. Chronic serotonergic enhancement results in a strengthening of LTP-like glutamatergic plasticity, which might partially explain the therapeutic impact of SSRIs in depression and other neuropsychiatric diseases.

  12. Transvertebral direct current stimulation paired with locomotor training in chronic spinal cord injury: A case study.

    Science.gov (United States)

    Powell, Elizabeth Salmon; Carrico, Cheryl; Raithatha, Ravi; Salyers, Emily; Ward, Andrea; Sawaki, Lumy

    2016-01-01

    This double-blind, sham-controlled, crossover case study combined transvertebral direct current stimulation (tvDCS) and locomotor training on a robot-assisted gait orthosis (LT-RGO). Determine whether cathodal tvDCS paired with LT-RGO leads to greater changes in function and neuroplasticity than sham tvDCS paired with LT-RGO. University of Kentucky (UK) HealthCare Stroke and Spinal Cord Neurorehabilitation Research at HealthSouth Cardinal Hill Hospital. A single subject with motor incomplete spinal cord injury (SCI) participated in 24 sessions of sham tvDCS paired with LT-RGO before crossover to 24 sessions of cathodal tvDCS paired with LT-RGO. Functional outcomes were measured with 10 Meter Walk Test (10MWT), 6 Minute Walk Test (6MWT), Spinal Cord Independence Measure-III (SCIM-III) mobility component, lower extremity manual muscle test (MMT), and Berg Balance Scale (BBS). Corticospinal changes were assessed using transcranial magnetic stimulation. Improvement in 10MWT speed, SCIM-III mobility component, and BBS occurred with both conditions. 6MWT worsened after sham tvDCS and improved after cathodal tvDCS. MMT scores for both lower extremities improved following sham tvDCS but decreased following cathodal tvDCS. Corticospinal excitability increased following cathodal tvDCS but not sham tvDCS. These results suggest that combining cathodal tvDCS and LT-RGO may improve functional outcomes, increase corticospinal excitability, and possibly decrease spasticity. Randomized controlled trials are needed to confirm these conclusions. This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR000117, and the HealthSouth Cardinal Hill Stroke and Spinal Cord Endowment (1215375670).

  13. Effects of Transcranial Direct-Current Stimulation on Neurosurgical Skill Acquisition: A Randomized Controlled Trial.

    Science.gov (United States)

    Ciechanski, Patrick; Cheng, Adam; Lopushinsky, Steven; Hecker, Kent; Gan, Liu Shi; Lang, Stefan; Zareinia, Kourosh; Kirton, Adam

    2017-12-01

    Recent changes in surgical training environments may have limited opportunities for trainees to gain proficiency in skill. Complex skills such as neurosurgery require extended periods of training. Methods to enhance surgical training are required to overcome duty-hour restrictions, to ensure the acquisition of skill proficiency. Transcranial direct-current stimulation (tDCS) can enhance motor skill learning, but is untested in surgical procedural training. We aimed to determine the effects of tDCS on simulation-based neurosurgical skill acquisition. Medical students were trained to acquire tumor resection skills using a virtual reality neurosurgical simulator. The primary outcome of change in tumor resection was scored at baseline, over 8 repetitions, post-training, and again at 6 weeks. Participants received anodal tDCS or sham over the primary motor cortex. Secondary outcomes included changes in brain resected, resection effectiveness, duration of excessive forces (EF) applied, and resection efficiency. Additional outcomes included tDCS tolerability. Twenty-two students consented to participate, with no dropouts over the course of the trial. Participants receiving tDCS intervention increased the amount of tumor resected, increased the effectiveness of resection, reduced the duration of EF applied, and improved resection efficiency. Little or no decay was observed at 6 weeks in both groups. No adverse events were documented, and sensation severity did not differ between stimulation groups. The addition of tDCS to neurosurgical training may enhance skill acquisition in a simulation-based environment. Trials of additional skills in high-skill residents, and translation to nonsimulated performance are needed to determine the potential utility of tDCS in surgical training. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Keane, Maureen; Deyo, Steve; Abosch, Aviva; Bajwa, Jawad A.; Johnson, Matthew D.

    2012-08-01

    Deep brain stimulation (DBS) in the ventral intermediate nucleus of thalamus (Vim) is known to exert a therapeutic effect on postural and kinetic tremor in patients with essential tremor (ET). For DBS leads implanted near the caudal border of Vim, however, there is an increased likelihood that one will also induce paresthesia side-effects by stimulating neurons within the sensory pathway of the ventral caudal (Vc) nucleus of thalamus. The aim of this computational study was to (1) investigate the neuronal pathways modulated by therapeutic, sub-therapeutic and paresthesia-inducing DBS settings in three patients with ET and (2) determine how much better an outcome could have been achieved had these patients been implanted with a DBS lead containing directionally segmented electrodes (dDBS). Multi-compartment neuron models of the thalamocortical, cerebellothalamic and medial lemniscal pathways were first simulated in the context of patient-specific anatomies, lead placements and programming parameters from three ET patients who had been implanted with Medtronic 3389 DBS leads. The models showed that in these patients, complete suppression of tremor was associated most closely with activating an average of 62% of the cerebellothalamic afferent input into Vim (n = 10), while persistent paresthesias were associated with activating 35% of the medial lemniscal tract input into Vc thalamus (n = 12). The dDBS lead design demonstrated superior targeting of the cerebello-thalamo-cortical pathway, especially in cases of misaligned DBS leads. Given the close proximity of Vim to Vc thalamus, the models suggest that dDBS will enable clinicians to more effectively sculpt current through and around thalamus in order to achieve a more consistent therapeutic effect without inducing side-effects.

  15. Differential modulation of corticospinal excitability by different current densities of anodal transcranial direct current stimulation.

    Directory of Open Access Journals (Sweden)

    Andisheh Bastani

    Full Text Available BACKGROUND: Novel non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS have been developed in recent years. TDCS-induced corticospinal excitability changes depend on two important factors current intensity and stimulation duration. Despite clinical success with existing tDCS parameters, optimal protocols are still not entirely set. OBJECTIVE/HYPOTHESIS: The current study aimed to investigate the effects of four different anodal tDCS (a-tDCS current densities on corticospinal excitability. METHODS: Four current intensities of 0.3, 0.7, 1.4 and 2 mA resulting in current densities (CDs of 0.013, 0.029, 0.058 and 0.083 mA/cm(2 were applied on twelve right-handed (mean age 34.5±10.32 yrs healthy individuals in different sessions at least 48 hours apart. a-tDCS was applied continuously for 10 minute, with constant active and reference electrode sizes of 24 and 35 cm(2 respectively. The corticospinal excitability of the extensor carpi radialis muscle (ECR was measured before and immediately after the intervention and at 10, 20 and 30 minutes thereafter. RESULTS: Post hoc comparisons showed significant differences in corticospinal excitability changes for CDs of 0.013 mA/cm(2 and 0.029 mA/cm(2 (P = 0.003. There were no significant differences between excitability changes for the 0.013 mA/cm(2 and 0.058 mA/cm(2 (P = 0.080 or 0.013 mA/cm(2 and 0.083 mA/cm(2 (P = 0.484 conditions. CONCLUSION: This study found that a-tDCS with a current density of 0.013 mA/cm(2 induces significantly larger corticospinal excitability changes than CDs of 0.029 mA/cm(2. The implication is that might help to avoid applying unwanted amount of current to the cortical areas.

  16. Transcranial direct current stimulation over multiple days enhances motor performance of a grip task.

    Science.gov (United States)

    Fan, Julie; Voisin, Julien; Milot, Marie-Hélène; Higgins, Johanne; Boudrias, Marie-Hélène

    2017-09-01

    Recovery of handgrip is critical after stroke since it is positively related to upper limb function. To boost motor recovery, transcranial direct current stimulation (tDCS) is a promising, non-invasive brain stimulation technique for the rehabilitation of persons with stroke. When applied over the primary motor cortex (M1), tDCS has been shown to modulate neural processes involved in motor learning. However, no studies have looked at the impact of tDCS on the learning of a grip task in both stroke and healthy individuals. To assess the use of tDCS over multiple days to promote motor learning of a grip task using a learning paradigm involving a speed-accuracy tradeoff in healthy individuals. In a double-blinded experiment, 30 right-handed subjects (mean age: 22.1±3.3 years) participated in the study and were randomly assigned to an anodal (n=15) or sham (n=15) stimulation group. First, subjects performed the grip task with their dominant hand while following the pace of a metronome. Afterwards, subjects trained on the task, at their own pace, over 5 consecutive days while receiving sham or anodal tDCS over M1. After training, subjects performed de novo the metronome-assisted task. The change in performance between the pre and post metronome-assisted task was used to assess the impact of the grip task and tDCS on learning. Anodal tDCS over M1 had a significant effect on the speed-accuracy tradeoff function. The anodal tDCS group showed significantly greater improvement in performance (39.28±15.92%) than the sham tDCS group (24.06±16.35%) on the metronome-assisted task, t(28)=2.583, P=0.015 (effect size d=0.94). Anodal tDCS is effective in promoting grip motor learning in healthy individuals. Further studies are warranted to test its potential use for the rehabilitation of fine motor skills in stroke patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. Deep Brain Stimulation of the Dentato-Rubro-Thalamic Tract: Outcomes of Direct Targeting for Tremor.

    Science.gov (United States)

    Fenoy, Albert J; Schiess, Mya C

    2017-07-01

    Targeting the dentato-rubro-thalamic tract (DRTt) has been suggested to be efficacious in deep brain stimulation (DBS) for tremor suppression, both in case reports and post-hoc analyses. This prospective observational study sought to analyze outcomes after directly targeting the DRTt in tremor patients. 20 consecutively enrolled intention tremor patients obtained pre-operative MRI with diffusion tensor (dTi) sequences. Mean baseline tremor amplitude based on The Essential Tremor Rating Assessment Scale was recorded. The DRTt was drawn for each individual on StealthViz software (Medtronic) using the dentate nucleus as the seed region and the ipsilateral pre-central gyrus as the end region and then directly targeted during surgery. Intraoperative testing confirmed successful tremor control. Post-operative analysis of electrode position relative to the DRTt was performed, as was post-operative assessment of tremor improvement. The mean age of patients was 66.8 years; mean duration of tremor was 16 years. Mean voltage for the L electrode = 3.4 V; R = 2.6 V. Mean distance from the center of the active electrode contact to the DRTt was 0.9 mm on the L, and 0.8 mm on the R. Improvement in arm tremor amplitude from baseline after DBS was significant (P tremor suppression. Accounting for hardware, software, and model limitations, depiction of the DRTt allows for placement of electrode contacts directly within the fiber tract for modulation despite any anatomical variation, which reproducibly resulted in good tremor control. © 2017 International Neuromodulation Society.

  18. Transcranial magnetic stimulation-induced global propagation of transient phase resetting associated with directional information flow

    Directory of Open Access Journals (Sweden)

    Masahiro eKawasaki

    2014-03-01

    Full Text Available Electroencephalogram (EEG phase synchronization analyses can reveal large-scale communication between distant brain areas. However, it is not possible to identify the directional information flow between distant areas using conventional phase synchronization analyses. In the present study, we applied transcranial magnetic stimulation (TMS to the occipital area in subjects who were resting with their eyes closed, and analyzed the spatial propagation of transient TMS-induced phase resetting by using the transfer entropy (TE, to quantify the causal and directional flow of information. The time-frequency EEG analysis indicated that the theta (5 Hz phase locking factor (PLF reached its highest value at the distant area (the motor area in this study, with a time lag that followed the peak of the transient PLF enhancements of the TMS-targeted area at the TMS onset. PPI (phase-preservation index analyses demonstrated significant phase resetting at the TMS-targeted area and distant area. Moreover, the TE from the TMS-targeted area to the distant area increased clearly during the delay that followed TMS onset. Interestingly, the time lags were almost coincident between the PLF and TE results (152 vs. 165 ms, which provides strong evidence that the emergence of the delayed PLF reflects the causal information flow. Such tendencies were observed only in the higher-intensity TMS condition, and not in the lower-intensity or sham TMS conditions. Thus, TMS may manipulate large-scale causal relationships between brain areas in an intensity-dependent manner. We demonstrated that single-pulse TMS modulated global phase dynamics and directional information flow among synchronized brain networks. Therefore, our results suggest that single-pulse TMS can manipulate both incoming and outgoing information in the TMS-targeted area associated with functional changes.

  19. Recurrent themes in the history of the home use of electrical stimulation: Transcranial direct current stimulation (tDCS) and the medical battery (1870-1920).

    Science.gov (United States)

    Wexler, Anna

    In recent years, neuroscientists and ethicists have warned of the dangers of the unsupervised home use of transcranial direct current stimulation (tDCS), in which individuals stimulate their own brains with low levels of electricity for self-improvement purposes. Although the home use of tDCS is often referred to as a novel phenomenon, in reality the late nineteenth and early twentieth century saw a proliferation of electrical stimulation devices for home use. In particular, the use of an object known as the medical battery bears a number of striking similarities to the modern-day use of tDCS. This article reviews a number of features thought to be unique to the present day home use of brain stimulation, with a particular focus on analogies between tDCS and the medical battery. Archival research was conducted at the Bakken Museum and at the American Medical Association's Historical Health Fraud Archives. Many of the features characterizing the contemporary home use tDCS-a do-it-yourself (DIY) movement, anti-medical establishment themes, conflicts between lay and professional usage-are a repetition of themes that occurred a century ago with regard to the medical battery. A number of features, however, seem to be unique to the present, such as the dominant discourse about risk and safety, the division between cranial and non-cranial stimulation, and utilization for cognitive enhancement purposes. Viewed in the long durée, the contemporary use of electrical stimulation at home is not a novel phenomenon, but rather the latest wave in a series of ongoing attempts by lay individuals to utilize electricity for therapeutic purposes. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

    Science.gov (United States)

    Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

    2015-07-01

    It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

  1. The difference between electrical microstimulation and direct electrical stimulation - towards new opportunities for innovative functional brain mapping?

    Science.gov (United States)

    Vincent, Marion; Rossel, Olivier; Hayashibe, Mitsuhiro; Herbet, Guillaume; Duffau, Hugues; Guiraud, David; Bonnetblanc, François

    2016-04-01

    Both electrical microstimulation (EMS) and direct electrical stimulation (DES) of the brain are used to perform functional brain mapping. EMS is applied to animal fundamental neuroscience experiments, whereas DES is performed in the operating theatre on neurosurgery patients. The objective of the present review was to shed new light on electrical stimulation techniques in brain mapping by comparing EMS and DES. There is much controversy as to whether the use of DES during wide-awake surgery is the 'gold standard' for studying the brain function. As part of this debate, it is sometimes wrongly assumed that EMS and DES induce similar effects in the nervous tissues and have comparable behavioural consequences. In fact, the respective stimulation parameters in EMS and DES are clearly different. More surprisingly, there is no solid biophysical rationale for setting the stimulation parameters in EMS and DES; this may be due to historical, methodological and technical constraints that have limited the experimental protocols and prompted the use of empirical methods. In contrast, the gap between EMS and DES highlights the potential for new experimental paradigms in electrical stimulation for functional brain mapping. In view of this gap and recent technical developments in stimulator design, it may now be time to move towards alternative, innovative protocols based on the functional stimulation of peripheral nerves (for which a more solid theoretical grounding exists).

  2. Plasma rich in growth factors (PRGF-Endoret) stimulates proliferation and migration of primary keratocytes and conjunctival fibroblasts and inhibits and reverts TGF-beta1-Induced myodifferentiation.

    Science.gov (United States)

    Anitua, Eduardo; Sanchez, Mikel; Merayo-Lloves, Jesus; De la Fuente, Maria; Muruzabal, Francisco; Orive, Gorka

    2011-08-01

    Plasma rich in growth factors (PRGF-Endoret) technology is an autologous platelet-enriched plasma obtained from patient's own blood, which after activation with calcium chloride allows the release of a pool of biologically active proteins that influence and promote a range of biological processes including cell recruitment, and growth and differentiation. Because ocular surface wound healing is mediated by different growth factors, we decided to explore the potential of PRGF-Endoret technology in stimulating the biological processes related with fibroblast-induced tissue repair. Furthermore, the anti-fibrotic properties of this technology were also studied. Blood from healthy donors was collected, centrifuged and, whole plasma column (WP) and the plasma fraction with the highest platelet concentration (F3) were drawn off, avoiding the buffy coat. Primary human cells including keratocytes and conjunctival fibroblasts were used to perform the "in vitro" investigations. The potential of PRGF-Endoret in promoting wound healing was evaluated by means of a proliferation and migration assays. Fibroblast cells were induced to myofibroblast differentiation after the treatment with 2.5 ng/mL of TGF-β1. The capability of WP and F3 to prevent and inhibit TGF-β1-induced differentiation was evaluated. Results show that this autologous approach significantly enhances proliferation and migration of both keratocytes and conjunctival fibroblasts. In addition, plasma rich in growth factors prevents and inhibits TGF-β1-induced myofibroblast differentiation. No differences were found between WP and F3 plasma fractions. These results suggest that PRGF-Endoret could reduce scarring while stimulating wound healing in ocular surface. F3 or whole plasma column show similar biological effects in keratocytes and conjunctival fibroblast cells.

  3. MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly

    International Nuclear Information System (INIS)

    Tian, Yuan; Hao, Shaobo; Ye, Minhua; Zhang, Anling; Nan, Yang; Wang, Guangxiu; Jia, Zhifan; Yu, Kai; Guo, Lianmei; Pu, Peiyu; Huang, Qiang; Zhong, Yue

    2015-01-01

    We demonstrated that IKBKE is overexpressed in human gliomas and that the downregulation of IKBKE markedly inhibits the proliferative and invasive abilities of glioma cells, which is consistent with the results reported by several different research groups. Therefore, IKBKE represents a promising therapeutic target for the treatment of glioma. In the present study, we verified that the microRNAs let-7b and let-7i target IKBKE through luciferase assays and found that let-7b/i mimics can knock down IKBKE and upregulate E-cadherin through western blot analysis. Moreover, the expression levels of let-7b/i were significantly lower in glioma cell lines than that in normal brain tissues, as determined by quantitative real-time PCR. Furthermore, let-7b/i inhibit the invasion and migration of glioma cells, as determined through wound healing and Transwell assays. The above-mentioned data suggest that let-7b/i inhibit the invasive ability of glioma cells by directly downregulating IKBKE and indirectly upregulating E-cadherin. - Highlights: • Let-7b and let-7i are downregulated in glioma cell lines. • IKBKE is a target gene of let-7b/i. • Let-7b/i inhibit the invasion and migration of glioma cells. • Let-7b/i upregulate E-cadherin by downregulating IKBKE

  4. MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Yuan; Hao, Shaobo [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Ye, Minhua [Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006 (China); Zhang, Anling [Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Nan, Yang [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Wang, Guangxiu; Jia, Zhifan [Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Yu, Kai; Guo, Lianmei [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Pu, Peiyu [Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Huang, Qiang, E-mail: huangqiang209@163.com [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Zhong, Yue, E-mail: zhongyue2457@sina.com [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China)

    2015-03-06

    We demonstrated that IKBKE is overexpressed in human gliomas and that the downregulation of IKBKE markedly inhibits the proliferative and invasive abilities of glioma cells, which is consistent with the results reported by several different research groups. Therefore, IKBKE represents a promising therapeutic target for the treatment of glioma. In the present study, we verified that the microRNAs let-7b and let-7i target IKBKE through luciferase assays and found that let-7b/i mimics can knock down IKBKE and upregulate E-cadherin through western blot analysis. Moreover, the expression levels of let-7b/i were significantly lower in glioma cell lines than that in normal brain tissues, as determined by quantitative real-time PCR. Furthermore, let-7b/i inhibit the invasion and migration of glioma cells, as determined through wound healing and Transwell assays. The above-mentioned data suggest that let-7b/i inhibit the invasive ability of glioma cells by directly downregulating IKBKE and indirectly upregulating E-cadherin. - Highlights: • Let-7b and let-7i are downregulated in glioma cell lines. • IKBKE is a target gene of let-7b/i. • Let-7b/i inhibit the invasion and migration of glioma cells. • Let-7b/i upregulate E-cadherin by downregulating IKBKE.

  5. Visualizing Transcranial Direct Current Stimulation (tDCS) in vivo using Magnetic Resonance Imaging

    Science.gov (United States)

    Jog, Mayank Anant

    Transcranial Direct Current Stimulation (tDCS) is a low-cost, non-invasive neuromodulation technique that has been shown to treat clinical symptoms as well as improve cognition. However, no techniques exist at the time of research to visualize tDCS currents in vivo. This dissertation presents the theoretical framework and experimental implementations of a novel MRI technique that enables non-invasive visualization of the tDCS electric current using magnetic field mapping. The first chapter establishes the feasibility of measuring magnetic fields induced by tDCS currents. The following chapter discusses the state of the art implementation that can measure magnetic field changes in individual subjects undergoing concurrent tDCS/MRI. The final chapter discusses how the developed technique was integrated with BOLD fMRI-an established MRI technique for measuring brain function. By enabling a concurrent measurement of the tDCS current induced magnetic field as well as the brain's hemodynamic response to tDCS, our technique opens a new avenue to investigate tDCS mechanisms and improve targeting.

  6. Impact of antipsychotic medication on transcranial direct current stimulation (tDCS) effects in schizophrenia patients.

    Science.gov (United States)

    Agarwal, Sri Mahavir; Bose, Anushree; Shivakumar, Venkataram; Narayanaswamy, Janardhanan C; Chhabra, Harleen; Kalmady, Sunil V; Varambally, Shivarama; Nitsche, Michael A; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

    2016-01-30

    Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotic's affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Transcranial Direct Current Stimulation (tDCS) Enhances the Excitability of Trigemino-Facial Reflex Circuits.

    Science.gov (United States)

    Cabib, Christopher; Cipullo, Federica; Morales, Merche; Valls-Solé, Josep

    2016-01-01

    Transcranial direct current stimulation (tDCS) causes a tiny burning sensation through activation of local cutaneous trigeminal afferents. Trigeminal sensory inputs from tDCS may generate excitability changes in the trigemino-facial reflex circuits. Sixteen healthy volunteers were submitted to 20 minutes tDCS sessions with two types of electrode-montage conditions: 1. Real vs Sham 'bi-hemispheric' tDCS (cathode/anode: C4/C3), for blinded assessment of effects, and 2. 'uni-hemispheric' tDCS (cathode/anode: Fp3/C3), for assessment of laterality of the effects. Supraorbital nerve stimuli were used to obtain blink reflexes before, during (10 minutes from onset) and after (30 minutes from onset) the tDCS session. Outcome measures were R2 habituation (R2H) to repeated stimuli, the blink reflex excitability recovery (BRER) to paired stimuli and the blink reflex inhibition by a prepulse (BRIP). Real but not sham bi-hemispheric tDCS caused a significant decrease of R2H and leftward shift of BRER curve (p tDCS on BRER and BRIP were larger on ipsilateral than on contralateral blink reflexes (p tDCS enhances the excitability of trigemino-facial reflex circuits. The finding of larger ipsilateral than contralateral effects suggests that sensitization through cutaneous trigeminal afferents adds on other possible mechanisms such as activation of cortico-nuclear or cortico-reticular connections. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Transcranial direct current stimulation does not affect lower extremity muscle strength training in healthy individuals

    DEFF Research Database (Denmark)

    Maeda, Kazuhei; Yamaguchi, Tomofumi; Tatemoto, Tsuyoshi

    2017-01-01

    The present study investigated the effects of anodal transcranial direct current stimulation (tDCS) on lower extremity muscle strength training in 24 healthy participants. In this triple-blind, sham-controlled study, participants were randomly allocated to the anodal tDCS plus muscle strength...... training (anodal tDCS) group or sham tDCS plus muscle strength training (sham tDCS) group. Anodal tDCS (2 mA) was applied to the primary motor cortex of the lower extremity during muscle strength training of the knee extensors and flexors. Training was conducted once every 3 days for 3 weeks (7 sessions......). Knee extensor and flexor peak torques were evaluated before and after the 3 weeks of training. After the 3-week intervention, peak torques of knee extension and flexion changed from 155.9 to 191.1 Nm and from 81.5 to 93.1 Nm in the anodal tDCS group. Peak torques changed from 164.1 to 194.8 Nm...

  9. Relationship of herpes simplex encephalitis and transcranial direct current stimulation--a case report.

    Science.gov (United States)

    Yang, Yuanbin; Xiao, Juan; Song, Haiqing; Wang, Ralph; Hussain, Mohammed; Song, Weiqun

    2015-04-01

    We report a rare case of relapsing herpes simplex encephalitis in a-37-year-old patient which was previously confirmed by positive polymerase chain reaction, herpes simplex virus (HSV) type1 IgG antibodies in cerebrospinal fluid and characterized on MRI. During the first admission, he was treated with continuous acyclovir treatment for one month with clinical improvement except for residual aphasia, for which he received a course of outpatient transcranial direct current stimulation (tDCS). A constant current of 1.2 mA was applied for 20 min twice daily. After the 4th day the patient was found to be irritable and uncooperative by staff and family members. A subsequent MRI showed significant deterioration of the lesion on comparison to the first MRI which led to discontinuation of tDCS.The relatively rapid exacerbation of HSV in only a few days is unusual. Our aim is to discuss if tDCS is related to HSV relapse and in doing so highlight possible mechanisms. Copyright © 2015. Published by Elsevier B.V.

  10. Transcranial direct current stimulation for hyperactivity and noncompliance in autistic disorder.

    Science.gov (United States)

    D'Urso, Giordano; Bruzzese, Dario; Ferrucci, Roberta; Priori, Alberto; Pascotto, Antonio; Galderisi, Silvana; Altamura, Alfredo Carlo; Bravaccio, Carmela

    2015-01-01

    To evaluate the safety, efficacy, and feasibility of inhibitory transcranial direct current stimulation (tDCS) for the treatment of behavioural abnormalities of autistic patients. Twelve young adult patients with autistic disorder were enrolled. All subjects presented intellectual disability and most of them had speech impairment. The Aberrant Behavior Checklist (ABC) was administered as the primary outcome measure before and after a 2-week tDCS course. All subjects received 10 daily applications of 20 min/1.5 mA/cathodal (inhibitory) tDCS over the left dorso-lateral pre-frontal cortex. Eight out of 10 study completers improved in their abnormal behaviours, reaching an average reduction of 26.7% of the total ABC score. The remaining two patients showed no changes. In the whole group of completers, among the five subscales contributing to the significant reduction of the total score, the most remarkable and statistically significant change was seen in the subscale assessing hyperactivity and non-compliance (-35.9%, P = 0.002). No adverse effects were reported. Inhibitory tDCS improved the ABC rating scores for autistic behaviours. Owing to its ease of use, cost-effectiveness and the limited availability of specific treatment strategies, tDCS might be a valid therapeutic option to be tested in autistic patients.

  11. High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

    Science.gov (United States)

    Meiron, Oded; Gale, Rena; Namestnic, Julia; Bennet-Back, Odeya; David, Jonathan; Gebodh, Nigel; Adair, Devin; Esmaeilpour, Zeinab; Bikson, Marom

    2018-01-01

    Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

  12. Neural correlates of mirth and laughter: a direct electrical cortical stimulation study.

    Science.gov (United States)

    Yamao, Yukihiro; Matsumoto, Riki; Kunieda, Takeharu; Shibata, Sumiya; Shimotake, Akihiro; Kikuchi, Takayuki; Satow, Takeshi; Mikuni, Nobuhiro; Fukuyama, Hidenao; Ikeda, Akio; Miyamoto, Susumu

    2015-05-01

    Laughter consists of both motor and emotional aspects. The emotional component, known as mirth, is usually associated with the motor component, namely, bilateral facial movements. Previous electrical cortical stimulation (ES) studies revealed that mirth was associated with the basal temporal cortex, inferior frontal cortex, and medial frontal cortex. Functional neuroimaging implicated a role for the left inferior frontal and bilateral temporal cortices in humor processing. However, the neural origins and pathways linking mirth with facial movements are still unclear. We hereby report two cases with temporal lobe epilepsy undergoing subdural electrode implantation in whom ES of the left basal temporal cortex elicited both mirth and laughter-related facial muscle movements. In one case with normal hippocampus, high-frequency ES consistently caused contralateral facial movement, followed by bilateral facial movements with mirth. In contrast, in another case with hippocampal sclerosis (HS), ES elicited only mirth at low intensity and short duration, and eventually laughter at higher intensity and longer duration. In both cases, the basal temporal language area (BTLA) was located within or adjacent to the cortex where ES produced mirth. In conclusion, the present direct ES study demonstrated that 1) mirth had a close relationship with language function, 2) intact mesial temporal structures were actively engaged in the beginning of facial movements associated with mirth, and 3) these emotion-related facial movements had contralateral dominance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Application and outcomes of therapy combining transcranial direct current stimulation and virtual reality: a systematic review.

    Science.gov (United States)

    Massetti, Thais; Crocetta, Tânia Brusque; Silva, Talita Dias da; Trevizan, Isabela Lopes; Arab, Claudia; Caromano, Fátima Aparecida; Monteiro, Carlos Bandeira de Mello

    2017-08-01

    To evaluate the methods and major outcomes of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) therapy in randomized controlled trials. A systematic review was performed following PRISMA guidelines using PubMed, PubMed Central, Web of Science and CAPES periodic databases, with no time restriction. The studies were screened for the following inclusion criteria: human subjects, combination of VR and tDCS methods, and randomized controlled study design. All potentially relevant articles were independently reviewed by two researchers, who reached a consensus on which articles met the inclusion criteria. The PEDro scale was used to evaluate the studies. Eleven studies were included, all of which utilized a variety of tDCS and VR application methods. The main outcomes were found to be beneficial in intervention groups of different populations, including improvements in body sway, gait, stroke recovery, pain management and vegetative reactions. The use of tDCS combined with VR showed positive results in both healthy and impaired patients. Future studies with larger sample sizes and homogeneous participants are required to confirm the benefits of tDCS and VR. Implications for Rehabilitation tDCS with VR intervention can be an alternative to traditional rehabilitation programs. tDCS with VR is a promising type of intervention with a variety of positive effects. Application of tDCS with VR is appropriated to both healthy and impaired patients. There is no consensus of tDCS with VR application.

  14. Wada-test, functional magnetic resonance imaging and direct electrical stimulation - brain mapping methods

    International Nuclear Information System (INIS)

    Minkin, K.; Tanova, R.; Busarski, A.; Penkov, M.; Penev, L.; Hadjidekov, V.

    2009-01-01

    Modern neurosurgery requires accurate preoperative and intraoperative localization of brain pathologies but also of brain functions. The presence of individual variations in healthy subjects and the shift of brain functions in brain diseases provoke the introduction of various methods for brain mapping. The aim of this paper was to analyze the most widespread methods for brain mapping: Wada-test, functional magnetic resonance imaging (fMRI) and intraoperative direct electrical stimulation (DES). This study included 4 patients with preoperative brain mapping using Wada-test and fMRI. Intraoperative mapping with DES during awake craniotomy was performed in one case. The histopathological diagnosis was low-grade glioma in 2 cases, cortical dysplasia (1 patient) and arteriovenous malformation (1 patient). The brain mapping permits total lesion resection in three of four patients. There was no new postoperative deficit despite surgery near or within functional brain areas. Brain plasticity provoking shift of eloquent areas from their usual locations was observed in two cases. The brain mapping methods allow surgery in eloquent brain areas recognized in the past as 'forbidden areas'. Each method has advantages and disadvantages. The precise location of brain functions and pathologies frequently requires combination of different brain mapping methods. (authors)

  15. Anodal Transcranial Direct Current Stimulation Promotes Frontal Compensatory Mechanisms in Healthy Elderly Subjects.

    Science.gov (United States)

    Cespón, Jesús; Rodella, Claudia; Rossini, Paolo M; Miniussi, Carlo; Pellicciari, Maria C

    2017-01-01

    Recent studies have demonstrated that transcranial direct current stimulation (tDCS) is potentially useful to improve working memory. In the present study, young and elderly subjects performed a working memory task ( n -back task) during an electroencephalogram recording before and after receiving anodal, cathodal, and sham tDCS over the left dorsolateral prefrontal cortex (DLPFC). We investigated modulations of behavioral performance and electrophysiological correlates of working memory processes (frontal and parietal P300 event-related potentials). A strong tendency to modulated working memory performance was observed after the application of tDCS. In detail, young, but not elderly, subjects benefited from additional practice in the absence of real tDCS, as indicated by their more accurate responses after sham tDCS. The cathodal tDCS had no effect in any group of participants. Importantly, anodal tDCS improved accuracy in elderly. Moreover, increased accuracy after anodal tDCS was correlated with a larger frontal P300 amplitude. These findings suggest that, in elderly subjects, improved working memory after anodal tDCS applied over the left DLPFC may be related to the promotion of frontal compensatory mechanisms, which are related to attentional processes.

  16. Transcranial Direct Current Stimulation, Symptomatology, and Cognition in Psychosis: A Qualitative Review

    Directory of Open Access Journals (Sweden)

    Tina Gupta

    2018-05-01

    Full Text Available Schizophrenia is a chronic, debilitating condition that affects approximately 1% of the population. Individuals diagnosed with schizophrenia typically exhibit positive (e.g., hallucinations and negative symptoms (e.g., anhedonia and impairments in cognitive function. Given the limitations of antipsychotic medication and psychotherapy in fully treating psychosis symptomatology, there has been increasing interest in other interventions such as transcranial direct current stimulation (tDCS. tDCS is a non-invasive neuromodulation technique, that is safe, cost-effective, and widely accessible. Here, we discuss treatment studies that seek to improve symptoms and cognitive performance in schizophrenia using tDCS. Currently within the literature, there is support for reductions in positive symptoms such as hallucinations after receiving tDCS. Further, studies indicate that tDCS can improve cognitive functioning, which is an area of investigation that is sorely needed, as it is unclear which types of interventions may be useful in ameliorating cognitive deficits among this group. Taken together, the evidence suggests that tDCS holds promise in improving symptoms and cognition. To that end, tDCS has critical clinical implications for this population.

  17. Anodal Transcranial Direct Current Stimulation Promotes Frontal Compensatory Mechanisms in Healthy Elderly Subjects

    Directory of Open Access Journals (Sweden)

    Jesús Cespón

    2017-12-01

    Full Text Available Recent studies have demonstrated that transcranial direct current stimulation (tDCS is potentially useful to improve working memory. In the present study, young and elderly subjects performed a working memory task (n-back task during an electroencephalogram recording before and after receiving anodal, cathodal, and sham tDCS over the left dorsolateral prefrontal cortex (DLPFC. We investigated modulations of behavioral performance and electrophysiological correlates of working memory processes (frontal and parietal P300 event-related potentials. A strong tendency to modulated working memory performance was observed after the application of tDCS. In detail, young, but not elderly, subjects benefited from additional practice in the absence of real tDCS, as indicated by their more accurate responses after sham tDCS. The cathodal tDCS had no effect in any group of participants. Importantly, anodal tDCS improved accuracy in elderly. Moreover, increased accuracy after anodal tDCS was correlated with a larger frontal P300 amplitude. These findings suggest that, in elderly subjects, improved working memory after anodal tDCS applied over the left DLPFC may be related to the promotion of frontal compensatory mechanisms, which are related to attentional processes.

  18. Anodal Transcranial Direct Current Stimulation Provokes Neuroplasticity in Repetitive Mild Traumatic Brain Injury in Rats

    Directory of Open Access Journals (Sweden)

    Ho Jeong Kim

    2017-01-01

    Full Text Available Repetitive mild traumatic brain injury (rmTBI provokes behavioral and cognitive changes. But the study about electrophysiologic findings and managements of rmTBI is limited. In this study, we investigate the effects of anodal transcranial direct current stimulation (tDCS on rmTBI. Thirty-one Sprague Dawley rats were divided into the following groups: sham, rmTBI, and rmTBI treated by tDCS. Animals received closed head mTBI three consecutive times a day. Anodal tDCS was applied to the left motor cortex. We evaluated the motor-evoked potential (MEP and the somatosensory-evoked potential (SEP. T2-weighted magnetic resonance imaging was performed 12 days after rmTBI. After rmTBI, the latency of MEP was prolonged and the amplitude in the right hind limb was reduced in the rmTBI group. The latency of SEP was delayed and the amplitude was decreased after rmTBI in the rmTBI group. In the tDCS group, the amplitude in both hind limbs was increased after tDCS in comparison with the values before rmTBI. Anodal tDCS after rmTBI seems to be a useful tool for promoting transient motor recovery through increasing the synchronicity of cortical firing, and it induces early recovery of consciousness. It can contribute to management of concussion in humans if further study is performed.

  19. Transcranial Direct Current Stimulation and Power Spectral Parameters: a tDCS/EEG co-registration study

    Directory of Open Access Journals (Sweden)

    Anna Lisa Mangia

    2014-08-01

    Full Text Available Transcranial direct current stimulation (tDCS delivers low electric currents to the brain through the scalp. Constant electric currents induce shifts in neuronal membrane excitability, resulting in secondary changes in cortical activity. Concomitant electroencephalography (EEG monitoring during tDCS can provide valuable information on the tDCS mechanisms of action. This study examined the effects of anodal tDCS on spontaneous cortical activity in a resting brain to disclose possible modulation of spontaneous oscillatory brain activity. EEG activity was measured in ten healthy subjects during and after a session of anodal stimulation of the postero-parietal cortex to detect the tDCS-induced alterations. Changes in the theta, alpha, beta and gamma power bands were investigated. Three main findings emerged: 1 an increase in theta band activity during the first minutes of stimulation; 2 an increase in alpha and beta power during and after stimulation; 3 a widespread activation in several brain regions.

  20. Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts

    DEFF Research Database (Denmark)

    Schneider, Linda; Cammer, Michael; Lehman, Jonathan

    2010-01-01

    Cell motility and migration play pivotal roles in numerous physiological and pathophysiological processes including development and tissue repair. Cell migration is regulated through external stimuli such as platelet-derived growth factor-AA (PDGF-AA), a key regulator in directional cell migration....... Here we used micropipette analysis to show that a normal chemosensory response to PDGF-AA in fibroblasts requires the primary cilium. In vitro and in vivo wound healing assays revealed that in ORPK mouse (IFT88(Tg737Rpw)) fibroblasts, where ciliary assembly is defective, chemotaxis towards PDGF-AA...

  1. Delayed enhancement of multitasking performance: Effects of anodal transcranial direct current stimulation on the prefrontal cortex.

    Science.gov (United States)

    Hsu, Wan-Yu; Zanto, Theodore P; Anguera, Joaquin A; Lin, Yung-Yang; Gazzaley, Adam

    2015-08-01

    The dorsolateral prefrontal cortex (DLPFC) has been proposed to play an important role in neural processes that underlie multitasking performance. However, this claim is underexplored in terms of direct causal evidence. The current study aimed to delineate the causal involvement of the DLPFC during multitasking by modulating neural activity with transcranial direct current stimulation (tDCS) prior to engagement in a demanding multitasking paradigm. The study is a single-blind, crossover, sham-controlled experiment. Anodal tDCS or sham tDCS was applied over left DLPFC in forty-one healthy young adults (aged 18-35 years) immediately before they engaged in a 3-D video game designed to assess multitasking performance. Participants were separated into three subgroups: real-sham (i.e., real tDCS in the first session, followed by sham tDCS in the second session 1 h later), sham-real (sham tDCS first session, real tDCS second session), and sham-sham (sham tDCS in both sessions). The real-sham group showed enhanced multitasking performance and decreased multitasking cost during the second session, compared to first session, suggesting delayed cognitive benefits of tDCS. Interestingly, performance benefits were observed only for multitasking and not on a single-task version of the game. No significant changes were found between the first and second sessions for either the sham-real or the sham-sham groups. These results suggest a causal role of left prefrontal cortex in facilitating the simultaneous performance of more than one task, or multitasking. Moreover, these findings reveal that anodal tDCS may have delayed benefits that reflect an enhanced rate of learning. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Amniotic Membrane Modifies the Genetic Program Induced by TGFß, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds.

    Directory of Open Access Journals (Sweden)

    Antonia Alcaraz

    Full Text Available Post-traumatic large-surface or deep wounds often cannot progress to reepithelialisation because they become irresponsive in the inflammatory stage, so intervention is necessary to provide the final sealing epidermis. Previously we have shown that Amniotic Membrane (AM induced a robust epithelialisation in deep traumatic wounds.To better understand this phenomenon, we used keratinocytes to investigate the effect of AM on chronic wounds. Using keratinocytes, we saw that AM treatment is able to exert an attenuating effect upon Smad2 and Smad3 TGFß-induced phosphorylation while triggering the activation of several MAPK signalling pathways, including ERK and JNK1, 2. This also has a consequence for TGFß-induced regulation on cell cycle control key players CDK1A (p21 and CDK2B (p15. The study of a wider set of TGFß regulated genes showed that the effect of AM was not wide but very concrete for some genes. TGFß exerted a powerful cell cycle arrest; the presence of AM however prevented TGFß-induced cell cycle arrest. Moreover, AM induced a powerful cell migration response that correlates well with the expression of c-Jun protein at the border of the healing assay. Consistently, the treatment with AM of human chronic wounds induced a robust expression of c-Jun at the wound border.The effect of AM on the modulation of TGFß responses in keratinocytes that favours proliferation together with AM-induced keratinocyte migration is the perfect match that allows chronic wounds to move on from their non-healing state and progress into epithelialization. Our results may explain why the application of AM on chronic wounds is able to promote epithelialisation.

  3. c-Kit mutation reduce intestinal epithelial cell proliferation and migration, but not influence intestinal permeability stimulated by lipopolysaccharide.

    Science.gov (United States)

    Xue, Hong; Wang, Feng Yun; Kang, Qian; Tang, Xu Dong

    2018-06-20

    The proto-oncogene c-kit, as a marker of interstitial cells of Cajal (ICCs) in the gastrointestinal tract, plays an important role in the ICCs. Although limited evidences showed c-kit is present in the colonic epithelium but its roles remain unclear. In the present study, we aimed to investigate the expression, location and function of c-kit in the intestinal epithelium. Immunofluorescence, western blotting, and RT-PCR were performed to detect the expression and location of c-kit in the intestinal mucosa of WT mice. We investigated intestinal epithelial proliferation and migration in vivo by performing 5-Bromodeoxyuridine (BrdU) incorporation and Ki-67 staining in WT and Wads m/m mice. An Ussing chamber with fluorescein-isothiocyanate dextran 4000 was used to detect the transepithelial electric resistance (TER), short circuit current (ISC) and permeability across ex vivo colon segments under control and endotoxaemia conditions. We demonstrated that c-kit was located and expressed in the gut crypt compartment in WT mice, which was demonstrated in the c-kit mutant mice (Wads m/m ). In addition, both the number of proliferating cells and the percentage of the distance migrated were lower in the Wads m/m mice than those in the WT mice. Moreover, the intestinal permeability, TER and tight junction were unaltered in the Wads m/m mice under endotoxic conditions compared with those in both the control condition and the WT mice. Altogether, these observations imply that the expression of c-kit in the colonic epithelium is involved in the proliferation and permeability of the colonic epithelium. Copyright © 2018. Published by Elsevier GmbH.

  4. Safety and feasibility of transcranial direct current stimulation in pediatric hemiparesis: randomized controlled preliminary study.

    Science.gov (United States)

    Gillick, Bernadette T; Feyma, Tim; Menk, Jeremiah; Usset, Michelle; Vaith, Amy; Wood, Teddi Jean; Worthington, Rebecca; Krach, Linda E

    2015-03-01

    Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation that has shown improved adult stroke outcomes. Applying tDCS in children with congenital hemiparesis has not yet been explored. The primary objective of this study was to explore the safety and feasibility of single-session tDCS through an adverse events profile and symptom assessment within a double-blind, randomized placebo-controlled preliminary study in children with congenital hemiparesis. A secondary objective was to assess the stability of hand and cognitive function. A double-blind, randomized placebo-controlled pretest/posttest/follow-up study was conducted. The study was conducted in a university pediatric research laboratory. Thirteen children, ages 7 to 18 years, with congenital hemiparesis participated. Adverse events/safety assessment and hand function were measured. Participants were randomly assigned to either an intervention group or a control group, with safety and functional assessments at pretest, at posttest on the same day, and at a 1-week follow-up session. An intervention of 10 minutes of 0.7 mA tDCS was applied to bilateral primary motor cortices. The tDCS intervention was considered safe if there was no individual decline of 25% or group decline of 2 standard deviations for motor evoked potentials (MEPs) and behavioral data and no report of adverse events. No major adverse events were found, including no seizures. Two participants did not complete the study due to lack of MEP and discomfort. For the 11 participants who completed the study, group differences in MEPs and behavioral data did not exceed 2 standard deviations in those who received the tDCS (n=5) and those in the control group (n=6). The study was completed without the need for stopping per medical monitor and biostatisticial analysis. A limitation of the study was the small sample size, with data available for 11 participants. Based on the results of this study, tDCS appears to be safe

  5. Transcutaneous spinal direct current stimulation of the lumbar and sacral spinal cord: a modelling study

    Science.gov (United States)

    Fernandes, Sofia R.; Salvador, Ricardo; Wenger, Cornelia; de Carvalho, Mamede; Miranda, Pedro C.

    2018-06-01

    Objective. Our aim was to perform a computational study of the electric field (E-field) generated by transcutaneous spinal direct current stimulation (tsDCS) applied over the thoracic, lumbar and sacral spinal cord, in order to assess possible neuromodulatory effects on spinal cord circuitry related with lower limb functions. Approach. A realistic volume conductor model of the human body consisting of 14 tissues was obtained from available databases. Rubber pad electrodes with a metallic connector and a conductive gel layer were modelled. The finite element (FE) method was used to calculate the E-field when a current of 2.5 mA was passed between two electrodes. The main characteristics of the E-field distributions in the spinal grey matter (spinal-GM) and spinal white matter (spinal-WM) were compared for seven montages, with the anode placed either over T10, T8 or L2 spinous processes (s.p.), and the cathode placed over right deltoid (rD), umbilicus (U) and right iliac crest (rIC) areas or T8 s.p. Anisotropic conductivity of spinal-WM and of a group of dorsal muscles near the vertebral column was considered. Main results. The average E-field magnitude was predicted to be above 0.15 V m-1 in spinal cord regions located between the electrodes. L2-T8 and T8-rIC montages resulted in the highest E-field magnitudes in lumbar and sacral spinal segments (>0.30 V m-1). E-field longitudinal component is 3 to 6 times higher than the ventral-dorsal and right-left components in both the spinal-GM and WM. Anatomical features such as CSF narrowing due to vertebrae bony edges or disks intrusions in the spinal canal correlate with local maxima positions. Significance. Computational modelling studies can provide detailed information regarding the electric field in the spinal cord during tsDCS. They are important to guide the design of clinical tsDCS protocols that optimize stimulation of application-specific spinal targets.

  6. Direct Imaging of Natural Fractures and Stress Compartments Stimulated by Hydraulic Fracturing

    Science.gov (United States)

    Lacazette, A.; Vermilye, J. M.

    2014-12-01

    This contribution will present results from passive seismic studies of hydraulic fracture treatments in North American and Asian basins. One of the key data types is a comparatively new surface-based seismic imaging product - "Tomographic Fracture Images®" (TFI®). The procedure is an extension of Seismic Emission Tomography (SET), which is well-established and widely used. Conventional microseismic results - microearthquake hypocenter locations, magnitudes, and focal mechanism solutions - are also obtained from the data via a branch of the processing workflow. TFI is accomplished by summing the individual time steps in a multidimensional SET hypervolume over extended periods of time, such as an entire frac stage. The dimensions of a SET hypervolume are the X, Y, and Z coordinates of the voxels, the time step (typically on the order of 100 milliseconds), and the seismic activity value. The resulting summed volume is skeletonized to produce images of the main fracture surfaces, which are known to occupy the maximum activity surfaces of the high activity clouds from theory, field studies, and experiments. The orientation vs. area of the resulting TFIs can be analyzed in detail and compared with independent data sets such as volumetric structural attributes from reflection seismic data and borehole fracture data. We find that the primary effect of hydraulic fracturing is to stimulate preexisting natural fracture networks and faults. The combination of TFIs with hypocenter distributions and microearthquake focal mechanisms provides detailed information on subsurface stress compartmentalization. Faults are directly imaged which allows discrimination of fault planes from auxiliary planes of focal mechanism solutions. Examples that will be shown include simultaneous movement on a thrust fault and tear fault and examples of radically different stress compartments (e.g. extensional vs. wrench faulting) stimulated during a single hydraulic fracture treatment. The figure

  7. Modulation of Speech Motor Learning with Transcranial Direct Current Stimulation of the Inferior Parietal Lobe

    Directory of Open Access Journals (Sweden)

    Mickael L. D. Deroche

    2017-12-01

    Full Text Available The inferior parietal lobe (IPL is a region of the cortex believed to participate in speech motor learning. In this study, we investigated whether transcranial direct current stimulation (tDCS of the IPL could influence the extent to which healthy adults (1 adapted to a sensory alteration of their own auditory feedback, and (2 changed their perceptual representation. Seventy subjects completed three tasks: a baseline perceptual task that located the phonetic boundary between the vowels /e/ and /a/; a sensorimotor adaptation task in which subjects produced the word “head” under conditions of altered or unaltered feedback; and a post-adaptation perceptual task identical to the first. Subjects were allocated to four groups which differed in current polarity and feedback manipulation. Subjects who received anodal tDCS to their IPL (i.e., presumably increasing cortical excitability lowered their first formant frequency (F1 by 10% in opposition to the upward shift in F1 in their auditory feedback. Subjects who received the same stimulation with unaltered feedback did not change their production. Subjects who received cathodal tDCS to their IPL (i.e., presumably decreasing cortical excitability showed a 5% adaptation to the F1 alteration similar to subjects who received sham tDCS. A subset of subjects returned a few days later to reiterate the same protocol but without tDCS, enabling assessment of any facilitatory effects of the previous tDCS. All subjects exhibited a 5% adaptation effect. In addition, across all subjects and for the two recording sessions, the phonetic boundary was shifted toward the vowel /e/ being repeated, consistently with the selective adaptation effect, but a correlation between perception and production suggested that anodal tDCS had enhanced this perceptual shift. In conclusion, we successfully demonstrated that anodal tDCS could (1 enhance the motor adaptation to a sensory alteration, and (2 potentially affect the

  8. Assessment of anodal and cathodal transcranial direct current stimulation (tDCS) on MMN-indexed auditory sensory processing.

    Science.gov (United States)

    Impey, Danielle; de la Salle, Sara; Knott, Verner

    2016-06-01

    Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation which uses a very weak constant current to temporarily excite (anodal stimulation) or inhibit (cathodal stimulation) activity in the brain area of interest via small electrodes placed on the scalp. Currently, tDCS of the frontal cortex is being used as a tool to investigate cognition in healthy controls and to improve symptoms in neurological and psychiatric patients. tDCS has been found to facilitate cognitive performance on measures of attention, memory, and frontal-executive functions. Recently, a short session of anodal tDCS over the temporal lobe has been shown to increase auditory sensory processing as indexed by the Mismatch Negativity (MMN) event-related potential (ERP). This preliminary pilot study examined the separate and interacting effects of both anodal and cathodal tDCS on MMN-indexed auditory pitch discrimination. In a randomized, double blind design, the MMN was assessed before (baseline) and after tDCS (2mA, 20min) in 2 separate sessions, one involving 'sham' stimulation (the device is turned off), followed by anodal stimulation (to temporarily excite cortical activity locally), and one involving cathodal stimulation (to temporarily decrease cortical activity locally), followed by anodal stimulation. Results demonstrated that anodal tDCS over the temporal cortex increased MMN-indexed auditory detection of pitch deviance, and while cathodal tDCS decreased auditory discrimination in baseline-stratified groups, subsequent anodal stimulation did not significantly alter MMN amplitudes. These findings strengthen the position that tDCS effects on cognition extend to the neural processing of sensory input and raise the possibility that this neuromodulatory technique may be useful for investigating sensory processing deficits in clinical populations. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. A Randomized Double-Blind Sham-Controlled Study of Transcranial Direct Current Stimulation for Treatment-Resistant Major Depression

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    Daniel eBlumberger

    2012-08-01

    Full Text Available Objectives: Transcranial direct current stimulation (tDCS has demonstrated some efficacy in treatment-resistant major depression (TRD. The majority of previous controlled studies have used anodal stimulation to the left dorsolateral prefrontal cortex (DLPFC and a control location such as the supraorbital region on for the cathode. Several open label studies have suggested effectiveness from anodal stimulation to the left DLPFC combined with cathodal stimulation to the right DLPFC. Thus, this study evaluated the efficacy of tDCS using anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC compared to sham tDCS. Methods: Subjects between the ages of 18 and 65 were recruited from a tertiary care university hospital. Twenty-four subjects with TRD and a 17-item Hamilton Depression Rating Scale (HDRS greater than 21 were randomized to receive tDCS or sham tDCS. The rates of remission were compared between the two treatment groups.Results: The remission rates did not differ significantly between the two groups using an intention to treat analysis. More subjects in the active tDCS group had failed a course of electroconvulsive therapy in the current depressive episode. Side effects did not differ between the two groups and in general the treatment was very well tolerated. Conclusion: Anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC was not efficacious in TRD. However, a number of methodological limitations warrant caution in generalizing from this study. Ongoing, controlled studies should provide further clarification on the efficacy of this stimulation configuration in TRD.

  10. Non-invasive brain stimulation and computational models in post-stroke aphasic patients: single session of transcranial magnetic stimulation and transcranial direct current stimulation. A randomized clinical trial

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    Michele Devido dos Santos

    2017-11-01

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: Patients undergoing the same neuromodulation protocol may present different responses. Computational models may help in understanding such differences. The aims of this study were, firstly, to compare the performance of aphasic patients in naming tasks before and after one session of transcranial direct current stimulation (tDCS, transcranial magnetic stimulation (TMS and sham, and analyze the results between these neuromodulation techniques; and secondly, through computational model on the cortex and surrounding tissues, to assess current flow distribution and responses among patients who received tDCS and presented different levels of results from naming tasks. DESIGN AND SETTING: Prospective, descriptive, qualitative and quantitative, double blind, randomized and placebo-controlled study conducted at Faculdade de Ciências Médicas da Santa Casa de São Paulo. METHODS: Patients with aphasia received one session of tDCS, TMS or sham stimulation. The time taken to name pictures and the response time were evaluated before and after neuromodulation. Selected patients from the first intervention underwent a computational model stimulation procedure that simulated tDCS. RESULTS: The results did not indicate any statistically significant differences from before to after the stimulation.The computational models showed different current flow distributions. CONCLUSIONS: The present study did not show any statistically significant difference between tDCS, TMS and sham stimulation regarding naming tasks. The patients’responses to the computational model showed different patterns of current distribution.

  11. Autism-relevant traits interact with temporoparietal junction stimulation effects on social cognition: a high-definition transcranial direct current stimulation and electroencephalography study.

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    Donaldson, Peter H; Kirkovski, Melissa; Rinehart, Nicole J; Enticott, Peter G

    2018-03-01

    The temporoparietal junction (TPJ) is implicated in mental and emotional state attribution, processes associated with autism-relevant traits. Transcranial direct current stimulation (tDCS) to the TPJ can influence social-cognitive performance. However, associations with electrophysiology and autism-relevant traits remain relatively unexamined. This study had two aims: first, exploring links between Autism-Spectrum Quotient (AQ) scores and social-cognitive performance; second, examining interactions between AQ scores and high-definition-tDCS (HD-tDCS) applied to the right TPJ in terms of mental/emotional state attribution and neurophysiological outcomes. Fifty-three participants completed mental/emotional state attribution tasks before and after HD-tDCS. Pre-stimulation mental state attribution accuracy was reduced in participants with higher AQ Switching scores. Cathodal stimulation was associated with reduced emotion attribution performance in participants with higher AQ Switching and AQ Social scores (the latter at trend-level). Anodal stimulation more frequently interacted with AQ Social scores in terms of neurophysiology, in particular regarding reduced delta power in the left compared to right TPJ, and trend-level positive interactions with P100 and P300 latencies during the emotion recognition task. Elements of attention/switching (AQ Switching) may subserve or underpin elements of social cognition (AQ Social), and cathodal and anodal stimulation may have differing effects depending on trait levels in these domains. This study makes an important and original contribution in terms of increasing understanding of how such trait-level variation might interact with the effects of tDCS and also extending previous studies with regard to understanding potential roles of the rTPJ in both attention and social cognition and how autism-relevant traits might influence TPJ function. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Electrophysiological and Behavioral Effects of Combined Transcranial Direct Current Stimulation and Alcohol Approach Bias Retraining in Hazardous Drinkers

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    den Uyl, T.E.; Gladwin, T.E.; Wiers, R.W.

    2016-01-01

    BACKGROUND: Cognitive bias modification (CBM) can be used to retrain automatic approach tendencies for alcohol. We investigated whether changing cortical excitability with transcranial direct current stimulation (tDCS) could enhance CBM effects in hazardous drinkers. We also studied the underlying

  13. Does transcranial direct current stimulation affect the learning of a fine sequential hand motor skill with motor imagery?

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    Sobierajewicz, Jagna; Jaskowski, Wojciech; van der Lubbe, Robert Henricus Johannes

    2017-01-01

    Learning a fine sequential hand motor skill, comparable to playing the piano or learning to type, improves not only due to physical practice, but also due to motor imagery. Previous studies revealed that transcranial direct current stimulation (tDCS) and motor imagery independently affect motor

  14. Slow oscillating transcranial direct current stimulation during sleep has a sleep-stabilizing effect in chronic insomnia: a pilot study.

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    Saebipour, Mohammad R; Joghataei, Mohammad T; Yoonessi, Ali; Sadeghniiat-Haghighi, Khosro; Khalighinejad, Nima; Khademi, Soroush

    2015-10-01

    Recent evidence suggests that lack of slow-wave activity may play a fundamental role in the pathogenesis of insomnia. Pharmacological approaches and brain stimulation techniques have recently offered solutions for increasing slow-wave activity during sleep. We used slow (0.75 Hz) oscillatory transcranial direct current stimulation during stage 2 of non-rapid eye movement sleeping insomnia patients for resonating their brain waves to the frequency of sleep slow-wave. Six patients diagnosed with either sleep maintenance or non-restorative sleep insomnia entered the study. After 1 night of adaptation and 1 night of baseline polysomnography, patients randomly received sham or real stimulation on the third and fourth night of the experiment. Our preliminary results show that after termination of stimulations (sham or real), slow oscillatory transcranial direct current stimulation increased the duration of stage 3 of non-rapid eye movement sleep by 33 ± 26 min (P = 0.026), and decreased stage 1 of non-rapid eye movement sleep duration by 22 ± 17.7 min (P = 0.028), compared with sham. Slow oscillatory transcranial direct current stimulation decreased stage 1 of non-rapid eye movement sleep and wake time after sleep-onset durations, together, by 55.4 ± 51 min (P = 0.045). Slow oscillatory transcranial direct current stimulation also increased sleep efficiency by 9 ± 7% (P = 0.026), and probability of transition from stage 2 to stage 3 of non-rapid eye movement sleep by 20 ± 17.8% (P = 0.04). Meanwhile, slow oscillatory transcranial direct current stimulation decreased transitions from stage 2 of non-rapid eye movement sleep to wake by 12 ± 6.7% (P = 0.007). Our preliminary results suggest a sleep-stabilizing role for the intervention, which may mimic the effect of sleep slow-wave-enhancing drugs. © 2015 European Sleep Research Society.

  15. Direct electrical stimulation using a battery-operated device for induction and modulation of colonic contractions in pigs.

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    Bertschi, Mattia; Schlageter, Vincent; Vesin, Jean-Marc; Aellen, Steve; Peloponissios, Nicolas; D'Ambrogio, Aris; Wiesel, Paul Herman; Givel, Jean-Claude; Kucera, Pavel; Virag, Nathalie

    2010-07-01

    Direct electrical stimulation of the colon offers a promising approach for the induction of propulsive colonic contractions by using an implantable device. The objective of this study was to assess the feasibility to induce colonic contractions using a commercially available battery-operated stimulator (maximum pulse width of 1 ms and maximum amplitude of 10 V). Three pairs of pacing electrodes were inserted into the cecal seromuscular layer of anesthetized pigs. During a first set of in vivo experiments conducted on six animals, a pacing protocol leading to cecum contractions was determined: stimulation bursts with 1 ms pulse width, 10 V amplitude (7-15 mA), 120 Hz frequency, and 30-s burst duration, repeated every 2-5 min. In a second testing phase, an evaluation of the pacing protocol was performed in four animals (120 stimulation bursts in total). By using the battery-operated stimulator, contractions of the cecum and movement of contents could be induced in 92% of all stimulations. A cecal shortening of about 30% and an average intraluminal pressure increase of 10.0 +/- 6.0 mmHg were observed.

  16. Transcranial direct current stimulation versus user training on improving online myoelectric control for amputees

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    Pan, Lizhi; Zhang, Dingguo; Jiang, Ning; Sheng, Xinjun; Zhu, Xiangyang

    2017-08-01

    Objective. Transcranial direct current stimulation (tDCS) and user training (UT) are two types of methods to improve myoelectric control performance for amputees. In this study, we compared the independent effect between tDCS and UT, and investigated the combined effect of tDCS and UT. Approach. An online paradigm of simultaneous and proportional control (SPC) based on electromyography (EMG) was adopted. The proposed experiments were conducted on six naïve unilateral trans-radial amputees. The subjects each received three types of 20 min interventions: active tDCS with motor training (tDCS  +  UT), active tDCS with quiet sitting (tDCS), and sham tDCS with motor training (UT). The interventions were applied at one week intervals in a randomized order. The subjects performed online control of a feedback arrow with two degrees of freedom (DoFs) to accomplish target reaching motor tasks in pre-sessions and post-sessions. We compared the performance, measured by completion rate, completion time, and efficiency coefficient, between pre-sessions and post-sessions. Main results. The results showed that the intervention tDCS  +  UT and tDCS significantly improved the online SPC performance (i.e. improved the completion rate; reduced the completion time; and improved the efficiency coefficient), while intervention UT did not significantly change the performance. The results also showed that the online SPC performance after intervention tDCS  +  UT and tDCS was not significantly different, but both were significantly better than that after intervention UT. Significance. tDCS could be an effective intervention to improve the online SPC performance in a short time.

  17. Moving Beyond the Brain: Transcutaneous Spinal Direct Current Stimulation in Post-Stroke Aphasia

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    Paola Marangolo

    2017-08-01

    Full Text Available Over the last 20 years, major advances in cognitive neuroscience have clearly shown that the language function is not restricted into the classical language areas but it involves brain regions, which had never previously considered. Indeed, recent lines of evidence have suggested that the processing of words associated to motor schemata, such as action verbs, modulates the activity of the sensorimotor cortex, which, in turn, facilitates its retrieval. To date, no studies have investigated whether the spinal cord, which is functionally connected to the sensorimotor system, might also work as an auxiliary support for language processing. We explored the combined effect of transcutaneous spinal direct current stimulation (tsDCS and language treatment in a randomized double-blind design for the recovery of verbs and nouns in 14 chronic aphasics. During each treatment, each subject received tsDCS (20 min, 2 mA over the thoracic vertebrae (10th vertebra in three different conditions: (1 anodic, (2 cathodic and (3 sham, while performing a verb and noun naming tasks. Each experimental condition was run in five consecutive daily sessions over 3 weeks. Overall, a significant greater improvement in verb naming was found during the anodic condition with respect to the other two conditions, which persisted at 1 week after the end of the treatment. No significant differences were present for noun naming among the three conditions. The hypothesis is advanced that anodic tsDCS might have influenced activity along the ascending somatosensory pathways, ultimately eliciting neurophysiological changes into the sensorimotor areas which, in turn, supported the retrieval of verbs. These results further support the evidence that action words, due to their sensorimotor semantic properties, are partly represented into the sensorimotor cortex. Moreover, they also document, for the first time, that tsDCS enhances verb recovery in chronic aphasia and it may

  18. Moving Beyond the Brain: Transcutaneous Spinal Direct Current Stimulation in Post-Stroke Aphasia

    Science.gov (United States)

    Marangolo, Paola; Fiori, Valentina; Shofany, Jacob; Gili, Tommaso; Caltagirone, Carlo; Cucuzza, Gabriella; Priori, Alberto

    2017-01-01

    Over the last 20 years, major advances in cognitive neuroscience have clearly shown that the language function is not restricted into the classical language areas but it involves brain regions, which had never previously considered. Indeed, recent lines of evidence have suggested that the processing of words associated to motor schemata, such as action verbs, modulates the activity of the sensorimotor cortex, which, in turn, facilitates its retrieval. To date, no studies have investigated whether the spinal cord, which is functionally connected to the sensorimotor system, might also work as an auxiliary support for language processing. We explored the combined effect of transcutaneous spinal direct current stimulation (tsDCS) and language treatment in a randomized double-blind design for the recovery of verbs and nouns in 14 chronic aphasics. During each treatment, each subject received tsDCS (20 min, 2 mA) over the thoracic vertebrae (10th vertebra) in three different conditions: (1) anodic, (2) cathodic and (3) sham, while performing a verb and noun naming tasks. Each experimental condition was run in five consecutive daily sessions over 3 weeks. Overall, a significant greater improvement in verb naming was found during the anodic condition with respect to the other two conditions, which persisted at 1 week after the end of the treatment. No significant differences were present for noun naming among the three conditions. The hypothesis is advanced that anodic tsDCS might have influenced activity along the ascending somatosensory pathways, ultimately eliciting neurophysiological changes into the sensorimotor areas which, in turn, supported the retrieval of verbs. These results further support the evidence that action words, due to their sensorimotor semantic properties, are partly represented into the sensorimotor cortex. Moreover, they also document, for the first time, that tsDCS enhances verb recovery in chronic aphasia and it may represent a

  19. Effects of Transcranial Direct Current Stimulation (tDCS) on Human Memory.

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    Matzen, Laura E.; Trumbo, Michael Christopher Stefan

    2014-10-01

    Training a person in a new knowledge base or skill set is extremely time consuming and costly, particularly in highly specialized domains such as the military and the intelligence community. Recent research in cognitive neuroscience has suggested that a technique called transcranial direct current stimulation (tDCS) has the potential to revolutionize training by enabling learners to acquire new skills faster, more efficiently, and more robustly (Bullard et al., 2011). In this project, we tested the effects of tDCS on two types of memory performance that are critical for learning new skills: associative memory and working memory. Associative memory is memory for the relationship between two items or events. It forms the foundation of all episodic memories, so enhancing associative memory could provide substantial benefits to the speed and robustness of learning new information. We tested the effects of tDCS on associative memory, using a real-world associative memory task: remembering the links between faces and names. Working memory refers to the amount of information that can be held in mind and processed at one time, and it forms the basis for all higher-level cognitive processing. We investigated the degree of transfer between various working memory tasks (the N-back task as a measure of verbal working memory, the rotation-span task as a measure of visuospatial working memory, and Raven's progressive matrices as a measure of fluid intelligence) in order to determine if tDCS-induced facilitation of performance is task-specific or general.

  20. Action of methotrexate and tofacitinib on directly stimulated and bystander-activated lymphocytes.

    Science.gov (United States)

    Piscianz, Elisa; Candilera, Vanessa; Valencic, Erica; Loganes, Claudia; Paron, Greta; De Iudicibus, Sara; Decorti, Giuliana; Tommasini, Alberto

    2016-07-01

    Chronic inflammation associated with autoimmune activation is characteristic of rheumatic diseases from childhood to adulthood. In recent decades, significant improvements in the treatment of these types of disease have been achieved using disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) and, more recently, using biologic inhibitors. The recent introduction of kinase inhibitors (for example, tofacitinib; Tofa) further increases the available ARDs. However, there are patients that do not respond to any treatment strategies, for whom combination therapies are proposed. The data regarding the combined action of different drugs is lacking and the knowledge of the mechanisms of ARDs and their actions upon pathogenic lymphocytes, which are hypothesized to sustain disease, is poor. An in vitro model of inflammation was developed in the current study, in which stimulated and unstimulated lymphocytes were cultured together, but tracked separately, to investigate the action of MTX and Tofa on the two populations. By analysing lymphocyte proliferation and activation, and cytokine secretion in the culture supernatants, it was established that, due to the presence of activated cells, unstimulated cells underwent a bystander activation that was modulated by the ARDs. Additionally, varying administration schedules were demonstrated to affect lymphocytes differently in vitro, either directly or via bystander activation. Furthermore, MTX and Tofa exerted different effects; while MTX showed an antiproliferative effect, Tofa marginally effected activation, although only a slight antiproliferative action, which could be potentiated by sequential treatment with MTX. Thus, it was hypothesized that these differences may be exploited in sequential therapeutic strategies, to maximize the anti‑rheumatic effect. These findings are notable and must be accounted for, as bystander‑activated cells in vivo could contribute to the spread of autoimmune activation

  1. Transcranial direct current stimulation reduces negative affect but not cigarette craving in overnight abstinent smokers

    Directory of Open Access Journals (Sweden)

    Jiansong eXu

    2013-09-01

    Full Text Available Transcranial direct current stimulation (tDCS can enhance cognitive control functions including attention and top-down regulation over negative affect and substance craving in both healthy and clinical populations, including early abstinent (~1.5 h smokers. The aim of this study was to assess whether tDCS modulates negative affect, cigarette craving, and attention of overnight abstinent tobacco dependent smokers. In this study, 24 smokers received a real and a sham session of tDCS after overnight abstinence from smoking on two different days. We applied anode to the left dorsal lateral prefrontal cortex (DLPFC and cathode to the right supra orbital area for 20min with a current of 2.0mA. We used self-report questionnaires Profile of Mood State (POMS to assess negative affect and Urge to Smoke (UTS Scale to assess craving for cigarette smoking, and a computerized visual target identification task to assess attention immediately before and after each tDCS. Smokers reported significantly greater reductions in POMS scores of total mood disturbance and scores of tension-anxiety, depression-dejection, and confusion-bewilderment subscales after real relative to sham tDCS. Furthermore, this reduction in negative affect positively correlated with the level of nicotine dependence as assessed by Fagerström scale. However, reductions in cigarette craving after real vs. sham tDCS did not differ, nor were there differences in reaction time or hit rate change on the visual task. Smokers did not report significant side effects of tDCS. This study demonstrates the safety of tDCS and its promising effect in ameliorating negative affect in overnight abstinent smokers. Its efficacy in treating tobacco dependence deserves further investigation.

  2. Interference effects of transcranial direct current stimulation over the right frontal cortex and adrenergic system on conditioned fear.

    Science.gov (United States)

    Nasehi, Mohammad; Soltanpour, Reyhaneh; Ebrahimi-Ghiri, Mohaddeseh; Zarrabian, Shahram; Zarrindast, Mohammad-Reza

    2017-11-01

    The effects of pharmacological interventions on fear memory have widely been studied, but there are very few studies about the effects of brain electrical stimulation on fear memory function. Therefore, our aim was to determine whether anodal/cathodal transcranial direct current stimulation (tDCS) over the right frontal cortex would modify propranolol-induced contextual and auditory fear memory deficits, before or after training. The adult NMRI male mice were randomly assigned into three groups: the sham group, the anodal tDCS group, and the cathodal tDCS group. Fear memories were evaluated using a classical fear conditioning apparatus. While the anodal stimulation did not affect fear retrieval, post-training cathodal stimulation improved fear memory retrieval. Regardless of when propranolol (0.1 mg/kg) was administered, it impaired fear memory retrieval. However, when anodal stimulation and propranolol were applied prior to the training, contextual fear memory retrieval was increased and auditory fear memory was reversed. An enhanced contextual retrieval was also observed when propranolol was administered prior to the training and stimulation occurred after the training. Only when the stimulation occurred prior to the training and propranolol was administered after the training was there a selective improvement in contextual fear memory retrieval, leaving the auditory fear memory retrieval impaired. Interestingly, cathodal stimulation improved the effects of propranolol on auditory fear memory only when it occurred prior to the training. The results highlight possible improving effects for anodal/cathodal tDCS on propranolol-induced deficits on fear memories. The timing of the interventions related to the specific phases of memory formation is important in modulating fear behaviors.

  3. Anodal transcranial direct current stimulation of the left dorsolateral prefrontal cortex enhances emotion recognition in depressed patients and controls.

    Science.gov (United States)

    Brennan, Sean; McLoughlin, Declan M; O'Connell, Redmond; Bogue, John; O'Connor, Stephanie; McHugh, Caroline; Glennon, Mark

    2017-05-01

    Transcranial direct current stimulation (tDCS) can enhance a range of neuropsychological functions but its efficacy in addressing clinically significant emotion recognition deficits associated with depression is largely untested. A randomized crossover placebo controlled study was used to investigate the effects of tDCS over the left dorsolateral prefrontal cortex (L-DLPFC) on a range of neuropsychological variables associated with depression as well as neural activity in the associated brain region. A series of computerized tests was administered to clinical (n = 17) and control groups (n = 20) during sham and anodal (1.5 mA) stimulation. Anodal tDCS led to a significant main effect for overall emotion recognition (p = .02), with a significant improvement in the control group (p = .04). Recognition of disgust was significantly greater in the clinical group (p = .01). Recognition of anger was significantly improved for the clinical group (p = .04) during anodal stimulation. Differences between groups for each of the six emotions at varying levels of expression found that at 40% during anodal stimulation, happy recognition significantly improved for the clinical group (p = .01). Anger recognition at 80% during anodal stimulation significantly improved for the clinical group (p = .02). These improvements were observed in the absence of any change in psychomotor speed or trail making ability during anodal stimulation. Working memory significantly improved during anodal stimulation for the clinical group but not for controls (p = .03). The tentative findings of this study indicate that tDCS can have a neuromodulatory effect on a range of neuropsychological variables. However, it is clear that there was a wide variation in responses to tDCS and that individual difference and different approaches to testing and stimulation have a significant impact on final outcomes. Nonetheless, tDCS remains a promising tool for future neuropsychological research.

  4. Dataset of acute repeated sessions of bifrontal transcranial direct current stimulation for treatment of intractable tinnitus: A randomized controlled trial

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    Ali Yadollahpour

    2017-12-01

    Full Text Available Transcranial direct current stimulation (tDCS has reportedly shown promising therapeutic effects for tinnitus (Forogh et al., 2016; Joos et al., 2014 [1,2]. Studies are ongoing to determine optimum treatment protocol and the site of stimulation. Findings of the early studies are heterogeneous and most studies have focused on single session tDCS and short follow-up periods. There is no study on repeated sessions of tDCS with long term follow-up. This study presents the results of a randomized clinical trial investigating the therapeutic effects of acute multi-session tDCS over dorsolateral prefrontal cortex (DLPFC on tinnitus symptoms and comorbid depression and anxiety in patients with chronic intractable tinnitus. The dataset includes the demographic information, audiometric assessments, tinnitus specific characteristics, and the response variables of the study. The response variables included the scores of tinnitus handicap inventory (THI, tinnitus loudness and tinnitus related distress based on 0–10 numerical visual analogue scale (VAS scores, beck depression inventory (BDI-II and beck anxiety inventory (BAI scores. The dataset included the scores of THI pre and immediately post intervention, and at one month follow-up; the tinnitus loudness and distress scores prior to intervention, and immediately, one hour, one week, and at one month after the last stimulation session. In addition, the BDI-II, and BAI scores pre and post intervention are included. The data of the real (n=25 and sham tDCS (n=17 groups are reported. The main manuscript of this dataset is 'Acute repeated sessions of bifrontal transcranial direct current stimulation for treatment of intractable tinnitus: a randomized controlled trial' (Bayat et al., submitted for publication [3]. Keywords: Transcranial direct current stimulation, Acute stimulations, Tinnitus, Depression, Anxiety, DLPFC

  5. Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory.

    Science.gov (United States)

    Jacobs, Joshua; Miller, Jonathan; Lee, Sang Ah; Coffey, Tom; Watrous, Andrew J; Sperling, Michael R; Sharan, Ashwini; Worrell, Gregory; Berry, Brent; Lega, Bradley; Jobst, Barbara C; Davis, Kathryn; Gross, Robert E; Sheth, Sameer A; Ezzyat, Youssef; Das, Sandhitsu R; Stein, Joel; Gorniak, Richard; Kahana, Michael J; Rizzuto, Daniel S

    2016-12-07

    Deep brain stimulation (DBS) has shown promise for treating a range of brain disorders and neurological conditions. One recent study showed that DBS in the entorhinal region improved the accuracy of human spatial memory. Based on this line of work, we performed a series of experiments to more fully characterize the effects of DBS in the medial temporal lobe on human memory. Neurosurgical patients with implanted electrodes performed spatial and verbal-episodic memory tasks. During the encoding periods of both tasks, subjects received electrical stimulation at 50 Hz. In contrast to earlier work, electrical stimulation impaired memory performance significantly in both spatial and verbal tasks. Stimulation in both the entorhinal region and hippocampus caused decreased memory performance. These findings indicate that the entorhinal region and hippocampus are causally involved in human memory and suggest that refined methods are needed to use DBS in these regions to improve memory. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Transcranial direct current stimulation in obsessive-compulsive disorder: emerging clinical evidence and considerations for optimal montage of electrodes.

    Science.gov (United States)

    Senço, Natasha M; Huang, Yu; D'Urso, Giordano; Parra, Lucas C; Bikson, Marom; Mantovani, Antonio; Shavitt, Roseli G; Hoexter, Marcelo Q; Miguel, Eurípedes C; Brunoni, André R

    2015-07-01

    Neuromodulation techniques for obsessive-compulsive disorder (OCD) treatment have expanded with greater understanding of the brain circuits involved. Transcranial direct current stimulation (tDCS) might be a potential new treatment for OCD, although the optimal montage is unclear. To perform a systematic review on meta-analyses of repetitive transcranianal magnetic stimulation (rTMS) and deep brain stimulation (DBS) trials for OCD, aiming to identify brain stimulation targets for future tDCS trials and to support the empirical evidence with computer head modeling analysis. Systematic reviews of rTMS and DBS trials on OCD in Pubmed/MEDLINE were searched. For the tDCS computational analysis, we employed head models with the goal of optimally targeting current delivery to structures of interest. Only three references matched our eligibility criteria. We simulated four different electrodes montages and analyzed current direction and intensity. Although DBS, rTMS and tDCS are not directly comparable and our theoretical model, based on DBS and rTMS targets, needs empirical validation, we found that the tDCS montage with the cathode over the pre-supplementary motor area and extra-cephalic anode seems to activate most of the areas related to OCD.

  7. Treatment of Memory Disorders in Gulf War Illness with High-Definition Transcranial Direct Cortical Stimulation

    Science.gov (United States)

    2017-10-01

    Stimulation PRINCIPAL INVESTIGATOR: John Hart, Jr., M.D. RECIPIENT: The University of Texas at Dallas Richardson, TX 75080 REPORT DATE: October 2017 TYPE...including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing...Cortical Stimulation 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Dr. John Hart Jr. 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER

  8. Checkpoints to the Brain: Directing Myeloid Cell Migration to the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Meredith Harrison-Brown

    2016-12-01

    Full Text Available Myeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding of the unique properties of these cells have inspired interest in their use as delivery vehicles for therapeutic genes, proteins, and drugs, or as “assistants” in the clean-up of aggregated proteins and other molecules when existing drainage systems are no longer adequate. The trafficking of myeloid cells from the periphery to the central nervous system is subject to complex cellular and molecular controls with several ‘checkpoints’ from the blood to their destination in the brain parenchyma. As important components of the neurovascular unit, the functional state changes associated with lineage heterogeneity of myeloid cells are increasingly recognized as important for disease progression. In this review, we discuss some of the cellular elements associated with formation and function of the neurovascular unit, and present an update on the impact of myeloid cells on central nervous system (CNS diseases in the laboratory and the clinic. We then discuss emerging strategies for harnessing the potential of site-directed myeloid cell homing to the CNS, and identify promising avenues for future research, with particular emphasis on the importance of untangling the functional heterogeneity within existing myeloid subsets.

  9. Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells.

    Science.gov (United States)

    Xu, Xin; Francis, Richard; Wei, Chih Jen; Linask, Kaari L; Lo, Cecilia W

    2006-09-01

    Connexin 43 knockout (Cx43alpha1KO) mice have conotruncal heart defects that are associated with a reduction in the abundance of cardiac neural crest cells (CNCs) targeted to the heart. In this study, we show CNCs can respond to changing fibronectin matrix density by adjusting their migratory behavior, with directionality increasing and speed decreasing with increasing fibronectin density. However, compared with wild-type CNCs, Cx43alpha1KO CNCs show reduced directionality and speed, while CNCs overexpressing Cx43alpha1 from the CMV43 transgenic mice show increased directionality and speed. Altered integrin signaling was indicated by changes in the distribution of vinculin containing focal contacts, and altered temporal response of Cx43alpha1KO and CMV43 CNCs to beta1 integrin function blocking antibody treatment. High resolution motion analysis showed Cx43alpha1KO CNCs have increased cell protrusive activity accompanied by the loss of polarized cell movement. They exhibited an unusual polygonal arrangement of actin stress fibers that indicated a profound change in cytoskeletal organization. Semaphorin 3A, a chemorepellent known to inhibit integrin activation, was found to inhibit CNC motility, but in the Cx43alpha1KO and CMV43 CNCs, cell processes failed to retract with semaphorin 3A treatment. Immunohistochemical and biochemical analyses suggested close interactions between Cx43alpha1, vinculin and other actin-binding proteins. However, dye coupling analysis showed no correlation between gap junction communication level and fibronectin plating density. Overall, these findings indicate Cx43alpha1 may have a novel function in mediating crosstalk with cell signaling pathways that regulate polarized cell movement essential for the directional migration of CNCs.

  10. Finding paradise: cues directing the migration of the waterfall climbing Hawaiian gobioid Sicyopterus stimpsoni.

    Science.gov (United States)

    Leonard, G; Maie, T; Moody, K N; Schrank, G D; Blob, R W; Schoenfuss, H L

    2012-07-01

    A series of waterfall-climbing trials were conducted to identify cues that direct the climbing of juvenile Sicyopterus stimpsoni. In the first experiment, whether climbing juveniles preferentially ascend water sources with conspecifics or whether the presence of just stream water is sufficient to attract fish to ascend a climbing path were assessed. In the second experiment, whether climbing juveniles create a trail of mucus that facilitates the ability of conspecifics to follow their lead was determined. The results indicate that juvenile S. stimpsoni are less likely to climb in waters devoid of organic cues but are strongly attracted to stream water with or without the odour of conspecifics. Once climbing, performance did not differ for juveniles climbing in differing water choices, suggesting an all-or-nothing commitment once climbing commences. Climbing S. stimpsoni did produce a mucous trail while climbing that was associated with a mucous gland that dramatically increases in size just prior to juveniles gaining the ability to climb. The trail was not followed closely by subsequent juveniles traversing the same channel, however, suggesting only weak trail-following in waterfall climbing S. stimpsoni. Previous genetic studies suggest that juvenile S. stimpsoni do not home to natal streams in the face of strong near-shore oceanic currents. Instead, these fish appear primarily to rely on cues that suggest the presence of organic growth in streams, a factor that may indicate suitable habitat in an ever-changing stream environment but which may also be vulnerable to interference through human activity. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

  11. Intra-Subject Consistency and Reliability of Response Following 2 mA Transcranial Direct Current Stimulation.

    Science.gov (United States)

    Dyke, Katherine; Kim, Soyoung; Jackson, Georgina M; Jackson, Stephen R

    Transcranial direct current stimulation (tDCS) is a popular non-invasive brain stimulation technique that has been shown to influence cortical excitability. While polarity specific effects have often been reported, this is not always the case, and variability in both the magnitude and direction of the effects have been observed. We aimed to explore the consistency and reliability of the effects of tDCS by investigating changes in cortical excitability across multiple testing sessions in the same individuals. A within subjects design was used to investigate the effects of anodal and cathodal tDCS applied to the motor cortex. Four experimental sessions were tested for each polarity in addition to two sham sessions. Transcranial magnetic stimulation (TMS) was used to measure cortical excitability (TMS recruitment curves). Changes in excitability were measured by comparing baseline measures and those taken immediately following 20 minutes of 2 mA stimulation or sham stimulation. Anodal tDCS significantly increased cortical excitability at a group level, whereas cathodal tDCS failed to have any significant effects. The sham condition also failed to show any significant changes. Analysis of intra-subject responses to anodal stimulation across four sessions suggest that the amount of change in excitability across sessions was only weakly associated, and was found to have poor reliability across sessions (ICC = 0.276). The effects of cathodal stimulation show even poorer reliability across sessions (ICC = 0.137). In contrast ICC analysis for the two sessions of sham stimulation reflect a moderate level of reliability (ICC = .424). Our findings indicate that although 2 mA anodal tDCS is effective at increasing cortical excitability at group level, the effects are unreliable across repeated testing sessions within individual participants. Our results suggest that 2 mA cathodal tDCS does not significantly alter cortical excitability immediately following

  12. Differential effects of bihemispheric and unihemispheric transcranial direct current stimulation in young and elderly adults in verbal learning.

    Science.gov (United States)

    Fiori, Valentina; Nitsche, Michael; Iasevoli, Luigi; Cucuzza, Gabriella; Caltagirone, Carlo; Marangolo, Paola

    2017-03-15

    For the past few years, the potential of transcranial direct current stimulation (tDCS) for the treatment of several pathologies has been investigated. In the language domain, several studies, in healthy and brain-damaged populations, have already shown that tDCS is effective in enhancing naming, repetition and semantic word generation. In those studies, different tDCS electrode configurations have been tested, however, a direct comparison between different montages in verbal learning has never been conducted. In this study, we aimed to explore the impact of bihemispheric and unihemispheric tDCS on verbal learning task performance in two groups (young vs. elderly). Fifteen healthy volunteers participated per group. Each participant received three stimulation conditions: unihemispheric anodal tDCS over the left temporal area, bihemispheric tDCS over the left (anodal) and right (cathodal) temporal areas and a sham condition. During active stimulation, tDCS (20min, 2mA) was applied while each participant learned twenty pseudowords (arbitrarily assigned to corresponding pictures). No significant differences were found between the three conditions for the young group with regard to accuracy and vocal reaction times. In contrast, in the elderly group, real stimulation improved performance compared to sham but bihemispheric tDCS was more efficient than unilateral stimulation. These results suggest that bihemispheric stimulation is more effective in improving language learning but this effect is age-dependent. The hypothesis is advanced that cortical changes in the course of aging might differentially impact on tDCS efficacy on behavioral performance. These data may also have implications for treatment of stroke patients with language impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS).

    Science.gov (United States)

    Lefaucheur, Jean-Pascal; Antal, Andrea; Ayache, Samar S; Benninger, David H; Brunelin, Jérôme; Cogiamanian, Filippo; Cotelli, Maria; De Ridder, Dirk; Ferrucci, Roberta; Langguth, Berthold; Marangolo, Paola; Mylius, Veit; Nitsche, Michael A; Padberg, Frank; Palm, Ulrich; Poulet, Emmanuel; Priori, Alberto; Rossi, Simone; Schecklmann, Martin; Vanneste, Sven; Ziemann, Ulf; Garcia-Larrea, Luis; Paulus, Walter

    2017-01-01

    A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson's disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer's disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10-24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform t

  14. Sources of variation influencing concordance between functional MRI and direct cortical stimulation in brain tumor surgery

    Directory of Open Access Journals (Sweden)

    Melanie A Morrison

    2016-10-01

    Full Text Available Object: Preoperative functional magnetic resonance imaging (fMRI remains a promising method to aid in the surgical management of patients diagnosed with brain tumors. For patients that are candidates for awake craniotomies, surgical decisions can potentially be improved by fMRI but this depends on the level of concordance between preoperative brain maps and the maps provided by the gold standard intraoperative method, direct cortical stimulation (DCS. There have been numerous studies of the concordance between fMRI and DCS using sensitivity and specificity measures, however the results are variable across studies and the key factors influencing variability are not well understood. Thus, the present work addresses the influence of technical factors on fMRI and DCS concordance. Methods: Motor and language mapping data were collected for a group of glioma patients (n = 14 who underwent both preoperative fMRI and intraoperative DCS in an awake craniotomy procedure for tumor removal. Normative fMRI data were also acquired in a healthy control group (n = 12. The fMRI and DCS mapping data were co-registered; true positive (TP, true negative (TN, false positive (FP and false negative (FN occurrences were tabulated over the exposed brain surface. Sensitivity and specificity were measured for the total group, and the motor and language sub-groups. The influence of grid placement, fMRI statistical thresholding, and task standardization were assessed. Correlations between proportions of agreement and error were carefully scrutinized to evaluate concordance more in-depth. Results: Concordance was significantly better for motor versus language mapping. There was an inverse relationship between TP and TN with increasing statistical threshold, and FP dominated the total error. Sensitivity and specificity were reduced when tasks were not standardized across fMRI and DCS. Conclusions: Although the agreement between fMRI and DCS is good, variability is introduced

  15. Does the Longer Application of Anodal-Transcranial Direct Current Stimulation Increase Corticomotor Excitability Further? A Pilot Study

    Directory of Open Access Journals (Sweden)

    Shapour Jaberzadeh

    2012-08-01

    Full Text Available Introduction: Anodal transcranial direct current stimulation (a-tDCS of the primary motor cortex (M1 has been shown to be effective in increasing corticomotor excitability.  Methods: We investigated whether longer applications of a-tDCS coincide with greater increases in corticomotor excitability compared to shorter application of a-tDCS. Ten right-handed healthy participants received one session of a-tDCS (1mA current with shorter (10 min and longer (10+10 min stimulation durations applied to the left M1 of extensor carpi radialis muscle (ECR. Corticomotor excitability following application of a-tDCS was assessed at rest with transcranial magnetic stimulation (TMS elicited motor evoked potentials (MEP and compared with baseline data for each participant.  Results: MEP amplitudes were increased following 10 min of a-tDCS by 67% (p = 0.001 with a further increase (32% after the second 10 min of a-tDCS (p = 0.005. MEP amplitudes remained elevated at 15 min post stimulation compared to baseline values by 65% (p = 0.02.  Discussion: The results demonstrate that longer application of a-tDCS within the recommended safety limits, increases corticomotor excitability with after effects of up to 15 minutes post stimulation.

  16. Does the Longer Application of Anodal-Transcranial Direct Current Stimulation Increase Corticomotor Excitability Further? A Pilot Study

    Directory of Open Access Journals (Sweden)

    Shapour Jaberzadeh

    2012-09-01

    Full Text Available Introduction: Anodal transcranial direct current stimulation (a-tDCS of the primary motor cortex (M1 has been shown to be effective in increasing corticomotor excitability.Methods: We investigated whether longer applications of a-tDCS coincide with greater increases in corticomotor excitability compared to shorter application of a-tDCS. Ten right-handed healthy participants received one session of a-tDCS(1mA current with shorter (10 min and longer (10+10 min stimulation durationsapplied to the left M1 of extensor carpi radialis muscle (ECR. Corticomotorexcitability following application of a-tDCS was assessed at rest with transcranial magnetic stimulation (TMS elicited motor evoked otentials (MEP and compared with baseline data for each participant.Results: MEP amplitudes were increased following 10 min of a-tDCS by 67%(p = 0.001 with a further increase (32% after the second 10 min of a-tDCS (p = 0.005. MEP amplitudes remained elevated at 15 min post stimulation compared to baseline values by 65% (p = 0.02.Discussion: The results demonstrate that longer application of a-tDCS within the recommended safety limits, increases corticomotor excitability with after effects of up to 15 minutes post stimulation.

  17. Cathodal Transcranial Direct Current Stimulation Over Left Dorsolateral Prefrontal Cortex Area Promotes Implicit Motor Learning in a Golf Putting Task.

    Science.gov (United States)

    Zhu, Frank F; Yeung, Andrew Y; Poolton, Jamie M; Lee, Tatia M C; Leung, Gilberto K K; Masters, Rich S W

    2015-01-01

    Implicit motor learning is characterized by low dependence on working memory and stable performance despite stress, fatigue, or multi-tasking. However, current paradigms for implicit motor learning are based on behavioral interventions that are often task-specific and limited when applied in practice. To investigate whether cathodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) area during motor learning suppressed working memory activity and reduced explicit verbal-analytical involvement in movement control, thereby promoting implicit motor learning. Twenty-seven healthy individuals practiced a golf putting task during a Training Phase while receiving either real cathodal tDCS stimulation over the left DLPFC area or sham stimulation. Their performance was assessed during a Test phase on another day. Verbal working memory capacity was assessed before and after the Training Phase, and before the Test Phase. Compared to sham stimulation, real stimulation suppressed verbal working memory activity after the Training Phase, but enhanced golf putting performance during the Training Phase and the Test Phase, especially when participants were required to multi-task. Cathodal tDCS over the left DLPFC may foster implicit motor learning and performance in complex real-life motor tasks that occur during sports, surgery or motor rehabilitation. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Transcranial direct current stimulation over the primary motor vs prefrontal cortex in refractory chronic migraine: A pilot randomized controlled trial.

    Science.gov (United States)

    Andrade, Suellen Marinho; de Brito Aranha, Renata Emanuela Lyra; de Oliveira, Eliane Araújo; de Mendonça, Camila Teresa Ponce Leon; Martins, Wanessa Kallyne Nascimento; Alves, Nelson Torro; Fernández-Calvo, Bernardino

    2017-07-15

    Although transcranial direct current stimulation (tDCS) represents a therapeutic option for the prophylaxis of chronic migraine, the target area for application of the electrical current to the cortex has not yet been well established. Here we sought to determine whether a treatment protocol involving 12 sessions of 2mA, 20min anodal stimulation of the left primary motor (M1) or dorsolateral prefrontal cortex (DLPFC) could offer clinical benefits in the management of pain from migraine. Thirteen participants were assessed before and after treatment, using the Headache Impact Test-6, Visual Analogue Scale and Medical Outcomes Study 36 - Item Short - Form Health Survey. After treatment, group DLPFC exhibited a better performance compared with groups M1 and sham. On intragroup comparison, groups DLPFC and M1 exhibited a greater reduction in headache impact and pain intensity and a higher quality of life after treatment. No significant change was found in group sham. The participants in group M1 exhibited more adverse effects, especially headache, heartburn, and sleepiness, than did those in the other two groups. Transcranial direct current stimulation is a safe and efficacious technique for treating chronic migraine. However, it should be kept in mind that the site of cortical stimulation might modulate the patient's response to treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Effects of transcranial direct current stimulation over left dorsolateral pFC on the attentional blink depend on individual baseline performance

    NARCIS (Netherlands)

    London, R.E.; Slagter, H.A.

    2015-01-01

    Selection mechanisms that dynamically gate only relevant perceptual information for further processing and sustained representation in working memory are critical for goal-directed behavior. We examined whether this gating process can be modulated by anodal transcranial direct current stimulation

  20. Stimulated Raman signals at conical intersections: Ab initio surface hopping simulation protocol with direct propagation of the nuclear wave function

    Energy Technology Data Exchange (ETDEWEB)

    Kowalewski, Markus, E-mail: mkowalew@uci.edu; Mukamel, Shaul, E-mail: smukamel@uci.edu [Department of Chemistry, University of California, Irvine, California 92697-2025 (United States)

    2015-07-28

    Femtosecond Stimulated Raman Spectroscopy (FSRS) signals that monitor the excited state conical intersections dynamics of acrolein are simulated. An effective time dependent Hamiltonian for two C—H vibrational marker bands is constructed on the fly using a local mode expansion combined with a semi-classical surface hopping simulation protocol. The signals are obtained by a direct forward and backward propagation of the vibrational wave function on a numerical grid. Earlier work is extended to fully incorporate the anharmonicities and intermode couplings.

  1. Stimulated Raman signals at conical intersections: Ab initio surface hopping simulation protocol with direct propagation of the nuclear wave function

    International Nuclear Information System (INIS)

    Kowalewski, Markus; Mukamel, Shaul

    2015-01-01

    Femtosecond Stimulated Raman Spectroscopy (FSRS) signals that monitor the excited state conical intersections dynamics of acrolein are simulated. An effective time dependent Hamiltonian for two C—H vibrational marker bands is constructed on the fly using a local mode expansion combined with a semi-classical surface hopping simulation protocol. The signals are obtained by a direct forward and backward propagation of the vibrational wave function on a numerical grid. Earlier work is extended to fully incorporate the anharmonicities and intermode couplings

  2. Inter-individual variability in optimal current direction for transcranial magnetic stimulation of the motor cortex

    DEFF Research Database (Denmark)

    Balslev, Daniela; Braet, Wouter; McAllister, Craig

    2007-01-01

    , stimulation in the majority of participants was most effective when the first current pulse flowed towards postero-lateral in the brain. However, in four participants, the optimal coil orientation deviated from this pattern. A principal component analysis using all eight orientations suggests that in our...

  3. The Effectiveness of Transcranial Direct Current Stimulation (tDCS on Working Memory in Patients with Major Depression

    Directory of Open Access Journals (Sweden)

    Mahboube Ebadi

    2017-08-01

    Full Text Available Abstract Background: The aim of this study was to evaluate the effectiveness of of transcranial direct current stimulation (tDCS on working memory in patients with major depression. Materials and Methods: The research method was quasi-experimental with pretest and post-test and follow-up with control group. The research population comprised female outpatient referrals to private psychiatric centers and psychological counseling centers in Tehran in the first half of 2016, They had received a diagnosis of depression by a psychiatrist at least once. Of these, 30 females were selected as a sample group with convenience sampling method and based on the criteria of inclusion and exclusion and were divided randomly into two groups , experimental (n = 15 and control (n = 15 group. The experimental group received transcranial direct current stimulation (tDCS in 10 sessions, While this intervention was not provided to the control group. The data were collected by N-BACK. Analysis of variance with repeated measurments was used to test the research hypothesis. Results: The results showed that transcranial direct current stimulation (tDCS had a significant effect on increasing working memory and the impact will continue to follow up. Conclusion: Therefore, this approach can be used to improve working memory in people with major depression.

  4. Modulation of Brain Activity with Noninvasive Transcranial Direct Current Stimulation (tDCS): Clinical Applications and Safety Concerns

    Science.gov (United States)

    Zhao, Haichao; Qiao, Lei; Fan, Dongqiong; Zhang, Shuyue; Turel, Ofir; Li, Yonghui; Li, Jun; Xue, Gui; Chen, Antao; He, Qinghua

    2017-01-01

    Transcranial direct current stimulation (tDCS) is a widely-used tool to induce neuroplasticity and modulate cortical function by applying weak direct current over the scalp. In this review, we first introduce the underlying mechanism of action, the brief history from discovery to clinical scientific research, electrode positioning and montages, and parameter setup of tDCS. Then, we review tDCS application in clinical samples including people with drug addiction, major depression disorder, Alzheimer's disease, as well as in children. This review covers the typical characteristics and the underlying neural mechanisms of tDCS treatment in such studies. This is followed by a discussion of safety, especially when the current intensity is increased or the stimulation duration is prolonged. Given such concerns, we provide detailed suggestions regarding safety procedures for tDCS operation. Lastly, future research directions are discussed. They include foci on the development of multi-tech combination with tDCS such as with TMS and fMRI; long-term behavioral and morphological changes; possible applications in other research domains, and more animal research to deepen the understanding of the biological and physiological mechanisms of tDCS stimulation. PMID:28539894

  5. Transcranial direct current stimulation (tDCS) for idiopathic Parkinson's disease.

    Science.gov (United States)

    Elsner, Bernhard; Kugler, Joachim; Pohl, Marcus; Mehrholz, Jan

    2016-07-18

    Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder, with the severity of the disability usually increasing with disease duration. IPD affects patients' health-related quality of life, disability, and impairment. Current rehabilitation approaches have limited effectiveness in improving outcomes in patients with IPD, but a possible adjunct to rehabilitation might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability, and hence to improve these outcomes in IPD. To assess the effectiveness of tDCS in improving motor and non-motor symptoms in people with IPD. We searched the following databases (until February 2016): the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library ; 2016 , Issue 2), MEDLINE, EMBASE, CINAHL, AMED, Science Citation Index, the Physiotherapy Evidence Database (PEDro), Rehabdata, and Inspec. In an effort to identify further published, unpublished, and ongoing trials, we searched trial registers and reference lists, handsearched conference proceedings, and contacted authors and equipment manufacturers. We included only randomised controlled trials (RCTs) and randomised controlled cross-over trials that compared tDCS versus control in patients with IPD for improving health-related quality of life , disability, and impairment. Two review authors independently assessed trial quality (JM and MP) and extracted data (BE and JM). If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports. We included six trials with a total of 137 participants. We found two studies with 45 participants examining the effects of tDCS compared to control (sham tDCS) on our primary outcome measure, impairment, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS). There was very low quality evidence for no effect of tDCS on change in global UPDRS score ( mean

  6. The effect of left frontal transcranial direct-current stimulation on propranolol-induced fear memory acquisition and consolidation deficits.

    Science.gov (United States)

    Nasehi, Mohammad; Khani-Abyaneh, Mozhgan; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2017-07-28

    Accumulating evidence supports the efficacy of transcranial direct current stimulation (tDCS) in modulating numerous cognitive functions. Despite the fact that tDCS has been used for the enhancement of memory and cognition, very few animal studies have addressed its impact on the modulation of fear memory. This study was designed to determine whether pre/post-training frontal tDCS application would alter fear memory acquisition and/or consolidation deficits induced by propranolol in NMRI mice. Results indicated that administration of β1-adrenoceptor blocker propranolol (0.1mg/kg) impaired fear memory retrieval. Pre/post-training application of anodal tDCS when propranolol was administered prior to training reversed contextual memory retrieval whereas only the anodal application prior to training could induce the same result in the auditory test. Meanwhile, anodal stimulation had no effect on fear memories by itself. Moreover, regardless of when cathode was applied and propranolol administered, their combination restored contextual memory retrieval, while only cathodal stimulation prior to training facilitated the contextual memory retrieval. Also, auditory memory retrieval was restored when cathodal stimulation and propranolol occurred prior to training but it was abolished when stimulation occurred after training and propranolol was administered prior to training. Collectively, our findings show that tDCS applied on the left frontal cortex of mice affects fear memory performance. This alteration seems to be task-dependent and varies depending on the nature and timing of the stimulation. In certain conditions, tDCS reverses the effect of propranolol. These results provide initial evidence to support the timely use of tDCS for the modulation of fear-related memories. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Pharmacological modulation of the short-lasting effects of antagonistic direct current-stimulation over the human motor cortex

    Directory of Open Access Journals (Sweden)

    Leila eChaieb

    2012-07-01

    Full Text Available Combined administration of transcranial direct current stimulation (tDCS with either pergolide (PGL or D-cycloserine (D-CYC can prolong the excitability-diminishing effects of cathodal, or the excitability enhancing effect of anodal stimulation for up to 24hrs poststimulation. However, it remains unclear whether the potentiation of the observed aftereffects is dominated by the polarity and duration of the stimulation, or the dual application of combined stimulation and drug administration. The present study looks at whether the aftereffects of oral administration of PGL (a D1/D2 agonist or D-CYC (a partial NMDA receptor agonist, in conjunction with the short duration antagonistic application of tDCS (either 5 min cathodal followed immediately by 5 min anodal or vice versa, that alone only induces short lasting aftereffects, can modulate cortical excitability in healthy human subjects, as revealed by a single-pulse MEP (motor-evoked-potential paradigm. Results indicate that the antagonistic application of DC currents induces short-term neuroplastic aftereffects that are dependent upon the polarity of the second application of short-duration tDCS. The application of D-cycloserine resulted in a reversal of this trend and so consequently a marked inhibition of cortical excitability with the cathodal-anodal stimulation order was observed. The administration of pergolide showed no significant aftereffects in either case. These results emphasise that the aftereffects of tDCS are dependent upon the stimulation orientation, and mirror the findings of other studies reporting the neuroplasticity inducing aftereffects of tDCS, and their prolongation when combined with the administration of CNS active drugs.

  8. Use of functional near-infrared spectroscopy to monitor cortical plasticity induced by transcranial direct current stimulation

    Science.gov (United States)

    Khan, Bilal; Hervey, Nathan; Stowe, Ann; Hodics, Timea; Alexandrakis, George

    2013-03-01

    Electrical stimulation of the human cortex in conjunction with physical rehabilitation has been a valuable approach in facilitating the plasticity of the injured brain. One such method is transcranial direct current stimulation (tDCS) which is a non-invasive method to elicit neural stimulation by delivering current through electrodes placed on the scalp. In order to better understand the effects tDCS has on cortical plasticity, neuroimaging techniques have been used pre and post tDCS stimulation. Recently, neuroimaging methods have discovered changes in resting state cortical hemodynamics after the application of tDCS on human subjects. However, analysis of the cortical hemodynamic activity for a physical task during and post tDCS stimulation has not been studied to our knowledge. A viable and sensitive neuroimaging method to map changes in cortical hemodynamics during activation is functional near-infrared spectroscopy (fNIRS). In this study, the cortical activity during an event-related, left wrist curl task was mapped with fNIRS before, during, and after tDCS stimulation on eight healthy adults. Along with the fNIRS optodes, two electrodes were placed over the sensorimotor hand areas of both brain hemispheres to apply tDCS. Changes were found in both resting state cortical connectivity and cortical activation patterns that occurred during and after tDCS. Additionally, changes to surface electromyography (sEMG) measurements of the wrist flexor and extensor of both arms during the wrist curl movement, acquired concurrently with fNIRS, were analyzed and related to the transient cortical plastic changes induced by tDCS.

  9. Effectiveness of anodal transcranial direct current stimulation in patients with chronic low back pain: Design, method and protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Luedtke Kerstin

    2011-12-01

    Full Text Available Abstract Background Electrical stimulation of central nervous system areas with surgically implanted stimulators has been shown to result in pain relief. To avoid the risks and side effects of surgery, transcranial direct current stimulation is an option to electrically stimulate the motor cortex through the skull. Previous research has shown that transcranial direct current stimulation relieves pain in patients with fibromyalgia, chronic neuropathic pain and chronic pelvic pain. Evidence indicates that the method is pain free, safe and inexpensive. Methods/Design A randomised controlled trial has been designed to evaluate the effect of transcranial direct current stimulation over the motor cortex for pain reduction in patients with chronic low back pain. It will also investigate whether transcranial direct current stimulation as a prior treatment enhances the symptom reduction achieved by a cognitive-behavioural group intervention. Participants will be randomised to receive a series of 5 days of transcranial direct current stimulation (2 mA, 20 mins or 20 mins of sham stimulation; followed by a cognitive-behavioural group programme. The primary outcome parameters will measure pain (Visual Analog Scale and disability (Oswestry Disability Index. Secondary outcome parameters will include the Fear Avoidance Beliefs Questionnaire, the Funktionsfragebogen Hannover (perceived function, Hospital Anxiety Depression Scale, bothersomeness and Health Related Quality of Life (SF 36, as well as Patient-Perceived Satisfactory Improvement. Assessments will take place immediately prior to the first application of transcranial direct current stimulation or sham, after 5 consecutive days of stimulation, immediately after the cognitive-behavioural group programme and at 4 weeks, 12 weeks and 24 weeks follow-up. Discussion This trial will help to determine, whether transcranial direct current stimulation is an effective treatment for patients with chronic low back

  10. Integrated treatment modality of cathodal-transcranial direct current stimulation with peripheral sensory stimulation affords neuroprotection in a rat stroke model.

    Science.gov (United States)

    Liu, Yu-Hang; Chan, Su Jing; Pan, Han-Chi; Bandla, Aishwarya; King, Nicolas K K; Wong, Peter Tsun Hon; Chen, You-Yin; Ng, Wai Hoe; Thakor, Nitish V; Liao, Lun-De

    2017-10-01

    Cathodal-transcranial direct current stimulation induces therapeutic effects in animal ischemia models by preventing the expansion of ischemic injury during the hyperacute phase of ischemia. However, its efficacy is limited by an accompanying decrease in cerebral blood flow. On the other hand, peripheral sensory stimulation can increase blood flow to specific brain areas resulting in rescue of neurovascular functions from ischemic damage. Therefore, the two modalities appear to complement each other to form an integrated treatment modality. Our results showed that hemodynamics was improved in a photothrombotic ischemia model, as cerebral blood volume and hemoglobin oxygen saturation ([Formula: see text]) recovered to 71% and 76% of the baseline values, respectively. Furthermore, neural activities, including somatosensory-evoked potentials (110% increase), the alpha-to-delta ratio (27% increase), and the [Formula: see text] ratio (27% decrease), were also restored. Infarct volume was reduced by 50% with a 2-fold preservation in the number of neurons and a 6-fold reduction in the number of active microglia in the infarct region compared with the untreated group. Grip strength was also better preserved (28% higher) compared with the untreated group. Overall, this nonpharmacological, nonintrusive approach could be prospectively developed into a clinical treatment modality.

  11. Transcranial magnetic stimulation with a half-sine wave pulse elicits direction-specific effects in human motor cortex

    DEFF Research Database (Denmark)

    Jung, Nikolai H; Delvendahl, Igor; Pechmann, Astrid

    2012-01-01

    Transcranial magnetic stimulation (TMS) commonly uses so-called monophasic pulses where the initial rapidly changing current flow is followed by a critically dampened return current. It has been shown that a monophasic TMS pulse preferentially excites different cortical circuits in the human motor...... hand area (M1-HAND), if the induced tissue current has a posterior-to-anterior (PA) or anterior-to-posterior (AP) direction. Here we tested whether similar direction-specific effects could be elicited in M1-HAND using TMS pulses with a half-sine wave configuration....

  12. Current direction-dependent modulation of human hand motor function by intermittent theta burst stimulation (iTBS).

    Science.gov (United States)

    Shirota, Yuichiro; Dhaka, Suman; Paulus, Walter; Sommer, Martin

    2017-05-22

    Transcranial magnetic stimulation (TMS) with different current directions can activate different sets of neurons. Current direction can also affect the results of repetitive TMS. To test the influence of uni-directional intermittent theta burst stimulation (iTBS) using different current directions, namely posteroanterior (PA) and anteroposterior (AP), on motor behaviour. In a cross-over design, PA- and AP-iTBS was applied over the left primary motor cortex in 19 healthy, right-handed volunteers. Performance of a finger-tapping task was recorded before and 0, 10, 20, and 30min after the iTBS. The task was conducted with the right and left hands separately at each time point. As a control, AP-iTBS with reduced intensity was applied to 14 participants in a separate session (AP weak condition). The finger-tapping count with the left hand was decreased after PA-iTBS. Neither AP- nor AP weak -iTBS altered the performance. Current direction had a significant impact on the after-effects of iTBS. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study.

    Directory of Open Access Journals (Sweden)

    Valborg Gudmundsdottir

    Full Text Available Glucagon-like peptide 1 (GLP-1 stimulated insulin secretion has a considerable heritable component as estimated from twin studies, yet few genetic variants influencing this phenotype have been identified. We performed the first genome-wide association study (GWAS of GLP-1 stimulated insulin secretion in non-diabetic individuals from the Netherlands Twin register (n = 126. This GWAS was enhanced using a tissue-specific protein-protein interaction network approach. We identified a beta-cell protein-protein interaction module that was significantly enriched for low gene scores based on the GWAS P-values and found support at the network level in an independent cohort from Tübingen, Germany (n = 100. Additionally, a polygenic risk score based on SNPs prioritized from the network was associated (P < 0.05 with glucose-stimulated insulin secretion phenotypes in up to 5,318 individuals in MAGIC cohorts. The network contains both known and novel genes in the context of insulin secretion and is enriched for members of the focal adhesion, extracellular-matrix receptor interaction, actin cytoskeleton regulation, Rap1 and PI3K-Akt signaling pathways. Adipose tissue is, like the beta-cell, one of the target tissues of GLP-1 and we thus hypothesized that similar networks might be functional in both tissues. In order to verify peripheral effects of GLP-1 stimulation, we compared the transcriptome profiling of ob/ob mice treated with liraglutide, a clinically used GLP-1 receptor agonist, versus baseline controls. Some of the upstream regulators of differentially expressed genes in the white adipose tissue of ob/ob mice were also detected in the human beta-cell network of genes associated with GLP-1 stimulated insulin secretion. The findings provide biological insight into the mechanisms through which the effects of GLP-1 may be modulated and highlight a potential role of the beta-cell expressed genes RYR2, GDI2, KIAA0232, COL4A1 and COL4A2 in GLP-1 stimulated

  14. Focalised stimulation using high definition transcranial direct current stimulation (HD-tDCS) to investigate declarative verbal learning and memory functioning.

    Science.gov (United States)

    Nikolin, Stevan; Loo, Colleen K; Bai, Siwei; Dokos, Socrates; Martin, Donel M

    2015-08-15

    Declarative verbal learning and memory are known to be lateralised to the dominant hemisphere and to be subserved by a network of structures, including those located in frontal and temporal regions. These structures support critical components of verbal memory, including working memory, encoding, and retrieval. Their relative functional importance in facilitating declarative verbal learning and memory, however, remains unclear. To investigate the different functional roles of these structures in subserving declarative verbal learning and memory performance by applying a more focal form of transcranial direct current stimulation, "High Definition tDCS" (HD-tDCS). Additionally, we sought to examine HD-tDCS effects and electrical field intensity distributions using computer modelling. HD-tDCS was administered to the left dorsolateral prefrontal cortex (LDLPFC), planum temporale (PT), and left medial temporal lobe (LMTL) to stimulate the hippocampus, during learning on a declarative verbal memory task. Sixteen healthy participants completed a single blind, intra-individual cross-over, sham-controlled study which used a Latin Square experimental design. Cognitive effects on working memory and sustained attention were additionally examined. HD-tDCS to the LDLPFC significantly improved the rate of verbal learning (p=0.03, η(2)=0.29) and speed of responding during working memory performance (p=0.02, η(2)=0.35), but not accuracy (p=0.12, η(2)=0.16). No effect of tDCS on verbal learning, retention, or retrieval was found for stimulation targeted to the LMTL or the PT. Secondary analyses revealed that LMTL stimulation resulted in increased recency (p=0.02, η(2)=0.31) and reduced mid-list learning effects (p=0.01, η(2)=0.39), suggesting an inhibitory effect on learning. HD-tDCS to the LDLPFC facilitates the rate of verbal learning and improved efficiency of working memory may underlie performance effects. This focal method of administrating tDCS has potential for probing

  15. Integrative network analysis highlights biological processes underlying GLP-1 stimulated insulin secretion: A DIRECT study

    DEFF Research Database (Denmark)

    Gudmundsdottir, Valborg; Pedersen, Helle Krogh; Allebrandt, Karla Viviani

    2018-01-01

    Glucagon-like peptide 1 (GLP-1) stimulated insulin secretion has a considerable heritable component as estimated from twin studies, yet few genetic variants influencing this phenotype have been identified. We performed the first genome-wide association study (GWAS) of GLP-1 stimulated insulin...... secretion in non-diabetic individuals from the Netherlands Twin register (n = 126). This GWAS was enhanced using a tissue-specific protein-protein interaction network approach. We identified a beta-cell protein-protein interaction module that was significantly enriched for low gene scores based on the GWAS...... P-values and found support at the network level in an independent cohort from Tübingen, Germany (n = 100). Additionally, a polygenic risk score based on SNPs prioritized from the network was associated (P

  16. The impact of cerebellar transcranial direct current stimulation (tDCS) on learning fine-motor sequences.

    Science.gov (United States)

    Shimizu, Renee E; Wu, Allan D; Samra, Jasmine K; Knowlton, Barbara J

    2017-01-05

    The cerebellum has been shown to be important for skill learning, including the learning of motor sequences. We investigated whether cerebellar transcranial direct current stimulation (tDCS) would enhance learning of fine motor sequences. Because the ability to generalize or transfer to novel task variations or circumstances is a crucial goal of real world training, we also examined the effect of tDCS on performance of novel sequences after training. In Study 1, participants received either anodal, cathodal or sham stimulation while simultaneously practising three eight-element key press sequences in a non-repeating, interleaved order. Immediately after sequence practice with concurrent tDCS, a transfer session was given in which participants practised three interleaved novel sequences. No stimulation was given during transfer. An inhibitory effect of cathodal tDCS was found during practice, such that the rate of learning was slowed in comparison to the anodal and sham groups. In Study 2, participants received anodal or sham stimulation and a 24 h delay was added between the practice and transfer sessions to reduce mental fatigue. Although this consolidation period benefitted subsequent transfer for both tDCS groups, anodal tDCS enhanced transfer performance. Together, these studies demonstrate polarity-specific effects on fine motor sequence learning and generalization.This article is part of the themed issue 'New frontiers for statistical learning in the cognitive sciences'. © 2016 The Author(s).

  17. Prefronto-Cerebellar Transcranial Direct Current Stimulation Improves Sleep Quality in Euthymic Bipolar Patients: A Brief Report

    Directory of Open Access Journals (Sweden)

    Amedeo Minichino

    2014-01-01

    Full Text Available Introduction. Sleep problems are common in bipolar disorder (BD and may persist during the euthymic phase of the disease. The aim of the study was to improve sleep quality of euthymic BD patients through the administration of prefronto-cerebellar transcranial direct current stimulation (tDCS. Methods. 25 euthymic outpatients with a diagnosis of BD Type I or II have been enrolled in the study. tDCS montage was as follows: cathode on the right cerebellar cortex and anode over the left dorsolateral prefrontal cortex (DLPFC; the intensity of stimulation was set at 2 mA and delivered for 20 min/die for 3 consecutive weeks. The Pittsburgh Sleep Quality Index (PSQI was used to assess sleep quality at baseline and after the tDCS treatment. Results. PSQI total score and all PSQI subdomains, with the exception of “sleep medication,” significantly improved after treatment. Discussion. This is the first study where a positive effect of tDCS on the quality of sleep in euthymic BD patients has been reported. As both prefrontal cortex and cerebellum may play a role in regulating sleep processes, concomitant cathodal (inhibitory stimulation of cerebellum and anodal (excitatory stimulation of DLPFC may have the potential to modulate prefrontal-thalamic-cerebellar circuits leading to improvements of sleep quality.

  18. Transcranial Direct Current Stimulation for Treating Depression in a Patient With Right Hemispheric Dominance: A Case Study.

    Science.gov (United States)

    Shiozawa, Pedro; da Silva, Mailu Enokibara; Cordeiro, Quirino

    2015-09-01

    We report the case of a 66-year-old male patient with major depressive disorder for the last 6 months. The patient had been diagnosed with dyslexia during childhood and was left-handed. The intervention protocol consisted in 10 consecutive daily transcranial direct current stimulation sessions. However, after 5 days of stimulation, the patient presented with intensification of depressive symptoms and panic attacks. It was hypothetized that the intensification of symptoms may have been due to stimulation protocol itself. Considering the patient was left-handed and presented comorbidity with dyslexia, there was a plausible hypothesis of right hemispheric dominance. This was corroborated by the Edinburgh Handedness Scale. In fact, dyslexic patients present right hemisphere dominance more frequently. The patient also presented a single photon emission computed tomography with a hypoperfusion area over the left posterior parietal lobe. After the patients agreement, a 10-day experimental repetitive transcranial magnetic stimulation low-frequency protocol over the left dorsolateral prefrontal cortex was started to inhibit the area, which was hypothetically hyperactivated following the rationale of right dominance. The patient presented amelioration of depressive and anxious symptoms. Given the hemispheric reversal we show in the present case study, however, it seems that therapies that are beneficial to right-handers could be detrimental to left-handers.

  19. Controlling the Anchoring Effect through Transcranial Direct Current Stimulation (tDCS to the Right Dorsolateral Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Jianbiao Li

    2017-06-01

    Full Text Available Selective accessibility mechanisms indicate that anchoring effects are results of selective retrieval of working memory. Neuroimaging studies have revealed that the right dorsolateral prefrontal cortex (DLPFC is closely related to memory retrieval and performance. However, no research has investigated the effect of changing the cortical excitability in right DLPFC on anchoring effects. Transcranial direct current stimulation (tDCS can modulate the excitability of the human cerebral cortex, while anodal and cathodal tDCS are postulated to increase or decrease cortical activity, respectively. In this study, we used tDCS to investigate whether effects of increased or decreased right DLPFC excitability influence anchoring effects in willingness to pay (WTP experiments. Ninety participants were first randomly assigned to receive either anodal, cathodal, or sham stimulation of 15 min, then they performed a valuation task regarding WTP. The results showed that anchoring effects were negatively related to activities of right DLPFC: the anodal stimulation diminished anchoring effects while the cathodal stimulation increased anchoring effects. These outcomes provide one of the first instances of neural evidence for the role of the right DLPFC in anchoring effects and support psychological explanations of the selective accessibility mechanisms and cognitive sets.

  20. On the ultrafast charge migration and subsequent charge directed reactivity in Cl⋯N halogen-bonded clusters following vertical ionization

    International Nuclear Information System (INIS)

    Chandra, Sankhabrata; Bhattacharya, Atanu; Periyasamy, Ganga

    2015-01-01

    In this article, we have presented ultrafast charge transfer dynamics through halogen bonds following vertical ionization of representative halogen bonded clusters. Subsequent hole directed reactivity of the radical cations of halogen bonded clusters is also discussed. Furthermore, we have examined effect of the halogen bond strength on the electron-electron correlation- and relaxation-driven charge migration in halogen bonded complexes. For this study, we have selected A-Cl (A represents F, OH, CN, NH 2 , CF 3 , and COOH substituents) molecules paired with NH 3 (referred as ACl:NH 3 complex): these complexes exhibit halogen bonds. To the best of our knowledge, this is the first report on purely electron correlation- and relaxation-driven ultrafast (attosecond) charge migration dynamics through halogen bonds. Both density functional theory and complete active space self-consistent field theory with 6-31 + G(d, p) basis set are employed for this work. Upon vertical ionization of NCCl⋯NH 3 complex, the hole is predicted to migrate from the NH 3 -end to the ClCN-end of the NCCl⋯NH 3 complex in approximately 0.5 fs on the D 0 cationic surface. This hole migration leads to structural rearrangement of the halogen bonded complex, yielding hydrogen bonding interaction stronger than the halogen bonding interaction on the same cationic surface. Other halogen bonded complexes, such as H 2 NCl:NH 3 , F 3 CCl:NH 3 , and HOOCCl:NH 3 , exhibit similar charge migration following vertical ionization. On the contrary, FCl:NH 3 and HOCl:NH 3 complexes do not exhibit any charge migration following vertical ionization to the D 0 cation state, pointing to interesting halogen bond strength-dependent charge migration

  1. On the ultrafast charge migration and subsequent charge directed reactivity in Cl⋯N halogen-bonded clusters following vertical ionization

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, Sankhabrata; Bhattacharya, Atanu, E-mail: atanub@ipc.iisc.ernet.in [Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore (India); Periyasamy, Ganga [Department of Chemistry, Central College Campus, Bangalore University, Bangalore (India)

    2015-06-28

    In this article, we have presented ultrafast charge transfer dynamics through halogen bonds following vertical ionization of representative halogen bonded clusters. Subsequent hole directed reactivity of the radical cations of halogen bonded clusters is also discussed. Furthermore, we have examined effect of the halogen bond strength on the electron-electron correlation- and relaxation-driven charge migration in halogen bonded complexes. For this study, we have selected A-Cl (A represents F, OH, CN, NH{sub 2}, CF{sub 3}, and COOH substituents) molecules paired with NH{sub 3} (referred as ACl:NH{sub 3} complex): these complexes exhibit halogen bonds. To the best of our knowledge, this is the first report on purely electron correlation- and relaxation-driven ultrafast (attosecond) charge migration dynamics through halogen bonds. Both density functional theory and complete active space self-consistent field theory with 6-31 + G(d, p) basis set are employed for this work. Upon vertical ionization of NCCl⋯NH{sub 3} complex, the hole is predicted to migrate from the NH{sub 3}-end to the ClCN-end of the NCCl⋯NH{sub 3} complex in approximately 0.5 fs on the D{sub 0} cationic surface. This hole migration leads to structural rearrangement of the halogen bonded complex, yielding hydrogen bonding interaction stronger than the halogen bonding interaction on the same cationic surface. Other halogen bonded complexes, such as H{sub 2}NCl:NH{sub 3}, F{sub 3}CCl:NH{sub 3}, and HOOCCl:NH{sub 3}, exhibit similar charge migration following vertical ionization. On the contrary, FCl:NH{sub 3} and HOCl:NH{sub 3} complexes do not exhibit any charge migration following vertical ionization to the D{sub 0} cation state, pointing to interesting halogen bond strength-dependent charge migration.

  2. Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS)

    Science.gov (United States)

    Alam, Mahtab; Truong, Dennis Q.; Khadka, Niranjan; Bikson, Marom

    2016-06-01

    Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that applies low amplitude current via electrodes placed on the scalp. Rather than directly eliciting a neuronal response, tDCS is believed to modulate excitability—enhancing or suppressing neuronal activity in regions of the brain depending on the polarity of stimulation. The specificity of tDCS to any therapeutic application derives in part from how electrode configuration determines the brain regions that are stimulated. Conventional tDCS uses two relatively large pads (>25 cm2) whereas high-definition tDCS (HD-tDCS) uses arrays of smaller electrodes to enhance brain targeting. The 4  ×  1 concentric ring HD-tDCS (one center electrode surrounded by four returns) has been explored in application where focal targeting of cortex is desired. Here, we considered optimization of concentric ring HD-tDCS for targeting: the role of electrodes in the ring and the ring’s diameter. Finite element models predicted cortical electric field generated during tDCS. High resolution MRIs were segmented into seven tissue/material masks of varying conductivities. Computer aided design (CAD) model of electrodes, gel, and sponge pads were incorporated into the segmentation. Volume meshes were generated and the Laplace equation (\

  3. Transcranial direct current stimulation reduces food-craving and measures of hyperphagia behavior in participants with Prader-Willi syndrome.

    Science.gov (United States)

    Bravo, Gabriela L; Poje, Albert B; Perissinotti, Iago; Marcondes, Bianca F; Villamar, Mauricio F; Manzardo, Ann M; Luque, Laura; LePage, Jean F; Stafford, Diane; Fregni, Felipe; Butler, Merlin G

    2016-03-01

    Prader-Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by intellectual disabilities and insatiable appetite with compulsive eating leading to severe obesity with detrimental health consequences. Transcranial direct current stimulation (tDCS) has been shown to modulate decision-making and cue-induced food craving in healthy adults. We conducted a pilot double blind, sham-controlled, multicenter study of tDCS modulation of food drive and craving in 10 adult PWS participants, 11 adult obese (OB) and 11 adult healthy-weight control (HWC) subjects. PWS and OB subjects received five consecutive daily sessions of active or sham tDCS over the right dorsolateral prefrontal cortex (DLPFC), while HWC received a single sham and active tDCS in a crossover design. Standardized psychometric instruments assessed food craving, drive and hyperphagia by self-report and caregiver assessment over 30 days. Robust baseline differences were observed in severity scores for the Three-Factor Eating Questionnaire (TFEQ) and Dykens Hyperphagia Questionnaire (DHQ) for PWS compared to HWC while obese participants were more similar to HWC. Active tDCS stimulation in PWS was associated with a significant change from baseline in TFEQ Disinhibition (Factor II) (Ƶ = 1.9, P food drive and behaviors impacting hyperphagia in PWS. Transcranial direct current stimulation may represent a straight-forward, low risk and low cost method to improve care, management and quality of life in PWS. © 2015 Wiley Periodicals, Inc.

  4. Investigating the functional neuroanatomy of concrete and abstract word processing through direct electric stimulation (DES) during awake surgery.

    Science.gov (United States)

    Orena, E F; Caldiroli, D; Acerbi, F; Barazzetta, I; Papagno, C

    2018-06-05

    Neuropsychological, neuroimaging and electrophysiological studies demonstrate that abstract and concrete word processing relies not only on the activity of a common bilateral network but also on dedicated networks. The neuropsychological literature has shown that a selective sparing of abstract relative to concrete words can be documented in lesions of the left anterior temporal regions. We investigated concrete and abstract word processing in 10 patients undergoing direct electrical stimulation (DES) for brain mapping during awake surgery in the left hemisphere. A lexical decision and a concreteness judgment task were added to the neuropsychological assessment during intra-operative monitoring. On the concreteness judgment, DES delivered over the inferior frontal gyrus significantly decreased abstract word accuracy while accuracy for concrete words decreased when the anterior temporal cortex was stimulated. These results are consistent with a lexical-semantic model that distinguishes between concrete and abstract words related to different neural substrates in the left hemisphere.

  5. Neurocognitive Effects of Transcranial Direct Current Stimulation in Arithmetic Learning and Performance: A Simultaneous tDCS-fMRI Study.

    Science.gov (United States)

    Hauser, Tobias U; Rütsche, Bruno; Wurmitzer, Karoline; Brem, Silvia; Ruff, Christian C; Grabner, Roland H

    A small but increasing number of studies suggest that non-invasive brain stimulation by means of transcranial direct current stimulation (tDCS) can modulate arithmetic processes that are essential for higher-order mathematical skills and that are impaired in dyscalculic individuals. However, little is known about the neural mechanisms underlying such stimulation effects, and whether they are specific to cognitive processes involved in different arithmetic tasks. We addressed these questions by applying tDCS during simultaneous functional magnetic resonance imaging (fMRI) while participants were solving two types of complex subtraction problems: repeated problems, relying on arithmetic fact learning and problem-solving by fact retrieval, and novel problems, requiring calculation procedures. Twenty participants receiving left parietal anodal plus right frontal cathodal stimulation were compared with 20 participants in a sham condition. We found a strong cognitive and neural dissociation between repeated and novel problems. Repeated problems were solved more accurately and elicited increased activity in the bilateral angular gyri and medial plus lateral prefrontal cortices. Solving novel problems, in contrast, was accompanied by stronger activation in the bilateral intraparietal sulci and the dorsomedial prefrontal cortex. Most importantly, tDCS decreased the activation of the right inferior frontal cortex while solving novel (compared to repeated) problems, suggesting that the cathodal stimulation rendered this region unable to respond to the task-specific cognitive demand. The present study revealed that tDCS during arithmetic problem-solving can modulate the neural activity in proximity to the electrodes specifically when the current demands lead to an engagement of this area. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Influence of Anodal Transcranial Direct Current Stimulation (tDCS) over the Right Angular Gyrus on Brain Activity during Rest

    Science.gov (United States)

    Clemens, Benjamin; Jung, Stefanie; Mingoia, Gianluca; Weyer, David; Domahs, Frank; Willmes, Klaus

    2014-01-01

    Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site. PMID:24760013

  7. A Randomized, Double-Blind, Sham-Controlled Trial of Transcranial Direct Current Stimulation in Attention-Deficit/Hyperactivity Disorder.

    Directory of Open Access Journals (Sweden)

    Camila Cosmo

    Full Text Available Current standardized treatments for cognitive impairment in attention-deficit/hyperactivity disorder remain limited and their efficacy restricted. Transcranial direct current stimulation (tDCS is a promising tool for enhancing cognitive performance in several neuropsychiatric disorders. Nevertheless, the effects of tDCS in reducing cognitive impairment in patients with attention-deficit/hyperactivity disorder (ADHD have not yet been investigated.A parallel, randomized, double-blind, sham-controlled trial was conducted to examine the efficacy of tDCS on the modulation of inhibitory control in adults with ADHD. Thirty patients were randomly allocated to each group and performed a go/no-go task before and after a single session of either anodal stimulation (1 mA over the left dorsolateral prefrontal cortex or sham stimulation.A nonparametric two-sample Wilcoxon rank-sum (Mann-Whitney test revealed no significant differences between the two groups of individuals with ADHD (tDCS vs. sham in regard to behavioral performance in the go/no go tasks. Furthermore, the effect sizes of group differences after treatment for the primary outcome measures-correct responses, impulsivity and omission errors--were small. No adverse events resulting from stimulation were reported.According to these findings, there is no evidence in support of the use of anodal stimulation over the left dorsolateral prefrontal cortex as an approach for improving inhibitory control in ADHD patients. To the best of our knowledge, this is the first clinical study to assess the cognitive effects of tDCS in individuals with ADHD. Further research is needed to assess the clinical efficacy of tDCS in this population.ClinicalTrials.gov NCT01968512.

  8. Influence of anodal transcranial direct current stimulation (tDCS) over the right angular gyrus on brain activity during rest.

    Science.gov (United States)

    Clemens, Benjamin; Jung, Stefanie; Mingoia, Gianluca; Weyer, David; Domahs, Frank; Willmes, Klaus

    2014-01-01

    Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site.

  9. Reduction of chronic abdominal pain in patients with inflammatory bowel disease through transcranial direct current stimulation: a randomized controlled trial.

    Science.gov (United States)

    Volz, Magdalena S; Farmer, Annabelle; Siegmund, Britta

    2016-02-01

    Inflammatory bowel disease (IBD) is frequently associated with chronic abdominal pain (CAP). Transcranial direct current stimulation (tDCS) has been proven to reduce chronic pain. This study aimed to investigate the effects of tDCS in patients with CAP due to IBD. This randomized, sham-controlled, double blind, parallel-designed study included 20 patients with either Crohn disease or ulcerative colitis with CAP (≥3/10 on the visual analog scale (VAS) in 3/6 months). Anodal or sham tDCS was applied over the primary motor cortex for 5 consecutive days (2 mA, 20 minutes). Assessments included VAS, pressure pain threshold, inflammatory markers, and questionnaires on quality of life, functional and disease specific symptoms (Irritable Bowel Syndrome-Severity Scoring System [IBS-SSS]), disease activity, and pain catastrophizing. Follow-up data were collected 1 week after the end of the stimulation. Statistical analyses were performed using analysis of variance and t tests. There was a significant reduction of abdominal pain in the anodal tDCS group compared with sham tDCS. This effect was evident in changes in VAS and pressure pain threshold on the left and right sides of the abdomen. In addition, 1 week after stimulation, pain reduction remained significantly decreased in the right side of the abdomen. There was also a significant reduction in scores on pain catastrophizing and on IBS-SSS when comparing both groups. Inflammatory markers and disease activity did not differ significantly between groups throughout the experiment. Transcranial direct current stimulation proved to be an effective and clinically relevant therapeutic strategy for CAP in IBD. The analgesic effects observed are unrelated to inflammation and disease activity, which emphasizes central pain mechanisms in CAP.

  10. Introducing graph theory to track for neuroplastic alterations in the resting human brain: a transcranial direct current stimulation study.

    Science.gov (United States)

    Polanía, Rafael; Paulus, Walter; Antal, Andrea; Nitsche, Michael A

    2011-02-01

    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for a few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be related to stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact of tDCS on cortical network function by functional connectivity and graph theoretical analysis of the BOLD fMRI spontaneous activity. fMRI resting-state datasets were acquired immediately before and after 10-min bipolar tDCS during rest, with the anode placed over the left primary motor cortex (M1) and the cathode over the contralateral frontopolar cortex. For each dataset, grey matter voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal connectivity degree and minimum path length maps were calculated and compared before and after tDCS. Nodal minimum path lengths significantly increased in the left somatomotor (SM1) cortex after anodal tDCS, which means that the number of direct functional connections from the left SM1 to topologically distant grey matter voxels significantly decreased. In contrast, functional coupling between premotor and superior parietal areas with the left SM1 significantly increased. Additionally, the nodal connectivity degree in the left posterior cingulate cortex (PCC) area as well as in the right dorsolateral prefrontal cortex (right DLPFC) significantly increased. In summary, we provide initial support that tDCS-induced neuroplastic alterations might be related to functional connectivity changes in the human brain. Additionally, we propose our approach as a powerful method to track for neuroplastic changes in the human brain. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Effects of Transcranial Direct Current Stimulation, Transcranial Pulsed Current Stimulation, and Their Combination on Brain Oscillations in Patients with Chronic Visceral Pain: A Pilot Crossover Randomized Controlled Study.

    Science.gov (United States)

    Thibaut, Aurore; Russo, Cristina; Hurtado-Puerto, Aura Maria; Morales-Quezada, Jorge Leon; Deitos, Alícia; Petrozza, John Christopher; Freedman, Steven; Fregni, Felipe

    2017-01-01

    Chronic visceral pain (CVP) syndromes are persistently painful disorders with a remarkable lack of effective treatment options. This study aimed at evaluating the effects of different neuromodulation techniques in patients with CVP on cortical activity, through electreocephalography (EEG) and on pain perception, through clinical tests. A pilot crossover randomized controlled study. Out-patient. Adults with CVP (>3 months). Participants received four interventions in a randomized order: (1) transcranial pulsed current stimulation (tPCS) and active transcranial direct current stimulation (tDCS) combined, (2) tPCS alone, (3) tDCS alone, and (4) sham condition. Resting state quantitative electroencephalography (qEEG) and pain assessments were performed before and after each intervention. Results were compared with a cohort of 47 healthy controls. We enrolled six patients with CVP for a total of 21 visits completed. Compared with healthy participants, patients with CVP showed altered cortical activity characterized by increased power in theta, alpha and beta bands, and a significant reduction in the alpha/beta ratio. Regarding tES, the combination of tDCS with tPCS had no effect on power in any of the bandwidths, nor brain regions. Comparing tPCS with tDCS alone, we found that tPCS induced higher increase in power within the theta and alpha bandwidths. This study confirms that patients with CVP present abnormal EEG-indexed cortical activity compared with healthy controls. Moreover, we showed that combining two types of neurostimulation techniques had no effect, whereas the two interventions, when applied individually, have different neural signatures.

  12. Stimulating cognition in schizophrenia: A controlled pilot study of the effects of prefrontal transcranial direct current stimulation upon memory and learning.

    Science.gov (United States)

    Orlov, Natasza D; Tracy, Derek K; Joyce, Daniel; Patel, Shinal; Rodzinka-Pasko, Joanna; Dolan, Hayley; Hodsoll, John; Collier, Tracy; Rothwell, John; Shergill, Sukhwinder S

    Schizophrenia is characterized by prominent cognitive deficits, impacting on memory and learning; these are strongly associated with the prefrontal cortex. To combine two interventions, transcranial direct current stimulation (tDCS) over the prefrontal cortex and cognitive training, to examine change in cognitive performance in patients with schizophrenia. A double blind, sham-controlled pilot study of 49 patients with schizophrenia, randomized into real or sham tDCS stimulation groups. Subjects participated in 4 days of cognitive training (days 1, 2, 14, 56) with tDCS applied at day-1 and day-14. The primary outcome measure was change in accuracy on working memory and implicit learning tasks from baseline. The secondary outcome measure was the generalization of learning to non-trained task, indexed by the CogState neuropsychological battery. Data analysis was conducted using multilevel modelling and multiple regressions. 24 participants were randomized to real tDCS and 25 to sham. The working memory task demonstrated a significant mean difference in performance in the tDCS treatment group: at day-2 (b = 0.68, CI 0.14-1.21; p = 0.044) and at day-56 (b = 0.71, 0.16-1.26; p = 0.044). There were no significant effects of tDCS on implicit learning. Trend evidence of generalization onto untrained tasks of attention and vigilance task (b = 0.40, 0.43-0.77; p = 0.058) was found. This is the first study to show a significant longer-term effect of tDCS on working memory in schizophrenia. Given the current lack of effective therapies for cognitive deficits, tDCS may offer an important novel approach to modulating brain networks to ameliorate cognitive deficits in schizophrenia. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Impairment of preoperative language mapping by lesion location: a functional magnetic resonance imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation study.

    Science.gov (United States)

    Ille, Sebastian; Sollmann, Nico; Hauck, Theresa; Maurer, Stefanie; Tanigawa, Noriko; Obermueller, Thomas; Negwer, Chiara; Droese, Doris; Boeckh-Behrens, Tobias; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

    2015-08-01

    Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is increasingly used and has already replaced functional MRI (fMRI) in some institutions for preoperative mapping of neurosurgical patients. Yet some factors affect the concordance of both methods with direct cortical stimulation (DCS), most likely by lesions affecting cortical oxygenation levels. Therefore, the impairment of the accuracy of rTMS and fMRI was analyzed and compared with DCS during awake surgery in patients with intraparenchymal lesions. Language mapping was performed by DCS, rTMS, and fMRI using an object-naming task in 27 patients with left-sided perisylvian lesions, and the induced language errors of each method were assigned to the cortical parcellation system. Subsequently, the receiver operating characteristics were calculated for rTMS and fMRI and compared with DCS as ground truth for regions with (w/) and without (w/o) the lesion in the mapped regions. The w/ subgroup revealed a sensitivity of 100% (w/o 100%), a specificity of 8% (w/o 5%), a positive predictive value of 34% (w/o: 53%), and a negative predictive value (NPV) of 100% (w/o: 100%) for the comparison of rTMS versus DCS. Findings for the comparison of fMRI versus DCS within the w/ subgroup revealed a sensitivity of 32% (w/o: 62%), a specificity of 88% (w/o: 60%), a positive predictive value of 56% (w/o: 62%), and a NPV of 73% (w/o: 60%). Although strengths and weaknesses exist for both rTMS and fMRI, the results show that rTMS is less affected by a brain lesion than fMRI, especially when performing mapping of language-negative cortical regions based on sensitivity and NPV.

  14. Effects of Transcranial Direct Current Stimulation, Transcranial Pulsed Current Stimulation, and Their Combination on Brain Oscillations in Patients with Chronic Visceral Pain: A Pilot Crossover Randomized Controlled Study

    Directory of Open Access Journals (Sweden)

    Aurore Thibaut

    2017-11-01

    Full Text Available ObjectiveChronic visceral pain (CVP syndromes are persistently painful disorders with a remarkable lack of effective treatment options. This study aimed at evaluating the effects of different neuromodulation techniques in patients with CVP on cortical activity, through electreocephalography (EEG and on pain perception, through clinical tests.DesignA pilot crossover randomized controlled study.SettingsOut-patient.SubjectsAdults with CVP (>3 months.MethodsParticipants received four interventions in a randomized order: (1 transcranial pulsed current stimulation (tPCS and active transcranial direct current stimulation (tDCS combined, (2 tPCS alone, (3 tDCS alone, and (4 sham condition. Resting state quantitative electroencephalography (qEEG and pain assessments were performed before and after each intervention. Results were compared with a cohort of 47 healthy controls.ResultsWe enrolled six patients with CVP for a total of 21 visits completed. Compared with healthy participants, patients with CVP showed altered cortical activity characterized by increased power in theta, alpha and beta bands, and a significant reduction in the alpha/beta ratio. Regarding tES, the combination of tDCS with tPCS had no effect on power in any of the bandwidths, nor brain regions. Comparing tPCS with tDCS alone, we found that tPCS induced higher increase in power within the theta and alpha bandwidths.ConclusionThis study confirms that patients with CVP present abnormal EEG-indexed cortical activity compared with healthy controls. Moreover, we showed that combining two types of neurostimulation techniques had no effect, whereas the two interventions, when applied individually, have different neural signatures.

  15. Predicting the behavioural impact of transcranial direct current stimulation: issues and limitations

    Directory of Open Access Journals (Sweden)

    Archy Otto De Berker

    2013-10-01

    Full Text Available The transcranial application of weak currents to the human brain has enjoyed a decade of success, providing a simple and powerful tool for non-invasively altering human brain function. However, our understanding of current delivery and its impact upon neural circuitry leaves much to be desired. We argue that the credibility of conclusions drawn with tDCS is contingent upon realistic explanations of how tDCS works, and that our present understanding of tDCS limits the technique’s use to localize function in the human brain. We outline two central issues where progress is required: the localization of currents, and predicting their functional consequence. We encourage experimenters to eschew simplistic explanations of mechanisms of transcranial current stimulation. We suggest the use of individualized current modelling, together with computational neurostimulation to inform mechanistic frameworks in which to interpret the physiological impact of tDCS. We hope that through mechanistically richer descriptions of current flow and action, insight into the biological processes by which transcranial currents influence behaviour can be gained, leading to more effective stimulation protocols and empowering conclusions drawn with tDCS.

  16. Feasibility and Clinical Utility of High-definition Transcranial Direct Current Stimulation in the Treatment of Persistent Hallucinations in Schizophrenia.

    Science.gov (United States)

    Bose, A; Shivakumar, V; Chhabra, H; Parlikar, R; Sreeraj, V S; Dinakaran, D; Narayanaswamy, J C; Venkatasubramanian, G

    2017-12-01

    Persistent auditory verbal hallucination is a clinically significant problem in schizophrenia. Recent studies suggest a promising role for add-on transcranial direct current stimulation (tDCS) in treatment. An optimised version of tDCS, namely high-definition tDCS (HD-tDCS), uses smaller electrodes arranged in a 4x1 ring configuration and may offer more focal and predictable neuromodulation than conventional tDCS. This case report illustrates the feasibility and clinical utility of add-on HD-tDCS over the left temporoparietal junction in a 4x1 ring configuration to treat persistent auditory verbal hallucination in schizophrenia.

  17. Battery powered thought: enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation.

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    Coffman, Brian A; Clark, Vincent P; Parasuraman, Raja

    2014-01-15

    This article reviews studies demonstrating enhancement with transcranial direct current stimulation (tDCS) of attention, learning, and memory processes in healthy adults. Given that these are fundamental cognitive functions, they may also mediate stimulation effects on other higher-order processes such as decision-making and problem solving. Although tDCS research is still young, there have been a variety of methods used and cognitive processes tested. While these different methods have resulted in seemingly contradictory results among studies, many consistent and noteworthy effects of tDCS on attention, learning, and memory have been reported. The literature suggests that although tDCS as typically applied may not be as useful for localization of function in the brain as some other methods of brain stimulation, tDCS may be particularly well-suited for practical applications involving the enhancement of attention, learning, and memory, in both healthy subjects and in clinical populations. © 2013 Elsevier Inc. All rights reserved.

  18. Focused transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex modulates specific domains of self-regulation.

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    Pripfl, Jürgen; Lamm, Claus

    2015-02-01

    Recent neuroscience theories suggest that different kinds of self-regulation may share a common psychobiological mechanism. However, empirical evidence for a domain general self-regulation mechanism is scarce. The aim of this study was to investigate whether focused anodal transcranial direct current stimulation (tDCS), facilitating the activity of the dorsolateral prefrontal cortex (dlPFC), acts on a domain general self-regulation mechanism and thus modulates both affective and appetitive self-regulation. Twenty smokers participated in this within-subject sham controlled study. Effects of anodal left, anodal right and sham tDCS over the dlPFC on affective picture appraisal and nicotine craving-cue appraisal were assessed. Anodal right tDCS over the dlPFC reduced negative affect in emotion appraisal, but neither modulated regulation of positive emotion appraisal nor of craving appraisal. Anodal left stimulation did not induce any significant effects. The results of our study show that domain specific self-regulation networks are at work in the prefrontal cortex. Focused tDCS modulation of this specific self-regulation network could probably be used during the first phase of nicotine abstinence, during which negative affect might easily result in relapse. These findings have implications for neuroscience models of self-regulation and are of relevance for the development of brain stimulation based treatment methods for neuropsychiatric disorders associated with self-regulation deficits. Copyright ©