Science.gov

Sample records for 50-491 stn 50-492

  1. SCIENTIFIC AND TECHNICAL INFORMATION NETWORK (STN INTERNATIONAL)

    EPA Science Inventory

    STN International (the Scientific and Technical Information Network) offers both a fee based online search service that provides accurate, up-to-date, specific information from over 200 scientific, technical, business, and patent databases, and also fee based WWW access to select...

  2. STN1 protects chromosome ends in Arabidopsis thaliana

    PubMed Central

    Song, Xiangyu; Leehy, Katherine; Warrington, Ross T.; Lamb, Jonathan C.; Surovtseva, Yulia V.; Shippen, Dorothy E.

    2008-01-01

    Telomeres shield the natural ends of chromosomes from nucleolytic attack, recognition as double-strand breaks, and inappropriate processing by DNA repair machinery. The trimeric Stn1/Ten1/Cdc13 complex is critical for chromosome end protection in Saccharomyces cerevisiae, while vertebrate telomeres are protected by shelterin, a complex of six proteins that does not include STN1 or TEN1. Recent studies demonstrate that Stn1 and Ten1 orthologs in Schizosaccharomyces pombe contribute to telomere integrity in a complex that is distinct from the shelterin components, Pot1 and Tpp1. Thus, chromosome-end protection may be mediated by distinct subcomplexes of telomere proteins. Here we report the identification of a STN1 gene in Arabidopsis that is essential for chromosome-end protection. AtSTN1 encodes an 18-kDa protein bearing a single oligonucleotide/oligosaccharide binding fold with significant sequence similarity to the yeast Stn1 proteins. Plants null for AtSTN1 display an immediate onset of growth and developmental defects and reduced fertility. These outward phenotypes are accompanied by catastrophic loss of telomeric and subtelomeric DNA, high levels of end-to-end chromosome fusions, increased G-overhang signals, and elevated telomere recombination. Thus, AtSTN1 is a crucial component of the protective telomere cap in Arabidopsis, and likely in other multicellular eukaryotes. PMID:19064932

  3. Comparative phosphoproteome profiling reveals a function of the STN8 kinase in fine-tuning of cyclic electron flow (CEF)

    PubMed Central

    Reiland, Sonja; Finazzi, Giovanni; Endler, Anne; Willig, Adrian; Baerenfaller, Katja; Grossmann, Jonas; Gerrits, Bertran; Rutishauser, Dorothea; Gruissem, Wilhelm; Rochaix, Jean-David; Baginsky, Sacha

    2011-01-01

    Important aspects of photosynthetic electron transport efficiency in chloroplasts are controlled by protein phosphorylation. Two thylakoid-associated kinases, STN7 and STN8, have distinct roles in short- and long-term photosynthetic acclimation to changes in light quality and quantity. Although some substrates of STN7 and STN8 are known, the complexity of this regulatory kinase system implies that currently unknown substrates connect photosynthetic performance with the regulation of metabolic and regulatory functions. We performed an unbiased phosphoproteome-wide screen with Arabidopsis WT and stn8 mutant plants to identify unique STN8 targets. The phosphorylation status of STN7 was not affected in stn8, indicating that kinases other than STN8 phosphorylate STN7 under standard growth conditions. Among several putative STN8 substrates, PGRL1-A is of particular importance because of its possible role in the modulation of cyclic electron transfer. The STN8 phosphorylation site on PGRL1-A is absent in both monocotyledonous plants and algae. In dicots, spectroscopic measurements with Arabidopsis WT, stn7, stn8, and stn7/stn8 double-mutant plants indicate a STN8-mediated slowing down of the transition from cyclic to linear electron flow at the onset of illumination. This finding suggests a possible link between protein phosphorylation by STN8 and fine-tuning of cyclic electron flow during this critical step of photosynthesis, when the carbon assimilation is not commensurate to the electron flow capacity of the chloroplast. PMID:21768351

  4. The Student Telescope Network (STN) experiment

    NASA Astrophysics Data System (ADS)

    Hannahoe, Ryan M.; Stencel, Robert E.; Bisque, Steve; Rice, Mike

    2003-02-01

    support of this effort, and acknowleedge in-kind support from the estate of William Herschel Womble. Details at website www.du.edu/~rstencel/stn.htm.

  5. Stn1-Ten1 is an Rpa2-Rpa3-like complex at telomeres

    SciTech Connect

    Sun, Jia; Yu, Eun Young; Yang, Yuting; Confer, Laura A; Sun, Steven H; Wan, Ke; Lue, Neal F; Lei, Ming

    2010-09-02

    In budding yeast, Cdc13, Stn1, and Ten1 form a heterotrimeric complex (CST) that is essential for telomere protection and maintenance. Previous bioinformatics analysis revealed a putative oligonucleotide/oligosaccharide-binding (OB) fold at the N terminus of Stn1 (Stn1N) that shows limited sequence similarity to the OB fold of Rpa2, a subunit of the eukaryotic ssDNA-binding protein complex replication protein A (RPA). Here we present functional and structural analyses of Stn1 and Ten1 from multiple budding and fission yeast. The crystal structure of the Candida tropicalis Stn1N complexed with Ten1 demonstrates an Rpa2N-Rpa3-like complex. In both structures, the OB folds of the two components pack against each other through interactions between two C-terminal helices. The structure of the C-terminal domain of Saccharomyces cerevisiae Stn1 (Stn1C) was found to comprise two related winged helix-turn-helix (WH) motifs, one of which is most similar to the WH motif at the C terminus of Rpa2, again supporting the notion that Stn1 resembles Rpa2. The crystal structure of the fission yeast Schizosaccharomyces pombe Stn1N-Ten1 complex exhibits a virtually identical architecture as the C. tropicalis Stn1N-Ten1. Functional analyses of the Candida albicans Stn1 and Ten1 proteins revealed critical roles for these proteins in suppressing aberrant telomerase and recombination activities at telomeres. Mutations that disrupt the Stn1-Ten1 interaction induce telomere uncapping and abolish the telomere localization of Ten1. Collectively, our structural and functional studies illustrate that, instead of being confined to budding yeast telomeres, the CST complex may represent an evolutionarily conserved RPA-like telomeric complex at the 3' overhangs that works in parallel with or instead of the well-characterized POT1-TPP1/TEBP{alpha}-{beta} complex.

  6. Effects of STN DBS on Memory Guided Force Control in Parkinson’s Disease (June 2007)

    PubMed Central

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

    2008-01-01

    This study examined the control of elbow force in nine patients with Parkinson’s disease when visual feedback was available and when visual feedback was removed to determine how medication (Meds) and unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) affect memory guided force control. Patients were examined in each of four treatment conditions: 1) off treatment; 2) Meds; 3) STN DBS; and 4) Meds plus STN DBS. With visual feedback available, there was no difference in force output across treatment conditions. When visual feedback was removed force output drifted under the target in both the off-treatment and the Meds conditions. However, when on STN DBS or Meds plus STN DBS force output drifted above the target. As such, only STN DBS had a significant effect on force output in the vision removed condition. Increased force output when on STN DBS may have occurred due to disruptions in the basal ganglia-thalamo-cortical circuitry. We suggest that modulation of output of the internal segment of the globus pallidus by STN DBS may drive the effect of STN DBS on memory guided force control. PMID:17601184

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

    PubMed

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

    2007-06-01

    This study examined the control of elbow force in nine patients with Parkinson's disease when visual feedback was available and when visual feedback was removed to determine how medication (Meds) and unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) affect memory guided force control. Patients were examined in each of four treatment conditions: 1) off treatment; 2) Meds; 3) STN DBS; and 4) Meds plus STN DBS. With visual feedback available, there was no difference in force output across treatment conditions. When visual feedback was removed force output drifted under the target in both the off-treatment and the Meds conditions. However, when on STN DBS or Meds plus STN DBS force output drifted above the target. As such, only STN DBS had a significant effect on force output in the vision removed condition. Increased force output when on STN DBS may have occurred due to disruptions in the basal ganglia-thalamo-cortical circuitry. We suggest that modulation of output of the internal segment of the globus pallidus by STN DBS may drive the effect of STN DBS on memory guided force control. PMID:17601184

  8. SOURCE APPORTIONMENT OF SEATTLE PM 2.5: A COMPARISON OF IMPROVE AND ENHANCED STN DATA SETS

    EPA Science Inventory

    Seattle, WA, STN and IMPROVE data sets with STN temperature resolved carbon peaks were analyzed with both the PMF and Unmix receptor models. In addition, the IMPROVE trace element data was combined with the major STN species to examine the role of IMPROVE metals. To compare the ...

  9. Stn1 is critical for telomere maintenance and long-term viability of somatic human cells

    PubMed Central

    Boccardi, Virginia; Razdan, Neetu; Kaplunov, Jessica; Mundra, Jyoti J; Kimura, Masayuki; Aviv, Abraham; Herbig, Utz

    2015-01-01

    Disruption of telomere maintenance pathways leads to accelerated entry into cellular senescence, a stable proliferative arrest that promotes aging-associated disorders in some mammals. The budding yeast CST complex, comprising Cdc13, Stn1, and Ctc1, is critical for telomere replication, length regulation, and end protection. Although mammalian homologues of CST have been identified recently, their role and function for telomere maintenance in normal somatic human cells are still incompletely understood. Here, we characterize the function of human Stn1 in cultured human fibroblasts and demonstrate its critical role in telomere replication, length regulation, and function. In the absence of high telomerase activity, shRNA-mediated knockdown of hStn1 resulted in aberrant and fragile telomeric structures, stochastic telomere attrition, increased telomere erosion rates, telomere dysfunction, and consequently accelerated entry into cellular senescence. Oxidative stress augmented the defects caused by Stn1 knockdown leading to almost immediate cessation of cell proliferation. In contrast, overexpression of hTERT suppressed some of the defects caused by hStn1 knockdown suggesting that telomerase can partially compensate for hStn1 loss. Our findings reveal a critical role for human Stn1 in telomere length maintenance and function, supporting the model that efficient replication of telomeric repeats is critical for long-term viability of normal somatic mammalian cells. PMID:25684230

  10. Construction and validation of a Sambucus nigra biosensor for cancer-associated STn antigen.

    PubMed

    Silva, M Luísa S; Gutiérrez, Evelin; Rodríguez, José A; Gomes, Catarina; David, Leonor

    2014-07-15

    A label-free electrochemical impedance spectroscopy biosensor for selective detection and discrimination of the cancer-associated sialyl-Tn (STn) antigen was developed by using Sambucus nigra agglutinin type I (SNA-I) as the recognition element. The SNA-I biosensor was constructed by immobilizing the lectin on screen-printed gold electrodes. The formation of a complex between SNA-I and STn-containing glycoproteins (transferrin and bovine submaxillary mucin) was monitored by measuring the impedance increase of the biosensor. The increase in electron transfer resistance was linearly proportional to the concentration of the glycoproteins up to 70 ng of transferrin and 40 ng of bovine submaxillary mucin, with a limit of detection of 20 ng for transferrin. Albumin, the most abundant serum protein, did not interfere in the detection of the STn-glycoproteins up to a concentration of 0.2 mg ml(-1). The developed lectin-based biosensor was used to evaluate the STn-expression in serum samples and discriminate samples from healthy individuals and patients with different types of malignant tumors, mostly carcinomas, where the increased expression of STn aberrant glycans is well established. This work demonstrates the feasibility of employing SNA-I to selectively recognize the STn epitope in glycoproteins and the use of the constructed biosensor was effective in the analysis of serum samples with the ability to discriminate in a fast way between cancer and healthy status. The proposed biosensor could be used for high-throughput, label-free profiling of the cancer-associated STn glycan expression in serum for diagnosis and therapy monitoring. PMID:24594592

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

    PubMed Central

    Shapiro, Mark B.; Vaillancourt, David E.; Sturman, Molly M.; Metman, Leo Verhagen; Bakay, Roy A. E.; Corcos, Daniel M.

    2008-01-01

    We quantified the effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) and medication on Parkinsonian rigidity using an objective measure of work about the elbow joint during a complete cycle of imposed 1-Hz sinusoidal oscillations. Resting and activated rigidity were analyzed in four experimental conditions: 1) off treatment; 2) on DBS; 3) on medication; and 4) on DBS plus medication. Rigidity at the elbow joint was also assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS). We tested ten patients who received STN DBS and ten age-matched neurologically healthy control subjects. The activated rigidity condition increased work in both Parkinson’s disease (PD) patients and control subjects. In PD patients, STN DBS reduced both resting and activated rigidity as indicated by work and the UPDRS rigidity score. This is the first demonstration that STN stimulation reduces rigidity using an objective measure such as work. In contrast, the presurgery dose of antiparkinsonian medication did not significantly improve the UPDRS rigidity score and reduced work only in the activated rigidity condition. Our results suggest that STN DBS may be more effective in alleviating rigidity in the upper limb of PD patients than medications administered at presurgery dosage level. PMID:17601186

  12. Articulatory Changes in Vowel Production following STN DBS and Levodopa Intake in Parkinson's Disease

    PubMed Central

    Martel Sauvageau, Vincent; Roy, Johanna-Pascale; Cantin, Léo; Prud'Homme, Michel; Langlois, Mélanie; Macoir, Joël

    2015-01-01

    Purpose. To investigate the impact of deep brain stimulation of the subthalamic nucleus (STN DBS) and levodopa intake on vowel articulation in dysarthric speakers with Parkinson's disease (PD). Methods. Vowel articulation was assessed in seven Quebec French speakers diagnosed with idiopathic PD who underwent STN DBS. Assessments were conducted on- and off-medication, first prior to surgery and then 1 year later. All recordings were made on-stimulation. Vowel articulation was measured using acoustic vowel space and formant centralization ratio. Results. Compared to the period before surgery, vowel articulation was reduced after surgery when patients were off-medication, while it was better on-medication. The impact of levodopa intake on vowel articulation changed with STN DBS: before surgery, levodopa impaired articulation, while it no longer had a negative effect after surgery. Conclusions. These results indicate that while STN DBS could lead to a direct deterioration in articulation, it may indirectly improve it by reducing the levodopa dose required to manage motor symptoms. These findings suggest that, with respect to speech production, STN DBS and levodopa intake cannot be investigated separately because the two are intrinsically linked. Along with motor symptoms, speech production should be considered when optimizing therapeutic management of patients with PD. PMID:26558134

  13. Methods for Surgical Targeting of the STN in Early-Stage Parkinson's Disease.

    PubMed

    Camalier, Corrie R; Konrad, Peter E; Gill, Chandler E; Kao, Chris; Remple, Michael R; Nasr, Hana M; Davis, Thomas L; Hedera, Peter; Phibbs, Fenna T; Molinari, Anna L; Neimat, Joseph S; Charles, David

    2014-01-01

    Patients with Parkinson's disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn-Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn-Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson's patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods. PMID:24678307

  14. Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects.

    PubMed

    Simon, Amos J; Lev, Atar; Zhang, Yong; Weiss, Batia; Rylova, Anna; Eyal, Eran; Kol, Nitzan; Barel, Ortal; Cesarkas, Keren; Soudack, Michalle; Greenberg-Kushnir, Noa; Rhodes, Michele; Wiest, David L; Schiby, Ginette; Barshack, Iris; Katz, Shulamit; Pras, Elon; Poran, Hana; Reznik-Wolf, Haike; Ribakovsky, Elena; Simon, Carlos; Hazou, Wadi; Sidi, Yechezkel; Lahad, Avishay; Katzir, Hagar; Sagie, Shira; Aqeilan, Haifa A; Glousker, Galina; Amariglio, Ninette; Tzfati, Yehuda; Selig, Sara; Rechavi, Gideon; Somech, Raz

    2016-07-25

    The analysis of individuals with telomere defects may shed light on the delicate interplay of factors controlling genome stability, premature aging, and cancer. We herein describe two Coats plus patients with telomere and genomic defects; both harbor distinct, novel mutations in STN1, a member of the human CTC1-STN1-TEN1 (CST) complex, thus linking this gene for the first time to a human telomeropathy. We characterized the patients' phenotype, recapitulated it in a zebrafish model and rescued cellular and clinical aspects by the ectopic expression of wild-type STN1 or by thalidomide treatment. Interestingly, a significant lengthy control of the gastrointestinal bleeding in one of our patients was achieved by thalidomide treatment, exemplifying a successful bed-to-bench-and-back approach. PMID:27432940

  15. Inhibition of Serratia marcescens Smj-11 biofilm formation by Alcaligenes faecalis STN17 crude extract

    NASA Astrophysics Data System (ADS)

    Lutfi, Zainal; Usup, Gires; Ahmad, Asmat

    2014-09-01

    Serratia marcescens biofilms are formed when they are bound to surfaces in aqueous environments. S. marcescens utilizes N-acylhomoserine lactone (AHL) as its quorum sensing signal molecule. The accumulation of AHL indicates the bacteria to produce matrices to form biofilms. Prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosin), which causes red pigmentation in the colonies, are also produced when the AHL reaches a certain threshold. The Alcaligenes faecalis STN17 crude extract is believed to inhibit quorum sensing in the S. marcescens Smj-11 and, thus, impedes its biofilm formation ability. A. faecalis STN17 was grown in marine broth, and ethyl acetate extraction was carried out. The crude compound of A. faecalis STN17 was diluted at high concentration (0.2-6.4 mg/mL) and was taken to confirm anti-biofilm activity through the crystal violet method in 96-wells plate. Then, the crude extract underwent purification using simple solvents partitioning test to discern the respective compounds that had the anti-biofilm activity under the crystal violet method. The crystal violet test showed that the crude did have anti-biofilm activity on S. marcescens Smj-11, but did not kill the cells. This finding signifies that the suppression of biofilm formation in S. marcescens by A. faecalis STN17 has a strong correlation. The partitioning test showed that A. faecalis STN17 crude extract has several compounds and only the compound(s) in chloroform showed activities. In conclusion, the crude extract of A. faecalis STN17 has the ability to inhibit S. marcescens Smj-11 biofilm formation.

  16. Inhibition of Serratia marcescens Smj-11 biofilm formation by Alcaligenes faecalis STN17 crude extract

    SciTech Connect

    Lutfi, Zainal; Ahmad, Asmat; Usup, Gires

    2014-09-03

    Serratia marcescens biofilms are formed when they are bound to surfaces in aqueous environments. S. marcescens utilizes N-acylhomoserine lactone (AHL) as its quorum sensing signal molecule. The accumulation of AHL indicates the bacteria to produce matrices to form biofilms. Prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosin), which causes red pigmentation in the colonies, are also produced when the AHL reaches a certain threshold. The Alcaligenes faecalis STN17 crude extract is believed to inhibit quorum sensing in the S. marcescens Smj-11 and, thus, impedes its biofilm formation ability. A. faecalis STN17 was grown in marine broth, and ethyl acetate extraction was carried out. The crude compound of A. faecalis STN17 was diluted at high concentration (0.2-6.4 mg/mL) and was taken to confirm anti-biofilm activity through the crystal violet method in 96-wells plate. Then, the crude extract underwent purification using simple solvents partitioning test to discern the respective compounds that had the anti-biofilm activity under the crystal violet method. The crystal violet test showed that the crude did have anti-biofilm activity on S. marcescens Smj-11, but did not kill the cells. This finding signifies that the suppression of biofilm formation in S. marcescens by A. faecalis STN17 has a strong correlation. The partitioning test showed that A. faecalis STN17 crude extract has several compounds and only the compound(s) in chloroform showed activities. In conclusion, the crude extract of A. faecalis STN17 has the ability to inhibit S. marcescens Smj-11 biofilm formation.

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

    PubMed Central

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

    2014-01-01

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

  18. STN area detection using K-NN classifiers for MER recordings in Parkinson patients during neurostimulator implant surgery

    NASA Astrophysics Data System (ADS)

    Schiaffino, L.; Rosado Muñoz, A.; Guerrero Martínez, J.; Francés Villora, J.; Gutiérrez, A.; Martínez Torres, I.; Kohan, y. D. R.

    2016-04-01

    Deep Brain Stimulation (DBS) applies electric pulses into the subthalamic nucleus (STN) improving tremor and other symptoms associated to Parkinson’s disease. Accurate STN detection for proper location and implant of the stimulating electrodes is a complex task and surgeons are not always certain about final location. Signals from the STN acquired during DBS surgery are obtained with microelectrodes, having specific characteristics differing from other brain areas. Using supervised learning, a trained model based on previous microelectrode recordings (MER) can be obtained, being able to successfully classify the STN area for new MER signals. The K Nearest Neighbours (K-NN) algorithm has been successfully applied to STN detection. However, the use of the fuzzy form of the K-NN algorithm (KNN-F) has not been reported. This work compares the STN detection algorithm of K-NN and KNN-F. Real MER recordings from eight patients where previously classified by neurophysiologists, defining 15 features. Sensitivity and specificity for the classifiers are obtained, Wilcoxon signed rank non-parametric test is used as statistical hypothesis validation. We conclude that the performance of KNN-F classifier is higher than K-NN with p<0.01 in STN specificity.

  19. Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines.

    PubMed

    Xiao, An; Zheng, Xiu-Jing; Song, Chengcheng; Gui, Yue; Huo, Chang-Xin; Ye, Xin-Shan

    2016-07-26

    Glycoprotein MUC1 is an attractive target for anti-tumor vaccine development. However, the weak immunogenicity of MUC1 remains a significant problem. To solve this problem, several STn derivatives with N-acetyl modifications were synthesized and incorporated into a 20-amino acid MUC1 tandem repeat sequence. The modified STn-MUC1 glycopeptides were further connected to a carrier protein keyhole limpet hemocyanin (KLH). The immunological effects of these synthetic vaccine conjugates were evaluated using the BALB/c mouse model. The results showed that vaccine V2 elicited higher titers of antibodies which cross-reacted with the native STn-MUC1 antigen. Moreover, the elicited antisera reacted with the STn-MUC1 antigen-positive tumor cells, indicating that the carbohydrate antigen modification strategy may hold potential to overcome the weak immunogenicity of natural MUC1 glycopeptides. PMID:27380866

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  2. Coordinated reset stimulation in a large-scale model of the STN-GPe circuit

    PubMed Central

    Ebert, Martin; Hauptmann, Christian; Tass, Peter A.

    2014-01-01

    Synchronization of populations of neurons is a hallmark of several brain diseases. Coordinated reset (CR) stimulation is a model-based stimulation technique which specifically counteracts abnormal synchrony by desynchronization. Electrical CR stimulation, e.g., for the treatment of Parkinson's disease (PD), is administered via depth electrodes. In order to get a deeper understanding of this technique, we extended the top-down approach of previous studies and constructed a large-scale computational model of the respective brain areas. Furthermore, we took into account the spatial anatomical properties of the simulated brain structures and incorporated a detailed numerical representation of 2 · 104 simulated neurons. We simulated the subthalamic nucleus (STN) and the globus pallidus externus (GPe). Connections within the STN were governed by spike-timing dependent plasticity (STDP). In this way, we modeled the physiological and pathological activity of the considered brain structures. In particular, we investigated how plasticity could be exploited and how the model could be shifted from strongly synchronized (pathological) activity to strongly desynchronized (healthy) activity of the neuronal populations via CR stimulation of the STN neurons. Furthermore, we investigated the impact of specific stimulation parameters especially the electrode position on the stimulation outcome. Our model provides a step forward toward a biophysically realistic model of the brain areas relevant to the emergence of pathological neuronal activity in PD. Furthermore, our model constitutes a test bench for the optimization of both stimulation parameters and novel electrode geometries for efficient CR stimulation. PMID:25505882

  3. Suppression of STN1 enhances the cytotoxicity of chemotherapeutic agents in cancer cells by elevating DNA damage

    PubMed Central

    Zhou, Qing; Chai, Weihang

    2016-01-01

    DNA damage-inducing agents are among the most effective treatment regimens in clinical chemotherapy. However, drug resistance and severe side effects caused by these agents greatly limit their efficacy. Sensitizing malignant cells to chemotherapeutic agents has long been a goal of chemotherapy. In the present study, suppression of STN1, a gene important for safeguarding genome stability, potentiated the anticancer effect of chemotherapeutic agents in tumor cells. Using multiple cancer cells from a variety of origins, it was observed that downregulation of STN1 resulted in a significant decrease in the half maximal inhibitory concentration values of several conventional anticancer agents. When cells are treated with anticancer agents, STN1 suppression leads to a decline in colony formation and diminished anchorage-independent growth. Furthermore, it was additionally observed that STN1 knockdown augmented the levels of DNA damage caused by damage-inducing agents. The present study concluded that suppression of STN1 enhances the cytotoxicity of damage-inducing chemotherapeutic agents by increasing DNA damage in cancer cells. PMID:27446354

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. Distinct effects of dopamine vs STN stimulation therapies in associative learning and retention in Parkinson disease.

    PubMed

    Ventre-Dominey, Jocelyne; Mollion, Hélène; Thobois, Stephane; Broussolle, Emmanuel

    2016-04-01

    Evidence has been provided in Parkinson's disease patients of cognitive impairments including visual memory and learning which can be partially compensated by dopamine medication or subthalamic nucleus stimulation. The effects of these two therapies can differ according to the learning processes involving the dorsal vs ventral part of the striatum. Here we aimed to investigate and compare the outcomes of dopamine vs stimulation treatment in Parkinson patient's ability to acquire and maintain over successive days their performance in visual working memory. Parkinson patients performed conditional associative learning embedded in visual (spatial and non spatial) working memory tasks over two consecutive days either ON or OFF dopaminergic drugs or STN stimulation depending on the group of patients studied. While Parkinson patients were more accurate and faster in memory tasks ON vs OFF stimulation independent of the day of testing, performance in medicated patients differed depending on the medication status during the initial task acquisition. Patients who learnt the task ON medication the first day were able to maintain or even improve their memory performance both OFF and ON medication on the second day after consolidation. These effects were observed only in patients with dopamine replacement with or without motor fluctuations. This enhancement in memory performance after having learnt under dopamine medication and not under STN stimulation was mostly significant in visuo-spatial working memory tasks suggesting that dopamine replacement in the depleted dorsal striatum is essential for retention and consolidation of learnt skill. PMID:26778783

  7. Efficient and Specific Detection of Salmonella in Food Samples Using a stn-Based Loop-Mediated Isothermal Amplification Method

    PubMed Central

    Srisawat, Mevaree; Panbangred, Watanalai

    2015-01-01

    The Salmonella enterotoxin (stn) gene exhibits high homology among S. enterica serovars and S. bongori. A set of 6 specific primers targeting the stn gene were designed for detection of Salmonella spp. using the loop-mediated isothermal amplification (LAMP) method. The primers amplified target sequences in all 102 strains of 87 serovars of Salmonella tested and no products were detected in 57 non-Salmonella strains. The detection limit in pure cultures was 5 fg DNA/reaction when amplified at 65°C for 25 min. The LAMP assay could detect Salmonella in artificially contaminated food samples as low as 220 cells/g of food without a preenrichment step. However, the sensitivity was increased 100-fold (~2 cells/g) following 5 hr preenrichment at 35°C. The LAMP technique, with a preenrichment step for 5 and 16 hr, was shown to give 100% specificity with food samples compared to the reference culture method in which 67 out of 90 food samples gave positive results. Different food matrixes did not interfere with LAMP detection which employed a simple boiling method for DNA template preparation. The results indicate that the LAMP method, targeting the stn gene, has great potential for detection of Salmonella in food samples with both high specificity and high sensitivity. PMID:26543859

  8. Cognitive and Psychiatric Effects of STN versus GPi Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Zhang, Xiao-Hua; Wang, Yun-Peng; Li, Ji-Ping; Li, Yong-Jie

    2016-01-01

    Background Deep brain stimulation (DBS) of either the subthalamic nucleus (STN) or the globus pallidus interna (GPi) can reduce motor symptoms in patients with Parkinson’s disease (PD) and improve their quality of life. However, the effects of STN DBS and GPi DBS on cognitive functions and their psychiatric effects remain controversial. The present meta-analysis was therefore performed to clarify these issues. Methods We searched the PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials databases. Other sources, including internet-based clinical trial registries and grey literature sources, were also searched. After searching the literature, two investigators independently performed literature screens to assess the quality of the included trials and to extract the data. The outcomes included the effects of STN DBS and GPi DBS on multiple cognitive domains, depression, anxiety, and quality of life. Results Seven articles related to four randomized controlled trials that included 521 participants were incorporated into the present meta-analysis. Compared with GPi DBS, STN DBS was associated with declines in selected cognitive domains after surgery, including attention, working memory and processing speed, phonemic fluency, learning and memory, and global cognition. However, there were no significant differences in terms of quality of life or psychiatric effects, such as depression and anxiety, between the two groups. Conclusions A selective decline in frontal-subcortical cognitive functions is observed after STN DBS in comparison with GPi DBS, which should not be ignored in the target selection for DBS treatment in PD patients. In addition, compared to GPi DBS, STN DBS does not affect depression, anxiety, and quality of life. PMID:27248139

  9. Activation of the Stt7/STN7 Kinase through Dynamic Interactions with the Cytochrome b6f Complex1[OPEN

    PubMed Central

    Shapiguzov, Alexey; Chai, Xin; Fucile, Geoffrey; Longoni, Paolo; Zhang, Lixin

    2016-01-01

    Photosynthetic organisms have the ability to adapt to changes in light quality by readjusting the cross sections of the light-harvesting systems of photosystem II (PSII) and photosystem I (PSI). This process, called state transitions, maintains the redox poise of the photosynthetic electron transfer chain and ensures a high photosynthetic yield when light is limiting. It is mediated by the Stt7/STN7 protein kinase, which is activated through the cytochrome b6f complex upon reduction of the plastoquinone pool. Its probable major substrate, the light-harvesting complex of PSII, once phosphorylated, dissociates from PSII and docks to PSI, thereby restoring the balance of absorbed light excitation energy between the two photosystems. Although the kinase is known to be inactivated under high-light intensities, the molecular mechanisms governing its regulation remain unknown. In this study we monitored the redox state of a conserved and essential Cys pair of the Stt7/STN7 kinase and show that it forms a disulfide bridge. We could not detect any change in the redox state of these Cys during state transitions and high-light treatment. It is only after prolonged anaerobiosis that this disulfide bridge is reduced. It is likely to be mainly intramolecular, although kinase activation may involve a transient covalently linked kinase dimer with two intermolecular disulfide bonds. Using the yeast two-hybrid system, we have mapped one interaction site of the kinase on the Rieske protein of the cytochrome b6f complex. PMID:26941194

  10. Loss-of-function of OsSTN8 suppresses the photosystem II core protein phosphorylation and interferes with the photosystem II repair mechanism in rice (Oryza sativa).

    PubMed

    Nath, Krishna; Poudyal, Roshan Sharma; Eom, Joon-Seob; Park, Yu Shin; Zulfugarov, Ismayil S; Mishra, Sujata R; Tovuu, Altanzaya; Ryoo, Nayeoon; Yoon, Ho-Sung; Nam, Hong Gil; An, Gynheung; Jeon, Jong-Seong; Lee, Choon-Hwan

    2013-11-01

    STN8 kinase is involved in photosystem II (PSII) core protein phosphorylation (PCPP). To examine the role of PCPP in PSII repair during high light (HL) illumination, we characterized a T-DNA insertional knockout mutant of the rice (Oryza sativa) STN8 gene. In this osstn8 mutant, PCPP was significantly suppressed, and the grana were thin and elongated. Upon HL illumination, PSII was strongly inactivated in the mutants, but the D1 protein was degraded more slowly than in wild-type, and mobilization of the PSII supercomplexes from the grana to the stromal lamellae for repair was also suppressed. In addition, higher accumulation of reactive oxygen species and preferential oxidation of PSII reaction center core proteins in thylakoid membranes were observed in the mutants during HL illumination. Taken together, our current data show that the absence of STN8 is sufficient to abolish PCPP in osstn8 mutants and to produce all of the phenotypes observed in the double mutant of Arabidopsis, indicating the essential role of STN8-mediated PCPP in PSII repair. PMID:24103067

  11. Closed-loop stimulation of a delayed neural fields model of parkinsonian STN-GPe network: a theoretical and computational study

    PubMed Central

    Detorakis, Georgios Is.; Chaillet, Antoine; Palfi, Stéphane; Senova, Suhan

    2015-01-01

    Several disorders are related to pathological brain oscillations. In the case of Parkinson's disease, sustained low-frequency oscillations (especially in the β-band, 13–30 Hz) correlate with motor symptoms. It is still under debate whether these oscillations are the cause of parkinsonian motor symptoms. The development of techniques enabling selective disruption of these β-oscillations could contribute to the understanding of the underlying mechanisms, and could be exploited for treatments. A particularly appealing technique is Deep Brain Stimulation (DBS). With clinical electrical DBS, electrical currents are delivered at high frequency to a region made of potentially heterogeneous neurons (the subthalamic nucleus (STN) in the case of Parkinson's disease). Even more appealing is DBS with optogenetics, which is until now a preclinical method using both gene transfer and deep brain light delivery and enabling neuromodulation at the scale of one given neural network. In this work, we rely on delayed neural fields models of STN and the external Globus Pallidus (GPe) to develop, theoretically validate and test in silico a closed-loop stimulation strategy to disrupt these sustained oscillations with optogenetics. First, we rely on tools from control theory to provide theoretical conditions under which sustained oscillations can be attenuated by a closed-loop stimulation proportional to the measured activity of STN. Second, based on this theoretical framework, we show numerically that the proposed closed-loop stimulation efficiently attenuates sustained oscillations, even in the case when the photosensitization effectively affects only 50% of STN neurons. We also show through simulations that oscillations disruption can be achieved when the same light source is used for the whole STN population. We finally test the robustness of the proposed strategy to possible acquisition and processing delays, as well as parameters uncertainty. PMID:26217171

  12. Subaru Telescope Network III (STN-III): more effective, more operation-oriented, and more inexpensive solutions for the observatory's needs

    NASA Astrophysics Data System (ADS)

    Noumaru, Junichi; Kawai, Jun A.; Schubert, Kiaina; Yagi, Masafumi; Takata, Tadafumi; Winegar, Tom; Scanlon, Tim; Nishida, Takuhiro; Fox, Camron; Hayasaka, James; Forester, Jason; Uchida, Kenji; Nakamura, Isamu; Tom, Richard; Koura, Norikazu; Yamamoto, Tadahiro; Tanoue, Toshiya; Yamada, Toru

    2008-07-01

    Subaru Telescope has recently replaced most equipment of Subaru Telescope Network II with the new equipment which includes 124TB of RAID system for data archive. Switching the data storage from tape to RAID enables users to access the data faster. The STN-III dropped some important components of STN-II, such as supercomputers, development & testing subsystem for Subaru Observation Control System, or data processing subsystem. On the other hand, we invested more computers to the remote operation system. Thanks to IT innovations, our LAN as well as the network between Hilo and summit were upgraded to gigabit network at the similar or even reduced cost from the previous system. As the result of the redesigning of the computer system by more focusing on the observatory operation, we greatly reduced the total cost for computer rental, purchase and maintenance.

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

    PubMed Central

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

    2015-01-01

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

  14. SUMOylation regulates telomere length by targeting the shelterin subunit Tpz1(Tpp1) to modulate shelterin-Stn1 interaction in fission yeast.

    PubMed

    Miyagawa, Keisuke; Low, Ross S; Santosa, Venny; Tsuji, Hiroki; Moser, Bettina A; Fujisawa, Shiho; Harland, Jennifer L; Raguimova, Olga N; Go, Andrew; Ueno, Masaru; Matsuyama, Akihisa; Yoshida, Minoru; Nakamura, Toru M; Tanaka, Katsunori

    2014-04-22

    Telomeres protect DNA ends of linear eukaryotic chromosomes from degradation and fusion, and ensure complete replication of the terminal DNA through recruitment of telomerase. The regulation of telomerase is a critical area of telomere research and includes cis regulation by the shelterin complex in mammals and fission yeast. We have identified a key component of this regulatory pathway as the SUMOylation [the covalent attachment of a small ubiquitin-like modifier (SUMO) to target proteins] of a shelterin subunit in fission yeast. SUMOylation is known to be involved in the negative regulation of telomere extension by telomerase; however, how SUMOylation limits the action of telomerase was unknown until now. We show that SUMOylation of the shelterin subunit TPP1 homolog in Schizosaccharomyces pombe (Tpz1) on lysine 242 is important for telomere length homeostasis. Furthermore, we establish that Tpz1 SUMOylation prevents telomerase accumulation at telomeres by promoting recruitment of Stn1-Ten1 to telomeres. Our findings provide major mechanistic insights into how the SUMOylation pathway collaborates with shelterin and Stn1-Ten1 complexes to regulate telomere length. PMID:24711392

  15. Production of superoxide from photosystem II-light harvesting complex II supercomplex in STN8 kinase knock-out rice mutants under photoinhibitory illumination.

    PubMed

    Poudyal, Roshan Sharma; Nath, Krishna; Zulfugarov, Ismayil S; Lee, Choon-Hwan

    2016-09-01

    When phosphorylation of Photosystem (PS) II core proteins is blocked in STN8 knock-out mutants of rice (Oryza sativa) under photoinhibitory illumination, the mobilization of PSII supercomplex is prevented. We have previously proposed that more superoxide (O2(-)) is produced from PSII in the mutant (Nath et al., 2013, Plant J. 76, 675-686). Here, we clarify the type and site for the generation of reactive oxygen species (ROS). Using both histochemical and fluorescence probes, we observed that, compared with wild-type (WT) leaves, levels of ROS, including O2(-) and hydrogen peroxide (H2O2), were increased when leaves from mutant plants were illuminated with excess light. However, singlet oxygen production was not enhanced under such conditions. When superoxide dismutase was inhibited, O2(-) production was increased, indicating that it is the initial event prior to H2O2 production. In thylakoids isolated from WT leaves, kinase was active in the presence of ATP, and spectrophotometric analysis of nitrobluetetrazolium absorbance for O2(-) confirmed that PSII-driven superoxide production was greater in the mutant thylakoids than in the WT. This contrast in levels of PSII-driven superoxide production between the mutants and the WT plants was confirmed by conducting protein oxidation assays of PSII particles from osstn8 leaves under strong illumination. Those assays also demonstrated that PSII-LHCII supercomplex proteins were oxidized more in the mutant, thereby implying that PSII particles incur greater damage even though D1 degradation during PSII-supercomplex mobilization is partially blocked in the mutant. These results suggest that O2(-) is the major form of ROS produced in the mutant, and that the damaged PSII in the supercomplex is the primary source of O2(-). PMID:27390892

  16. Deep brain stimulation induces BOLD activation in motor and non-motor networks: An fMRI comparison study of STN and EN/GPi DBS in large animals

    PubMed Central

    Min, Hoon-Ki; Hwang, Sun-Chul; Marsh, Michael P.; Kim, Inyong; Knight, Emily; Striemer, Bryan; Felmlee, Joel P.; Welker, Kirk M.; Blaha, Charles D.; Chang, Su-Youne; Bennet, Kevin E.; Lee, Kendall H.

    2012-01-01

    The combination of deep brain stimulation (DBS) and functional MRI (fMRI) is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. The goal of this study was to trace DBS-induced global neuronal network activation in a large animal model by monitoring the blood oxygenation level-dependent (BOLD) response on fMRI. We conducted DBS in normal anesthetized pigs, targeting the subthalamic nucleus (STN) (n=7) and the entopeduncular nucleus (EN), the non-primate analogue of the primate globus pallidus interna (n=4). Using a normalized functional activation map for group analysis and the application of general linear modeling across subjects, we found that both STN and EN DBS significantly increased BOLD activation in the ipsilateral sensorimotor network (FDR < 0.001). In addition, we found differential, target-specific, non-motor network effects. In each group the activated brain areas showed a distinctive correlation pattern forming a group of network connections. Results suggest that the scope of DBS extends beyond an ablation-like effect and that it may have modulatory effects not only on circuits that facilitate motor function but also on those involved in higher cognitive and emotional processing. Taken together, our results show that the swine model for DBS fMRI, which conforms to human implanted DBS electrode configurations and human neuroanatomy, may be a useful platform for translational studies investigating the global neuromodulatory effects of DBS. PMID:22967832

  17. The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer

    PubMed Central

    Munkley, Jennifer; Oltean, Sebastian; Vodák, Daniel; Wilson, Brian T.; Livermore, Karen E.; Zhou, Yan; Star, Eleanor; Floros, Vasileios I.; Johannessen, Bjarne; Knight, Bridget; McCullagh, Paul; McGrath, John; Crundwell, Malcolm; Skotheim, Rolf I.; Robson, Craig N.; Leung, Hing Y.; Harries, Lorna W.; Rajan, Prabhakar; Mills, Ian G.; Elliott, David J.

    2015-01-01

    Patterns of glycosylation are important in cancer, but the molecular mechanisms that drive changes are often poorly understood. The androgen receptor drives prostate cancer (PCa) development and progression to lethal metastatic castration-resistant disease. Here we used RNA-Seq coupled with bioinformatic analyses of androgen-receptor (AR) binding sites and clinical PCa expression array data to identify ST6GalNAc1 as a direct and rapidly activated target gene of the AR in PCa cells. ST6GalNAc1 encodes a sialytransferase that catalyses formation of the cancer-associated sialyl-Tn antigen (sTn), which we find is also induced by androgen exposure. Androgens induce expression of a novel splice variant of the ST6GalNAc1 protein in PCa cells. This splice variant encodes a shorter protein isoform that is still fully functional as a sialyltransferase and able to induce expression of the sTn-antigen. Surprisingly, given its high expression in tumours, stable expression of ST6GalNAc1 in PCa cells reduced formation of stable tumours in mice, reduced cell adhesion and induced a switch towards a more mesenchymal-like cell phenotype in vitro. ST6GalNAc1 has a dynamic expression pattern in clinical datasets, being significantly up-regulated in primary prostate carcinoma but relatively down-regulated in established metastatic tissue. ST6GalNAc1 is frequently upregulated concurrently with another important glycosylation enzyme GCNT1 previously associated with prostate cancer progression and implicated in Sialyl Lewis X antigen synthesis. Together our data establishes an androgen-dependent mechanism for sTn antigen expression in PCa, and are consistent with a general role for the androgen receptor in driving important coordinate changes to the glycoproteome during PCa progression. PMID:26452038

  18. The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson’s Disease

    PubMed Central

    2011-01-01

    T-Type Ca2+ channel inhibitors hold tremendous therapeutic potential for the treatment of pain, epilepsy, sleep disorders, essential tremor, and other neurological disorders; however, a lack of truly selective tools has hindered basic research, and selective tools from the pharmaceutical industry are potentially burdened with intellectual property (IP) constraints. Thus, an MLPCN high-throughput screen (HTS) was conducted to identify novel T-type Ca2+ channel inhibitors free from IP constraints, and freely available through the MLPCN, for use by the biomedical community to study T-type Ca2+ channels. While the HTS provided numerous hits, these compounds could not be optimized to the required level of potency to be appropriate tool compounds. Therefore, a scaffold hopping approach, guided by SurflexSim, ultimately afforded ML218 (CID 45115620), a selective T-type Ca2+ (Cav3.1, Cav3.2, Cav3.3) inhibitor (Cav3.2, IC50 = 150 nM in Ca2+ flux; Cav3.2 IC50 = 310 nM; and Cav3.3 IC50 = 270 nM, respectively in patch clamp electrophysiology) with good DMPK properties, acceptable in vivo rat PK, and excellent brain levels. Electrophysiology studies in subthalamic nucleus (STN) neurons demonstrated robust effects of ML218 on the inhibition of T-type calcium current, inhibition of low threshold spike, and rebound burst activity. Based on the basal ganglia circuitry in Parkinson’s disease (PD), the effects of ML218 in STN neurons suggest a therapeutic role for T-type Ca2+ channel inhibitors, and ML218 was found to be orally efficacious in haloperidol-induced catalepsy, a preclinical PD model, with comparable efficacy to an A2A antagonist, a clinically validated PD target. ML218 proves to be a powerful new probe to study T-type Ca2+ function in vitro and in vivo, and freely available. PMID:22368764

  19. COMPARISON OF DATA FROM THE STN AND IMPROVE NETWORKS

    EPA Science Inventory

    Two national chemical speciation-monitoring networks operate currently within the United States. The Interagency Monitoring of Protected Visual Environments (IMPROVE) monitoring network operates primarily in rural areas collecting aerosol and optical data to better understand th...

  20. Perceived Changes in Communication as an Effect of STN Surgery in Parkinson's Disease: A Qualitative Interview Study

    PubMed Central

    Ahlberg, Emilia; Laakso, Katja; Hartelius, Lena

    2011-01-01

    The aim of the present study was to explore four individuals' perspective of the way their speech and communication changed as a result of subthalamic nucleus deep brain stimulation treatment for Parkinson's disease. Interviews of two men and two women were analyzed using qualitative content analysis. Three themes emerged as a result of the analysis. The first theme included sub-themes describing both increased and unexpected communication difficulties such as a more vulnerable speech function, re-emerging stuttering and cognitive difficulties affecting communication. The second theme comprised strategies to improve communication, using different speech techniques and communicative support, as well as trying to achieve changes in medical and stimulation parameters. The third theme included descriptions of mixed feelings surrounding the surgery. Participants described the surgery as an unavoidable dramatic change, associated both with improved quality of life but also uncertainty and lack of information, particularly regarding speech and communication changes. Despite negative effects on speech, the individuals were generally very pleased with the surgical outcome. More information before surgery regarding possible side effects on speech, meeting with a previously treated patient and possibly voice and speech therapy before or after surgery are suggested to facilitate the adjustment to the new speech conditions. PMID:21876840

  1. Perceived Changes in Communication as an Effect of STN Surgery in Parkinson's Disease: A Qualitative Interview Study.

    PubMed

    Ahlberg, Emilia; Laakso, Katja; Hartelius, Lena

    2011-01-01

    The aim of the present study was to explore four individuals' perspective of the way their speech and communication changed as a result of subthalamic nucleus deep brain stimulation treatment for Parkinson's disease. Interviews of two men and two women were analyzed using qualitative content analysis. Three themes emerged as a result of the analysis. The first theme included sub-themes describing both increased and unexpected communication difficulties such as a more vulnerable speech function, re-emerging stuttering and cognitive difficulties affecting communication. The second theme comprised strategies to improve communication, using different speech techniques and communicative support, as well as trying to achieve changes in medical and stimulation parameters. The third theme included descriptions of mixed feelings surrounding the surgery. Participants described the surgery as an unavoidable dramatic change, associated both with improved quality of life but also uncertainty and lack of information, particularly regarding speech and communication changes. Despite negative effects on speech, the individuals were generally very pleased with the surgical outcome. More information before surgery regarding possible side effects on speech, meeting with a previously treated patient and possibly voice and speech therapy before or after surgery are suggested to facilitate the adjustment to the new speech conditions. PMID:21876840

  2. High Light-Dependent Phosphorylation of Photosystem II Inner Antenna CP29 in Monocots Is STN7 Independent and Enhances Nonphotochemical Quenching1

    PubMed Central

    Betterle, Nico; Ballottari, Matteo; Baginsky, Sacha; Bassi, Roberto

    2015-01-01

    Phosphorylation of the photosystem II antenna protein CP29 has been reported to be induced by excess light and further enhanced by low temperature, increasing resistance to these stressing factors. Moreover, high light-induced CP29 phosphorylation was specifically found in monocots, both C3 and C4, which include the large majority of food crops. Recently, knockout collections have become available in rice (Oryza sativa), a model organism for monocots. In this work, we have used reverse genetics coupled to biochemical and physiological analysis to elucidate the molecular basis of high light-induced phosphorylation of CP29 and the mechanisms by which it exerts a photoprotective effect. We found that kinases and phosphatases involved in CP29 phosphorylation are distinct from those reported to act in State 1-State 2 transitions. In addition, we elucidated the photoprotective role of CP29 phosphorylation in reducing singlet oxygen production and enhancing excess energy dissipation. We thus established, in monocots, a mechanistic connection between phosphorylation of CP29 and nonphotochemical quenching, two processes so far considered independent from one another. PMID:25501945

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

    PubMed

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

    2016-10-15

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

  4. HETEROSYNAPTIC REGULATION OF EXTERNAL GLOBUS PALLIDUS INPUTS TO THE SUBTHALAMIC NUCLEUS BY MOTOR CORTEX

    PubMed Central

    Chu, Hong-Yuan; Atherton, Jeremy F.; Wokosin, David; Surmeier, D. James; Bevan, Mark D.

    2014-01-01

    SUMMARY The two principal movement-suppressing pathways of the basal ganglia, the so-called hyperdirect and indirect pathways interact within the subthalamic nucleus (STN). An appropriate level and pattern of hyperdirect pathway cortical excitation and indirect pathway external globus pallidus (GPe) inhibition of the STN are critical for normal movement and greatly perturbed in Parkinson’s disease. Here, we demonstrate that motor cortical inputs to the STN heterosynaptically regulate through activation of postsynaptic NMDA receptors the number of functional GABAA receptor-mediated GPe-STN inputs. Thus, a homeostatic mechanism, intrinsic to the STN, balances cortical excitation by adjusting the strength of GPe inhibition. However, following loss of dopamine, excessive cortical activation of STN NMDA receptors triggers GPe-STN inputs to strengthen abnormally, contributing to the emergence of pathological, correlated activity. PMID:25578364

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

    PubMed Central

    Kim, Han-Joon; Jeon, Beom S.; Paek, Sun Ha

    2015-01-01

    Subthalamic deep brain stimulation (STN DBS) is an established treatment for the motor symptoms in patients with advanced Parkinson’s disease (PD). In addition to improvements in motor symptoms, many studies have reported changes in various nonmotor symptoms (NMSs) after STN DBS in patients with PD. Psychiatric symptoms, including depression, apathy, anxiety, and impulsivity, can worsen or improve depending on the electrical stimulation parameters, the locations of the stimulating contacts within the STN, and changes in medications after surgery. Global cognitive function is not affected by STN DBS, and there is no increase in the incidence of dementia after STN DBS compared to that after medical treatment, although clinically insignificant declines in verbal fluency have been consistently reported. Pain, especially PD-related pain, improves with STN DBS. Evidence regarding the effects of STN DBS on autonomic symptoms and sleep-related problems is limited and remains conflicting. Many symptoms of nonmotor fluctuations, which are occasionally more troublesome than motor fluctuations, improve with STN DBS. Although it is clear that NMSs are not target symptoms for STN DBS, NMSs have a strong influence on the quality of life of patients with PD, and clinicians should thus be aware of these NMSs when deciding whether to perform surgery and should pay attention to changes in these symptoms after STN DBS to ensure the optimal care for patients. PMID:26090080

  6. Toxin-induced pore formation is hindered by intermolecular hydrogen bonding in sphingomyelin bilayers.

    PubMed

    García-Linares, Sara; Palacios-Ortega, Juan; Yasuda, Tomokazu; Åstrand, Mia; Gavilanes, José G; Martínez-del-Pozo, Álvaro; Slotte, J Peter

    2016-06-01

    Sticholysin I and II (StnI and StnII) are pore-forming toxins that use sphingomyelin (SM) for membrane binding. We examined how hydrogen bonding among membrane SMs affected the StnI- and StnII-induced pore formation process, resulting in bilayer permeabilization. We compared toxin-induced permeabilization in bilayers containing either SM or dihydro-SM (lacking the trans Δ(4) double bond of the long-chain base), since their hydrogen-bonding properties are known to differ greatly. We observed that whereas both StnI and StnII formed pores in unilamellar vesicles containing palmitoyl-SM or oleoyl-SM, the toxins failed to similarly form pores in vesicles prepared from dihydro-PSM or dihydro-OSM. In supported bilayers containing OSM, StnII bound efficiently, as determined by surface plasmon resonance. However, StnII binding to supported bilayers prepared from dihydro-OSM was very low under similar experimental conditions. The association of the positively charged StnII (at pH7.0) with unilamellar vesicles prepared from OSM led to a concentration-dependent increase in vesicle charge, as determined from zeta-potential measurements. With dihydro-OSM vesicles, a similar response was not observed. Benzyl alcohol, which is a small hydrogen-bonding compound with affinity to lipid bilayer interfaces, strongly facilitated StnII-induced pore formation in dihydro-OSM bilayers, suggesting that hydrogen bonding in the interfacial region originally prevented StnII from membrane binding and pore formation. We conclude that interfacial hydrogen bonding was able to affect the membrane association of StnI- and StnII, and hence their pore forming capacity. Our results suggest that other types of protein interactions in bilayers may also be affected by hydrogen-bonding origination from SMs. PMID:26975250

  7. Subthalamic 6-OHDA-induced lesion attenuates levodopa-induced dyskinesias in the rat model of Parkinson's disease.

    PubMed

    Marin, C; Bonastre, M; Mengod, G; Cortés, R; Rodríguez-Oroz, M C; Obeso, J A

    2013-12-01

    The subthalamic nucleus (STN) receives direct dopaminergic innervation from the substantia nigra pars compacta that degenerates in Parkinson's disease. The present study aimed to investigate the role of dopaminergic denervation of STN in the origin of levodopa-induced dyskinesias. Rats were distributed in four groups which were concomitantly lesioned with 6-OHDA or vehicle (sham) in the STN and in the medial forebrain bundle (MFB) as follows: a) MFB-sham plus STN-sham, b) MFB-sham plus STN-lesion, c) MFB-lesion plus STN-sham, and d) MFB-lesion plus STN-lesion. Four weeks after lesions, animals were treated with levodopa (6mg/kg with 15mg/kg benserazide i.p.) twice daily for 22 consecutive days. Abnormal involuntary movements were measured. In situ hybridization was performed measuring the expression of striatal preproenkephalin, preprodynorphin, STN cytochrome oxidase (CO) and nigral GAD67 mRNAs. STN 6-OHDA denervation did not induce dyskinesias in levodopa-treated MFB-sham animals but attenuated axial (p<0.05), limb (p<0.05) and orolingual (p<0.01) dyskinesias in rats with a concomitant lesion of the nigrostriatal pathway. The attenuation of dyskinesias was associated with a decrease in the ipsilateral STN CO mRNA levels (p<0.05). No significant differences between MFB-lesion plus STN-sham and MFB-lesion plus STN-lesion groups in the extent of STN dopaminergic denervation were observed. Moreover, intrasubthalamic microinfusion of dopamine in the MFB-lesion plus STN-lesion group triggered orolingual (p<0.01), but not axial or limb, dyskinesias. These results suggest that dopaminergic STN innervation influences the expression of levodopa-induced dyskinesias but also the existence of non dopaminergic-mediated mechanisms. STN noradrenergic depletion induced by 6-OHDA in the STN needs to be taken in account as a possible mechanism explaining the attenuation of dyskinesias in the combined lesion group. PMID:24140562

  8. The Subthalamic Nucleus During Decision-Making With Multiple Alternatives

    PubMed Central

    Bogacz, Rafal; Schäfer, Andreas; Neumann, Jane; Turner, Robert; Forstmann, Birte U.

    2016-01-01

    Several prominent neurocomputational models predict that an increase of choice alternatives is modulated by increased activity in the subthalamic nucleus (STN). In turn, increased STN activity allows prolonged accumulation of information. At the same time, areas in the medial frontal cortex such as the anterior cingulate cortex (ACC) and the pre-SMA are hypothesized to influence the information processing in the STN. This study set out to test concrete predictions of STN activity in multiple-alternative decision-making using a multimodal combination of 7 Tesla structural and functional Magnetic Resonance Imaging, and ancestral graph (AG) modeling. The results are in line with the predictions in that increased STN activity was found with an increasing amount of choice alternatives. In addition, our study shows that activity in the ACC is correlated with activity in the STN without directly modulating it. This result sheds new light on the information processing streams between medial frontal cortex and the basal ganglia. PMID:26178078

  9. Neurophysiological modulation of the subthalamic nucleus by pallidal stimulation in Parkinson's disease

    PubMed Central

    Sterio, D; Rezai, A; Mogilner, A; Zonenshayn, M; Gracies, J; Kathirithamby, K; Beric, A

    2002-01-01

    Objectives: Current models of basal ganglia dysfunction in Parkinson's disease suggest a pivotal role of subthalamic nucleus (STN) hyperactivity. There is a direct excitatory output to the globus pallidus internus (GPi), which in turn hyperinhibits the motor thalamus and leads to a lack of cortical facilitation. The model, however, does not address the reciprocal influence of GPi on STN activity. Methods: Measurement of immediate changes in STN single cell activity after GPi deep brain stimulation (DBS). Results: An opposite effect of GPi DBS in the dorsal versus ventral STN was found. There was an almost exclusive reduction of firing rate in the dorsal region of the STN, whereas the cells in the ventral region exhibited facilitation similar to the recordings from the substantia nigra pars reticulata. Conclusion: Although these findings require confirmation, they suggest that the current theories of GPi DBS action, which do not include a GPi-STN modulation, are most likely incomplete. PMID:11861688

  10. The subthalamic nucleus during decision-making with multiple alternatives.

    PubMed

    Keuken, Max C; Van Maanen, Leendert; Bogacz, Rafal; Schäfer, Andreas; Neumann, Jane; Turner, Robert; Forstmann, Birte U

    2015-10-01

    Several prominent neurocomputational models predict that an increase of choice alternatives is modulated by increased activity in the subthalamic nucleus (STN). In turn, increased STN activity allows prolonged accumulation of information. At the same time, areas in the medial frontal cortex such as the anterior cingulate cortex (ACC) and the pre-SMA are hypothesized to influence the information processing in the STN. This study set out to test concrete predictions of STN activity in multiple-alternative decision-making using a multimodal combination of 7 Tesla structural and functional Magnetic Resonance Imaging, and ancestral graph (AG) modeling. The results are in line with the predictions in that increased STN activity was found with an increasing amount of choice alternatives. In addition, our study shows that activity in the ACC is correlated with activity in the STN without directly modulating it. This result sheds new light on the information processing streams between medial frontal cortex and the basal ganglia. PMID:26178078

  11. Subthalamic nucleus deep brain stimulation induces impulsive action when patients with Parkinson's disease act under speed pressure.

    PubMed

    Pote, Inês; Torkamani, Mariam; Kefalopoulou, Zinovia-Maria; Zrinzo, Ludvic; Limousin-Dowsey, Patricia; Foltynie, Thomas; Speekenbrink, Maarten; Jahanshahi, Marjan

    2016-07-01

    The subthalamic nucleus (STN) is proposed to modulate response thresholds and speed-accuracy trade-offs. In situations of conflict, the STN is considered to raise response thresholds, allowing time for the accumulation of information to occur before a response is selected. Conversely, speed pressure is thought to reduce the activity of the STN and lower response thresholds, resulting in fast, errorful responses. In Parkinson's disease (PD), subthalamic nucleus deep brain stimulation (STN-DBS) reduces the activity of the nucleus and improves motor symptoms. We predicted that the combined effects of STN stimulation and speed pressure would lower STN activity and lead to fast, errorful responses, hence resulting in impulsive action. We used the motion discrimination 'moving-dots' task to assess speed-accuracy trade-offs, under both speed and accuracy instructions. We assessed 12 patients with PD and bilateral STN-DBS and 12 age-matched healthy controls. Participants completed the task twice, and the patients completed it once with STN-DBS on and once with STN-DBS off, with order counterbalanced. We found that STN stimulation was associated with significantly faster reaction times but more errors under speed instructions. Application of the drift diffusion model showed that stimulation resulted in lower response thresholds when acting under speed pressure. These findings support the involvement of the STN in the modulation of speed-accuracy trade-offs and establish for the first time that speed pressure alone, even in the absence of conflict, can result in STN stimulation inducing impulsive action in PD. PMID:26892884

  12. High-frequency electrical stimulation of the subthalamic nucleus excites target structures in a model using c-fos immunohistochemistry.

    PubMed

    Shehab, S; D'souza, C; Ljubisavljevic, M; Redgrave, P

    2014-06-13

    Deep-brain stimulation at high frequencies (HFS) directed to the subthalamic nucleus (STN) is used increasingly to treat patients with Parkinson's disease. However, the mechanism of action by which HFS of the STN achieves its therapeutic effects remains unresolved. Insofar as lesions of the STN have similar therapeutic benefit, a favored hypothesis is that HFS acts by suppressing neural activity in the STN. The purpose of the present study was to exploit prior observations that exposure to ether anesthesia in a rodent model evokes c-fos expression (a marker of neural activation) in the STN and its efferent structures, the globus pallidus, entopeduncular nucleus and substantia nigra. We showed first that exposure to ether induced a profound oscillatory pattern of neural activity in the STN and SNr, which could explain the marked induction of c-fos immunoreactivity in these structures. Secondly, inhibition of the STN by local injections of the GABA agonist, muscimol, suppressed ether-evoked c-fos expression in all target structures. This showed that excitation of target structures in the ether model originated, at least in part, from the STN. Thirdly, and contrary to expectation, HFS of the STN increased further the expression of c-fos in the STN target structures of animals treated with ether. Finally, we demonstrated, in the absence of ether treatment, that HFS and chemical stimulation of the STN with local injections of kainic acid both induced c-fos expression in the globus pallidus, entopeduncular nucleus and substantia nigra. Together these results suggest that the principal action of STN stimulation at high frequencies is to excite rather than inhibit its efferent targets. Given that Parkinsonism has been associated with increased levels of inhibitory output activity from the basal ganglia, it is unlikely that excitation of output structures revealed in this study provides a basis for deep-brain stimulation's therapeutic action. PMID:24755486

  13. Expression profile of mucin-associated sialyl-Tn antigen in Chinese patients with different colorectal lesions (adenomas, carcinomas)

    PubMed Central

    Xu, Feng; Fan, Cuizhen; Fan, Shanshan; Liu, Fuquan; Wen, Tao; An, Guangyu; Feng, Guosheng

    2015-01-01

    Background: The sialyl-Tn (sTn) antigen is a mucin-associated carbohydrate antigen expressed by numerous human carcinomas, and is also claimed to be a prognostic factor in colorectal cancer. But the associations between sTn and colorectal cancer remain elusive and controversial. Here, we investigated the expression profile of sTn antigen in a series of human colorectal tissue samples including normal colon, colorectal adenomas, and colorectal carcinomas (CRCs), with an aim to analyzing whether sTn plays a role in the progression and development of Chinese patients with CRCs. Methods: Immunohistochemical staining of sTn antigen was performed in formalin-fixed, paraffin-embedded colonic sections from 4 healthy controls, 44 patients with colorectal adenomas, and 186 patients with primary CRCs. Results: No sTn antigen was detected in normal colonic tissues. There were 41 of 44 patients with colorectal adenomas (93.2%), and 141 of 186 patients with CRCs (75.8%) found to express sTn antigen. The patterns of sTn localization were different in adenomas and carcinomas of colonic tissues. Colorectal adenomas showed predominant supranuclear distribution of sTn antigen, while carcinomas revealed apical membrane, mucin droplet and diffuse cytoplasmic localization. Notably, sTn was significantly associated with the degree of differentiation (P = 0.006) and perineural invasion (P = 0.041) of the tumors, but was independent of age, gender, tumor location, depth of penetration, status of lymph nodes, lymphovascular invasion and TNM stage. Conclusions: These results indicate that sTn may play a role in initiating colorectal carcinogenesis and promoting tumor progression. Determination of sTn expression and localization may assist in evaluating malignant status of colorectal lesions. PMID:26617889

  14. Observations of minor planets.

    NASA Astrophysics Data System (ADS)

    Observations made at the following stations are published: Bucharest, Catania, Caussols, Cent. Astron. Yebes, Cerro Tololo Interam. Obs., Chirorin, Crimean Astrophys. Obs. (52nd Report), Eur. South. Obs., Falkensee, Geisei, Goethe Link Obs., Göttingen, Haute Provence, Hemingford Abbots, JCPM Oi Stn., Kambah (near Canberra), Kitt Peak, Klet', Le Creusot, Lick Obs., Lincoln Lab., Lowell Obs., Lowell Obs. Anderson Mesa Stn., Madonnna di Dossobuono, Mt. John Obs., Mt. Palomar, Oak Ridge Obs., Purple Mountain Obs., Quonochontaug Stn. (Rhode Island), Reintal, S. Vittore (Bologna), Seewalchen, Siding Spring, Skalnaté Pleso, Spec. Astrophys. Obs., Steward Obs., Sydney, Tautenburg, Telford, Tokyo Obs. Kiso Stn., Turku, Zimmerwald.

  15. Magnetic resonance imaging of the subthalamic nucleus for deep brain stimulation.

    PubMed

    Chandran, Arjun S; Bynevelt, Michael; Lind, Christopher R P

    2016-01-01

    The subthalamic nucleus (STN) is one of the most important stereotactic targets in neurosurgery, and its accurate imaging is crucial. With improving MRI sequences there is impetus for direct targeting of the STN. High-quality, distortion-free images are paramount. Image reconstruction techniques appear to show the greatest promise in balancing the issue of geometrical distortion and STN edge detection. Existing spin echo- and susceptibility-based MRI sequences are compared with new image reconstruction methods. Quantitative susceptibility mapping is the most promising technique for stereotactic imaging of the STN. PMID:26295914

  16. Effects of neurostimulation for advanced Parkinson’s disease patients on motor symptoms: A multiple-treatments meta-analysas of randomized controlled trials

    PubMed Central

    Xie, Cheng-Long; Shao, Bei; Chen, Jie; Zhou, Yi; Lin, Shi-Yi; Wang, Wen-Wen

    2016-01-01

    Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). We aim to evaluate the efficacy of GPi (globus pallidus internus), STN (subthalamic nucleus)-DBS and medical therapy for PD. We conducted a systematic review and multiple-treatments meta-analysis to investigate the efficacy of neurostimulation and medical therapy for PD patients. Sixteen eligible studies were included in this analysis. We pooled the whole data and found obvious difference between GPi-DBS versus medical therapy and STN-DBS versus medical therapy in terms of UPDRS scores (Unified Parkinson’s Disease Rating Scale). Meanwhile, we found GPi-DBS had the similar efficacy on the UPDRS scores when compared with STN-DBS. What is more, quality of life, measured by PDQ-39 (Parkinson’s disease Questionnaire) showed greater improvement after GPi-DBS than STN-DBS. Five studies showed STN-DBS was more effective for reduction in medication than GPi-DBS. Overall, either GPi-DBS or STN-DBS was an effective technique to control PD patients’ symptoms and improved their functionality and quality of life. Meanwhile, the UPDRS scores measuring parkinsonian symptoms revealed no significant difference between GPi-DBS and STN-DBS. STN-DBS was more effective for reduction in medication than GPi-DBS. Alternatively, GPi-DBS was more effective for improving the PDQ-39 score than STN-DBS. PMID:27142183

  17. Effects of neurostimulation for advanced Parkinson's disease patients on motor symptoms: A multiple-treatments meta-analysas of randomized controlled trials.

    PubMed

    Xie, Cheng-Long; Shao, Bei; Chen, Jie; Zhou, Yi; Lin, Shi-Yi; Wang, Wen-Wen

    2016-01-01

    Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). We aim to evaluate the efficacy of GPi (globus pallidus internus), STN (subthalamic nucleus)-DBS and medical therapy for PD. We conducted a systematic review and multiple-treatments meta-analysis to investigate the efficacy of neurostimulation and medical therapy for PD patients. Sixteen eligible studies were included in this analysis. We pooled the whole data and found obvious difference between GPi-DBS versus medical therapy and STN-DBS versus medical therapy in terms of UPDRS scores (Unified Parkinson's Disease Rating Scale). Meanwhile, we found GPi-DBS had the similar efficacy on the UPDRS scores when compared with STN-DBS. What is more, quality of life, measured by PDQ-39 (Parkinson's disease Questionnaire) showed greater improvement after GPi-DBS than STN-DBS. Five studies showed STN-DBS was more effective for reduction in medication than GPi-DBS. Overall, either GPi-DBS or STN-DBS was an effective technique to control PD patients' symptoms and improved their functionality and quality of life. Meanwhile, the UPDRS scores measuring parkinsonian symptoms revealed no significant difference between GPi-DBS and STN-DBS. STN-DBS was more effective for reduction in medication than GPi-DBS. Alternatively, GPi-DBS was more effective for improving the PDQ-39 score than STN-DBS. PMID:27142183

  18. Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to cocaine within the reward circuit.

    PubMed

    Hachem-Delaunay, Sabira; Fournier, Marie-Line; Cohen, Candie; Bonneau, Nicolas; Cador, Martine; Baunez, Christelle; Le Moine, Catherine

    2015-08-01

    The subthalamic nucleus (STN) is a critical component of a complex network controlling motor, associative and limbic functions. High-frequency stimulation (HFS) of the STN is an effective therapy for motor symptoms in Parkinsonian patients and can also reduce their treatment-induced addictive behaviors. Preclinical studies have shown that STN HFS decreases motivation for cocaine while increasing that for food, highlighting its influence on rewarding and motivational circuits. However, the cellular substrates of these effects remain unknown. Our objectives were to characterize the cellular consequences of STN HFS with a special focus on limbic structures and to elucidate how STN HFS may interfere with acute cocaine effects in these brain areas. Male Long-Evans rats were subjected to STN HFS (130 Hz, 60 μs, 50-150 μA) for 30 min before an acute cocaine injection (15 mg/kg) and sacrificed 10 min following the injection. Neuronal reactivity was analyzed through the expression of two immediate early genes (Arc and c-Fos) to decipher cellular responses to STN HFS and cocaine. STN HFS only activated c-Fos in the globus pallidus and the basolateral amygdala, highlighting a possible role on emotional processes via the amygdala, with a limited effect by itself in other structures. Interestingly, and despite some differential effects on Arc and c-Fos expression, STN HFS diminished the c-Fos response induced by acute cocaine in the striatum. By preventing the cellular effect of cocaine in the striatum, STN HFS might thus decrease the reinforcing properties of the drug, which is in line with the inhibitory effect of STN HFS on the rewarding and reinforcing properties of cocaine. PMID:25982833

  19. Functional Connectivity Differences of the Subthalamic Nucleus Related to Parkinson's Disease.

    PubMed

    Mathys, Christian; Caspers, Julian; Langner, Robert; Südmeyer, Martin; Grefkes, Christian; Reetz, Kathrin; Moldovan, Alexia-Sabine; Michely, Jochen; Heller, Julia; Eickhoff, Claudia R; Turowski, Bernd; Schnitzler, Alfons; Hoffstaedter, Felix; Eickhoff, Simon B

    2016-03-01

    A typical feature of Parkinson's disease (PD) is pathological activity in the subthalamic nucleus (STN). Here, we tested whether in patients with PD under dopaminergic treatment functional connectivity of the STN differs from healthy controls (HC) and whether some brain regions show (anti-) correlations between functional connectivity with STN and motor symptoms. We used functional magnetic resonance imaging to investigate whole-brain resting-state functional connectivity with STN in 54 patients with PD and 55 HC matched for age, gender, and within-scanner motion. Compared to HC, we found attenuated negative STN-coupling with Crus I of the right cerebellum and with right ventromedial prefrontal regions in patients with PD. Furthermore, we observed enhanced negative STN-coupling with bilateral intraparietal sulcus/superior parietal cortex, right sensorimotor, right premotor, and left visual cortex compared to HC. Finally, we found a decline in positive STN-coupling with the left insula related to severity of motor symptoms and a decline of inter-hemispheric functional connectivity between left and right STN with progression of PD-related motor symptoms. Motor symptom related uncoupling of the insula, a key region in the saliency network and for executive function, from the STN might be associated with well-known executive dysfunction in PD. Moreover, uncoupling between insula and STN might also induce an insufficient setting of thresholds for the discrimination between relevant and irrelevant salient environmental stimuli, explaining observations of disturbed response control in PD. In sum, motor symptoms in PD are associated with a reduced coupling between STN and a key region for executive function. PMID:26700444

  20. Thylakoid Protein Phosphorylation in Higher Plant Chloroplasts Optimizes Electron Transfer under Fluctuating Light1[C][OA

    PubMed Central

    Tikkanen, Mikko; Grieco, Michele; Kangasjärvi, Saijaliisa; Aro, Eva-Mari

    2010-01-01

    Several proteins of photosystem II (PSII) and its light-harvesting antenna (LHCII) are reversibly phosphorylated according to light quantity and quality. Nevertheless, the interdependence of protein phosphorylation, nonphotochemical quenching, and efficiency of electron transfer in the thylakoid membrane has remained elusive. These questions were addressed by investigating in parallel the wild type and the stn7, stn8, and stn7 stn8 kinase mutants of Arabidopsis (Arabidopsis thaliana), using the stn7 npq4, npq4, npq1, and pgr5 mutants as controls. Phosphorylation of PSII-LHCII proteins is strongly and dynamically regulated according to white light intensity. Yet, the changes in phosphorylation do not notably modify the relative excitation energy distribution between PSII and PSI, as typically occurs when phosphorylation is induced by “state 2” light that selectively excites PSII and induces the phosphorylation of both the PSII core and LHCII proteins. On the contrary, under low-light conditions, when excitation energy transfer from LHCII to reaction centers is efficient, the STN7-dependent LHCII protein phosphorylation guarantees a balanced distribution of excitation energy to both photosystems. The importance of this regulation diminishes at high light upon induction of thermal dissipation of excitation energy. Lack of the STN7 kinase, and thus the capacity for equal distribution of excitation energy to PSII and PSI, causes relative overexcitation of PSII under low light but not under high light, leading to disturbed maintenance of fluent electron flow under fluctuating light intensities. The physiological relevance of the STN7-dependent regulation is evidenced by severely stunted phenotypes of the stn7 and stn7 stn8 mutants under strongly fluctuating light conditions. PMID:19965965

  1. Delayed synchronization of activity in cortex and subthalamic nucleus following cortical stimulation in the rat

    PubMed Central

    Magill, Peter J; Sharott, Andrew; Bolam, J Paul; Brown, Peter

    2006-01-01

    Oscillations may play a role in the functional organization of cortico-basal ganglia-thalamocortical circuits, and it is important to understand their underlying mechanisms. The cortex often drives basal ganglia (BG) activity, and particularly, oscillatory activity in the subthalamic nucleus (STN). However, the STN may also indirectly influence cortex. The aim of this study was to characterize the delayed (>200 ms) responses of STN neurons to synchronized cortical inputs, focusing on their relationship with oscillatory cortical activity. We recorded the short-latency and delayed responses of STN units and frontal electrocorticogram (ECoG) to cortical stimulation in anaesthetized rats. Similar to previous studies, stimulation of ipsilateral frontal cortex, but not temporal cortex, evoked a short-latency triphasic response, followed by a sustained reduction or pause in firing, in rostral STN units. Caudal STN units did not show the short-latency triphasic response but often displayed a prolonged firing reduction. Oscillations in STN unit activity and ECoG were common after this sustained firing reduction, particularly between 200 and 600 ms after frontal cortical stimulation. These delayed oscillations were significantly coherent in a broad frequency band of 5–30 Hz. Coherence with ECoG at 5–15 Hz was observed throughout STN, though coherence at 15–30 Hz was largely restricted to rostral STN. Furthermore, oscillatory responses at 5–30 Hz in rostral STN predominantly led those in cortex (mean latency of 29 ms) after frontal cortical stimulation. These findings suggest that STN neurons responding to corticosubthalamic inputs may provide a delayed input to cortex, via BG output nuclei, and thence, thalamocortical pathways. PMID:16709634

  2. Changes in handwriting resulting from bilateral high-frequency stimulation of the subthalamic nucleus in Parkinson's disease.

    PubMed

    Siebner, H R; Ceballos-Baumann, A; Standhardt, H; Auer, C; Conrad, B; Alesch, F

    1999-11-01

    High-frequency stimulation of the subthalamic nucleus (STN) is a promising therapeutic approach in patients with severely disabling Parkinson's disease (PD). Whereas STN stimulation improves the cardinal signs of PD, little is known about the effects of STN stimulation on fine manual skills like handwriting. Therefore, the present study investigated the changes in handwriting during bilateral STN stimulation in 12 patients with advanced PD. Dopaminergic medication was discontinued at least 12 hours before the study. The patients were asked to write a standardized sentence repetitively. Five samples of the patient's script were recorded during effective bilateral STN stimulation and 1 hour after both stimulators had been switched off. The movements of the tip of the pencil were recorded using a digitizing tablet. Handwriting movements were segmented into subsequent up- and down-strokes, and a stroke-based kinematic analysis of handwriting was performed. During high-frequency STN stimulation, handwriting movements became faster and smoother indicating a partial restoration of an "open-loop" automatic performance. In addition, STN stimulation gave rise to a significant increase in the mean vertical stroke length demonstrating a stimulation-related reduction in micrographia. The present data underscores the importance of the STN in "open-loop" performance of highly skilled sequential hand movements. PMID:10584671

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

    PubMed Central

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

    2008-01-01

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

  4. Effects of Medication and Subthalamic Nucleus Deep Brain Stimulation on Tongue Movements in Speakers with Parkinson's Disease Using Electropalatography: A Pilot Study

    ERIC Educational Resources Information Center

    Hartinger, Mariam; Tripoliti, Elina; Hardcastle, William J.; Limousin, Patricia

    2011-01-01

    Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using…

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  7. Subthalamic Nucleus Stimulation and Dysarthria in Parkinson's Disease: A PET Study

    ERIC Educational Resources Information Center

    Pinto, Serge; Thobois, Stephane; Costes, Nicolas; Le Bars, Didier; Benabid, Alim-Louis; Broussolle, Emmanuel; Pollak, Pierre; Gentil, Michele

    2004-01-01

    In Parkinson's disease, functional imaging studies during limb motor tasks reveal cerebral activation abnormalities that can be reversed by subthalamic nucleus (STN) stimulation. The effect of STN stimulation on parkinsonian dysarthria has not, however, been investigated using PET. The aim of the present study was to evaluate the effect of STN…

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

    PubMed

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

    2015-02-01

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

  9. Effect of unilateral versus bilateral electrostimulation in subthalamic nucleus on speech in Parkinsons disease

    NASA Astrophysics Data System (ADS)

    Wang, Emily; Verhagen Metman, Leo; Bakay, Roy; Arzbaecher, Jean; Bernard, Bryan

    2001-05-01

    Previously, it was found that 16 right-handed patients with idiopathic Parkinsons disease who underwent unilateral implantation of deep brain stimulator in subthalamic nucleus (STN) showed significant improvement in their nonspeech motor functions. Eight of the 16 patients had stimulator in the left STN and eight in the right STN. In contrast, their speech function showed very mild improvement that was limited to the respiratory/phonotory subsystems. Further, there seemed a trend that the patients with right STN stimulation did better than those with left STN stimulation. It was speculated that the difference might be due to a micro lesion caused by the surgical procedure to the corticobulbar fibers run in the left internal capsule. This paper reports speech changes associated with bilateral DBS in STN in four of the 16 subjects who elected to have deep brain stimulator implanted in STN on the opposite side of the brain at a later time. Results show negative changes in speech after bilateral DBS in STN. The changes were not limited to the micro lesion effect due to the surgery itself, but also related to the active stimulation on the dominant hemisphere for speech processing. [Work supported by NIH.

  10. Sialyl-Tn antigen expression occurs early during human mammary carcinogenesis and is associated with high nuclear grade and aneuploidy.

    PubMed

    Cho, S H; Sahin, A; Hortobagyi, G N; Hittelman, W N; Dhingra, K

    1994-12-15

    Sialyl-Tn (STn) antigen represents an aberrant glycosylation product of cell surface mucin in adenocarcinomas. We studied its expression in 40 breast carcinomas (35 of which included in situ carcinomas) by performing immunostaining with B72.3 monoclonal antibody. STn expression was observed in 50% of cases and was equally frequent in in situ and in invasive carcinomas. Positive STn staining significantly correlated with high nuclear grade (P = 0.001), aneuploidy (P < 0.001) and high S-phase fraction (P = 0.02). No correlation was observed between STn staining and age, menopausal status, presence of invasive component, or hormone receptor positivity. STn staining may provide an objective marker of dedifferentiation of breast tumors and should be investigated further for its prognostic value in breast cancers and as a biomarker of malignant transformation of breast epithelium. PMID:7987817

  11. Does bilateral stimulation of the subthalamic nucleus aggravate apathy in Parkinson's disease?

    PubMed Central

    Czernecki, V; Pillon, B; Houeto, J; Welter, M; Mesnage, V; Agid, Y; Dubois, B

    2005-01-01

    Objective: High frequency stimulation of the subthalamic nucleus (STN) dramatically decreases motor disability in patients with Parkinson"s disease (PD), but has been reported to aggravate apathy. The aim of this study was to analyse the effect of STN stimulation on motivation and reward sensitivity in a consecutive series of PD patients. Methods: Apathy and reward sensitivity (Apathy Scale, Stimulus-Reward Learning, Reversal, Extinction, and Gambling tasks) were assessed in 18 PD patients treated by bilateral STN stimulation ("on" and "off" conditions) compared with 23 matched patients undergoing long term treatment with levodopa ("on" and "off" conditions). Results: Apathy decreased under both STN stimulation and levodopa treatment, whereas explicit and implicit stimulus reward learning was unchanged. Conclusions: Bilateral STN stimulation in PD patients does not necessarily have a negative effect on motivation and reward sensitivity and can even improve apathy provided patients have been appropriately selected for neurosurgery. PMID:15897497

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

    PubMed

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

    2015-02-01

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

  13. NMDA Receptors Containing the GluN2D Subunit Control Neuronal Function in the Subthalamic Nucleus.

    PubMed

    Swanger, Sharon A; Vance, Katie M; Pare, Jean-François; Sotty, Florence; Fog, Karina; Smith, Yoland; Traynelis, Stephen F

    2015-12-01

    The GluN2D subunit of the NMDA receptor is prominently expressed in the basal ganglia and associated brainstem nuclei, including the subthalamic nucleus (STN), globus pallidus, striatum, and substantia nigra. However, little is known about how GluN2D-containing NMDA receptors contribute to synaptic activity in these regions. Using Western blotting of STN tissue punches, we demonstrated that GluN2D is expressed in the rat STN throughout development [age postnatal day 7 (P7)-P60] and in the adult (age P120). Immunoelectron microscopy of the adult rat brain showed that GluN2D is predominantly expressed in dendrites, unmyelinated axons, and axon terminals within the STN. Using subunit-selective allosteric modulators of NMDA receptors (TCN-201, ifenprodil, CIQ, and DQP-1105), we provide evidence that receptors containing the GluN2B and GluN2D subunits mediate responses to exogenously applied NMDA and glycine, as well as synaptic NMDA receptor activation in the STN of rat brain slices. EPSCs in the STN were mediated primarily by AMPA and NMDA receptors and GluN2D-containing NMDA receptors controlled the slow deactivation time course of EPSCs in the STN. In vivo recordings from the STN of anesthetized adult rats demonstrated that the spike firing rate was increased by the GluN2C/D potentiator CIQ and decreased by the GluN2C/D antagonist DQP-1105, suggesting that NMDA receptor activity can influence STN output. These data indicate that the GluN2B and GluN2D NMDA receptor subunits contribute to synaptic activity in the STN and may represent potential therapeutic targets for modulating subthalamic neuron activity in neurological disorders such as Parkinson's disease. PMID:26631477

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

    PubMed

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

    2013-05-15

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

  15. Soil Carbon and Nitrogen Changes following Afforestation of Marginal Cropland across a Precipitation Gradient in Loess Plateau of China

    PubMed Central

    Lü, Yihe; Liu, Guohua; Fu, Bojie

    2014-01-01

    Cropland afforestation has been widely found to increase soil organic carbon (SOC) and soil total nitrogen (STN); however, the magnitudes of SOC and STN accumulation and regulating factors are less studied in dry, marginal lands, and therein the interaction between soil carbon and nitrogen is not well understood. We examined the changes in SOC and STN in younger (5–9-year-old) and older (25–30-year-old) black locust (Robinia pseudoacacia L., an N-fixing species) plantations that were established on former cropland along a precipitation gradient (380 to 650 mm) in the semi-arid Loess Plateau of China. The SOC and STN stocks of cropland and plantations increased linearly with precipitation increase, respectively, accompanying an increase in the plantation net primary productivity and the soil clay content along the increasing precipitation gradient. The SOC stock of cropland decreased in younger plantations and increased in older plantations after afforestation, and the amount of the initial loss of SOC during the younger plantations’ establishment increased with precipitation increasing. By contrast, the STN stock of cropland showed no decrease in the initial afforestation while tending to increase with plantation age, and the changes in STN were not related to precipitation. The changes in STN and SOC showed correlated and were precipitation-dependent following afforestation, displaying a higher relative gain of SOC to STN as precipitation decreased. Our results suggest that the afforestation of marginal cropland in Loess Plateau can have a significant effect on the accumulation of SOC and STN, and that precipitation has a significant effect on SOC accumulation but little effect on STN retention. The limitation effect of soil nitrogen on soil carbon accumulation is more limited in the drier area rather than in the wetter sites. PMID:24416408

  16. Neural Correlates of Decision Thresholds in the Human Subthalamic Nucleus.

    PubMed

    Herz, Damian M; Zavala, Baltazar A; Bogacz, Rafal; Brown, Peter

    2016-04-01

    If humans are faced with difficult choices when making decisions, the ability to slow down responses becomes critical in order to avoid suboptimal choices. Current models of decision making assume that the subthalamic nucleus (STN) mediates this function by elevating decision thresholds, thereby requiring more evidence to be accumulated before responding [1-9]. However, direct electrophysiological evidence for the exact role of STN during adjustment of decision thresholds is lacking. Here, we show that trial-by-trial variations in STN low-frequency oscillatory activity predict adjustments of decision thresholds before subjects make a response. The relationship between STN activity and decision thresholds critically depends on the subjects' level of cautiousness. While increased oscillatory activity of the STN predicts elevated decision thresholds during high levels of cautiousness, it predicts decreased decision thresholds during low levels of cautiousness. This context-dependent relationship may be mediated by increased influence of the medial prefrontal cortex (mPFC)-STN pathway on decision thresholds during high cautiousness. Subjects who exhibit a stronger increase in phase alignment of low-frequency oscillatory activity in mPFC and STN before making a response have higher decision thresholds and commit fewer erroneous responses. Together, our results demonstrate that STN low-frequency oscillatory activity and corresponding mPFC-STN coupling are involved in determining how much evidence subjects accumulate before making a decision. This finding might explain why deep-brain stimulation of the STN can impair subjects' ability to slow down responses and can induce impulsive suboptimal decisions. PMID:26996501

  17. Neural Correlates of Decision Thresholds in the Human Subthalamic Nucleus

    PubMed Central

    Herz, Damian M.; Zavala, Baltazar A.; Bogacz, Rafal; Brown, Peter

    2016-01-01

    Summary If humans are faced with difficult choices when making decisions, the ability to slow down responses becomes critical in order to avoid suboptimal choices. Current models of decision making assume that the subthalamic nucleus (STN) mediates this function by elevating decision thresholds, thereby requiring more evidence to be accumulated before responding [1, 2, 3, 4, 5, 6, 7, 8, 9]. However, direct electrophysiological evidence for the exact role of STN during adjustment of decision thresholds is lacking. Here, we show that trial-by-trial variations in STN low-frequency oscillatory activity predict adjustments of decision thresholds before subjects make a response. The relationship between STN activity and decision thresholds critically depends on the subjects’ level of cautiousness. While increased oscillatory activity of the STN predicts elevated decision thresholds during high levels of cautiousness, it predicts decreased decision thresholds during low levels of cautiousness. This context-dependent relationship may be mediated by increased influence of the medial prefrontal cortex (mPFC)-STN pathway on decision thresholds during high cautiousness. Subjects who exhibit a stronger increase in phase alignment of low-frequency oscillatory activity in mPFC and STN before making a response have higher decision thresholds and commit fewer erroneous responses. Together, our results demonstrate that STN low-frequency oscillatory activity and corresponding mPFC-STN coupling are involved in determining how much evidence subjects accumulate before making a decision. This finding might explain why deep-brain stimulation of the STN can impair subjects’ ability to slow down responses and can induce impulsive suboptimal decisions. PMID:26996501

  18. The Subthalamic Nucleus in Primary Dystonia: Single-Unit Discharge Characteristics

    PubMed Central

    Schrock, Lauren E.; Ostrem, Jill L.; Turner, Robert S.; Shimamoto, Shoichi A.

    2009-01-01

    Most models of dystonia pathophysiology predict alterations of activity in the basal ganglia thalamocortical motor circuit. The globus pallidus interna (GPi) shows bursting and oscillatory neuronal discharge in both human dystonia and in animal models, but it is not clear which intrinsic basal ganglia pathways are implicated in this abnormal output. The subthalamic nucleus (STN) receives prominent excitatory input directly from cortical areas implicated in dystonia pathogenesis and inhibitory input from the external globus pallidus. The goal of this study was to elucidate the role of the STN in dystonia by analyzing STN neuronal discharge in patients with idiopathic dystonia. Data were collected in awake patients undergoing microelectrode recording for implantation of STN deep brain stimulation electrodes. We recorded 62 STN neurons in 9 patients with primary dystonia. As a comparison group, we recorded 143 STN neurons in 20 patients with Parkinson's disease (PD). Single-unit activity was discriminated off-line by principal component analysis and evaluated with respect to discharge rate, bursting, and oscillatory activity. The mean STN discharge rate in dystonia patients was 26.3 Hz (SD 13.6), which was lower than that in the PD patients (35.6 Hz, SD 15.2), but higher than published values for subjects without basal ganglia dysfunction. Oscillatory activity was found in both disorders, with a higher proportion of units oscillating in the beta range in PD. Bursting discharge was a prominent feature of both dystonia and PD, whereas sensory receptive fields were expanded in PD compared with dystonia. The STN firing characteristics, in conjunction with those previously published for GPi, suggest that bursting and oscillatory discharge in basal ganglia output may be transmitted via pathways involving the STN and provide a pathophysiologic rationale for STN as a surgical target in dystonia. PMID:19846625

  19. Subthalamic nucleus high-frequency stimulation generates a concomitant synaptic excitation–inhibition in substantia nigra pars reticulata

    PubMed Central

    Bosch, Clémentine; Degos, Bertrand; Deniau, Jean-Michel; Venance, Laurent

    2011-01-01

    Abstract Deep brain stimulation is an efficient treatment for various neurological pathologies and a promising tool for neuropsychiatric disorders. This is particularly exemplified by high-frequency stimulation of the subthalamic nucleus (STN-HFS), which has emerged as an efficient symptomatic treatment for Parkinson's disease. How STN-HFS works is still not fully elucidated. With dual patch-clamp recordings in rat brain slices, we analysed the cellular responses of STN stimulation on SNr neurons by simultaneously recording synaptic currents and firing activity. We showed that STN-HFS caused an increase of the spontaneous spiking activity in half of SNr neurons while the remaining ones displayed a decrease. At the synaptic level, STN stimulation triggered inward current in 58% of whole-cell recorded neurons and outward current in the remaining ones. Using a pharmacological approach, we showed that STN-HFS-evoked responses were mediated in all neurons by a balance between AMPA/NMDA receptors and GABAA receptors, whose ratio promotes either a net excitation or a net inhibition. Interestingly, we observed a higher excitation occurrence in 6-hydroxydopamine (6-OHDA)-treated rats. In vivo injections of phaseolus revealed that GABAergic pallido-nigral fibres travel through the STN whereas striato-nigral fibres travel below it. Therefore, electrical stimulation of the STN does not only recruit glutamatergic axons from the STN, but also GABAergic passing fibres probably from the globus pallidus. For the first time, we showed that STN-HFS induces concomitant excitatory–inhibitory synaptic currents in SNr neurons by recruitment of efferences and passing fibres allowing a tight control on basal ganglia outflow. PMID:21690190

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

    PubMed

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

    2015-11-01

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

  1. The subthalamic nucleus keeps you high on emotion: behavioral consequences of its inactivation

    PubMed Central

    Pelloux, Yann; Meffre, Julie; Giorla, Elodie; Baunez, Christelle

    2014-01-01

    The subthalamic nucleus (STN) belongs to the basal ganglia and is the current target for the surgical treatment of neurological and psychiatric disorders such as Parkinson’s Disease (PD) and obsessive compulsive disorders (OCD), but also a proposed site for the treatment of addiction. It is therefore very important to understand its functions in order to anticipate and prevent possible side-effects in the patients. Although the involvement of the STN is well documented in motor, cognitive and motivational processes, less is known regarding emotional processes. Here we have investigated the direct consequences of STN inactivation by excitotoxic lesions on emotional processing and reinforcement in the rat. We have used various behavioral procedures to assess affect for neutral, positive and negative reinforcers in STN lesioned rats. STN lesions reduced affective responses for positive (sweet solutions) and negative (electric foot shock, Lithium Chloride-induced sickness) reinforcers while they had no effect on responses for a more neutral reinforcer (novelty induced place preference (NIPP)). Furthermore, when given the choice between saccharine, a sweet but non caloric solution, and glucose, a more bland but caloric solution, in contrast to sham animals that preferred saccharine, STN lesioned animals preferred glucose over saccharine. Taken altogether these results reveal that STN plays a critical role in emotional processing. These results, in line with some clinical observations in PD patients subjected to STN surgery, suggest possible emotional side-effects of treatments targeting the STN. They also suggest that the increased motivation for sucrose previously reported cannot be due to increased pleasure, but could be responsible for the decreased motivation for cocaine reported after STN inactivation. PMID:25538581

  2. Soil carbon and nitrogen changes following afforestation of marginal cropland across a precipitation gradient in Loess Plateau of China.

    PubMed

    Chang, Ruiying; Jin, Tiantian; Lü, Yihe; Liu, Guohua; Fu, Bojie

    2014-01-01

    Cropland afforestation has been widely found to increase soil organic carbon (SOC) and soil total nitrogen (STN); however, the magnitudes of SOC and STN accumulation and regulating factors are less studied in dry, marginal lands, and therein the interaction between soil carbon and nitrogen is not well understood. We examined the changes in SOC and STN in younger (5-9-year-old) and older (25-30-year-old) black locust (Robinia pseudoacacia L., an N-fixing species) plantations that were established on former cropland along a precipitation gradient (380 to 650 mm) in the semi-arid Loess Plateau of China. The SOC and STN stocks of cropland and plantations increased linearly with precipitation increase, respectively, accompanying an increase in the plantation net primary productivity and the soil clay content along the increasing precipitation gradient. The SOC stock of cropland decreased in younger plantations and increased in older plantations after afforestation, and the amount of the initial loss of SOC during the younger plantations' establishment increased with precipitation increasing. By contrast, the STN stock of cropland showed no decrease in the initial afforestation while tending to increase with plantation age, and the changes in STN were not related to precipitation. The changes in STN and SOC showed correlated and were precipitation-dependent following afforestation, displaying a higher relative gain of SOC to STN as precipitation decreased. Our results suggest that the afforestation of marginal cropland in Loess Plateau can have a significant effect on the accumulation of SOC and STN, and that precipitation has a significant effect on SOC accumulation but little effect on STN retention. The limitation effect of soil nitrogen on soil carbon accumulation is more limited in the drier area rather than in the wetter sites. PMID:24416408

  3. Subthalamic nucleus long-range synchronization—an independent hallmark of human Parkinson's disease

    PubMed Central

    Moshel, Shay; Shamir, Reuben R.; Raz, Aeyal; de Noriega, Fernando R.; Eitan, Renana; Bergman, Hagai; Israel, Zvi

    2013-01-01

    Beta-band synchronous oscillations in the dorsolateral region of the subthalamic nucleus (STN) of human patients with Parkinson's disease (PD) have been frequently reported. However, the correlation between STN oscillations and synchronization has not been thoroughly explored. The simultaneous recordings of 2390 multi-unit pairs recorded by two parallel microelectrodes (separated by fixed distance of 2 mm, n = 72 trajectories with two electrode tracks >4 mm STN span) in 57 PD patients undergoing STN deep brain stimulation surgery were analyzed. Automatic procedures were utilized to divide the STN into dorsolateral oscillatory and ventromedial non-oscillatory regions, and to quantify the intensity of STN oscillations and synchronicity. Finally, the synchronicity of simultaneously vs. non-simultaneously recorded pairs were compared using a shuffling procedure. Synchronization was observed predominately in the beta range and only between multi-unit pairs in the dorsolateral oscillatory region (n = 615). In paired recordings between sites in the dorsolateral and ventromedial (n = 548) and ventromedial-ventromedial region pairs (n = 1227), no synchronization was observed. Oscillation and synchronicity intensity decline along the STN dorsolateral-ventromedial axis suggesting a fuzzy border between the STN regions. Synchronization strength was significantly correlated to the oscillation power, but synchronization was no longer observed following shuffling. We conclude that STN long-range beta oscillatory synchronization is due to increased neuronal coupling in the Parkinsonian brain and does not merely reflect the outcome of oscillations at similar frequency. The neural synchronization in the dorsolateral (probably the motor domain) STN probably augments the pathological changes in firing rate and patterns of subthalamic neurons in PD patients. PMID:24312018

  4. NMDA Receptors Containing the GluN2D Subunit Control Neuronal Function in the Subthalamic Nucleus

    PubMed Central

    Swanger, Sharon A.; Vance, Katie M.; Pare, Jean-François; Sotty, Florence; Fog, Karina; Smith, Yoland

    2015-01-01

    The GluN2D subunit of the NMDA receptor is prominently expressed in the basal ganglia and associated brainstem nuclei, including the subthalamic nucleus (STN), globus pallidus, striatum, and substantia nigra. However, little is known about how GluN2D-containing NMDA receptors contribute to synaptic activity in these regions. Using Western blotting of STN tissue punches, we demonstrated that GluN2D is expressed in the rat STN throughout development [age postnatal day 7 (P7)–P60] and in the adult (age P120). Immunoelectron microscopy of the adult rat brain showed that GluN2D is predominantly expressed in dendrites, unmyelinated axons, and axon terminals within the STN. Using subunit-selective allosteric modulators of NMDA receptors (TCN-201, ifenprodil, CIQ, and DQP-1105), we provide evidence that receptors containing the GluN2B and GluN2D subunits mediate responses to exogenously applied NMDA and glycine, as well as synaptic NMDA receptor activation in the STN of rat brain slices. EPSCs in the STN were mediated primarily by AMPA and NMDA receptors and GluN2D-containing NMDA receptors controlled the slow deactivation time course of EPSCs in the STN. In vivo recordings from the STN of anesthetized adult rats demonstrated that the spike firing rate was increased by the GluN2C/D potentiator CIQ and decreased by the GluN2C/D antagonist DQP-1105, suggesting that NMDA receptor activity can influence STN output. These data indicate that the GluN2B and GluN2D NMDA receptor subunits contribute to synaptic activity in the STN and may represent potential therapeutic targets for modulating subthalamic neuron activity in neurological disorders such as Parkinson's disease. SIGNIFICANCE STATEMENT The subthalamic nucleus (STN) is a key component of the basal ganglia, a group of subcortical nuclei that control movement and are dysregulated in movement disorders such as Parkinson's disease. Subthalamic neurons receive direct excitatory input, but the pharmacology of excitatory

  5. Modulatory effect of subthalamic nucleus on the development of fatigue during exhausting exercise: an in vivo electrophysiological and microdialysis study in rats.

    PubMed

    Wang, Dalei; Liu, Xiaoli; Qiao, Decai

    2012-01-01

    The purpose of the study was to investigate the modulatory effect of changes of subthalamic nucleus (STN) activity on the development of central fatigue during exhausting exercise, and reveal the possible mechanism that might affect STN activity from the perspective of neurotransmitters. Rats were randomly divided into electrophysiology and microdialysis study groups. For electrophysiological study, electrical activity in sensorimotor cortex and STN were simultaneously recorded before, during and 90min after the exhausting exercise. For microdialysis study, extracellular fluid of STN was continuously collected with a microdialysis probe and glutamate (Glu), gamma-aminobutyric acid (GABA) levels were subsequently detected with high performance liquid chromatography (HPLC). The behavioral studies showed that rats ran well initiatively with the treadmill exercise in the beginning, 45 ± 11.5min later, movement capacity reduced obviously (which was termed as 'early fatigue'). Correspondingly, STN activity increased significantly compared with rest condition (p < 0.05), while, cortex activity decreased significantly (p < 0.05). Subsequently, rats continued their exercise with minor external stimulation till exhaustion. Cortex activity reached the minimum value under exhaustion condition, while STN activity changed insignificantly (p > 0.05). For microdialysis study, the dynamic change of Glu/GABA ratio was consistent with the change of STN activity during the development of 'early fatigue' rather than the development of exhaustion. In conclusion, the present study shows that, the development of the cortex fatigue during exhausting exercise consists of two phases, 'early fatigue' and exhaustion. Our results suggest that, dynamic changes of STN activity are closely relevant to the development of 'early fatigue' rather than exhaustion, and the changes of STN activity during the development of 'early fatigue' might be partly related to the variance of Glu and GABA levels in

  6. Self-Reported Executive Functioning in Everyday Life in Parkinson's Disease after Three Months of Subthalamic Deep Brain Stimulation

    PubMed Central

    Pham, Uyen Ha Gia; Andersson, Stein; Toft, Mathias; Pripp, Are Hugo; Konglund, Ane Eidahl; Dietrichs, Espen; Malt, Ulrik Fredrik; Skogseid, Inger Marie; Haraldsen, Ira Ronit Hebolt; Solbakk, Anne-Kristin

    2015-01-01

    Objective. Studies on the effect of subthalamic deep brain stimulation (STN-DBS) on executive functioning in Parkinson's disease (PD) are still controversial. In this study we compared self-reported daily executive functioning in PD patients before and after three months of STN-DBS. We also examined whether executive functioning in everyday life was associated with motor symptoms, apathy, and psychiatric symptoms. Method. 40 PD patients were examined with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), the Symptom Checklist 90-Revised (SCL-90-R), and the Apathy Evaluation Scale (AES-S). Results. PD patients reported significant improvement in daily life executive functioning after 3 months of STN-DBS. Anxiety scores significantly declined, while other psychiatric symptoms remained unchanged. The improvement of self-reported executive functioning did not correlate with motor improvement after STN-DBS. Apathy scores remained unchanged after surgery. Only preoperative depressed mood had predictive value to the improvement of executive function and appears to prevent potentially favorable outcomes from STN-DBS on some aspects of executive function. Conclusion. PD patients being screened for STN-DBS surgery should be evaluated with regard to self-reported executive functioning. Depressive symptoms in presurgical PD patients should be treated. Complementary information about daily life executive functioning in PD patients might enhance further treatment planning of STN-DBS. PMID:26167329

  7. Bilateral subthalamic nucleus stimulation improves balance control in Parkinson's disease

    PubMed Central

    Colnat-Coulbois, S; Gauchard, G; Maillard, L; Barroche, G; Vespignani, H; Auque, J; Perrin, P.

    2005-01-01

    Background: Parkinson's disease (PD), the most common basal ganglia degenerative disease, affects balance control, especially when patients change balance strategy during postural tasks. Bilateral chronic stimulation of the subthalamic nucleus (STN) is therapeutically useful in advanced PD, and reduces the motor signs of patients. Nevertheless, the effects of STN stimulation on postural control are still debatable. Aims: To assess the impact of bilateral STN stimulation on balance control in PD and to determine how basal ganglia related sensorimotor modifications act on neurosensorial organisation of balance and motor postural programming. Methods: Twelve subjects aged 45–70 years underwent unified Parkinson's disease rating scale motor (part III) clinical tests, static and dynamic posturography, including sensory organisation and adaptation tests, shortly before and six months after bilateral implantation of electrodes into the STN. Results: The postoperative static test showed an improvement in postural control precision both in eyes open and eyes closed conditions. The dynamic test highlighted the decreased number of falls and the ability of the patients to develop more appropriate sensorimotor strategies when stimulated. The sensory organisation test showed an improvement of equilibrium score and, thus, a better resolution of sensorial conflicts. Conclusions: STN stimulation allowed a reduction in rigidity and therefore an improvement in the ability to use muscular proprioception as reliable information, resulting in vestibulo-proprioceptive conflict suppression. STN stimulation has a synergistic effect with levodopa for postural control. Accordingly, non-dopaminergic pathways could be involved in postural regulation and STN stimulation may influence the functioning of these pathways. PMID:15897498

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

    PubMed

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

    2015-06-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor impairments in Parkinson's disease (PD) but its effect on the motivational regulation of action control is still not fully understood. We investigated whether DBS of the STN influences the ability of PD patients to act for anticipated reward or loss, or whether DBS improves action execution independent of motivational valence. 16 PD patients (12 male, mean age = 58.5 ± 10.17 years) treated with bilateral STN-DBS and an age- and gender-matched group of healthy controls (HC) performed a go/no-go task whose contingencies explicitly decouple valence and action. Patients were tested with (ON) and without (OFF) active STN stimulation. For HC, there was a benefit in performing rewarded actions when compared to actions that avoided punishment. PD patients showed such a benefit reliably only when STN stimulation was ON. In fact, the relative behavioral benefit for go for reward over go to avoid losing was stronger in the PD patients under DBS ON than in HC. In PD patients, rather than generally improving motor functions independent of motivational valence, modulation of the STN by DBS improves action execution specifically when rewards are anticipated. Thus, STN-DBS establishes a reliable congruency between action and reward ("Pavlovian congruency") and remarkably enhances it over the level observed in HC. PMID:25929662

  9. [Single and Network Neuron Activity of Subthalamic Nucleus at Impulsive and Delayed (Self-Control) Reactions in Choice Behavior].

    PubMed

    Sidorina, V V; Gerasimova, Yu A; Kuleshova, E P; Merzhanova, G Kh

    2015-01-01

    During our experiments on cats was investigated the subthalamic neuron activity at different types of behavior in case of reinforcement choice depending on its value and availability. In chronic experiences the multiunit activity in subthalamic nucleus (STN) and orbitofrontal cortex (FC) has been recorded. Multiunit activity was analyzed over frequency and network properties of spikes. It was shown, that STN neurons reaction to different reinforcements and conditional stimulus at short- or long-delay reactions was represented by increasing or decreasing of frequency of single neurons. However the same STN neu- rons responded with increasing of frequency of single neuron during expectation of mix-bread-meat and decreasing--during the meat expectation. It has been revealed, that the number of STN interneuron interactions was authentic more at impulsive behavior than at self-control choice of behavior. The number of interactions between FC and STN neurons within intervals of 0-30 Ms was authentic more at display impulsive than during self-control behavior. These results suppose that FC and STN neurons participate in integration of reinforcement estimation; and distinctions in a choice of behavior are defined by the local and distributed interneuron interactions of STN and FC. PMID:26601504

  10. Subthalamic nucleus stimulation affects fear and sadness recognition in Parkinson's disease.

    PubMed

    Péron, Julie; Biseul, Isabelle; Leray, Emmanuelle; Vicente, Siobhan; Le Jeune, Florence; Drapier, Sophie; Drapier, Dominique; Sauleau, Paul; Haegelen, Claire; Vérin, Marc

    2010-01-01

    Bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) can produce emotional disorders that have been linked to disturbance of the STN's limbic territory. The aim of this study was to confirm the impairment of the recognition of facial emotions (RFE) induced by STN DBS, not only ruling out the effect of the disease's natural progression in relation to the effect of DBS, but also assessing the influence of modifications in dopamine replacement therapy (DRT) following STN DBS. RFE was investigated in 24 PD patients who underwent STN DBS and 20 PD patients treated with apomorphine. They were assessed 3 months before and after treatment. The 2 patient groups were compared with a group of 30 healthy matched controls. The results showed that RFE for negative emotions (fear and sadness) was impaired in only the STN DBS group in the posttreatment condition and was unrelated to DRT. Results confirm the selective reduction of RFE induced by STN DBS, due neither to the disease's natural progression nor to modifications in DRT. PMID:20063943

  11. The Role of Sialyl-Tn in Cancer

    PubMed Central

    Munkley, Jennifer

    2016-01-01

    Activation of an aberrant glycosylation pathway in cancer cells can lead to expression of the onco-foetal sialyl-Tn (sTn) antigen. STn is a truncated O-glycan containing a sialic acid α-2,6 linked to GalNAc α-O-Ser/Thr and is associated with an adverse outcome and poor prognosis in cancer patients. The biosynthesis of the sTn antigen has been linked to the expression of the sialytransferase ST6GalNAc1, and also to mutations in and loss of heterozygosity of the COSMC gene. sTn neo- or over-expression occurs in many types of epithelial cancer including gastric, colon, breast, lung, oesophageal, prostate and endometrial cancer. sTn is believed to be carried by a variety of glycoproteins and may influence protein function and be involved in tumour development. This review discusses how the role of sTn in cancer development and tumour cell invasiveness might be organ specific and occur through different mechanisms depending on each cancer type or subtype. As the sTn-antigen is expressed early in carcinogenesis targeting sTn in cancer may enable the targeting of tumours from the earliest stage. PMID:26927062

  12. Glycine: an alternative transmitter candidate of the pallidosubthalamic projection neurons in the rat

    SciTech Connect

    Takada, M.; Hattori, T.

    1987-08-22

    Autoradiographic retrograde tracing techniques with radioactive transmitters were used to analyse the identity of a putative transmitter in the rat pallidosubthalamic (GP-STN) pathway. One to 2 hours after the stereotaxic injection of /sup 3/H-glycine restricted to the STN, a large number of neuronal somata were radiolabeled in the GP. No comparable labeling was observed following the injection of /sup 3/H-gamma-aminobutyric acid (/sup 3/H-GABA) into the same nucleus even with survival times as long as 6 hours. Specifically, no significant somatic labeling was detected either in the GP or in the caudoputamen (CPU). Only when /sup 3/H-GABA was injected into the substantia nigra did CPU and GP neurons become labeled. On the contrary, STN neuronal somata were invariably labeled 6 hours after the intrapallidal injection of /sup 3/H-GABA, whereas no perikaryal labeling was observed in the STN after /sup 3/H-glycine injection into the GP. The perikaryal labeling was prevented in all cases by intraventricular administration of colchicine 1 day before the isotope injections. The observations suggest that /sup 3/H-glycine was preferentially transported retrogradely through the GP-STN pathway, and /sup 3/H-GABA through the STN-GP projection. In view of the recent controversy on the role of GABA as a putative transmitter of the GP-STN projection, we now propose glycine as an alternative transmitter candidate of these critically situated neurons in the basal ganglia.

  13. Sialyl-Tn in Cancer: (How) Did We Miss the Target?

    PubMed Central

    Julien, Sylvain; Videira, Paula A.; Delannoy, Philippe

    2012-01-01

    Sialyl-Tn antigen (STn) is a short O-glycan containing a sialic acid residue α2,6-linked to GalNAcα-O-Ser/Thr. The biosynthesis of STn is mediated by a specific sialyltransferase termed ST6GalNAc I, which competes with O-glycans elongating glycosyltransferases and prevents cancer cells from exhibiting longer O-glycans. While weakly expressed by fetal and normal adult tissues, STn is expressed by more than 80% of human carcinomas and in all cases, STn detection is associated with adverse outcome and decreased overall survival for the patients. Because of its pan-carcinoma expression associated with an adverse outcome, an anti-cancer vaccine, named Theratope, has been designed towards the STn epitope. In spite of the great enthusiasm around this immunotherapy, Theratope failed on Phase III clinical trial. However, in lieu of missing this target, one should consider to revise the Theratope design and the actual facts. In this review, we highlight the many lessons that can be learned from this failure from the immunological standpoint, as well as from the drug design and formulation and patient selection. Moreover, an irrefutable knowledge is arising from novel immunotherapies targeting other carbohydrate antigens and STn carrier proteins, such as MUC1, that will warrantee the future development of more successful anti-STn immunotherapy strategies. PMID:24970145

  14. Inhibitory control and error monitoring by human subthalamic neurons

    PubMed Central

    Bastin, J; Polosan, M; Benis, D; Goetz, L; Bhattacharjee, M; Piallat, B; Krainik, A; Bougerol, T; Chabardès, S; David, O

    2014-01-01

    The subthalamic nucleus (STN) has been shown to be implicated in the control of voluntary action, especially during tasks involving conflicting choice alternatives or rapid response suppression. However, the precise role of the STN during nonmotor functions remains controversial. First, we tested whether functionally distinct neuronal populations support different executive control functions (such as inhibitory control or error monitoring) even within a single subterritory of the STN. We used microelectrode recordings during deep brain stimulation surgery to study extracellular activity of the putative associative-limbic part of the STN while patients with severe obsessive-compulsive disorder performed a stop-signal task. Second, 2–4 days after the surgery, local field potential recordings of STN were used to test the hypothesis that STN oscillations may also reflect executive control signals. Extracellular recordings revealed three functionally distinct neuronal populations: the first one fired selectively before and during motor responses, the second one selectively increased their firing rate during successful inhibitory control, and the last one fired selectively during error monitoring. Furthermore, we found that beta band activity (15–35 Hz) rapidly increased during correct and incorrect behavioral stopping. Taken together, our results provide critical electrophysiological support for the hypothesized role of the STN in the integration of motor and cognitive-executive control functions. PMID:25203170

  15. High-Frequency Stimulation of the Subthalamic Nucleus Counteracts Cortical Expression of Major Histocompatibility Complex Genes in a Rat Model of Parkinson’s Disease

    PubMed Central

    Grieb, Benjamin; Engler, Gerhard; Sharott, Andrew; von Nicolai, Constantin; Streichert, Thomas; Papageorgiou, Ismini; Schulte, Alexander; Westphal, Manfred; Lamszus, Katrin; Engel, Andreas K.

    2014-01-01

    High-frequency stimulation of the subthalamic nucleus (STN-HFS) is widely used as therapeutic intervention in patients suffering from advanced Parkinson’s disease. STN-HFS exerts a powerful modulatory effect on cortical motor control by orthodromic modulation of basal ganglia outflow and via antidromic activation of corticofugal fibers. However, STN-HFS-induced changes of the sensorimotor cortex are hitherto unexplored. To address this question at a genomic level, we performed mRNA expression analyses using Affymetrix microarray gene chips and real-time RT-PCR in sensorimotor cortex of parkinsonian and control rats following STN-HFS. Experimental parkinsonism was induced in Brown Norway rats by bilateral nigral injections of 6-hydroxydopamine and was assessed histologically, behaviorally, and electrophysiologically. We applied prolonged (23h) unilateral STN-HFS in awake and freely moving animals, with the non-stimulated hemisphere serving as an internal control for gene expression analyses. Gene enrichment analysis revealed strongest regulation in major histocompatibility complex (MHC) related genes. STN-HFS led to a cortical downregulation of several MHC class II (RT1-Da, Db1, Ba, and Cd74) and MHC class I (RT1CE) encoding genes. The same set of genes showed increased expression levels in a comparison addressing the effect of 6-hydroxydopamine lesioning. Hence, our data suggest the possible association of altered microglial activity and synaptic transmission by STN-HFS within the sensorimotor cortex of 6-hydroxydopamine treated rats. PMID:24621597

  16. Subthalamic nucleus activity dissociates proactive and reactive inhibition in patients with Parkinson's disease.

    PubMed

    Benis, Damien; David, Olivier; Lachaux, Jean-Philippe; Seigneuret, Eric; Krack, Paul; Fraix, Valérie; Chabardès, Stéphan; Bastin, Julien

    2014-05-01

    Models of action selection postulate the critical involvement of the subthalamic nucleus (STN), especially in reactive inhibition processes when inappropriate responses to a sudden stimulus must be overridden. The STN could also play a key role during proactive inhibition, when subjects prepare to potentially suppress their actions. Here, we hypothesized that STN responses to reactive and proactive inhibitory control might be driven by different underlying mechanisms with specific temporal profiles. Direct neural recordings in twelve Parkinson's disease patients during a modified stop signal task (SST) revealed a decrease of beta band activity (βA, 13-35Hz) in the STN during reactive inhibition of smaller amplitude and shorter duration than during motor execution. Crucially, the onset latency of this relative increase of βA took place before the stop signal reaction time. It could thus be thought of as a "stop" signal inhibiting thalamo-cortical activity that would have supported motor execution. Finally, results also revealed a higher level of βA in the STN during proactive inhibition, which correlated with patient's inhibitory performances. We propose that βA in the STN would here participate in the implementation of a "hold your horse" signal to delay motor responses, thus prioritizing accuracy as compared to speed. In brief, our results provide strong electrophysiological support for the hypothesized role of the STN during executive control underlying proactive and reactive response suppression. PMID:24368260

  17. Subthalamic nucleus local field potential activity during the Eriksen flanker task reveals a novel role for theta phase during conflict monitoring.

    PubMed

    Zavala, Baltazar; Brittain, John-Stuart; Jenkinson, Ned; Ashkan, Keyoumars; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Green, Alexander L; Aziz, Tipu; Zaghloul, Kareem; Brown, Peter

    2013-09-11

    The subthalamic nucleus (STN) is thought to play a central role in modulating responses during conflict. Computational models have suggested that the location of the STN in the basal ganglia, as well as its numerous connections to conflict-related cortical structures, allows it to be ideally situated to act as a global inhibitor during conflict. Additionally, recent behavioral experiments have shown that deep brain stimulation to the STN results in impulsivity during high-conflict situations. However, the precise mechanisms that mediate the "hold-your-horses" function of the STN remain unclear. We recorded from deep brain stimulation electrodes implanted bilaterally in the STN of 13 human subjects with Parkinson's disease while they performed a flanker task. The incongruent trials with the shortest reaction times showed no behavioral or electrophysiological differences from congruent trials, suggesting that the distracter stimuli were successfully ignored. In these trials, cue-locked STN theta band activity demonstrated phase alignment across trials and was followed by a periresponse increase in theta power. In contrast, incongruent trials with longer reaction times demonstrated a relative reduction in theta phase alignment followed by higher theta power. Theta phase alignment negatively correlated with subject reaction time, and theta power positively correlated with trial reaction time. Thus, when conflicting stimuli are not properly ignored, disruption of STN theta phase alignment may help operationalize the hold-your-horses role of the nucleus, whereas later increases in the amplitude of theta oscillations may help overcome this function. PMID:24027276

  18. Subthalamic Nucleus Stimulation Increases Brain Derived Neurotrophic Factor in the Nigrostriatal System and Primary Motor Cortex

    PubMed Central

    Spieles-Engemann, Anne L.; Steece-Collier, Kathy; Behbehani, Michael M.; Collier, Timothy J.; Wohlgenant, Susan L.; Kemp, Christopher J.; Cole-Strauss, Allyson; Levine, Nathan D.; Gombash, Sara E.; Thompson, Valerie B.; Lipton, Jack W.; Sortwell, Caryl E.

    2011-01-01

    The mechanisms underlying the effects of long-term deep brain stimulation of the subthalamic nucleus (STN DBS) as a therapy for Parkinson’s disease (PD) remain poorly understood. The present study examined whether functionally effective, long-term STN DBS modulates glial cell line-derived neurotrophic factor (GDNF) and/or brain-derived neurotrophic factor (BDNF) in both unlesioned and unilateral 6-hydroxydopamine lesioned rats. Lesioned rats that received two weeks of continuous unilateral STN DBS exhibited significant improvements in parkinsonian motor behaviors in tests of forelimb akinesia and rearing activity. Unilateral STN DBS did not increase GDNF in the nigrostriatal system, primary motor cortex (M1), or hippocampus of unlesioned rats. In contrast, unilateral STN DBS increased BDNF protein 2–3 fold bilaterally in the nigrostriatal system with the location (substantia nigra vs. striatum) dependent upon lesion status. Further, BDNF protein was bilaterally increased in M1 cortex by as much as 2 fold regardless of lesion status. STN DBS did not impact cortical regions that receive less input from the STN. STN DBS also was associated with bilateral increases in BDNF mRNA in the substantia nigra (SN) and internal globus pallidus (GPi). The increase observed in GPi was completely blocked by pretreatment with 5-Methyl-10,11-dihydro-5 H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), suggesting that the activation of N-methyl-D-aspartate (NMDA) receptors was involved in this phenomenon. The upregulation of BDNF associated with long term STN DBS suggest that this therapy may exert pronounced and underappreciated effects on plasticity in the basal ganglia circuitry that may play a role in the symptomatic effects of this therapy as well as support the neuroprotective effect of stimulation documented in this rat model. PMID:22328911

  19. Spatial Distribution of Soil Organic Carbon and Total Nitrogen Based on GIS and Geostatistics in a Small Watershed in a Hilly Area of Northern China

    PubMed Central

    Peng, Gao; Bing, Wang; Guangpo, Geng; Guangcan, Zhang

    2013-01-01

    The spatial variability of soil organic carbon (SOC) and total nitrogen (STN) levels is important in both global carbon-nitrogen cycle and climate change research. There has been little research on the spatial distribution of SOC and STN at the watershed scale based on geographic information systems (GIS) and geostatistics. Ninety-seven soil samples taken at depths of 0–20 cm were collected during October 2010 and 2011 from the Matiyu small watershed (4.2 km2) of a hilly area in Shandong Province, northern China. The impacts of different land use types, elevation, vegetation coverage and other factors on SOC and STN spatial distributions were examined using GIS and a geostatistical method, regression-kriging. The results show that the concentration variations of SOC and STN in the Matiyu small watershed were moderate variation based on the mean, median, minimum and maximum, and the coefficients of variation (CV). Residual values of SOC and STN had moderate spatial autocorrelations, and the Nugget/Sill were 0.2% and 0.1%, respectively. Distribution maps of regression-kriging revealed that both SOC and STN concentrations in the Matiyu watershed decreased from southeast to northwest. This result was similar to the watershed DEM trend and significantly correlated with land use type, elevation and aspect. SOC and STN predictions with the regression-kriging method were more accurate than those obtained using ordinary kriging. This research indicates that geostatistical characteristics of SOC and STN concentrations in the watershed were closely related to both land-use type and spatial topographic structure and that regression-kriging is suitable for investigating the spatial distributions of SOC and STN in the complex topography of the watershed. PMID:24391791

  20. An age-related shift of resting-state functional connectivity of the subthalamic nucleus: a potential mechanism for compensating motor performance decline in older adults

    PubMed Central

    Mathys, Christian; Hoffstaedter, Felix; Caspers, Julian; Caspers, Svenja; Südmeyer, Martin; Grefkes, Christian; Eickhoff, Simon B.; Langner, Robert

    2014-01-01

    Healthy aging is associated with decline in basic motor functioning and higher motor control. Here, we investigated age-related differences in the brain-wide functional connectivity (FC) pattern of the subthalamic nucleus (STN), which plays an important role in motor response control. As earlier studies revealed functional coupling between STN and basal ganglia, which both are known to influence the conservativeness of motor responses on a superordinate level, we tested the hypothesis that STN FC with the striatum becomes dysbalanced with age. To this end, we performed a seed-based resting-state analysis of fMRI data from 361 healthy adults (mean age: 41.8, age range: 18–85) using bilateral STN as the seed region of interest. Age was included as a covariate to identify regions showing age-related changes of FC with the STN seed. The analysis revealed positive FC of the STN with several previously described subcortical and cortical regions like the anterior cingulate and sensorimotor cortex, as well as not-yet reported regions including central and posterior insula. With increasing age, we observed reduced positive FC with caudate nucleus, thalamus, and insula as well as increased positive FC with sensorimotor cortex and putamen. Furthermore, an age-related reduction of negative FC was found with precuneus and posterior cingulate cortex. We suggest that this reduced de-coupling of brain areas involved in self-relevant but motor-unrelated cognitive processing (i.e. precuneus and posterior cingulate cortex) from the STN motor network may represent a potential mechanism behind the age-dependent decline in motor performance. At the same time, older adults appear to compensate for this decline by releasing superordinate motor control areas, in particular caudate nucleus and insula, from STN interference while increasing STN-mediated response control over lower level motor areas like sensorimotor cortex and putamen. PMID:25100995

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

    PubMed Central

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

    2012-01-01

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

  2. Arachnophobia alleviated by subthalamic nucleus stimulation for Parkinson's disease.

    PubMed

    Allert, Niels; Gippert, Sabrina M; Sajonz, Bastian E A; Nelles, Christoph; Bewernick, Bettina; Schlaepfer, Thomas E; Coenen, Volker A

    2016-06-01

    We report on a Parkinson patient with motor fluctuations and dyskinesias in whom deep brain stimulation (DBS) of the subthalamic nucleus (STN) not only improved motor symptoms but also pre-existing arachnophobia. Arachnophobia had been unchanged by the course of Parkinson's disease but rapidly improved with STN-DBS. Both, motor effects and the improvement of arachnophobia were stable during 2 years follow-up. To our knowledge this is the first report on STN stimulation effects on a specific phobia. PMID:27198699

  3. Temperature dependence of the deformation behavior of type 316 stainless steel after low temperature neutron irradiation

    SciTech Connect

    Robertson, J.P.; Rowcliffe, A.F.; Grossbeck, M.L.; Ioka, Ikuo; Jitsukawa, Shiro

    1996-12-31

    A single heat of solution annealed 316 ss was irradiated to 7 and 18 dpa at 60, 200, 330, and 400 C. Tensile properties were studied vs dose and temperature. Large changes in yield strength, deformation mode, strain to necking (STN), and strain hardening capacity were seen. Magnitude of the changes are dependent on both irradiation temperature and neutron dose. Irradiation can more than triple the yield strength and decrease STN to <0.5% under certain conditions. A maximum increase in yield strength and a minimum in STN occur after irradiation at 330 C but failure mode remains ductile.

  4. The Subthalamic Nucleus, oscillations and conflict

    PubMed Central

    Zavala, Baltazar; Zaghloul, Kareem; Brown, Peter

    2014-01-01

    The subthalamic nucleus (STN), which is currently the most common target for deep brain stimulation for Parkinson’s disease, has received increased attention over the past few years for the roles it may play in functions beyond simple motor control. In this article we will highlight several of the theoretical, interventional, and electrophysiological studies that have implicated the STN in response inhibition. Most influential amongst this evidence has been the reported effect of STN deep brain stimulation in increasing impulsive responses in the laboratory setting. Yet, how this relates to pathological impulsivity in patient’s everyday lives remains uncertain. PMID:25688872

  5. Effects of dopaminergic and subthalamic stimulation on musical performance.

    PubMed

    van Vugt, Floris T; Schüpbach, Michael; Altenmüller, Eckart; Bardinet, Eric; Yelnik, Jérôme; Hälbig, Thomas D

    2013-05-01

    Although subthalamic-deep brain stimulation (STN-DBS) is an efficient treatment for Parkinson's disease (PD), its effects on fine motor functions are not clear. We present the case of a professional violinist with PD treated with STN-DBS. DBS improved musical articulation, intonation and emotional expression and worsened timing relative to a timekeeper (metronome). The same effects were found for dopaminergic treatment. These results suggest that STN-DBS, mimicking the effects of dopaminergic stimulation, improves fine-tuned motor behaviour whilst impairing timing precision. PMID:23232663

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

    PubMed

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

    2004-03-01

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

  7. The Mathematics of Dispatchability Revisited

    NASA Technical Reports Server (NTRS)

    Morris, Paul

    2016-01-01

    Dispatchability is an important property for the efficient execution of temporal plans where the temporal constraints are represented as a Simple Temporal Network (STN). It has been shown that every STN may be reformulated as a dispatchable STN, and dispatchability ensures that the temporal constraints need only be satisfied locally during execution. Recently it has also been shown that Simple Temporal Networks with Uncertainty, augmented with wait edges, are Dynamically Controllable provided every projection is dispatchable. Thus, the dispatchability property has both theoretical and practical interest. One thing that hampers further work in this area is the underdeveloped theory. The existing definitions are expressed in terms of algorithms, and are less suitable for mathematical proofs. In this paper, we develop a new formal theory of dispatchability in terms of execution sequences. We exploit this to prove a characterization of dispatchability involving the structural properties of the STN graph. This facilitates the potential application of the theory to uncertainty reasoning.

  8. Determinants of neuronal firing pattern in the guinea-pig subthalamic nucleus: an in vivo and in vitro comparison.

    PubMed

    Overton, P G; Greenfield, S A

    1995-01-01

    To ascertain the extent to which neuronal firing pattern in the subthalamic nucleus (STN) is determined by afferent inputs, a comparison was made between STN neurons recorded in vivo and in vitro (a largely denervated preparation). In vivo, the majority of cells exhibited an irregular firing pattern, although some showed evidence of burst firing. In contrast, all cells had a regular firing pattern in vitro. Electrical stimulation of the striatopallidal complex in vivo induced a short latency inhibition in STN neurons, followed by a burst of spikes. These effects could be reproduced in vitro; hyperpolarising pulses gave rist to a slow depolarising potential upon termination, which was accompanied by a burst of action potentials. Hence, the evidence suggests that afferents play an important role in determining the firing pattern of STN neurons. However, the cells also possess intrinsic membrane properties which allow inputs to trigger either single spikes or bursts. PMID:8619908

  9. Movement-related changes in local and long-range synchronization in Parkinson’s disease revealed by simultaneous magnetoencephalography and intracranial recordings

    PubMed Central

    Litvak, Vladimir; Eusebio, Alexandre; Jha, Ashwani; Oostenveld, Robert; Barnes, Gareth; Foltynie, Tom; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan I.; Friston, Karl; Brown, Peter

    2012-01-01

    Functional neurosurgery has afforded the opportunity to assess interactions between populations of neurons in the human cerebral cortex and basal ganglia in patients with Parkinson’s disease (PD). Interactions occur over a wide range of frequencies, and the functional significance of those above 30 Hz is particularly unclear. Do they improve movement and, if so, in what way? We acquired simultaneously magnetoencephalography (MEG) and direct recordings from the subthalamic nucleus (STN) in 17 PD patients. We examined the effect of synchronous and sequential finger movements and of the dopamine prodrug levodopa on induced power in the contralateral primary motor cortex (M1) and STN and on the coherence between the two structures. We observed discrete peaks in M1 and STN power over 60-90 Hz and 300-400 Hz. All these power peaks increased with movement and levodopa treatment. Only STN activity over 60-90 Hz was coherent with activity in M1. Directionality analysis showed that STN gamma activity at 60-90 Hz tended to drive gamma activity in M1. The effects of levodopa on both local and distant synchronisation over 60-90 Hz correlated with the degree of improvement in bradykinesia-rigidity, as did local STN activity at 300-400 Hz. Despite this, there were no effects of movement type, nor interactions between movement type and levodopa in the STN, nor in the coherence between STN and M1. We conclude that synchronisation over 60-90 Hz in the basal ganglia cortical network is prokinetic, but likely through a modulatory effect rather than any involvement in explicit motor processing. PMID:22855804

  10. The Good and Bad Differentially Encoded within the Subthalamic Nucleus in Rats

    PubMed Central

    Breysse, Emmanuel; Pelloux, Yann

    2015-01-01

    Abstract The subthalamic nucleus (STN) has only recently been added into the reward circuit. It has been shown to encode information regarding rewards (4% sucrose, 32% cocaine). To investigate the encoding of negative value, STN neurons were recorded in rats performing a task using discriminative stimuli predicting various rewards and especially during the replacement of a positive reinforcer (4% sucrose) by an aversive reinforcer (quinine). The results show that STN neurons encode information relative to both positive and aversive reinforcers via specialized subpopulations. The specialization is reset when the context is modified (change from a favorable context (4% vs 32% sucrose) to an unfavorable context (quinine vs 32% sucrose). An excitatory response to the cue light predicting the reward seems to be associated with the preferred situation, suggesting that STN plays a role in encoding the relative value of rewards. STN also seems to play a critical role in the encoding of execution error. Indeed, various subpopulations of neurons responding exclusively at early (i.e., “oops neurons”) or at correct lever release were identified. The oops neurons respond mostly when the preferred reward (32% sucrose) is missed. Furthermore, STN neurons respond to reward omission, suggesting a role in reward prediction error. These properties of STN neurons strengthen its position in the reward circuit as a key cerebral structure through which reward-related processes are mediated. It is particularly important given the fact that STN is the target of surgical treatment for Parkinson’s disease and obsessive compulsive disorders, and has been suggested for the treatment of addiction as well. PMID:26478913

  11. Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy.

    PubMed

    Welter, M-L; Burbaud, P; Fernandez-Vidal, S; Bardinet, E; Coste, J; Piallat, B; Borg, M; Besnard, S; Sauleau, P; Devaux, B; Pidoux, B; Chaynes, P; Tézenas du Montcel, S; Bastian, A; Langbour, N; Teillant, A; Haynes, W; Yelnik, J; Karachi, C; Mallet, L

    2011-01-01

    Functional and connectivity changes in corticostriatal systems have been reported in the brains of patients with obsessive-compulsive disorder (OCD); however, the relationship between basal ganglia activity and OCD severity has never been adequately established. We recently showed that deep brain stimulation of the subthalamic nucleus (STN), a central basal ganglia nucleus, improves OCD. Here, single-unit subthalamic neuronal activity was analysed in 12 OCD patients, in relation to the severity of obsessions and compulsions and response to STN stimulation, and compared with that obtained in 12 patients with Parkinson's disease (PD). STN neurons in OCD patients had lower discharge frequency than those in PD patients, with a similar proportion of burst-type activity (69 vs 67%). Oscillatory activity was present in 46 and 68% of neurons in OCD and PD patients, respectively, predominantly in the low-frequency band (1-8 Hz). In OCD patients, the bursty and oscillatory subthalamic neuronal activity was mainly located in the associative-limbic part. Both OCD severity and clinical improvement following STN stimulation were related to the STN neuronal activity. In patients with the most severe OCD, STN neurons exhibited bursts with shorter duration and interburst interval, but higher intraburst frequency, and more oscillations in the low-frequency bands. In patients with best clinical outcome with STN stimulation, STN neurons displayed higher mean discharge, burst and intraburst frequencies, and lower interburst interval. These findings are consistent with the hypothesis of a dysfunction in the associative-limbic subdivision of the basal ganglia circuitry in OCD's pathophysiology. PMID:22832400

  12. Identification of (2S,3S)-β-Methyltryptophan as the Real Biosynthetic Intermediate of Antitumor Agent Streptonigrin

    PubMed Central

    Kong, Dekun; Zou, Yi; Zhang, Zhang; Xu, Fei; Brock, Nelson L.; Zhang, Liping; Deng, Zixin; Lin, Shuangjun

    2016-01-01

    Streptonigrin is a potent antitumor antibiotic, active against a wide range of mammalian tumor cells. It was reported that its biosynthesis relies on (2S,3R)-β-methyltryptophan as an intermediate. In this study, the biosynthesis of (2S,3R)-β-methyltryptophan and its isomer (2S,3S)-β-methyltryptophan by enzymes from the streptonigrin biosynthetic pathway is demonstrated. StnR is a pyridoxal 5′-phosphate (PLP)-dependent aminotransferase that catalyzes a transamination between L-tryptophan and β-methyl indolepyruvate. StnQ1 is an S-adenosylmethionine (SAM)-dependent C-methyltransferase and catalyzes β-methylation of indolepyruvate to generate (R)-β-methyl indolepyruvate. Although StnR exhibited a significant preference for (S)-β-methyl indolepyruvate over the (R)-epimer, StnQ1 and StnR together catalyze (2S,3R)-β-methyltryptophan formation from L-tryptophan. StnK3 is a cupin superfamily protein responsible for conversion of (R)-β-methyl indolepyruvate to its (S)-epimer and enables (2S,3S)-β-methyltryptophan biosynthesis from L-tryptophan when combined with StnQ1 and StnR. Most importantly, (2S,3S)-β-methyltryptophan was established as the biosynthetic intermediate of the streptonigrin pathway by feeding experiments with a knockout mutant, contradicting the previous proposal that stated (2S,3R)-β-methyltryptophan as the intermediate. These data set the stage for the complete elucidation of the streptonigrin biosynthetic pathway, which would unlock the potential of creating new streptonigrin analogues by genetic manipulation of the biosynthetic machinery. PMID:26847951

  13. The subthalamic nucleus. Part I: development, cytology, topography and connections.

    PubMed

    Marani, Enrico; Heida, Tjitske; Lakke, Egbert A J F; Usunoff, Kamen G

    2008-01-01

    This monograph (Part I of two volumes) on the subthalamic nucleus (STN) accentuates the gap between experimental animal and human information concerning subthalamic development, cytology, topography and connections. The light and electron microscopical cytology focuses on the open nucleus concept and the neuronal types present in the STN. The cytochemistry encompasses enzymes, NO, glial fibrillary acidic protein (GFAP), calcium binding proteins, and receptors (dopamine, cannabinoid, opioid, glutamate, gamma-aminobutyric acid (GABA), serotonin, cholinergic, and calcium channels). The ontogeny of the subthalamic cell cord is also reviewed. The topography concerns the rat, cat, baboon and human STN. The descriptions of the connections are also given from a historical point of view. Recent tracer studies on the rat nigro-subthalamic connection revealed contralateral projections. Part II of the two volumes (volume 199) on the subthalamic nucleus (STN) starts with a systemic model of the basal ganglia to evaluate the position of the STN in the direct, indirect and hyperdirect pathways. A summary of in vitro studies is given, describing STN spontaneous activity as well as responses to depolarizing and hyperpolarizing inputs and high-frequency stimulation. STN bursting activity and the underlying ionic mechanisms are investigated. Deep brain stimulation used for symptomatic treatment of Parkinson's disease is discussed in terms of the elements that are influenced and its hypothesized mechanisms. This part of the monograph explores the pedunculopontine-subthalamic connections and summarizes attempts to mimic neurotransmitter actions of the pedunculopontine nucleus in cell cultures and high-frequency stimulation on cultured dissociated rat subthalamic neurons. STN cell models--single- and multi-compartment models and system-level models are discussed in relation to subthalamic function and dysfunction. Parts I and II are compared. PMID:18727483

  14. The subthalamic nucleus part II: modelling and simulation of activity.

    PubMed

    Heida, Tjitske; Marani, Enrico; Usunoff, Kamen G

    2008-01-01

    Part I of The Subthalamic Nucleus (volume 198) (STN) accentuates the gap between experimental animal and human information concerning subthalamic development, cytology, topography and connections.The light and electron microscopical cytology focuses on the open nucleus concept and the neuronal types present in the STN. The cytochemistry encompasses enzymes, NO, glial fibrillary acidic protein (GFAP), calcium binding proteins, and receptors (dopamine, cannabinoid, opioid, glutamate, gamma-aminobutyric acid (GABA), serotonin, cholinergic, and calcium channels). The ontogeny of the subthalamic cell cord is also reviewed. The topography concerns the rat, cat, baboon and human STN. The descriptions of the connections are also given from a historical point of view. Recent tracer studies on the rat nigro-subthalamic connection revealed contralateral projections. This monograph (Part II of the two volumes) on the subthalamic nucleus (STN) starts with a systemic model of the basal ganglia to evaluate the position of the STN in the direct, indirect and hyperdirect pathways. A summary of in vitro studies is given, describing STN spontaneous activity as well as responses to depolarizing and hyperpolarizing inputs and high-frequency stimulation. STN bursting activity and the underlying ionic mechanisms are investigated. Deep brain stimulation used for symptomatic treatment of Parkinson's disease is discussed in terms of the elements that are influenced and its hypothesized mechanisms. This part of the monograph explores the pedunculopontine-subthalamic connections and summarizes attempts to mimic neurotransmitter actions of the pedunculopontine nucleus in cell cultures and high-frequency stimulation on cultured dissociated rat subthalamic neurons. STN cell models - single- and multi-compartment models and system-level models are discussed in relation to subthalamic function and dysfunction. Parts I and II are compared. PMID:18727495

  15. Mismatch negativity-like potential (MMN-like) in the subthalamic nuclei in Parkinson's disease patients.

    PubMed

    Minks, Eduard; Jurák, Pavel; Chládek, Jan; Chrastina, Jan; Halámek, Josef; Shaw, Daniel J; Bareš, Martin

    2014-12-01

    An infrequent change to an otherwise repetitive sequence of stimuli leads to the generation of mismatch negativity (MMN), even in the absence of attention. This evoked negative response occurs in the scalp-recorded electroencephalogram (EEG) over the temporal and frontal cortices, 100-250 ms after onset of the deviant stimulus. The MMN is used to detect sensory information processing. The aim of our study was to investigate whether MMN can be recorded in the subthalamic nuclei (STN) as evidence of auditory information processing on an unconscious level within this structure. To our knowledge, MMN has never been recorded in the human STN. We recorded intracerebral EEG using a MMN paradigm in five patients with Parkinson's disease (PD) who were implanted with depth electrodes in the subthalamic nuclei (STN). We found far-field MMN when intracerebral contacts were connected to an extracranial reference electrode. In all five PD patients (and nine of ten intracerebral electrodes), we also found near-field MMN-like potentials when intracerebral contacts were referenced to one another, and in some electrodes, we observed phase reversals in these potentials. The mean time-to-peak latency of the intracerebral MMN-like potentials was 214 ± 38 ms (median 219 ms). We reveal MMN-like potentials in bilateral STN. This finding provides evidence that STN receives sensory (auditory) information from other structures. The question for further research is whether STN receives such signals through a previously described hyperdirect pathway between STN and frontal cortex (a known generator of the MMN potential) and if the STN contributes to sensorimotor integration. PMID:24809684

  16. Continuous bilateral infusion of vigabatrin into the subthalamic nucleus: Effects on seizure threshold and GABA metabolism in two rat models.

    PubMed

    Gey, Laura; Gernert, Manuela; Löscher, Wolfgang

    2016-07-01

    The subthalamic nucleus (STN) plays a crucial role as a regulator of basal ganglia outflow but also influences the activity of cortical and limbic structures, so that it is widely used as a therapeutic target in different brain diseases, including epilepsy. In addition to electrical stimulation of the STN, targeted delivery of anti-seizure drugs to the STN may constitute an alternative treatment approach in patients with pharmacoresistant epilepsy. In the present experimental study, we investigated the anti-seizure and adverse effects of chronic infusion of vigabatrin into the STN of rats. Vigabatrin is a clinically approved anti-seizure drug, which acts by increasing brain GABA levels by irreversibly inhibiting GABA-aminotransferase (GABA-T). Based on functional and neurochemical effects of acute STN microinjection, doses for continuous infusion were calculated and administered, using an innovative drug infusion technology. Bilateral infusion of only 10μg/day vigabatrin over 3weeks into the STN resulted in an almost complete inhibition of GABA-T and 4-fold increase in GABA in the target region, which was associated with a significant increase in seizure threshold, determined once weekly by i.v. infusion of pentylenetetrazole (PTZ). Lower doses or unilateral infusion were less effective, both on PTZ seizures and on kindled seizures. Bilateral infusion into substantia nigra pars reticulata was less effective and more toxic than STN infusion. In part of the rats, tolerance to the anti-seizure effect developed. The data demonstrate that chronic administration of very low, nontoxic doses of vigabatrin into STN is an effective means of increasing local GABA concentrations and seizure threshold. PMID:26976738

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

    PubMed

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

    2011-10-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can induce nonmotor side effects such as behavioral and mood disturbances or body weight gain in Parkinson's disease (PD) patients. We hypothesized that some of these problems could be related to an altered attribution of incentive salience (ie, emotional relevance) to rewarding and aversive stimuli. Twenty PD patients (all men; mean age ± SD, 58.3 ± 6 years) in bilateral STN DBS switched ON and OFF conditions and 18 matched controls rated pictures selected from the International Affective Picture System according to emotional valence (unpleasantness/pleasantness) and arousal on 2 independent visual scales ranging from 1 to 9. Eighty-four pictures depicting primary rewarding (erotica and food) and aversive fearful (victims and threat) and neutral stimuli were selected for this study. In the STN DBS ON condition, the PD patients attributed lower valence scores to the aversive pictures compared with the OFF condition (P < .01) and compared with controls (P < .01). The difference between the OFF condition and controls was less pronounced (P < .05). Furthermore, postoperative weight gain correlated with arousal ratings from the food pictures in the STN DBS ON condition (P < .05 compensated for OFF condition). Our results suggest that STN DBS increases activation of the aversive motivational system so that more relevance is attributed to aversive fearful stimuli. In addition, STN DBS-related sensitivity to food reward stimuli cues might drive DBS-treated patients to higher food intake and subsequent weight gain. PMID:21780183

  18. Effects of Deep Brain Stimulation and Medication on Strength, Bradykinesia, and Electromyographic Patterns of the Ankle Joint in Parkinson’s Disease

    PubMed Central

    Vaillancourt, David E.; Prodoehl, Janey; Sturman, Molly M.; Bakay, Roy A.E.; Metman, Leo Verhagen; Corcos, Daniel M.

    2008-01-01

    We investigated the control of movement in 12 patients with Parkinson’s disease (PD) after they received surgically implanted high-frequency stimulating electrodes in the subthalamic nucleus (STN). The experiment studied ankle strength, movement velocity, and the associated electromyographic patterns in PD patients, six of whom had tremor at the ankle. The patients were studied off treatment, ON STN deep brain stimulation (DBS), on medication, and on medication plus STN DBS. Twelve matched control subjects were also examined. Medication alone and STN DBS alone increased patients’ ankle strength, ankle velocity, agonist muscle burst amplitude, and agonist burst duration, while reducing the number of agonist bursts during movement. These findings were similar for PD patients with and without tremor. The combination of medication plus STN DBS normalized maximal strength at the ankle joint, but ankle movement velocity and electromyographic patterns were not normalized. The findings are the first to demonstrate that STN DBS and medication increase strength and movement velocity at the ankle joint. PMID:16124011

  19. Subthalamic nucleus stimulation affects orbitofrontal cortex in facial emotion recognition: a pet study

    PubMed Central

    Le Jeune, F.; Péron, J.; Biseul, I.; Fournier, S.; Sauleau, P.; Drapier, S.; Haegelen, C.; Drapier, D.; Millet, B.; Garin, E.; Herry, J.-Y.; Malbert, C.-H.

    2008-01-01

    Deep brain stimulation (DBS) of the bilateral subthalamic nucleus (STN) in Parkinson's disease is thought to produce adverse events such as emotional disorders, and in a recent study, we found fear recognition to be impaired as a result. These changes have been attributed to disturbance of the STN's limbic territory and would appear to confirm that the negative emotion recognition network passes through the STN. In addition, it is now widely acknowledged that damage to the orbitofrontal cortex (OFC), especially the right side, can result in impaired recognition of facial emotions (RFE). In this context, we hypothesized that this reduced recognition of fear is correlated with modifications in the cerebral glucose metabolism of the right OFC. The objective of the present study was first, to reinforce our previous results by demonstrating reduced fear recognition in our Parkinson's disease patient group following STN DBS and, second, to correlate these emotional performances with glucose metabolism using 18FDG-PET. The 18FDG-PET and RFE tasks were both performed by a cohort of 13 Parkinson's disease patients 3 months before and 3 months after surgery for STN DBS. As predicted, we observed a significant reduction in fear recognition following surgery and obtained a positive correlation between these neuropsychological results and changes in glucose metabolism, especially in the right OFC. These results confirm the role of the STN as a key basal ganglia structure in limbic circuits. PMID:18490359

  20. Effects of Deep Brain Stimulation on Pausing During Spontaneous Speech in Parkinson’s Disease

    PubMed Central

    Ahn, Ji Sook; Van Lancker Sidtis, Diana; Sidtis, John J.

    2016-01-01

    The present study examined pausing patterns in spontaneous speech as a measure of the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on parkinsonian speech. Pauses reflect various aspects of speech and language processes, including motor initiation and linguistic planning. Relatively little attention has been given to pauses in determining the effect of STN-DBS. An examination of pausing may be helpful to understanding how this form of therapy affects these behaviors. Seven individuals with Parkinson’s disease who received surgery for bilateral STN-DBS participated. Spontaneous speech samples were elicited in both the ON and OFF STN-DBS condition. Findings indicated that long pauses (250–3000 ms) in spontaneous speech were significantly shorter and more frequent in the STN-DBS ON condition. Furthermore, the proportion of nonlinguistic boundary pauses was significantly greater with stimulation. The findings support previous studies suggesting that speech motor control and lexical retrieval may be affected by STN-DBS. PMID:26848252

  1. 2NH and 3OH are crucial structural requirements in sphingomyelin for sticholysin II binding and pore formation in bilayer membranes.

    PubMed

    Maula, Terhi; Isaksson, Y Jenny E; García-Linares, Sara; Niinivehmas, Sanna; Pentikäinen, Olli T; Kurita, Mayuko; Yamaguchi, Shou; Yamamoto, Tetsuya; Katsumura, Shigeo; Gavilanes, José G; Martínez-del-Pozo, Alvaro; Slotte, J Peter

    2013-05-01

    Sticholysin II (StnII) is a pore-forming toxin from the sea anemone Stichodactyla heliantus which belongs to the large actinoporin family. The toxin binds to sphingomyelin (SM) containing membranes, and shows high binding specificity for this lipid. In this study, we have examined the role of the hydrogen bonding groups of the SM long-chain base (i.e., the 2NH and the 3OH) for StnII recognition. We prepared methylated SM-analogs which had reduced hydrogen bonding capability from 2NH and 3OH. Both surface plasmon resonance experiments, and isothermal titration calorimetry measurements indicated that StnII failed to bind to bilayers containing methylated SM-analogs, whereas clear binding was seen to SM-containing bilayers. StnII also failed to induce calcein release (i.e., pore formation) from vesicles made to contain methylated SM-analogs, but readily induced calcein release from SM-containing vesicles. Molecular modeling of SM docked to the phosphocholine binding site of StnII indicated that the 2NH and 3OH groups were likely to form a hydrogen bond with Tyr135. In addition, it appeared that Tyr111 and Tyr136 could donate hydrogen bonds to phosphate oxygen, thus stabilizing SM binding to the toxin. We conclude that the interfacial hydrogen bonding properties of SM, in addition to the phosphocholine head group, are crucial for high-affinity SM/StnII-interaction. PMID:23376330

  2. The Striatum and Subthalamic Nucleus as Independent and Collaborative Structures in Motor Control

    PubMed Central

    Tewari, Alia; Jog, Rachna; Jog, Mandar S.

    2016-01-01

    The striatum and the subthalamic nucleus (STN) are two separate input structures into the basal ganglia (BG). Accordingly, research to date has primarily focused on the distinct roles of these structures in motor control and cognition, often through investigation of Parkinson’s disease (PD). Both structures are divided into sensorimotor, associative, and limbic subdivisions based on cortical connectivity. The more recent discovery of the STN as an input structure into the BG drives comparison of these two structures and their respective roles in cognition and motor control. This review compares the role of the striatum and STN in motor response inhibition and execution, competing motor programs, feedback based learning, and response planning. Through comparison, it is found that the striatum and STN have highly independent roles in motor control but also collaborate in order to execute desired actions. There is also the possibility that inhibition or activation of one of these structures indirectly contributes to the function of other connected anatomical structures. Both structures contribute to selective motor response inhibition, which forms the basis of many tasks, but the STN additionally contributes to global inhibition through the hyperdirect pathway. Research is warranted on the functional connectivity of the network for inhibition involving the rIFG, preSMA, striatum, and STN. PMID:26973474

  3. Photosynthetic lesions can trigger accelerated senescence in Arabidopsis thaliana

    PubMed Central

    Wang, Jing; Leister, Dario; Bolle, Cordelia

    2015-01-01

    Senescence is a highly regulated process characterized by the active breakdown of cells, which ultimately leads to the death of plant organs or whole plants. In annual plants such as Arabidopsis thaliana senescence can be observed in each individual leaf. Whether deficiencies in photosynthesis promote the induction of senescence was investigated by monitoring chlorophyll degradation, photosynthetic parameters, and reactive oxygen species accumulation in photosynthetic mutants. Several mutations affecting components of the photosynthetic apparatus, including psal-2, psan-2, and psbs, were found to lead to premature or faster senescence, as did simultaneous inactivation of the STN7 and STN8 kinases. Premature senescence is apparently not directly linked to an overall reduction in photosynthesis but to perturbations in specific aspects of the process. Dark-induced senescence is accelerated in mutants affected in linear electron flow, especially psad2-1, psan-2, and pete2-1, as well as in stn7 and stn8 mutants and STN7 and STN8 overexpressor lines. Interestingly, no direct link with ROS production could be observed. PMID:26272903

  4. A Genetic Analysis of the Stoned Locus and Its Interaction with Dunce, Shibire and Suppressor of Stoned Variants of Drosophila Melanogaster

    PubMed Central

    Petrovich, T. Z.; Merakovsky, J.; Kelly, L. E.

    1993-01-01

    The genetic complementation patterns of both behavioral and lethal alleles at the stoned locus have been characterized. Mosaic analysis of a stoned lethal allele suggests that stoned functions either in the nervous system or in both the nervous system and musculature, but is not required for gross neural development. The behavioral alleles stn(ts) and stn(C), appear to be defective in a diametrically opposite sense, show interallelic complementation, and indicate distinct roles for the stoned gene product in the visual system and in motor coordination. A number of other neurological mutations have been investigated for their possible interaction with the viable stoned alleles. Mutations at two loci, dunce and shibire, act synergistically with the stn(ts) mutations to cause lethality, but fail to interact with stn(C). A third variant (Suppressor of stoned) has been identified which can suppress the debilitation associated with the stn(ts) mutations. These data, together with a previously identified interaction between the stn(ts) and tan mutants, indicate a central role for the stoned gene product in neuronal function, and suggests that the stoned gene product interacts, either directly or indirectly, with the neural cAMP second messenger system, with the synaptic membrane recycling pathway via dynamin, and with biogenic amine metabolism. PMID:8462853

  5. Synergistic Action of Actinoporin Isoforms from the Same Sea Anemone Species Assembled into Functionally Active Heteropores.

    PubMed

    Rivera-de-Torre, Esperanza; García-Linares, Sara; Alegre-Cebollada, Jorge; Lacadena, Javier; Gavilanes, José G; Martínez-Del-Pozo, Álvaro

    2016-07-01

    Among the toxic polypeptides secreted in the venom of sea anemones, actinoporins are the pore-forming toxins whose toxic activity relies on the formation of oligomeric pores within biological membranes. Intriguingly, actinoporins appear as multigene families that give rise to many protein isoforms in the same individual displaying high sequence identities but large functional differences. However, the evolutionary advantage of producing such similar isotoxins is not fully understood. Here, using sticholysins I and II (StnI and StnII) from the sea anemone Stichodactyla helianthus, it is shown that actinoporin isoforms can potentiate each other's activity. Through hemolysis and calcein releasing assays, it is revealed that mixtures of StnI and StnII are more lytic than equivalent preparations of the corresponding isolated isoforms. It is then proposed that this synergy is due to the assembly of heteropores because (i) StnI and StnII can be chemically cross-linked at the membrane and (ii) the affinity of sticholysin mixtures for the membrane is increased with respect to any of them acting in isolation, as revealed by isothermal titration calorimetry experiments. These results help us understand the multigene nature of actinoporins and may be extended to other families of toxins that require oligomerization to exert toxicity. PMID:27129251

  6. Subthalamic deep brain stimulation in Parkinson׳s disease has no significant effect on perceptual timing in the hundreds of milliseconds range

    PubMed Central

    Cope, Thomas E.; Grube, Manon; Mandal, Arnab; Cooper, Freya E.; Brechany, Una; Burn, David J.; Griffiths, Timothy D.

    2014-01-01

    Bilateral, high-frequency stimulation of the basal ganglia (STN-DBS) is in widespread use for the treatment of the motor symptoms of Parkinson׳s disease (PD). We present here the first psychophysical investigation of the effect of STN-DBS upon perceptual timing in the hundreds of milliseconds range, with both duration-based (absolute) and beat-based (relative) tasks; 13 patients with PD were assessed with their STN-DBS ‘on’, ‘off’, and then ‘on’ again. Paired parametric analyses revealed no statistically significant differences for any task according to DBS status. We demonstrate, from the examination of confidence intervals, that any functionally relevant effect of STN-DBS on relative perceptual timing is statistically unlikely. For absolute, duration-based timing, we demonstrate that the activation of STN-DBS may either worsen performance or have no effect, but that it is unlikely to lead to significant improvement. Although these results are negative they have important implications for our understanding of perceptual timing and its relationship to motor functions within the timing network of the brain. They imply that the mechanisms involved in the perceptual processing of temporal information are likely to be functionally independent from those that underpin movement. Further, they suggest that the connections between STN and the subtantia nigra and globus pallidus are unlikely to be critical to beat-based perceptual timing. PMID:24613477

  7. Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion

    PubMed Central

    Schweizer, Nadine; Pupe, Stéfano; Arvidsson, Emma; Nordenankar, Karin; Smith-Anttila, Casey J. A.; Mahmoudi, Souha; Andrén, Anna; Dumas, Sylvie; Rajagopalan, Aparna; Lévesque, Daniel; Leão, Richardson N.; Wallén-Mackenzie, Åsa

    2014-01-01

    The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses Vglut2 and Pitx2, and by conditional targeting of this subpopulation we reduced Vglut2 expression levels in the STN by 40%, leaving Pitx2 expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knockout mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that Vglut2-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects. PMID:24821804

  8. Neuropsychology Review Submission

    PubMed Central

    Rossi, P. Justin; Okun, Michael S.

    2016-01-01

    It has been well documented that deep brain stimulation (DBS) of the subthalamic nucleus (STN) to address some of the disabling motor symptoms of Parkinson’s disease (PD) can evoke unintended effects, especially on non-motor behavior. This observation has catalyzed more than a decade of research concentrated on establishing trends and identifying potential mechanisms for these non-motor effects. While many issues remain unresolved, the collective result of many research studies and clinical observations has been a general recognition of the role of the STN in mediating limbic function. In particular, the STN has been implicated in impulse control and the related construct of valence processing. A better understanding of STN involvement in these phenomena could have important implications for treating impulse control disorders (ICDs). ICDs affect up to 40% of PD patients on dopamine agonist therapy and approximately 15% of PD patients overall. ICDs have been reported to be associated with STN DBS. In this paper we will focus on impulse control and review pre-clinical, clinical, behavioral, imaging, and electrophysiological studies pertaining to the limbic function of the STN. PMID:26577509

  9. Real-time refinement of subthalamic nucleus targeting using Bayesian decision-making on the root mean square measure.

    PubMed

    Moran, Anan; Bar-Gad, Izhar; Bergman, Hagai; Israel, Zvi

    2006-09-01

    The subthalamic nucleus (STN) is a major target for treatment of advanced Parkinson's disease patients undergoing deep brain stimulation surgery. Microelectrode recording (MER) is used in many cases to identify the target nucleus. A real-time procedure for identifying the entry and exit points of the STN would improve the outcome of this targeting procedure. We used the normalized root mean square (NRMS) of a short (5 seconds) MER sampled signal and the estimated anatomical distance to target (EDT) as the basis for this procedure. Electrode tip location was defined intraoperatively by an expert neurophysiologist to be before, within, or after the STN. Data from 46 trajectories of 27 patients were used to calculate the Bayesian posterior probability of being in each of these locations, given RMS-EDT pair values. We tested our predictions on each trajectory using a bootstrapping technique, with the rest of the trajectories serving as a training set and found the error in predicting the STN entry to be (mean +/- SD) 0.18 +/- 0.84, and 0.50 +/- 0.59 mm for STN exit point, which yields a 0.30 +/- 0.28 mm deviation from the expert's target center. The simplicity and computational ease of RMS calculation, its spike sorting-independent nature and tolerance to electrode parameters of this Bayesian predictor, can lead directly to the development of a fully automated intraoperative physiological procedure for the refinement of imaging estimates of STN borders. PMID:16763982

  10. Effects of subthalamic nucleus stimulation and levodopa on the autonomic nervous system in Parkinson's disease

    PubMed Central

    Ludwig, Janne; Remien, Piet; Guballa, Christoph; Binder, Andreas; Binder, Sabine; Schattschneider, Jörn; Herzog, Jan; Volkmann, Jens; Deuschl, Günther; Wasner, Gunnar; Baron, Ralf

    2007-01-01

    Dysfunctions of the autonomic nervous system (ANS) are common in Parkinson's disease (PD). Regarding motor disability, deep brain stimulation of the subthalamic nucleus (STN) is an effective treatment option in long lasting PD. The aims of this study were to examine whether STN stimulation has an influence on functions of the ANS and to compare these effects to those induced by levodopa. Blood pressure (BP) and heart rate (HR) during rest and orthostatic conditions, HR variability (HRV) and breathing‐induced cutaneous sympathetic vasoconstriction (CVC) were tested in 14 PD patients treated with STN stimulation during “ON” and “OFF” condition of the stimulator. The effects of a single dose of levodopa on ANS were tested in 15 PD patients without DBS. STN stimulation had no influence on cardiovascular ANS functions, whereas CVC was significantly increased. In contrast, levodopa significantly lowered BP and HR at rest and enhanced orthostatic hypotension. Further, HRV, skin perfusion and temperature increased after administration of levodopa. Our results suggest that in contrast to levodopa, STN stimulation has only minor effects on autonomic functions. Since less pharmacotherapy is needed after STN stimulation, reduced levodopa intake results in relative improvement of autonomic function in deep brain stimulated PD patients. PMID:17371906

  11. The Subthalamic Nucleus, Limbic Function, and Impulse Control.

    PubMed

    Rossi, P Justin; Gunduz, Aysegul; Okun, Michael S

    2015-12-01

    It has been well documented that deep brain stimulation (DBS) of the subthalamic nucleus (STN) to address some of the disabling motor symptoms of Parkinson's disease (PD) can evoke unintended effects, especially on non-motor behavior. This observation has catalyzed more than a decade of research concentrated on establishing trends and identifying potential mechanisms for these non-motor effects. While many issues remain unresolved, the collective result of many research studies and clinical observations has been a general recognition of the role of the STN in mediating limbic function. In particular, the STN has been implicated in impulse control and the related construct of valence processing. A better understanding of STN involvement in these phenomena could have important implications for treating impulse control disorders (ICDs). ICDs affect up to 40% of PD patients on dopamine agonist therapy and approximately 15% of PD patients overall. ICDs have been reported to be associated with STN DBS. In this paper we will focus on impulse control and review pre-clinical, clinical, behavioral, imaging, and electrophysiological studies pertaining to the limbic function of the STN. PMID:26577509

  12. Depression and intelligence in patients with Parkinson's disease and deep-brain stimulation.

    PubMed

    Schadt, Courtney R; Cox, Katie L; Tramontana, Michael G; Byrne, Daniel W; Davis, Thomas L; Fang, John Y; Konrad, Peter E; Padaliya, Bhavna; Mutter, Robert W; Gill, Chandler E; Richardson, Caralee R; Charles, P David

    2006-07-01

    The goal of this study is to examine the association of depression with intelligence and education in patients with Parkinson's disease treated with bilateral subthalamic nucleus stimulation (STN-DBS). The literature has been contradictory concerning depression in Parkinson's disease patients. Some studies have shown less depression in Parkinson's disease patients with more education not treated with STN-DBS. Other recently published studies indicate that STN-DBS improves the depression associated with Parkinson's disease. No studies have examined the correlation of these factors with depression in Parkinson's disease patients treated with STN-DBS. We administered the Beck Depression Inventory (BDI) pre- and postoperatively to 21 Parkinson's disease patients (seven women, 14 men, ages 49-75) who underwent STN-DBS. The postoperative scores of the lower 50th percentile (n=8) of the Verbal Comprehensive Index of the Wechsler Adult Intelligence Scale (WAIS-III) decreased significantly (P=0.036), while the upper 50th percentile (n=13) remained nearly constant (P=0.802). Furthermore, as the education increased from highschool to graduate level, patients demonstrated less improvement in depressive symptoms postoperatively. These findings suggest that Parkinson's disease patients with lower intelligence test scores and less education benefit more with regards to depressive symptomatology after STN-DBS than patients with higher scores and education. PMID:16895282

  13. Influence of propofol and fentanyl on deep brain stimulation of the subthalamic nucleus.

    PubMed

    Kim, Wonki; Song, In Ho; Lim, Yong Hoon; Kim, Mi-Ryoung; Kim, Young Eun; Hwang, Jae Ha; Kim, In Keyoung; Song, Sang Woo; Kim, Jin Wook; Lee, Woong-Woo; Kim, Han-Joon; Kim, Cheolyoung; Kim, Hee Chan; Kim, In Young; Park, Hee Pyoung; Kim, Dong Gyu; Jeon, Beom Seok; Paek, Sun Ha

    2014-09-01

    We investigated the effect of propofol and fentanyl on microelectrode recording (MER) and its clinical applicability during subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. We analyzed 8 patients with Parkinson's disease, underwent bilateral STN DBS with MER. Their left sides were done under awake and then their right sides were done with a continuous infusion of propofol and fentanyl under local anesthesia. The electrode position was evaluated by preoperative MRI and postoperative CT. The clinical outcomes were assessed at six months after surgery. We isolated single unit activities from the left and the right side MERs. There was no significant difference in the mean firing rate between the left side MERs (38.7 ± 16.8 spikes/sec, n=78) and the right side MERs (35.5 ± 17.2 spikes/sec, n=66). The bursting pattern of spikes was more frequently observed in the right STN than in the left STN. All the electrode positions were within the STNs on both sides and the off-time Unified Parkinson's Disease Rating Scale part III scores at six months after surgery decreased by 67% of the preoperative level. In this study, a continuous infusion of propofol and fentanyl did not significantly interfere with the MER signals from the STN. The results of this study suggest that propofol and fentanyl can be used for STN DBS in patients with advanced Parkinson's disease improving the overall experience of the patients. PMID:25246748

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

    PubMed Central

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

    2016-01-01

    Objective Reduced verbal fluency (VF) has been reported in patients with Parkinson’s disease (PD), especially those treated by Deep Brain Stimulation of the subthalamic nucleus (STN DBS). To delineate the nature of this dysfunction we aimed at identifying the particular VF-related operations modified by STN DBS. Method Eleven PD patients performed VF tasks in their STN DBS ON and OFF condition. To differentiate VF-components modulated by the stimulation, a temporal cluster analysis was performed, separating production spurts (i.e., ‘clusters’ as correlates of automatic activation spread within lexical fields) from slower cluster transitions (i.e., ‘switches’ reflecting set-shifting towards new lexical fields). The results were compared to those of eleven healthy control subjects. Results PD patients produced significantly more switches accompanied by shorter switch times in the STN DBS ON compared to the STN DBS OFF condition. The number of clusters and time intervals between words within clusters were not affected by the treatment state. Although switch behavior in patients with DBS ON improved, their task performance was still lower compared to that of healthy controls. Discussion Beyond impacting on motor symptoms, STN DBS seems to influence the dynamics of cognitive procedures. Specifically, the results are in line with basal ganglia roles for cognitive switching, in the particular case of VF, from prevailing lexical concepts to new ones. PMID:27575379

  15. Evaluation of MODIS surrogates for meteorological humidity data in east Africa.

    PubMed

    Lin, Shengpan; Moore, Nathan J; Messina, Joseph P; Wu, Jiaping

    2013-01-01

    Satellite remote sensing technology has shown promising results in characterizing the environment in which plants and animals thrive. Remote sensing scientists, biologists, and epidemiologists are adopting remotely sensed imagery to compensate for the paucity of weather information measured by weather stations. With measured humidity from three stations as baselines, our study reveals that Normalised Difference Vegetation Index (NDVI) and atmosphere saturation deficits at the 780 hPa pressure level (D MODIS), both of which were derived from the MODerate-resolution Imaging Spectroradiometer (MODIS) sensor, were significantly correlated with station saturation deficits (D stn)(ȣrȣ = 0.42-0.63, p < 0.001). These metrics have the potential to estimate saturation deficits over east Africa. Four to nine days of lags were found in the NDVI responding to D stn. For the daily estimations of D stn, D MODIS had a better performance than the NDVI. However, both of them poorly explained the variances in daily D stn using simple regression models (adj. R (2) = 0.17-0.39). When the estimation temporal scale was changed to 16-day, their performances were similar, and both were better than daily estimations. For D stn estimations at coarser geographic scales, given that many factors such as soil, vegetation, slope, aspect, and wind speed might complicate the NDVI response lags and model construction, D MODIS is more favourable as a proxy of the saturation deficit over ground due to its simple relationship with D stn. PMID:23956475

  16. The effects of high frequency subthalamic stimulation on balance performance and fear of falling in patients with Parkinson's disease

    PubMed Central

    Nilsson, Maria H; Fransson, Per-Anders; Jarnlo, Gun-Britt; Magnusson, Måns; Rehncrona, Stig

    2009-01-01

    Background Balance impairment is one of the most distressing symptoms in Parkinson's disease (PD) even with pharmacological treatment (levodopa). A complementary treatment is high frequency stimulation in the subthalamic nucleus (STN). Whether STN stimulation improves postural control is under debate. The aim of this study was to explore the effects of STN stimulation alone on balance performance as assessed with clinical performance tests, subjective ratings of fear of falling and posturography. Methods Ten patients (median age 66, range 59–69 years) with bilateral STN stimulation for a minimum of one year, had their anti-PD medications withdrawn overnight. Assessments were done both with the STN stimulation turned OFF and ON (start randomized). In both test conditions, the following were assessed: motor symptoms (descriptive purposes), clinical performance tests, fear of falling ratings, and posturography with and without vibratory proprioceptive disturbance. Results STN stimulation alone significantly (p = 0.002) increased the scores of the Berg balance scale, and the median increase was 6 points. The results of all timed performance tests, except for sharpened Romberg, were significantly (p ≤ 0.016) improved. The patients rated their fear of falling as less severe, and the total score of the Falls-Efficacy Scale(S) increased (p = 0.002) in median with 54 points. All patients completed posturography when the STN stimulation was turned ON, but three patients were unable to do so when it was turned OFF. The seven patients with complete data showed no statistical significant difference (p values ≥ 0.109) in torque variance values when comparing the two test situations. This applied both during quiet stance and during the periods with vibratory stimulation, and it was irrespective of visual input and sway direction. Conclusion In this sample, STN stimulation alone significantly improved the results of the clinical performance tests that mimic activities in

  17. Investigation of a novel protonic/electronic ceramic composite material as a candidate for hydrogen separation membranes

    NASA Astrophysics Data System (ADS)

    Fish, Jason S.

    A novel ceramic protonic/electronic conductor composite BaCe 0.2Zr0.7Y0.1O3-delta / Sr0.95 Ti0.9Nb0.1O3-delta (BCZY27/STN95: BS27) has been synthesized, and its electrical properties and hydrogen permeability have been investigated. The volume ratio of the STN95 phase was varied from 50 - 70 % to test the effects on conductivity and hydrogen permeability. BCZY27 and STN95 powders were prepared by solid-state reaction, and membrane samples were fabricated through conventional and spark plasma sintering techniques. The phase composition, density, and microstructure were compared between the sintering methodologies. Total conductivities of 0.01 - 0.06 S·cm -1 were obtained in wet (+1 % H2O) dilute H2/(N 2, He, Ar) from 600 - 800 °C for 50 volume % STN95. With increasing STN content (60 and 70 volume %), conductivity generally increased, though remained lower than predicted by standard effective medium models, even at 70 volume % STN95. A new effective medium model was proposed, which accounted for an interfacial resistance term associated with the heterojunctions formed between the BCZY27 and STN95 phases. Better fits for the measured data were achieved with this new method, although some effects remain unexplained. Discrepancies between the model and experiment were attributed to space charge effects, grain boundary resistances, and insulating impurity phase formation during synthesis. Dense BS27 samples were tested for high-temperature hydrogen permeation and a measured flux of 0.006 mumol·cm-2·s -1 was recorded for a 50 volume % STN95 sample at 700 °C, using dry argon as a sweep gas. This value represents a modest improvement on other ceramic composite membranes, but remains short of targets for commercialization. Persistent leaks in the flux experiments generated a shallower hydrogen gradient across the samples, although this p(H2) on the sweep side simultaneously decreased the oxygen partial pressure gradient across the sample and preserved the reduced state

  18. Late Consequential Surgical Bed Soft Tissue Necrosis in Advanced Oropharyngeal Squamous Cell Carcinomas Treated With Transoral Robotic Surgery and Postoperative Radiation Therapy

    SciTech Connect

    Lukens, J. Nicholas; Lin, Alexander; Gamerman, Victoria; Mitra, Nandita; Grover, Surbhi; McMenamin, Erin M.; Weinstein, Gregory S.; O'Malley, Bert W.; Cohen, Roger B.; Orisamolu, Abimbola; Ahn, Peter H.; Quon, Harry

    2014-08-01

    Purpose: A subset of patients with oropharyngeal squamous cell carcinoma (OP-SCC) managed with transoral robotic surgery (TORS) and postoperative radiation therapy (PORT) developed soft tissue necrosis (STN) in the surgical bed months after completion of PORT. We investigated the frequency and risk factors. Materials and Methods: This retrospective analysis included 170 consecutive OP-SCC patients treated with TORS and PORT between 2006 and 2012, with >6 months' of follow-up. STN was defined as ulceration of the surgical bed >6 weeks after completion of PORT, requiring opioids, biopsy, or hyperbaric oxygen therapy. Results: A total of 47 of 170 patients (28%) had a diagnosis of STN. Tonsillar patients were more susceptible than base-of-tongue (BOT) patients, 39% (41 of 104) versus 9% (6 of 66), respectively. For patients with STN, median tumor size was 3.0 cm (range 1.0-5.6 cm), and depth of resection was 2.2 cm (range 1.0-5.1 cm). Median radiation dose and dose of fraction to the surgical bed were 6600 cGy and 220 cGy, respectively. Thirty-one patients (66%) received concurrent chemotherapy. Median time to STN was 2.5 months after PORT. All patients had resolution of STN after a median of 3.7 months. Multivariate analysis identified tonsillar primary (odds ratio [OR] 4.73, P=.01), depth of resection (OR 3.12, P=.001), total radiation dose to the resection bed (OR 1.51 per Gy, P<.01), and grade 3 acute mucositis (OR 3.47, P=.02) as risk factors for STN. Beginning May 2011, after implementing aggressive avoidance of delivering >2 Gy/day to the resection bed mucosa, only 8% (2 of 26 patients) experienced STN (all grade 2). Conclusions: A subset of OP-SCC patients treated with TORS and PORT are at risk for developing late consequential surgical bed STN. Risk factors include tonsillar location, depth of resection, radiation dose to the surgical bed, and severe mucositis. STN risk is significantly decreased with carefully avoiding a radiation dosage of >2 Gy/day to the

  19. Expectation Modulates the Effect of Deep Brain Stimulation on Motor and Cognitive Function in Tremor-Dominant Parkinson's Disease

    PubMed Central

    Keitel, Ariane; Ferrea, Stefano; Südmeyer, Martin; Schnitzler, Alfons; Wojtecki, Lars

    2013-01-01

    Expectation contributes to placebo and nocebo responses in Parkinson's disease (PD). While there is evidence for expectation-induced modulations of bradykinesia, little is known about the impact of expectation on resting tremor. Subthalamic nucleus (STN) deep brain stimulation (DBS) improves cardinal PD motor symptoms including tremor whereas impairment of verbal fluency (VF) has been observed as a potential side-effect. Here we investigated how expectation modulates the effect of STN-DBS on resting tremor and its interaction with VF. In a within-subject-design, expectation of 24 tremor-dominant PD patients regarding the impact of STN-DBS on motor symptoms was manipulated by verbal suggestions (positive [placebo], negative [nocebo], neutral [control]). Patients participated with (MedON) and without (MedOFF) antiparkinsonian medication. Resting tremor was recorded by accelerometry and bradykinesia of finger tapping and diadochokinesia were assessed by a 3D ultrasound motion detection system. VF was quantified by lexical and semantic tests. In a subgroup of patients, the effect of STN-DBS on tremor was modulated by expectation, i.e. tremor decreased (placebo response) or increased (nocebo response) by at least 10% as compared to the control condition while no significant effect was observed for the overall group. Interestingly, nocebo responders in MedON were additionally characterized by significant impairment in semantic verbal fluency. In contrast, bradykinesia was not affected by expectation. These results indicate that the therapeutic effect of STN-DBS on tremor can be modulated by expectation in a subgroup of patients and suggests that tremor is also among the parkinsonian symptoms responsive to placebo and nocebo interventions. While positive expectations enhanced the effect of STN-DBS by further decreasing the magnitude of tremor, negative expectations counteracted the therapeutic effect and at the same time exacerbated a side-effect often associated with STN

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

    PubMed Central

    Wojtecki, Lars; Storzer, Lena; Schnitzler, Alfons

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    Objective. The clinical effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) as a treatment for Parkinson’s disease are sensitive to the location of the DBS lead within the STN. New high density (HD) lead designs have been created which are hypothesized to provide additional degrees of freedom in shaping the stimulating electric field. The objective of this study is to compare the performances of a new HD lead with a conventional cylindrical contact (CC) lead. Approach. A computational model, consisting of a finite element electric field model combined with multi-compartment neuron and axon models representing different neural populations in the subthalamic region, was used to evaluate the two leads. We compared ring-mode and steering-mode stimulation with the HD lead to single contact stimulation with the CC lead. These stimulation modes were tested for the lead: (1) positioned in the centroid of the STN, (2) shifted 1 mm towards the internal capsule (IC), and (3) shifted 2 mm towards the IC. Under these conditions, we quantified the number of STN neurons that were activated without activating IC fibers, which are known to cause side-effects. Main results. The modeling results show that the HD lead is able to mimic the stimulation effect of the CC lead. Additionally, in steering-mode stimulation there was a significant increase of activated STN neurons compared to the CC mode. Significance. From the model simulations we conclude that the HD lead in steering-mode with optimized stimulation parameter selection can stimulate more STN cells. Next, the clinical impact of the increased number of activated STN cells should be tested and balanced across the increased complexity of identifying the optimized stimulation parameter settings for the HD lead.

  2. Unilateral Subthalamic Nucleus Stimulation Has a Measurable Ipsilateral Effect on Rigidity And Bradykinesia in Parkinson Disease

    PubMed Central

    Tabbal, Samer D.; Ushe, Mwiza; Mink, Jonathan W.; Revilla, Fredy J.; Wernle, Angie R.; Hong, Minna; Karimi, Morvarid; Perlmutter, Joel S.

    2008-01-01

    Background Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function in Parkinson disease (PD). However, little is known about the quantitative effects on motor behavior of unilateral STN DBS. Methods In 52 PD subjects with STN DBS, we quantified in a double-blinded manner rigidity (n= 42), bradykinesia (n= 38), and gait speed (n= 45). Subjects were tested in four DBS conditions: both on, left on, right on and both off. A force transducer was used to measure rigidity across the elbow, and gyroscopes were used to measure angular velocity of hand rotations for bradykinesia. About half of the subjects were rated using the Unified Parkinson Disease Rating Scale (part III) motor scores for arm rigidity and repetitive hand rotation simultaneously during the kinematic measurements. Subjects were timed walking 25 feet. Results All subjects had significant improvement with bilateral STN DBS. Contralateral, ipsilateral and bilateral stimulation significantly reduced rigidity and bradykinesia. Bilateral stimulation improved rigidity more than unilateral stimulation of either side, but there was no significant difference between ipsilateral and contralateral stimulation. Although bilateral stimulation also increased hand rotation velocity more than unilateral stimulation of either side, contralateral stimulation increased hand rotation significantly more than ipsilateral stimulation. All stimulation conditions improved walking time but bilateral stimulation provided the greatest improvement. Conclusions Unilateral STN DBS decreased rigidity and bradykinesia contralaterally as well ipsilaterally. As expected, bilateral DBS improved gait more than unilateral DBS. These findings suggest that unilateral STN DBS alters pathways that affect rigidity and bradykinesia bilaterally but do not support the clinical use of unilateral STN DBS since bilateral DBS clearly provides greater benefit. PMID:18329019

  3. Buspirone requires the intact nigrostriatal pathway to reduce the activity of the subthalamic nucleus via 5-HT1A receptors.

    PubMed

    Sagarduy, A; Llorente, J; Miguelez, C; Morera-Herreras, T; Ruiz-Ortega, J A; Ugedo, L

    2016-03-01

    The most effective treatment for Parkinson's disease (PD), l-DOPA, induces dyskinesia after prolonged use. We have previously shown that in 6-hydroxydopamine (6-OHDA) lesioned rats rendered dyskinetic by prolonged l-DOPA administration, lesion of the subthalamic nucleus (STN) reduces not only dyskinesias but also buspirone antidyskinetic effect. This study examined the effect of buspirone on STN neuron activity. Cell-attached recordings in parasagittal slices from naïve rats showed that whilst serotonin excited the majority of STN neurons, buspirone showed an inhibitory main effect but only in 27% of the studied cells which was prevented by the 5-HT1A receptor selective antagonist WAY-100635. Conversely, single-unit extracellular recordings were performed in vivo on STN neurons from four different groups, i.e., control, chronically treated with l-DOPA, 6-OHDA lesioned and lesioned treated with l-DOPA (dyskinetic) rats. In control animals, systemic-buspirone administration decreased the firing rate in a dose-dependent manner in every cell studied. This effect, prevented by WAY-100635, was absent in 6-OHDA lesioned rats and was not modified by prolonged l-DOPA administration. Altogether, buspirone in vivo reduces consistently the firing rate of the STN neurons through 5-HT1A receptors whereas ex vivo buspirone seems to affect only a small population of STN neurons. Furthermore, the lack of effect of buspirone in 6-OHDA lesioned rats, suggests the requirement of not only the activation of 5-HT1A receptors but also an intact nigrostriatal pathway for buspirone to inhibit the STN activity. PMID:26687972

  4. Metabolic correlates of subthalamic nucleus activity in Parkinson's disease.

    PubMed

    Lin, Tanya P; Carbon, Maren; Tang, Chengke; Mogilner, Alon Y; Sterio, Djordje; Beric, Aleksandar; Dhawan, Vijay; Eidelberg, David

    2008-05-01

    Overactivity of subthalamic nucleus (STN) neurons is a consistent feature of Parkinson's disease (PD) and is a target of therapy for this disorder. However, the relationship of STN firing rate to regional brain function is not known. We scanned 17 PD patients with (18)F-fluorodeoxyglucose (FDG) PET to measure resting glucose metabolism before the implantation of STN deep brain stimulation electrodes. Spontaneous STN firing rates were recorded during surgery and correlated with preoperative regional glucose metabolism on a voxel-by-voxel basis. We also examined the relationship between firing rate and the activity of metabolic brain networks associated with the motor and cognitive manifestations of the disease. Mean firing rates were 47.2 +/- 6.1 and 48.7 +/- 8.5 Hz for the left and right hemispheres, respectively. These measures correlated (P < 0.007) with glucose metabolism in the putamen and globus pallidus, which receive projections from this structure. Significant correlations (P < 0.0005) were also evident in the primary motor (BA4) and dorsolateral prefrontal (BA46/10) cortical areas. The activity of both the motor (P < 0.0001) and the cognitive (P < 0.006) PD-related metabolic networks was elevated in these patients. STN firing rates correlated with the activity of the former (P < 0.007) but not the latter network (P = 0.39). The findings suggest that the functional pathways associated with motor disability in PD are linked to the STN firing rate. These pathways are likely to mediate the clinical benefit that is seen following targeted STN interventions for this disease. PMID:18400841

  5. GABAA-receptor activation in the subthalamic nucleus compensates behavioral asymmetries in the hemiparkinsonian rat.

    PubMed

    Petri, David; Pum, Martin; Vesper, Jan; Huston, Joseph P; Schnitzler, Alfons

    2013-09-01

    The subthalamic nucleus (STN) has a pivotal role in the pathophysiology of Parkinson's disease (PD). Modulation of STN activity (by lesions, pharmacological or electrical stimulation) has been shown to improve motor parameters in PD patients and in animal models of PD. In an attempt to characterize the neurochemical bases for such antiparkinsonian action, we address specific neurotransmitter systems via local pharmacological manipulation of the STN in hemiparkinsonian rats. Here, we have focused on the GABAergic and glutamatergic receptors in the STN. In animals with unilateral 6-hydroxydopamine lesions of the nigro-striatal tract, we administered either the selective GABAA-agonist muscimol (0.5 μg and 1.0 μg), the non-competitive N-methyl-d-aspartate (NMDA)-antagonist MK-801 (dizocilpine; 2.5 μg), or vehicle (0.25 μl) into the STN. The effects of GABAergic and glutamatergic modulation of the STN on motor parameters were assessed by gauging rotational behavior and locomotion. Application of muscimol ipsilateral to the side of dopamine-depletion influenced turning behavior in a dose-dependent fashion, with the low dose re-adjusting turning behavior to a non-biased distribution, and the high dose evoking contraversive turning. The administration of MK-801 did not have such effects. These findings give evidence for the involvement of GABAergic activation in the STN in the compensation of motor asymmetries in the hemiparkinsonian rat, whereas N-methyl-d-aspartate (NMDA)-antagonism was ineffective in this model of PD. PMID:23727148

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

    PubMed

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

    2016-01-01

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

  7. Subthalamic nucleus activity in the awake hemiparkinsonian rat: relationships with motor and cognitive networks.

    PubMed

    Delaville, Claire; McCoy, Alex J; Gerber, Colin M; Cruz, Ana V; Walters, Judith R

    2015-04-29

    Oscillatory activity in both beta and gamma ranges has been recorded in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients and linked to motor function, with beta activity considered antikinetic, and gamma activity, prokinetic. However, the extent to which nonmotor networks contribute to this activity is unclear. This study uses hemiparkinsonian rats performing a treadmill walking task to compare synchronized STN local field potential (LFP) activity with activity in motor cortex (MCx) and medial prefrontal cortex (mPFC), areas involved in motor and cognitive processes, respectively. Data show increases in STN and MCx 29-36 Hz LFP spectral power and coherence after dopamine depletion, which are reduced by apomorphine and levodopa treatments. In contrast, recordings from mPFC 3 weeks after dopamine depletion failed to show peaks in 29-36 Hz LFP power. However, mPFC and STN both showed peaks in the 45-55 Hz frequency range in LFP power and coherence during walking before and 21 days after dopamine depletion. Interestingly, power in this low gamma range was transiently reduced in both mPFC and STN after dopamine depletion but recovered by day 21. In contrast to the 45-55 Hz activity, the amplitude of the exaggerated 29-36 Hz rhythm in the STN was modulated by paw movement. Furthermore, as in PD patients, after dopamine treatment a third band (high gamma) emerged in the lesioned hemisphere. The results suggest that STN integrates activity from both motor and cognitive networks in a manner that varies with frequency, behavioral state, and the integrity of the dopamine system. PMID:25926466

  8. Cognition and Depression Following Deep Brain Stimulation of the Subthalamic Nucleus and Globus Pallidus Pars Internus in Parkinson's Disease: A Meta-Analysis.

    PubMed

    Combs, Hannah L; Folley, Bradley S; Berry, David T R; Segerstrom, Suzanne C; Han, Dong Y; Anderson-Mooney, Amelia J; Walls, Brittany D; van Horne, Craig

    2015-12-01

    Parkinson's disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel p-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated. PMID:26459361

  9. Subthalamic Nucleus Activity in the Awake Hemiparkinsonian Rat: Relationships with Motor and Cognitive Networks

    PubMed Central

    Delaville, Claire; McCoy, Alex J.; Gerber, Colin M.; Cruz, Ana V.

    2015-01-01

    Oscillatory activity in both beta and gamma ranges has been recorded in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients and linked to motor function, with beta activity considered antikinetic, and gamma activity, prokinetic. However, the extent to which nonmotor networks contribute to this activity is unclear. This study uses hemiparkinsonian rats performing a treadmill walking task to compare synchronized STN local field potential (LFP) activity with activity in motor cortex (MCx) and medial prefrontal cortex (mPFC), areas involved in motor and cognitive processes, respectively. Data show increases in STN and MCx 29–36 Hz LFP spectral power and coherence after dopamine depletion, which are reduced by apomorphine and levodopa treatments. In contrast, recordings from mPFC 3 weeks after dopamine depletion failed to show peaks in 29–36 Hz LFP power. However, mPFC and STN both showed peaks in the 45–55 Hz frequency range in LFP power and coherence during walking before and 21 days after dopamine depletion. Interestingly, power in this low gamma range was transiently reduced in both mPFC and STN after dopamine depletion but recovered by day 21. In contrast to the 45–55 Hz activity, the amplitude of the exaggerated 29–36 Hz rhythm in the STN was modulated by paw movement. Furthermore, as in PD patients, after dopamine treatment a third band (high gamma) emerged in the lesioned hemisphere. The results suggest that STN integrates activity from both motor and cognitive networks in a manner that varies with frequency, behavioral state, and the integrity of the dopamine system. PMID:25926466

  10. The Prefrontal Cortex Achieves Inhibitory Control by Facilitating Subcortical Motor Pathway Connectivity

    PubMed Central

    Hughes, Laura E.; Anderson, Michael C.; Rowe, James B.

    2015-01-01

    Communication between the prefrontal cortex and subcortical nuclei underpins the control and inhibition of behavior. However, the interactions in such pathways remain controversial. Using a stop-signal response inhibition task and functional imaging with analysis of effective connectivity, we show that the lateral prefrontal cortex influences the strength of communication between regions in the frontostriatal motor system. We compared 20 generative models that represented alternative interactions between the inferior frontal gyrus, presupplementary motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during response inhibition. Bayesian model selection revealed that during successful response inhibition, the inferior frontal gyrus modulates an excitatory influence of the preSMA on the STN, thereby amplifying the downstream polysynaptic inhibition from the STN to the motor cortex. Critically, the strength of the interaction between preSMA and STN, and the degree of modulation by the inferior frontal gyrus, predicted individual differences in participants' stopping performance (stop-signal reaction time). We then used diffusion-weighted imaging with tractography to assess white matter structure in the pathways connecting these three regions. The mean diffusivity in tracts between preSMA and the STN, and between the inferior frontal gyrus and STN, also predicted individual differences in stopping efficiency. Finally, we found that white matter structure in the tract between preSMA and STN correlated with effective connectivity of the same pathway, providing important cross-modal validation of the effective connectivity measures. Together, the results demonstrate the network dynamics and modulatory role of the prefrontal cortex that underpin individual differences in inhibitory control. PMID:25589771

  11. The antidepressant effects of ventromedial prefrontal cortex stimulation is associated with neural activation in the medial part of the subthalamic nucleus.

    PubMed

    Lim, Lee Wei; Janssen, Marcus L F; Kocabicak, Ersoy; Temel, Yasin

    2015-02-15

    The nucleus accumbens (NAc), ventromedial prefrontal cortex (vmPFC), and cingulate gyrus (Cg) are key regions in the control of mood-related behaviors. Electrical stimulation of these areas induces antidepressant-like effects in both patients and animal models. Another structure whose limbic connections are receiving more interest in the context of mood-related behaviors is the medial part of the subthalamic nucleus (STN). Here, we tested the hypothesis that the mood-related effects of NAc, vmPFC, and Cg are accompanied by changes in the neural activity of the STN. We performed high-frequency stimulation (HFS) of the NAc, vmPFC, and Cg. Animals were behaviorally tested for hedonia and forced swim immobility; and the cellular activities in the different parts of the STN were assessed by means of c-Fos immunoreactivity (c-Fos-ir). Our results showed that HFS of the NAc and vmPFC, but not Cg reduced anhedonic-like and forced swim immobility behaviors. Interestingly, there was a significant increase of c-Fos-ir in the medial STN with HFS of the vmPFC, but not the NAc and Cg as compared to the sham. Correlation analysis showed that the medial STN is associated with the antidepressant-like behaviors in vmPFC HFS animals. No behavioral correlation was found with respect to behavioral outcome and activity in the lateral STN. In conclusion, HFS of the vmPFC induced profound antidepressant-like effects with enhanced neural activity in the medial part of the STN. PMID:25446757

  12. Globus pallidus neurons dynamically regulate the activity pattern of subthalamic nucleus neurons through the frequency-dependent activation of postsynaptic GABAA and GABAB receptors.

    PubMed

    Hallworth, Nicholas E; Bevan, Mark D

    2005-07-01

    Reciprocally connected GABAergic neurons of the globus pallidus (GP) and glutamatergic neurons of the subthalamic nucleus (STN) are a putative generator of pathological rhythmic burst firing in Parkinson's disease (PD). Burst firing of STN neurons may be driven by rebound depolarization after barrages of GABA(A) receptor (GABA(A)R)-mediated IPSPs arising from pallidal fibers. To determine the conditions under which pallidosubthalamic transmission activates these and other postsynaptic GABARs, a parasagittal mouse brain slice preparation was developed in which pallidosubthalamic connections were preserved. Intact connectivity was first confirmed through the injection of a neuronal tracer into the GP. Voltage-clamp and gramicidin-based perforated-patch current-clamp recordings were then used to study the relative influences of GABA(A)R- and GABA(B)R-mediated pallidosubthalamic transmission on STN neurons. Spontaneous phasic, but not tonic, activation of postsynaptic GABA(A)Rs reduced the frequency and disrupted the rhythmicity of autonomous firing in STN neurons. However, postsynaptic GABA(B)Rs were only sufficiently activated to impact STN firing when pallidosubthalamic transmission was elevated or pallidal fibers were synchronously activated by electrical stimulation. In a subset of neurons, rebound burst depolarizations followed high-frequency, synchronous stimulation of pallidosubthalamic fibers. Although GABA(B)R-mediated hyperpolarization was itself sufficient to generate rebound bursts, coincident activation of postsynaptic GABA(A)Rs produced longer and more intense burst firing. These findings elucidate a novel route through which burst activity can be generated in the STN, and suggest that GABARs on STN neurons could act in a synergistic manner to generate abnormal burst activity in PD. PMID:16000620

  13. Decisions Made with Less Evidence Involve Higher Levels of Corticosubthalamic Nucleus Theta Band Synchrony.

    PubMed

    Zavala, Baltazar; Tan, Huiling; Little, Simon; Ashkan, Keyoumars; Green, Alexander L; Aziz, Tipu; Foltynie, Thomas; Zrinzo, Ludvic; Zaghloul, Kareem; Brown, Peter

    2016-06-01

    The switch between automatic action selection and more controlled forms of decision-making is a dynamic process thought to involve both cortical and subcortical structures. During sensory conflict, medial pFC oscillations in the theta band (<8 Hz) drive those of the subthalamic nucleus (STN), and this is thought to increase the threshold of evidence needed for one competing response to be selected over another. Here, we were interested in testing whether STN activity is also altered by the rate at which evidence is presented during a congruent dot motion task absent of any explicit sensory conflict. By having a series of randomly moving dots gradually transform to congruent motion at three different rates (slow, medium, fast), we were able to show that a slower rate increased the time it took participants to make a response but did not alter the total amount of evidence that was integrated before the response. Notably, this resulted in a decision being made with a lower amount of instantaneous evidence during the slow and medium trials. Consistent with the idea that medial pFC-STN activity is involved in executing cognitive control, the higher levels of ambiguity during these trials were associated with increased theta band synchrony between the cortex and the STN, with the cortical oscillations Granger-causal to those of the STN. These results further confirm the involvement of the STN in decision-making and suggest that the disruption of this network may underlie some of the unwanted cognitive deficits associated with STN deep brain stimulation. PMID:26845109

  14. High Frequency Stimulation of the Subthalamic Nucleus Leads to Presynaptic GABA(B)-Dependent Depression of Subthalamo-Nigral Afferents

    PubMed Central

    Dvorzhak, Anton; Gertler, Christoph; Harnack, Daniel; Grantyn, Rosemarie

    2013-01-01

    Patients with akinesia benefit from chronic high frequency stimulation (HFS) of the subthalamic nucleus (STN). Among the mechanisms contributing to the therapeutic success of HFS-STN might be a suppression of activity in the output region of the basal ganglia. Indeed, recordings in the substantia nigra pars reticulata (SNr) of fully adult mice revealed that HFS-STN consistently produced a reduction of compound glutamatergic excitatory postsynaptic currents at a time when the tetrodotoxin-sensitive components of the local field potentials had already recovered after the high frequency activation. These observations suggest that HFS-STN not only alters action potential conduction on the way towards the SNr but also modifies synaptic transmission within the SNr. A classical conditioning-test paradigm was then designed to better separate the causes from the indicators of synaptic depression. A bipolar platinum-iridium macroelectrode delivered conditioning HFS trains to a larger group of fibers in the STN, while a separate high-ohmic glass micropipette in the rostral SNr provided test stimuli at minimal intensity to single fibers. The conditioning-test interval was set to 100 ms, i.e. the time required to recover the excitability of subthalamo-nigral axons after HFS-STN. The continuity of STN axons passing from the conditioning to the test sites was examined by an action potential occlusion test. About two thirds of the subthalamo-nigral afferents were occlusion-negative, i.e. they were not among the fibers directly activated by the conditioning STN stimulation. Nonetheless, occlusion-negative afferents exhibited signs of presynaptic depression that could be eliminated by blocking GABA(B) receptors with CGP55845 (1 µM). Further analysis of single fiber-activated responses supported the proposal that the heterosynaptic depression of synaptic glutamate release during and after HFS-STN is mainly caused by the tonic release of GABA from co-activated striato

  15. Soft Tissue Necrosis in Head and Neck Cancer Patients After Transoral Robotic Surgery or Wide Excision With Primary Closure Followed by Radiation Therapy

    PubMed Central

    Yun Hee, Lee; Kim, Yeon Sil; Chung, Mi Joo; Yu, Mina; Jung, So Lyung; Yoo, Ie Ryung; Lee, Youn Soo; Kim, Min Sik; Sun, Dong Il; Kang, Jin Hyung

    2016-01-01

    Abstract Risk factors were evaluated for surgical bed soft tissue necrosis (STN) in head and neck cancer patients treated with postoperative radiation therapy (PORT) after transoral robotic surgery (TORS) or wide excision with primary closure. Sixty-seven patients were evaluated. STN was defined as ulceration and necrosis of the surgical bed or persistently unhealed high-grade acute mucositis with pain after PORT. The median RT dose of primary site was 63.6 Gy (range, 45–67.15 Gy) with 2 Gy/fx (range 1.8–2.2 Gy/fx). Total 41 patients (61.2%) were treated with concurrent chemoradiotherapy. The median follow-up period was 26 months. STN was diagnosed in 13 patients (19.4%). Most of the patients were treated with oral steroids, antibiotics, and analgesics and the lesions were eventually improved (median of 6 months after PORT). STN did not influence local control. A depth of invasion (DOI > 1.4 cm, odds ratio [OR] 14.04, p = 0.004) and maximum dose/fraction (CTVpmax/fx > 2.3 Gy, OR 6.344, p = 0.043) and grade 3 acute mucositis (OR 6.090, p = 0.054) were related to STN. The 12 (23.5%) of 51 oropharyngeal cancer patients presented STN, and the risk factors were DOI > 1.2 cm (OR 21.499, P = 0.005), CTVpmax/fx > 2.3 Gy (OR 12.972, P = 0.021) and grade 3 acute mucositis (OR 10.537, P = 0.052). Patients treated with TORS or WE with primary closure followed by PORT had a high risk of surgical bed STN. STN risk factors included DOI (>1.2–1.4 cm) and CTVpmax/fx (>2.3 Gy). Radiation therapy after TORS must be carefully designed to prevent STN. PMID:26945367

  16. Three-dimensional structure of the actinoporin sticholysin I. Influence of long-distance effects on protein function.

    PubMed

    García-Linares, Sara; Castrillo, Inés; Bruix, Marta; Menéndez, Margarita; Alegre-Cebollada, Jorge; Martínez-del-Pozo, Álvaro; Gavilanes, José G

    2013-04-01

    Actinoporins are water-soluble proteins with the ability to form pores upon insertion into biological membranes. They constitute a family of proteins with high degree of sequence identities but different hemolytic activities, suggesting that minor conformational arrangements result in major functional changes. A good example of this situation is the sea anemone Stichodactyla helianthus which produces two very similar actinoporins, sticholysins I (StnI) and II (StnII), but of very different hemolytic efficiency. Within this idea, given that the high resolution three-dimensional structure of StnII is already known, we have now solved that one corresponding to StnI in order to analyze the influence of particular residues on the conformation and activity of these proteins. In addition, random mutagenesis has been also used to produce five less hemolytic variants of StnI. All these mutations map to functionally relevant regions because they are probably involved in conformational changes associated with pore formation, which take place after membrane binding, and involve long-distance rearrangements of the polypeptide chain of actinoporins. PMID:23376038

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

    PubMed Central

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

    2009-01-01

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

  18. Continuous High-Frequency Stimulation of the Subthalamic Nucleus Improves Cell Survival and Functional Recovery Following Dopaminergic Cell Transplantation in Rodents.

    PubMed

    Furlanetti, Luciano L; Cordeiro, Joacir Graciolli; Cordeiro, Karina Kohn; García, Joanna A; Winkler, Christian; Lepski, Guilherme A; Coenen, Volker A; Nikkhah, Guido; Döbrössy, Máté D

    2015-01-01

    Subthalamic nucleus (STN) high-frequency stimulation (HFS) is a routine treatment in Parkinson's disease (PD), with confirmed long-term benefits. An alternative, but still experimental, treatment is cell replacement and restorative therapy based on transplanted dopaminergic neurons. The current experiment evaluated the potential synergy between neuromodulation and grafting by studying the effect of continuous STN-HFS on the survival, integration, and functional efficacy of ventral mesencephalic dopaminergic precursors transplanted into a unilateral 6-hydroxydopamine medial forebrain bundle lesioned rodent PD model. One group received continuous HFS of the ipsilateral STN starting a week prior to intrastriatal dopaminergic neuron transplantation, whereas the sham-stimulated group did not receive STN-HFS but only dopaminergic grafts. A control group was neither lesioned nor transplanted. Over the following 7 weeks, the animals were probed on a series of behavioral tasks to evaluate possible graft and/or stimulation-induced functional effects. Behavioral and histological data suggest that STN-HFS significantly increased graft cell survival, graft-host integration, and functional recovery. These findings might open an unexplored road toward combining neuromodulative and neuroregenerative strategies to treat severe neurologic conditions. PMID:25857428

  19. Optimal target localization for subthalamic stimulation in patients with Parkinson disease

    PubMed Central

    Schüpbach, Michael; Czernecki, Virginie; Karachi, Carine; Fernandez-Vidal, Sara; Golmard, Jean-Louis; Serra, Giulia; Navarro, Soledad; Welaratne, Arlette; Hartmann, Andréas; Mesnage, Valérie; Pineau, Fanny; Cornu, Philippe; Pidoux, Bernard; Worbe, Yulia; Zikos, Panayiotis; Grabli, David; Galanaud, Damien; Bonnet, Anne-Marie; Belaid, Hayat; Dormont, Didier; Vidailhet, Marie; Mallet, Luc; Houeto, Jean-Luc; Bardinet, Eric; Yelnik, Jerome; Agid, Yves

    2014-01-01

    Objective: To further determine the causes of variable outcome from deep brain stimulation of the subthalamic nucleus (DBS-STN) in patients with Parkinson disease (PD). Methods: Data were obtained from our cohort of 309 patients with PD who underwent DBS-STN between 1996 and 2009. We examined the relationship between the 1-year motor, cognitive, and psychiatric outcomes and (1) preoperative PD clinical features, (2) MRI measures, (3) surgical procedure, and (4) locations of therapeutic contacts. Results: Pre- and postoperative results were obtained in 262 patients with PD. The best motor outcome was obtained when stimulating contacts were located within the STN as compared with the zona incerta (64% vs 49% improvement). Eighteen percent of the patients presented a postoperative cognitive decline, which was found to be principally related to the surgical procedure. Other factors predictive of poor cognitive outcome were perioperative confusion and psychosis. Nineteen patients showed a stimulation-induced hypomania, which was related to both the form of the disease (younger age, shorter disease duration, higher levodopa responsiveness) and the ventral contact location. Postoperative depression was more frequent in patients already showing preoperative depressive and/or residual axial motor symptoms. Conclusion: In this homogeneous cohort of patients with PD, we showed that (1) the STN is the best target to improve motor symptoms, (2) postoperative cognitive deficit is mainly related to the surgery itself, and (3) stimulation-induced hypomania is related to a combination of both the disease characteristics and a more ventral STN location. PMID:24647024

  20. Deep Brain Stimulation of the Subthalamic Nucleus Improves Reward-Based Decision-Learning in Parkinson's Disease

    PubMed Central

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

    2011-01-01

    Recently, the subthalamic nucleus (STN) has been shown to be critically involved in decision-making, action selection, and motor control. Here we investigate the effect of deep brain stimulation (DBS) of the STN on reward-based decision-learning in patients diagnosed with Parkinson's disease (PD). We determined computational measures of outcome evaluation and reward prediction from PD patients who performed a probabilistic reward-based decision-learning task. In previous work, these measures covaried with activation in the nucleus caudatus (outcome evaluation during the early phases of learning) and the putamen (reward prediction during later phases of learning). We observed that stimulation of the STN motor regions in PD patients served to improve reward-based decision-learning, probably through its effect on activity in frontostriatal motor loops (prominently involving the putamen and, hence, reward prediction). In a subset of relatively younger patients with relatively shorter disease duration, the effects of DBS appeared to spread to more cognitive regions of the STN, benefiting loops that connect the caudate to various prefrontal areas importantfor outcome evaluation. These results highlight positive effects of STN stimulation on cognitive functions that may benefit PD patients in daily-life association-learning situations. PMID:21519377

  1. Maximal subthalamic beta hypersynchrony of the local field potential in Parkinson's disease is located in the central region of the nucleus.

    PubMed

    de Solages, Camille; Hill, Bruce C; Yu, Hong; Henderson, Jaimie M; Bronte-Stewart, Helen

    2011-12-01

    A pathological marker of Parkinson's disease is the existence of abnormal synchrony of neuronal activity within the beta frequency range (13-35 Hz) in the subthalamic nucleus (STN). Recent studies examining the topography of this rhythm have located beta hypersynchrony in the most dorsal part of the STN. In contrast, this study of the topography of the local field potential beta oscillations in 18 STNs with a 1 mm spatial resolution revealed that the point of maximal beta hypersynchrony was located at 53 ± 24% of the trajectory span from the dorsal to the ventral borders of the STN (corresponding to a 3.0 ± 1.6 mm depth for a 5.9 ± 0.75 mm STN span). This suggests that maximal beta hypersynchrony is located in the central region of the nucleus and that further investigation should be done before using STN spectral profiles as an indicator for guiding placement of deep brain stimulation leads. PMID:21205981

  2. Beta-coupled high-frequency activity and beta-locked neuronal spiking in the subthalamic nucleus of Parkinson's disease.

    PubMed

    Yang, Andrew I; Vanegas, Nora; Lungu, Codrin; Zaghloul, Kareem A

    2014-09-17

    Beta frequency (13-30 Hz) oscillatory activity in the subthalamic nucleus (STN) of Parkinson's disease (PD) has been shown to influence the temporal dynamics of high-frequency oscillations (HFOs; 200-500 Hz) and single neurons, potentially compromising the functional flexibility of the motor circuit. We examined these interactions by simultaneously recording both local field potential and single-unit activity from the basal ganglia of 15 patients with PD during deep brain stimulation (DBS) surgery of the bilateral STN. Phase-amplitude coupling (PAC) in the STN was specific to beta phase and HFO amplitude, and this coupling was strongest at the dorsal STN border. We found higher beta-HFO PAC near DBS lead contacts that were clinically effective compared with the remaining non-effective contacts, indicating that PAC may be predictive of response to STN DBS. Neuronal spiking was locked to the phase of 8-30 Hz oscillations, and the spatial topography of spike-phase locking (SPL) was similar to that of PAC. Comparisons of PAC and SPL showed a lack of spatiotemporal correlations. Beta-coupled HFOs and field-locked neurons had different preferred phase angles and did not co-occur within the same cycle of the modulating oscillation. Our findings provide additional support that beta-HFO PAC may be central to the pathophysiology of PD and suggest that field-locked neurons alone are not sufficient for the emergence of beta-coupled HFOs. PMID:25232117

  3. The influence of subthalamic nucleus stimulation on pragmatic language production in Parkinson's disease.

    PubMed

    Van Lier, Sam; Batens, Katja; Santens, Patrick; Van Roost, Dirk; Van Herreweghe, Mieke; De Letter, Miet

    2016-06-01

    While the influence of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the comprehension of pragmatic language in Parkinson's disease (PD) has been the focus of studies, its impact on production, however, has yet to be elucidated. (1) Investigating the inf luence of DBS STN on pragmatic language production in spontaneous speech by comparing different stimulation conditions and (2) evaluating the effect of asymmetric dopaminergic denervation. This paper included 18 patients with advanced idiopathic PD with STN DBS. [Ten PD patients with predominantly left hemispheric dopamine denervation (PD-left) and eight PD patients with predominantly right-hemispheric dopamine denervation (PD-right).] The pragmatic components 'communicative functions' and 'conversational skills' were evaluated by analysing the spontaneous language production in four stimulation conditions. STN stimulation did not appear to influence the pragmatic production skills. Only when asymmetric dopamine depletion was taken into account the parameter 'giving an explanation' interaction was detectable. STN DBS appears to have some influence on the production of pragmatic language depending on asymmetric dopaminergic denervation. Suggestions are made for further research of pragmatic production in Parkinson's disease. PMID:26442686

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

    PubMed Central

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

    2015-01-01

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

  5. Overlapping functions of stonin 2 and SV2 in sorting of the calcium sensor synaptotagmin 1 to synaptic vesicles

    PubMed Central

    Kaempf, Natalie; Kochlamazashvili, Gaga; Puchkov, Dmytro; Maritzen, Tanja; Bajjalieh, Sandra M.; Kononenko, Natalia L.; Haucke, Volker

    2015-01-01

    Neurotransmission involves the calcium-regulated exocytic fusion of synaptic vesicles (SVs) and the subsequent retrieval of SV membranes followed by reformation of properly sized and shaped SVs. An unresolved question is whether each SV protein is sorted by its own dedicated adaptor or whether sorting is facilitated by association between different SV proteins. We demonstrate that endocytic sorting of the calcium sensor synaptotagmin 1 (Syt1) is mediated by the overlapping activities of the Syt1-associated SV glycoprotein SV2A/B and the endocytic Syt1-adaptor stonin 2 (Stn2). Deletion or knockdown of either SV2A/B or Stn2 results in partial Syt1 loss and missorting of Syt1 to the neuronal surface, whereas deletion of both SV2A/B and Stn2 dramatically exacerbates this phenotype. Selective missorting and degradation of Syt1 in the absence of SV2A/B and Stn2 impairs the efficacy of neurotransmission at hippocampal synapses. These results indicate that endocytic sorting of Syt1 to SVs is mediated by the overlapping activities of SV2A/B and Stn2 and favor a model according to which SV protein sorting is guarded by both cargo-specific mechanisms as well as association between SV proteins. PMID:26015569

  6. Older Candidates for Subthalamic Deep Brain Stimulation in Parkinson's Disease Have a Higher Incidence of Psychiatric Serious Adverse Events

    PubMed Central

    Cozac, Vitalii V.; Ehrensperger, Michael M.; Gschwandtner, Ute; Hatz, Florian; Meyer, Antonia; Monsch, Andreas U.; Schuepbach, Michael; Taub, Ethan; Fuhr, Peter

    2016-01-01

    Objective: To investigate the incidence of serious adverse events (SAE) of subthalamic deep brain stimulation (STN-DBS) in elderly patients with Parkinson's disease (PD). Methods: We investigated a group of 26 patients with PD who underwent STN-DBS at mean age 63.2 ± 3.3 years. The operated patients from the EARLYSTIM study (mean age 52.9 ± 6.6) were used as a comparison group. Incidences of SAE were compared between these groups. Results: A higher incidence of psychosis and hallucinations was found in these elderly patients compared to the younger patients in the EARLYSTIM study (p < 0.01). Conclusions: The higher incidence of STN-DBS-related psychiatric complications underscores the need for comprehensive psychiatric pre- and postoperative assessment in older DBS candidates. However, these psychiatric SAE were transient, and the benefits of DBS clearly outweighed its adverse effects. PMID:27375478

  7. Subthalamic nucleus stimulation reverses mediofrontal influence over decision threshold.

    PubMed

    Cavanagh, James F; Wiecki, Thomas V; Cohen, Michael X; Figueroa, Christina M; Samanta, Johan; Sherman, Scott J; Frank, Michael J

    2011-11-01

    It takes effort and time to tame one's impulses. Although medial prefrontal cortex (mPFC) is broadly implicated in effortful control over behavior, the subthalamic nucleus (STN) is specifically thought to contribute by acting as a brake on cortico-striatal function during decision conflict, buying time until the right decision can be made. Using the drift diffusion model of decision making, we found that trial-to-trial increases in mPFC activity (EEG theta power, 4-8 Hz) were related to an increased threshold for evidence accumulation (decision threshold) as a function of conflict. Deep brain stimulation of the STN in individuals with Parkinson's disease reversed this relationship, resulting in impulsive choice. In addition, intracranial recordings of the STN area revealed increased activity (2.5-5 Hz) during these same high-conflict decisions. Activity in these slow frequency bands may reflect a neural substrate for cortico-basal ganglia communication regulating decision processes. PMID:21946325

  8. The Evolution of the Society of Trauma Nurses' Leadership Institute.

    PubMed

    Krichten, Amy; Kyle, Amber

    2015-01-01

    The Society of Trauma Nurses (STN) understands the increasing complexity of trauma care and the vital leadership role nurses play. In 2009, the STN took the initiative to form a Leadership Committee tasked with researching the possibility of developing a mechanism to offer trauma leaders opportunities in leadership development. Investigation and collaboration among the committee members, with input from the Board of Directors and the organization's executive director, resulted in the STN Leadership Institute. The Leadership Institute design is to equip trauma nurses with the tools needed to effectively lead from the bedside to the boardroom and beyond through web-based modules. Operationalization of the plan took intense focus and dedicated leadership. Following a pilot study, the initial cohort ran the first quarter of 2015. Because of the positive feedback and identified opportunities for improvement, the program will continue to be offered with further expansion planning underway. PMID:26574939

  9. Telomere Capping Proteins are Structurally Related to RPA with an additional Telomere-Specific Domain

    SciTech Connect

    Gelinas, A.; Paschini, M; Reyes, F; Heroux, A; Batey, R; Lundblad, V; Wuttke, D

    2009-01-01

    Telomeres must be capped to preserve chromosomal stability. The conserved Stn1 and Ten1 proteins are required for proper capping of the telomere, although the mechanistic details of how they contribute to telomere maintenance are unclear. Here, we report the crystal structures of the C-terminal domain of the Saccharomyces cerevisiae Stn1 and the Schizosaccharomyces pombe Ten1 proteins. These structures reveal striking similarities to corresponding subunits in the replication protein A complex, further supporting an evolutionary link between telomere maintenance proteins and DNA repair complexes. Our structural and in vivo data of Stn1 identify a new domain that has evolved to support a telomere-specific role in chromosome maintenance. These findings endorse a model of an evolutionarily conserved mechanism of DNA maintenance that has developed as a result of increased chromosomal structural complexity.

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

    PubMed

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

    2014-07-01

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

  11. Increased extracellular dopamine and 5-hydroxytryptamine levels contribute to enhanced subthalamic nucleus neural activity during exhausting exercise.

    PubMed

    Hu, Y; Liu, X; Qiao, D

    2015-09-01

    The purpose of the study was to explore the mechanism underlying the enhanced subthalamic nucleus (STN) neural activity during exhausting exercise from the perspective of monoamine neurotransmitters and changes of their corresponding receptors. Rats were randomly divided into microdialysis and immunohistochemistry study groups. For microdialysis study, extracellular fluid of the STN was continuously collected with a microdialysis probe before, during and 90 min after one bout of exhausting exercise. Dopamine (DA) and 5-hydroxytryptamine (5-HT) levels were subsequently detected with high-performance liquid chromatography (HPLC). For immunohistochemistry study, the expression of DRD2 and HT2C receptors in the STN, before, immediately after and 90 min after exhaustion was detected through immunohistochemistry technique. Microdialysis study results showed that the extracellular DA and 5-HT neurotransmitters increased significantly throughout the procedure of exhausting exercise and the recovery period (P<0.05 or P<0.01). Immunohistochemistry study results showed that the expression levels of DRD2 and HT2C in the rat STN immediately after exhausting exercise and at the time point of 90 min after exhaustion were both higher than those of the rest condition, but the difference was not significant (P>0.05). Our results suggest that the increased extracellular DA and 5-HT in the STN might be one important factor leading to the enhanced STN neural activity and the development of fatigue during exhausting exercise. This study may essentially offer useful evidence for better understanding of the mechanism of the central type of exercise-induced fatigue. PMID:26424920

  12. Subthalamic Stimulation Reduces Vowel Space at the Initiation of Sustained Production: Implications for Articulatory Motor Control in Parkinson’s Disease

    PubMed Central

    Sidtis, John J.; Alken, Amy G.; Tagliati, Michele; Alterman, Ron; Van Lancker Sidtis, Diana

    2016-01-01

    Background: Stimulation of the subthalamic nuclei (STN) is an effective treatment for Parkinson’s disease, but complaints of speech difficulties after surgery have been difficult to quantify. Speech measures do not convincingly account for such reports. Objective: This study examined STN stimulation effects on vowel production, in order to probe whether DBS affects articulatory posturing. The objective was to compare positioning during the initiation phase with the steady prolongation phase by measuring vowel spaces for three “corner” vowels at these two time frames. Methods: Vowel space was measured over the initial 0.25 sec of sustained productions of high front (/i/), high back (/u/) and low vowels (/a/), and again during a 2 sec segment at the midpoint. Eight right-handed male subjects with bilateral STN stimulation and seven age-matched male controls were studied based on their participation in a larger study that included functional imaging. Mean values: age = 57±4.6 yrs; PD duration = 12.3±2.7 yrs; duration of DBS = 25.6±21.2 mos, and UPDRS III speech score = 1.6±0.7. STN subjects were studied off medication at their therapeutic DBS settings and again with their stimulators off, counter-balanced order. Results: Vowel space was larger in the initiation phase compared to the midpoint for both the control and the STN subjects off stimulation. With stimulation on, however, the initial vowel space was significantly reduced to the area measured at the mid-point. For the three vowels, the acoustics were differentially affected, in accordance with expected effects of front versus back position in the vocal tract. Conclusions: STN stimulation appears to constrain initial articulatory gestures for vowel production, raising the possibility that articulatory positions normally used in speech are similarly constrained. PMID:27003219

  13. Deep brain stimulation of the subthalamic nucleus preferentially alters the translational profile of striatopallidal neurons in an animal model of Parkinson's disease

    PubMed Central

    Visanji, Naomi P.; Kamali Sarvestani, Iman; Creed, Meaghan C.; Shams Shoaei, Zahra; Nobrega, José N.; Hamani, Clement; Hazrati, Lili-Naz

    2015-01-01

    Deep brain stimulation targeting the subthalamic nucleus (STN-DBS) is an effective surgical treatment for the motor symptoms of Parkinson's disease (PD), the precise neuronal mechanisms of which both at molecular and network levels remain a topic of debate. Here we employ two transgenic mouse lines, combining translating ribosomal affinity purification (TRAP) with bacterial artificial chromosome expression (Bac), to selectively identify changes in translational gene expression in either Drd1a-expressing striatonigral or Drd2-expressing striatopallidal medium spiny neurons (MSNs) of the striatum following STN-DBS. 6-hydroxydopamine lesioned mice received either 5 days stimulation via a DBS electrode implanted in the ipsilateral STN or 5 days sham treatment (no stimulation). Striatal polyribosomal RNA was selectively purified from either Drd2 or Drd1a MSNs using the TRAP method and gene expression profiling performed. We identified eight significantly altered genes in Drd2 MSNs (Vps33b, Ppp1r3c, Mapk4, Sorcs2, Neto1, Abca1, Penk1, and Gapdh) and two overlapping genes in Drd1a MSNs (Penk1 and Ppp1r3c) implicated in the molecular mechanisms of STN-DBS. A detailed functional analysis, using a further 728 probes implicated in STN-DBS, suggested an increased ability to receive excitation (mediated by increased dendritic spines, increased calcium influx and enhanced excitatory post synaptic potentials) accompanied by processes that would hamper the initiation of action potentials, transport of neurotransmitters from soma to axon terminals and vesicular release in Drd2-expressing MSNs. Finally, changes in expression of several genes involved in apoptosis as well as cholesterol and fatty acid metabolism were also identified. This increased understanding of the molecular mechanisms induced by STN-DBS may reveal novel targets for future non-surgical therapies for PD. PMID:26106299

  14. Functional improvement after subthalamic stimulation in Parkinson's disease: a non-equivalent controlled study with 12–24 month follow up

    PubMed Central

    Capecci, M; Ricciuti, R; Burini, D; Bombace, V; Provinciali, L; Iacoangeli, M; Scerrati, M; Ceravolo, M

    2005-01-01

    Objective: This study aimed to assess the effectiveness of chronic bilateral STN-S in improving the functional status of PD patients compared with patients treated with drugs alone. Methods: Controlled study of disability index changes over 12 and 24 month chronic STN stimulation. Of 39 patients with advanced PD meeting CAPSIT criteria for STN-S, 23 underwent surgery; 16 patients decided against surgery and continued on drug schedule adjustments. Functional status was measured using the Activities of Daily Living section of the Unified Parkinson's Disease Rating Scale (UPDRS-ADL), Brown's Disability Scale, and Functional Independence Measure. UPDRS motor score and subscores for selected items, levodopa equivalent daily dose, and Beck Depression Inventory scores were also monitored. Results: T12 follow up data were available for all 39 patients and T24 data for 13 STN-S and 8 control subjects. Compared with controls, STN-S patients experienced significant or highly significant improvements in all independence measures at both 12 and 24 months (time x treatment effect T12: F = 19.5, p = 0.00008; T24: F = 6.2, p = 0.005). Forward stepwise regression for independent predictors of the yearly rate of UPDRS-ADL score modification in the entire sample showed that treatment was the only factor significantly associated with functional status change (beta coefficient –0.54, t value –2.5, p = 0.02), whereas other variables—UPDRS motor score, BDI, and age at disease onset and enrolment—were not in the equation. Conclusion: STN-S is an effective therapeutic option in advanced PD. It induced a consistent improvement of functional abilities over two years to an extent that was not achieved with drug therapy alone. PMID:15897496

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

    PubMed

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

    2016-06-01

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

  16. Comparison of frequencies of non motor symptoms in Indian Parkinson’s disease patients on medical management versus deep brain stimulation: A case-control study

    PubMed Central

    Rukmini Mridula, Kandadai; Borgohain, Rupam; Jabeen, Shaik Afshan; Padmaja, Gaddamanugu; Bandaru, VCS Srinivasarao; Ankathi, Praveen; Kanikannan, Meena A; Ali Khan, Mohammed Shujath

    2015-01-01

    Background: Non motor symptoms (NMS) of idiopathic Parkinson’s disease (PD) are a major cause of disability and recognition of these symptoms and treatment is important for comprehensive health care. Deep brain stimulation of bilateral subthalamic nucleus deep brain stimulation (STN DBS) has been shown to improve motor symptoms in PD and effects on NMS are unknown. To investigate the NMS among PD patients who underwent STN DBS. Methods: We recruited prospectively 56 patients with PD, who had undergone bilateral STN DBS and 53 age and duration of illness matched PD patients on dopaminergic therapy (controls). NMS were assessed using 30 item questionnaire NMS Quest. These questions evaluated 9 domains, gastrointestinal, urinary, cardiovascular, sexual, cognition (apathy/attention/memory), anxiety/depression, hallucinations/delusions, sleep and miscellaneous. Comparison was done on individual symptoms as well as in various domains. This study was carried at Nizam’s Institution of Medical Sciences and study period was from January 2011 to December 2012. Results: Patients who underwent STN DBS had a significantly lower mean total score on NMS quest (6.7 ± 3.8) compared to controls (8.4 ± 3.7) (P < 0.00100). Symptoms in the domains of cardiovascular, gastrointestinal, sleep were significantly less frequent while sexual disturbances were significantly more frequent among patients compared to controls. On individual symptom analysis, nocturia  (P < 0.00010), unexplained pains (P < 0.00010), nausea and vomiting, constipation, lightheadedness, depression, and insomnia were less prevalent, while sexual disturbances were significantly more common in STN DBS group compared to controls. Conclusion: Bilateral STN DBS not only improves the motor symptoms but also improves many NMS in PD patients. PMID:26056553

  17. Motor behaviors in the sheep evoked by electrical stimulation of the subthalamic nucleus.

    PubMed

    Lentz, Linnea; Zhao, Yan; Kelly, Matthew T; Schindeldecker, William; Goetz, Steven; Nelson, Dwight E; Raike, Robert S

    2015-11-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to treat movement disorders, including advanced Parkinson's disease (PD). The pathogenesis of PD and the therapeutic mechanisms of DBS are not well understood. Large animal models are essential for investigating the mechanisms of PD and DBS. The purpose of this study was to develop a novel sheep model of STN DBS and quantify the stimulation-evoked motor behaviors. To do so, a large sample of animals was chronically-implanted with commercial DBS systems. Neuroimaging and histology revealed that the DBS leads were implanted accurately relative to the neurosurgical plan and also precisely relative to the STN. It was also possible to repeatedly conduct controlled evaluations of stimulation-evoked motor behavior in the awake-state. The evoked motor responses depended on the neuroanatomical location of the electrode contact selected for stimulation, as contacts proximal to the STN evoked movements at significantly lower voltages. Tissue stimulation modeling demonstrated that selecting any of the contacts stimulated the STN, whereas selecting the relatively distal contacts often also stimulated thalamus but only the distal-most contact stimulated internal capsule. The types of evoked motor behaviors were specific to the stimulation frequency, as low but not high frequencies consistently evoked movements resembling human tremor or dyskinesia. Electromyography confirmed that the muscle activity underlying the tremor-like movements in the sheep was consistent with human tremor. Overall, this work establishes that the sheep is a viable a large-animal platform for controlled testing of STN DBS with objective motor outcomes. Moreover, the results support the hypothesis that exaggerated low-frequency activity within individual nodes of the motor network can drive symptoms of human movement disorders, including tremor and dyskinesia. PMID:26231574

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

    PubMed Central

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

    2011-01-01

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

  19. Deep brain stimulation of the subthalamic nucleus preferentially alters the translational profile of striatopallidal neurons in an animal model of Parkinson's disease.

    PubMed

    Visanji, Naomi P; Kamali Sarvestani, Iman; Creed, Meaghan C; Shams Shoaei, Zahra; Nobrega, José N; Hamani, Clement; Hazrati, Lili-Naz

    2015-01-01

    Deep brain stimulation targeting the subthalamic nucleus (STN-DBS) is an effective surgical treatment for the motor symptoms of Parkinson's disease (PD), the precise neuronal mechanisms of which both at molecular and network levels remain a topic of debate. Here we employ two transgenic mouse lines, combining translating ribosomal affinity purification (TRAP) with bacterial artificial chromosome expression (Bac), to selectively identify changes in translational gene expression in either Drd1a-expressing striatonigral or Drd2-expressing striatopallidal medium spiny neurons (MSNs) of the striatum following STN-DBS. 6-hydroxydopamine lesioned mice received either 5 days stimulation via a DBS electrode implanted in the ipsilateral STN or 5 days sham treatment (no stimulation). Striatal polyribosomal RNA was selectively purified from either Drd2 or Drd1a MSNs using the TRAP method and gene expression profiling performed. We identified eight significantly altered genes in Drd2 MSNs (Vps33b, Ppp1r3c, Mapk4, Sorcs2, Neto1, Abca1, Penk1, and Gapdh) and two overlapping genes in Drd1a MSNs (Penk1 and Ppp1r3c) implicated in the molecular mechanisms of STN-DBS. A detailed functional analysis, using a further 728 probes implicated in STN-DBS, suggested an increased ability to receive excitation (mediated by increased dendritic spines, increased calcium influx and enhanced excitatory post synaptic potentials) accompanied by processes that would hamper the initiation of action potentials, transport of neurotransmitters from soma to axon terminals and vesicular release in Drd2-expressing MSNs. Finally, changes in expression of several genes involved in apoptosis as well as cholesterol and fatty acid metabolism were also identified. This increased understanding of the molecular mechanisms induced by STN-DBS may reveal novel targets for future non-surgical therapies for PD. PMID:26106299

  20. Effects of focused ion beam milling on electron backscatter diffraction patterns in strontium titanate and stabilized zirconia.

    PubMed

    Saowadee, N; Agersted, K; Bowen, J R

    2012-06-01

    This study investigates the effect of focused ion beam (FIB) current and accelerating voltage on electron backscatter diffraction pattern quality of yttria-stabilized zirconia (YSZ) and Nb-doped strontium titanate (STN) to optimize data quality and acquisition time for 3D-EBSD experiments by FIB serial sectioning. Band contrast and band slope were used to describe the pattern quality. The FIB probe currents investigated ranged from 100 to 5000 pA and the accelerating voltage was either 30 or 5 kV. The results show that 30 kV FIB milling induced a significant reduction of the pattern quality of STN samples compared to a mechanically polished surface but yielded a high pattern quality on YSZ. The difference between STN and YSZ pattern quality is thought to be caused by difference in the degree of ion damage as their backscatter coefficients and ion penetration depths are virtually identical. Reducing the FIB probe current from 5000 to 100 pA improved the pattern quality by 20% for STN but only showed a marginal improvement for YSZ. On STN, a conductive coating can help to improve the pattern quality and 5 kV polishing can lead to a 100% improvement of the pattern quality relatively to 30 kV FIB milling. For 3D-EBSD experiments of a material such as STN, it is recommended to combine a high kV FIB milling and low kV polishing for each slice in order to optimize the data quality and acquisition time. PMID:22582798

  1. Three-dimensional SPACE fluid-attenuated inversion recovery at 3 T to improve subthalamic nucleus lead placement for deep brain stimulation in Parkinson's disease: from preclinical to clinical studies.

    PubMed

    Senova, Suhan; Hosomi, Koichi; Gurruchaga, Jean-Marc; Gouello, Gaëtane; Ouerchefani, Naoufel; Beaugendre, Yara; Lepetit, Hélène; Lefaucheur, Jean-Pascal; Badin, Romina Aron; Dauguet, Julien; Jan, Caroline; Hantraye, Philippe; Brugières, Pierre; Palfi, Stéphane

    2016-08-01

    OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established therapy for motor symptoms in patients with pharmacoresistant Parkinson's disease (PD). However, the procedure, which requires multimodal perioperative exploration such as imaging, electrophysiology, or clinical examination during macrostimulation to secure lead positioning, remains challenging because the STN cannot be reliably visualized using the gold standard, T2-weighted imaging (T2WI) at 1.5 T. Thus, there is a need to improve imaging tools to better visualize the STN, optimize DBS lead implantation, and enlarge DBS diffusion. METHODS Gradient-echo sequences such as those used in T2WI suffer from higher distortions at higher magnetic fields than spin-echo sequences. First, a spin-echo 3D SPACE (sampling perfection with application-optimized contrasts using different flip angle evolutions) FLAIR sequence at 3 T was designed, validated histologically in 2 nonhuman primates, and applied to 10 patients with PD; their data were clinically compared in a double-blind manner with those of a control group of 10 other patients with PD in whom STN targeting was performed using T2WI. RESULTS Overlap between the nonhuman primate STNs segmented on 3D-histological and on 3D-SPACE-FLAIR volumes was high for the 3 most anterior quarters (mean [± SD] Dice scores 0.73 ± 0.11, 0.74 ± 0.06, and 0.60 ± 0.09). STN limits determined by the 3D-SPACE-FLAIR sequence were more consistent with electrophysiological edges than those determined by T2WI (0.9 vs 1.4 mm, respectively). The imaging contrast of the STN on the 3D-SPACE-FLAIR sequence was 4 times higher (p < 0.05). Improvement in the Unified Parkinson's Disease Rating Scale Part III score (off medication, on stimulation) 12 months after the operation was higher for patients who underwent 3D-SPACE-FLAIR-guided implantation than for those in whom T2WI was used (62.2% vs 43.6%, respectively; p < 0.05). The total electrical energy

  2. Dominant efficiency of nonregular patterns of subthalamic nucleus deep brain stimulation for Parkinson’s disease and obsessive-compulsive disorder in a data-driven computational model

    NASA Astrophysics Data System (ADS)

    Karamintziou, Sofia D.; Deligiannis, Nick G.; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stephan; David, Olivier; Stathis, Pantelis G.; Tagaris, George A.; Boviatsis, Efstathios J.; Sakas, Damianos E.; Polychronaki, Georgia E.; Tsirogiannis, George L.; Nikita, Konstantina S.

    2016-02-01

    Objective. Almost 30 years after the start of the modern era of deep brain stimulation (DBS), the subthalamic nucleus (STN) still constitutes a standard stimulation target for advanced Parkinson’s disease (PD), but the use of STN-DBS is also now supported by level I clinical evidence for treatment-refractory obsessive-compulsive disorder (OCD). Disruption of neural synchronization in the STN has been suggested as one of the possible mechanisms of action of standard and alternative patterns of STN-DBS at a local level. Meanwhile, recent experimental and computational modeling evidence has signified the efficiency of alternative patterns of stimulation; however, no indications exist for treatment-refractory OCD. Here, we comparatively simulate the desynchronizing effect of standard (regular at 130 Hz) versus temporally alternative (in terms of frequency, temporal variability and the existence of bursts or pauses) patterns of STN-DBS for PD and OCD, by means of a stochastic dynamical model and two microelectrode recording (MER) datasets. Approach. The stochastic model is fitted to subthalamic MERs acquired during eight surgical interventions for PD and eight surgical interventions for OCD. For each dynamical system simulated, we comparatively assess the invariant density (steady-state phase distribution) as a measure inversely related to the desynchronizing effect yielded by the applied patterns of stimulation. Main results. We demonstrate that high (130 Hz)—and low (80 Hz)—frequency irregular patterns of stimulation, and low-frequency periodic stimulation interrupted by bursts of pulses, yield in both pathologic conditions a significantly stronger desynchronizing effect compared with standard STN-DBS, and distinct alternative patterns of stimulation. In PD, values of the invariant density measure are proven to be optimal at the dorsolateral oscillatory region of the STN including sites with the optimal therapeutic window. Significance. In addition to providing

  3. Bilateral subthalamic nucleus stimulation improves health-related quality of life in Parkinsonian patients.

    PubMed

    Erola, Tuomo; Karinen, Petri; Heikkinen, Esa; Tuominen, Juho; Haapaniemi, Tarja; Koivukangas, John; Myllylä, Vilho

    2005-03-01

    Parkinson's disease (PD) is a common neurological disorder. Recently, bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an option in the treatment of severe PD. We measured the health-related quality of life (HRQoL) of 27 parkinsonian patients, who underwent a bilateral STN-operation. The instruments used for the evaluation of the HRQoL were the Parkinson's Disease Questionnaire (PDQ-39) and the Finnish version of the Nottingham Health Profile (NHP). We found that the quality of life significantly improved when measured with both HRQoL scales. Clinical improvement and improvement in HRQoL were positively correlated. PMID:15734666

  4. Subthalamic Nucleus Deep Brain Stimulation Modulate Catecholamine Levels with Significant Relations to Clinical Outcome after Surgery in Patients with Parkinson’s Disease

    PubMed Central

    Yamamoto, Tatsuya; Uchiyama, Tomoyuki; Higuchi, Yoshinori; Asahina, Masato; Hirano, Shigeki; Yamanaka, Yoshitaka; Kuwabara, Satoshi

    2015-01-01

    Aims Although subthalamic nucleus deep brain stimulation (STN-DBS) is effective in patients with advanced Parkinson’s disease (PD), its physiological mechanisms remain unclear. Because STN-DBS is effective in patients with PD whose motor symptoms are dramatically alleviated by L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, the higher preoperative catecholamine levels might be related to the better clinical outcome after surgery. We aimed to examine the correlation between the preoperative catecholamine levels and postoperative clinical outcome after subthalamic nucleus deep brain stimulation. The effectiveness of STN-DBS in the patient who responded well to dopaminergic medication suggest the causal link between the dopaminergic system and STN-DBS. We also examined how catecholamine levels were modulated after subthalamic stimulation. Methods In total 25 patients with PD were enrolled (Mean age 66.2 ± 6.7 years, mean disease duration 11.6 ± 3.7 years). Mean levodopa equivalent doses were 1032 ± 34.6 mg before surgery. Cerebrospinal fluid and plasma catecholamine levels were measured an hour after oral administration of antiparkinsonian drugs before surgery. The mean Unified Parkinson’s Disease Rating Scale scores (UPDRS) and the Parkinson’s disease Questionnaire-39 (PDQ-39) were obtained before and after surgery. Of the 25 patients, postoperative cerebrospinal fluid and plasma were collected an hour after oral administration of antiparkinsonian drugs during on stimulation at follow up in 11 patients. Results Mean levodopa equivalent doses significantly decreased after surgery with improvement in motor functions and quality of life. The preoperative catecholamine levels had basically negative correlations with postoperative motor scores and quality of life, suggesting that higher preoperative catecholamine levels were related to better outcome after STN-DBS. The preoperative plasma levels of L-DOPA had significantly negative correlations with

  5. Surgical Treatment of Dyskinesia in Parkinson’s Disease

    PubMed Central

    Munhoz, Renato P.; Cerasa, Antonio; Okun, Michael S.

    2014-01-01

    One of the main indications for stereotactic surgery in Parkinson’s disease (PD) is the control of levodopa-induced dyskinesia. This can be achieved by pallidotomy and globus pallidus internus (GPi) deep brain stimulation (DBS) or by subthalamotomy and subthalamic nucleus (STN) DBS, which usually allow for a cut down in the dosage of levodopa. DBS has assumed a pivotal role in stereotactic surgical treatment of PD and, in fact, ablative procedures are currently considered surrogates, particularly when bilateral procedures are required, as DBS does not produce a brain lesion and the stimulator can be programed to induce better therapeutic effects while minimizing adverse effects. Interventions in either the STN and the GPi seem to be similar in controlling most of the other motor aspects of PD, nonetheless, GPi surgery seems to induce a more particular and direct effect on dyskinesia, while the anti-dyskinetic effect of STN interventions is mostly dependent on a reduction of dopaminergic drug dosages. Hence, the si ne qua non-condition for a reduction of dyskinesia when STN interventions are intended is their ability to allow for a reduction of levodopa dosage. Pallidal surgery is indicated when dyskinesia is a dose-limiting factor for maintaining or introducing higher adequate levels of dopaminergic therapy. Also medications used for the treatment of PD may be useful for the improvement of several non-motor aspects of the disease, including sleep, psychiatric, and cognitive domains, therefore, dose reduction of medication withdrawal are not always a fruitful objective. PMID:24808889

  6. Effects of Stimulation of the Subthalamic Nucleus on Naming and Reading Nouns and Verbs in Parkinson's Disease

    ERIC Educational Resources Information Center

    Silveri, Maria Caterina; Ciccarelli, Nicoletta; Baldonero, Eleonora; Piano, Carla; Zinno, Massimiliano; Soleti, Francesco; Bentivoglio, Anna Rita; Albanese, Alberto; Daniele, Antonio

    2012-01-01

    An impairment for verbs has been described in patients with Parkinson's disease (PD), suggesting that a disruption of frontal-subcortical circuits may result in dysfunction of the neural systems involved in action-verb processing. A previous study suggested that deep brain stimulation (DBS) of the subthalamic nucleus (STN) during verb generation…

  7. Submyelin potassium accumulation may functionally block subsets of local axons during deep brain stimulation: a modeling study

    NASA Astrophysics Data System (ADS)

    Bellinger, S. C.; Miyazawa, G.; Steinmetz, P. N.

    2008-09-01

    Deep brain stimulation has been used for over a decade to relieve the symptoms of Parkinson's disease, although its mechanism of action remains poorly understood. To better understand the direct effects of DBS on central neurons, a computational model of a myelinated axon has been constructed which includes the effects of K+ accumulation within the peri-axonal space. Using best estimates of anatomic and electrogenic model parameters for in vivo STN axons, the model predicts a functional block along the axon due to K+ accumulation in the submyelin space. The functional block occurs for a range of model parameters: high stimulation frequencies (>130 Hz); high extracellular K+ concentrations (>3 × 10-3 M); low maximum Na+/K+ ATPase current densities (<0.026 A m-2); low diffusion coefficients for K+ diffusion out of the submyelin space (<2.4 × 10-9 m2 s-1); small periaxonal space widths of the myelin attachment sections (<2.7 × 10-9 m) and perinodal/internodal sections (<8.4 × 10-9 m). These results suggest that therapeutic DBS of the STN likely results in a functional block for many STN axons, although a subset of STN axons may also be activated at the stimulating frequency.

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  10. Articulatory Closure Proficiency in Patients with Parkinson's Disease Following Deep Brain Stimulation of the Subthalamic Nucleus and Caudal Zona Incerta

    ERIC Educational Resources Information Center

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

    2014-01-01

    Purpose: The present study aimed at comparing the effects of deep brain stimulation (DBS) treatment of the subthalamic nucleus (STN) and the caudal zona incerta (cZi) on the proficiency in achieving oral closure and release during plosive production of people with Parkinson's disease. Method: Nineteen patients participated preoperatively and…

  11. Method to Select Metropolitan Areas of Epidemiologic Interest for Enhanced Air Quality Monitoring

    EPA Science Inventory

    The U.S. Environmental Protection Agency’s current Speciation Trends Network (STN) covers most major U.S. metropolitan areas and a wide range of particulate matter (PM) constituents and gaseous co-pollutants. However, using filter-based methods, most PM constituents are measured ...

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

    PubMed Central

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

    2016-01-01

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

  13. Characteristic laryngoscopic findings in Parkinson's disease patients after subthalamic nucleus deep brain stimulation and its correlation with voice disorder.

    PubMed

    Tsuboi, Takashi; Watanabe, Hirohisa; Tanaka, Yasuhiro; Ohdake, Reiko; Yoneyama, Noritaka; Hara, Kazuhiro; Ito, Mizuki; Hirayama, Masaaki; Yamamoto, Masahiko; Fujimoto, Yasushi; Kajita, Yasukazu; Wakabayashi, Toshihiko; Sobue, Gen

    2015-12-01

    Speech and voice disorders are one of the most common adverse effects in Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS). However, the pathophysiology of voice and laryngeal dysfunction after STN-DBS remains unclear. We assessed 47 PD patients (22 treated with bilateral STN-DBS (PD-DBS) and 25 treated medically (PD-Med); all patients in both groups matched by age, sex, disease duration, and motor and cognitive function) using the objective and subjective voice assessment batteries (GRBAS scale and Voice Handicap Index), and laryngoscopy. Laryngoscopic examinations revealed that PD-DBS patients showed a significantly higher incidence of incomplete glottal closure (77 vs 48 %; p = 0.039), hyperadduction of the false vocal folds (73 vs 44 %; p = 0.047), anteroposterior hypercompression (50 vs 20 %; p = 0.030) and asymmetrical glottal movement (50 vs 16 %; p = 0.002) than PD-Med patients. On- and off-stimulation assessment revealed that STN-DBS could induce or aggravate incomplete glottal closure, hyperadduction of the false vocal folds, anteroposterior hypercompression, and asymmetrical glottal movement. Incomplete glottal closure and hyperadduction of the false vocal folds significantly correlated with breathiness and strained voice, respectively (r = 0.590 and 0.539). We should adjust patients' DBS settings in consideration of voice and laryngeal functions as well as motor function. PMID:26254905

  14. Blockade of mGluR glutamate receptors in the subthalamic nucleus ameliorates motor asymmetry in an animal model of Parkinson's disease.

    PubMed

    Phillips, Janice M; Lam, Hoa A; Ackerson, Larry C; Maidment, Nigel T

    2006-01-01

    It has been suggested that Group I metabotropic glutamate receptor antagonists could have potential therapeutic value in the treatment of Parkinson's disease. There is evidence that when given systemically, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a metabotropic glutamate receptor type 5 (mGluR5) antagonist, produces anti-parkinsonian effects in animal models, but the site of action has not been directly established. In the present study, we examined whether the subthalamic nucleus (STN) and its output structures may mediate such an effect using a unilateral rat model of Parkinson's disease. A battery of simple behavioral tests, reliably sensitive to dopamine depletion, was applied consecutively: (i) prior to surgery; (ii) 3 weeks following a unilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta; (iii) at 1 h, 24 h and 4 days following a microinjection of MPEP, via an indwelling cannula, into the STN, entopeduncular nucleus (EP) or substantia nigra zona reticulata. Unilaterally dopamine-depleted animals typically had severe motor and sensorimotor asymmetries 3 weeks following surgery. Microinjection of 25 nmol MPEP into the STN of these animals significantly attenuated these asymmetries relative to vehicle. Further microinjections of lower doses (5 and 10 nmol) revealed a dose-response effect. Microinjection of MPEP into either the EP or substantia nigra zona reticulata was without effect. These data suggest that MPEP may act at the level of the STN to reduce glutamatergic overactivity and thereby induce anti-parkinsonian effects. PMID:16420425

  15. Subthalamic deep brain stimulation reduces pathological information transmission to the thalamus in a rat model of parkinsonism

    PubMed Central

    Anderson, Collin J.; Sheppard, Daylan T.; Huynh, Rachel; Anderson, Daria Nesterovich; Polar, Christian A.; Dorval, Alan D.

    2015-01-01

    The degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to parkinsonian motor symptoms via changes in electrophysiological activity throughout the basal ganglia. High-frequency deep brain stimulation (DBS) partially treats these symptoms, but the mechanisms are unclear. We hypothesize that motor symptoms of Parkinson’s disease (PD) are associated with increased information transmission from basal ganglia output neurons to motor thalamus input neurons and that therapeutic DBS of the subthalamic nucleus (STN) treats these symptoms by reducing this extraneous information transmission. We tested these hypotheses in a unilateral, 6-hydroxydopamine-lesioned rodent model of hemiparkinsonism. Information transfer between basal ganglia output neurons and motor thalamus input neurons increased in both the orthodromic and antidromic directions with hemiparkinsonian (hPD) onset, and these changes were reversed by behaviorally therapeutic STN-DBS. Omnidirectional information increases in the parkinsonian state underscore the detrimental nature of that pathological information and suggest a loss of information channel independence. Therapeutic STN-DBS reduced that pathological information, suggesting an effective increase in the number of independent information channels. We interpret these data with a model in which pathological information and fewer information channels diminishes the scope of possible motor activities, driving parkinsonian symptoms. In this model, STN-DBS restores information-channel independence by eliminating or masking the parkinsonism-associated information, and thus enlarges the scope of possible motor activities, alleviating parkinsonian symptoms. PMID:26217192

  16. JOHNS HOPKINS PARTICULATE MATTER RESEARCH CENTER

    EPA Science Inventory

    Project 1
    Project 1 has completed much of its proposed work, having previously characterized the variation in the PM-associated risk for hospitalization and mortality across the country and also analyzed the available data from the STN for the years 2000-2...

  17. Software for Information Storage and Retrieval Tested, Evaluated and Compared: Part VI--Various Additional Programs.

    ERIC Educational Resources Information Center

    Sieverts, Eric G.; And Others

    1993-01-01

    Reports on tests evaluating nine microcomputer software packages designed for information storage and retrieval: BRS-Search, dtSearch, InfoBank, Micro-OPC, Q&A, STN-PFS, Strix, TINman, and ZYindex. Tables and narrative evaluations detail results related to security, hardware, user features, search capability, indexing, input, maintenance of files,…

  18. Registration of 'Guymon' wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    'Guymon' (Reg. No. CV-_______, PI 643133) is a hard white (HW) winter wheat (Triticum aestivum L.) cultivar developed and released cooperatively by the Oklahoma Agric. Exp. Stn. (AES) and the USDA-ARS in 2005. It is recommended for grain-only and dual-purpose production systems in an area of the so...

  19. Registration of ‘Ok102’ Wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    ‘Ok102’ (Reg. no. CV-941, PI 632635) is a hard red winter wheat (Triticum aestivum L.) developed cooperatively by the Oklahoma Agric. Exp. Stn. and the USDA-ARS. Ok102 was released in March 2002, primarily on the basis of its resistance to several foliar diseases, excellent milling quality, and desi...

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

    PubMed

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

    2016-01-01

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

  1. Reward circuit DBS improves Parkinson's gait along with severe depression and OCD.

    PubMed

    Williams, Nolan R; Hopkins, Thomas R; Short, E Baron; Sahlem, Gregory L; Snipes, Jonathan; Revuelta, Gonzalo J; George, Mark S; Takacs, Istvan

    2016-01-01

    A 59-year-old Caucasian man with a past history of Parkinson's disease (PD) status post-bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), who also had treatment-resistant (TR) obsessive-compulsive disorder (OCD), and treatment-resistant depression (TRD), presented for further evaluation and management of his TR OCD. After an unsuccessful attempt to treat his OCD by reprogramming his existing STN DBS, he was offered bilateral ventral capsule/ventral striatum (VC/VS) DBS surgery. In addition to the expected improvement in OCD symptoms, he experienced significant improvement in both PD-related apathy and depression along with resolution of suicidal ideation. Furthermore, the patient's festinating gait dramatically improved. This case demonstrates that DBS of both the STN and VC/VS appears to have an initial signal of safety and tolerability. This is the first instance where both the STN and the VC/VS DBS targets have been implanted in an individual and the first case where a patient with PD has received additional DBS in mood-regulatory circuitry. PMID:26644268

  2. A Novel Concept for the Search and Retrieval of the Derwent Markush Resource Database.

    PubMed

    Barth, Andreas; Stengel, Thomas; Litterst, Edwin; Kraut, Hans; Matuszczyk, Henry; Ailer, Franz; Hajkowski, Steve

    2016-05-23

    The representation of and search for generic chemical structures (Markush) remains a continuing challenge. Several research groups have addressed this problem, and over time a limited number of practical solutions have been proposed. Today there are two large commercial providers of Markush databases: Chemical Abstracts Service (CAS) and Thomson Reuters. The Thomson Reuters "Derwent" Markush database is currently offered via the online services Questel and STN and as a data feed for in-house use. The aim of this paper is to briefly review the existing Markush systems (databases plus search engines) and to describe our new approach for the implementation of the Derwent Markush Resource on STN. Our new approach demonstrates the integration of the Derwent Markush Resource database into the existing chemistry-focused STN platform without loss of detail. This provides compatibility with other structure and Markush databases on STN and at the same time makes it possible to deploy the specific features and functions of the Derwent approach. It is shown that the different Markush languages developed by CAS and Derwent can be combined into a single general Markush description. In this concept the generic nodes are grouped together in a unique hierarchy where all chemical elements and fragments can be integrated. As a consequence, both systems are searchable using a single structure query. Moreover, the presented concept could serve as a promising starting point for a common generalized description of Markush structures. PMID:27123583

  3. [Parkinson's disease and cortico-Basal Ganglia circuits].

    PubMed

    Pan, Ming-Kai; Tai, Chun-Hwei; Kuo, Chung-Chin

    2010-09-01

    Cortico-basal ganglia circuit model has been studied extensively after it was first proposed by Alexander and Crutcher in 1990. This model accurately predicted the hyperactivity of indirect pathway and subthalamic nucleus(STN) in the dopamine deficiency state of Parkinson's disease (PD), prompting the experimental approaches of lesioning STN in parkinsonian primates. Application of these successful experiences with STN lesions in the reversal of parkinsonian symptoms to human PD patients facilitates the development of STN deep brain stimulation (DBS), which has become one of the most important therapies for PD in recent years. Although the classical model of the cortico-basal ganglia circuits by Alexander and Crutcher has provided many important insights into the basal ganglia function, the functional role of cortico-subthalamic "hyperdirect" pathway in the circuits has been relatively neglected. The first part of this article summarizes recent development concerning the cortico-basal ganglia circuits, especially emphasizing the importance of the hyperdirect pathway. In the second part of this article, we would describe the analyses of gross corticobasal ganglia circuit electrophysiological findings, especially emphasizing the coherence between two oscillating signals. We would also discuss the correlation between these parameters and the motor dysfunction, and its pathophysiological implications in PD. PMID:20824544

  4. Dialog Alternatives: A Power Searcher's Checklist.

    ERIC Educational Resources Information Center

    Kassel, Amelia; Drebes, Karen Ann

    1998-01-01

    Discusses Dialog's recent new pricing structure and its effects on librarians and other information professionals. Presents charts that compare Dialog databases with other search services (Dow Jones Interactive, LEXIS-NEXIS, OCLC FirstSearch, Ovid, Questel-Orbit, SilverPlatter, and STN) and Dialog via other channels (DataStar, Dialog Select,…

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

    PubMed

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

    2013-01-30

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

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

    PubMed

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

    2016-10-01

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

  7. Conflict-dependent dynamic of subthalamic nucleus oscillations during moral decisions.

    PubMed

    Fumagalli, Manuela; Giannicola, Gaia; Rosa, Manuela; Marceglia, Sara; Lucchiari, Claudio; Mrakic-Sposta, Simona; Servello, Domenico; Pacchetti, Claudio; Porta, Mauro; Sassi, Marco; Zangaglia, Roberta; Franzini, Angelo; Albanese, Alberto; Romito, Luigi; Piacentini, Sylvie; Zago, Stefano; Pravettoni, Gabriella; Barbieri, Sergio; Priori, Alberto

    2011-01-01

    Although lesional, neuroimaging, and brain stimulation studies have provided an insight into the neural mechanisms of judgement and decision-making, all these works focused on the cerebral cortex, without investigating the role of subcortical structures such as the basal ganglia. Besides being an effective therapeutic tool, deep brain stimulation (DBS) allows local field potential (LFP) recordings through the stimulation electrodes thus providing a physiological "window" on human subcortical structures. In this study we assessed whether subthalamic nucleus LFP oscillations are modulated by processing of moral conflictual, moral nonconflictual, and neutral statements. To do so, in 16 patients with Parkinson's disease (8 men) bilaterally implanted with subthalamic nucleus (STN) electrodes for DBS, we recorded STN LFPs 4 days after surgery during a moral decision task. During the task, recordings from the STN showed changes in LFP oscillations. Whereas the 14--30 Hz band (beta) changed during the movement executed to perform the task, the 5--13 Hz band (low-frequency) changed when subjects evaluated the content of statements. Low-frequency band power increased significantly more during conflictual than during nonconflictual or neutral sentences. We conclude that STN responds specifically to conflictual moral stimuli, and could be involved in conflictual decisions of all kinds, not only those for moral judgment. LFP oscillations provide novel direct evidence that the neural processing of conflictual decision-making spreads beyond the cortex to the basal ganglia and encompasses a specific subcortical conflict-dependent component. PMID:21061226

  8. Near-infrared stimulation on globus pallidus and subthalamus

    NASA Astrophysics Data System (ADS)

    Yoo, Minsu; Koo, Ho; Kim, Minsun; Kim, Hyoung-Ihl; Kim, Sohee

    2013-12-01

    Near-infrared stimulation (NIS) is an emerging technique used to evoke action potentials in nervous systems. Its efficacy of evoking action potentials has been demonstrated in different nerve tissues. However, few studies have been performed using NIS to stimulate the deep brain structures, such as globus pallidus (GP) and subthalamic nucleus (STN). Male Sprague-Dawley rats were randomly divided into GP stimulation group (n=11) and STN stimulation group (n=6). After introducing optrodes stereotaxically into the GP or STN, we stimulated neural tissue for 2 min with continuous near-infrared light of 808 nm while varying the radiant exposure from 40 to 10 mW. The effects were investigated with extracellular recordings and the temperature rises at the stimulation site were also measured. NIS was found to elicit excitatory responses in eight out of 11 cases (73%) and inhibitory responses in three cases in the GP stimulation group, whereas it predominantly evoked inhibitory responses in seven out of eight cases (87.5%) and an excitatory response in one case in STN stimulation group. Only radiation above 20 mW, accompanying temperature increases of more than 2°C, elicited a statistically significant neural response (p<0.05). The responsiveness to NIS was linearly dependent on the power of radiation exposure.

  9. Changes of oscillatory activity in the subthalamic nucleus during obsessive-compulsive disorder symptoms: two case reports.

    PubMed

    Bastin, Julien; Polosan, Mircea; Piallat, Brigitte; Krack, Paul; Bougerol, Thierry; Chabardès, Stéphan; David, Olivier

    2014-11-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has positive and negative effects on mood and cognition, as shown in patients suffering from Parkinson's disease (PD) and severe obsessive-compulsive disorders (OCD). Such behavioural and clinical effects suggest that the STN has an important function in limbic circuitry, which still needs to be clarified from electrophysiological recordings. Here we report two exceptional cases of OCD patients in whom local field potentials (LFP) of the anterior STN were directly recorded during acute obsessive-compulsive symptoms. We found significant symptom-related changes in different frequency bands, with no clear preferential oscillatory pattern. The overall modified STN activity during OCD symptoms suggests a mixture of both pathological and compensatory mechanisms that would reflect the maintenance of an over stable motor/cognitive/emotional set. Whether this activity propagates throughout the entire cognitive-limbic loops that are impaired in OCD is an interesting question for future research in larger series of patients. PMID:24552693

  10. Cognitive Changes following Bilateral Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease: A Meta-Analysis

    PubMed Central

    Meng, Xiangyu; Xiao, Jinsong; Zhang, Junjian

    2016-01-01

    Background. Nowadays, it has been largely acknowledged that deep brain stimulation of subthalamic nucleus (STN DBS) can alleviate motor symptoms of Parkinson's disease, but its effects on cognitive function remain unclear, which are not given enough attention by many clinical doctors and researchers. To date, 3 existing meta-analyses focusing on this issue included self-control studies and have not drawn consistent conclusions. The present study is the first to compare effect sizes of primary studies that include control groups, hoping to reveal the net cognitive outcomes after STN DBS and the clinical significance. Methods. A structured literature search was conducted using strict criteria. Only studies with control group could be included. Data on age, duration of disease, levodopa equivalent dosage (LED), and multiple cognitive scales were collected and pooled. Results. Of 172 articles identified, 10 studies (including 3 randomized controlled trials and 7 nonrandomized controlled studies) were eligible for inclusion. The results suggest that STN DBS results in decreased global cognition, memory, verbal fluency, and executive function compared with control group. No significant difference is found in other cognitive domains. Conclusions. STN DBS seems relatively safe with respect to cognitive function, and further studies should focus on the exact mechanisms of possible verbal deterioration after surgery in the future. PMID:27314016

  11. FACS array profiling identifies Ecto-5' nucleotidase as a striatopallidal neuron-specific gene involved in striatal-dependent learning.

    PubMed

    Ena, Sabrina L; De Backer, Jean-François; Schiffmann, Serge N; de Kerchove d'Exaerde, Alban

    2013-05-15

    The striatopallidal (STP) and striatonigral (STN) neurons constitute the main neuronal populations of the striatum. Despite the increasing knowledge concerning their involvement in multiple tasks associated with the striatum, it is still challenging to understand the precise differential functions of these two neuronal populations and to identify and study new genes involved in these functions. Here, we describe a reliable approach, applied on adult mouse brain, to generate specific STP and STN neuron gene profiles. STP and STN neurons were identified in the same animal using the transgenic Adora2A-Cre × Z/EG mouse model combined with retrograde labeling, respectively. Gene profiling was generated from FACS-purified neurons leading to the identification of new STP and STN neuron-specific genes. Knock-down models based on Cre-dependent lentiviral vector were developed to investigate their function either in striatal or in STP neurons. Thereby, we demonstrate that ecto-5'-nucleotidase (NT5e) is specifically expressed in STP neurons and is at the origin of most of the extracellular adenosine produced in the striatum. Behavioral analysis of striatal and STP neuron knock-down mouse models as well as NT5e knock-out mice demonstrates the implication of this STP neuron enzyme in motor learning. PMID:23678122

  12. Confirmation of functional zones within the human subthalamic nucleus: Patterns of connectivity and sub-parcellation using diffusion weighted imaging

    PubMed Central

    Lambert, Christian; Zrinzo, Ludvic; Nagy, Zoltan; Lutti, Antoine; Hariz, Marwan; Foltynie, Thomas; Draganski, Bogdan; Ashburner, John; Frackowiak, Richard

    2012-01-01

    The subthalamic nucleus (STN) is a small, glutamatergic nucleus situated in the diencephalon. A critical component of normal motor function, it has become a key target for deep brain stimulation in the treatment of Parkinson's disease. Animal studies have demonstrated the existence of three functional sub-zones but these have never been shown conclusively in humans. In this work, a data driven method with diffusion weighted imaging demonstrated that three distinct clusters exist within the human STN based on brain connectivity profiles. The STN was successfully sub-parcellated into these regions, demonstrating good correspondence with that described in the animal literature. The local connectivity of each sub-region supported the hypothesis of bilateral limbic, associative and motor regions occupying the anterior, mid and posterior portions of the nucleus respectively. This study is the first to achieve in-vivo, non-invasive anatomical parcellation of the human STN into three anatomical zones within normal diagnostic scan times, which has important future implications for deep brain stimulation surgery. PMID:22173294

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

    PubMed

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

    2012-01-01

    Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson's disease (PD). The authors review the current literature to identify the clinical correlates associated with subthalamic nucleus (STN) DBS-induced hypomania/mania in PD patients. Ventromedial electrode placement has been most consistently implicated in the induction of STN DBS-induced mania. There is some evidence of symptom amelioration when electrode placement is switched to a more dorsolateral contact. Additional clinical correlates may include unipolar stimulation, higher voltage (>3 V), male sex, and/or early-onset PD. STN DBS-induced psychiatric adverse events emphasize the need for comprehensive psychiatric presurgical evaluation and follow-up in PD patients. Animal studies and prospective clinical research, combined with advanced neuroimaging techniques, are needed to identify clinical correlates and underlying neurobiological mechanisms of STN DBS-induced mania. Such working models would serve to further our understanding of the neurobiological underpinnings of mania and contribute valuable new insight toward development of future DBS mood-stabilization therapies. PMID:22450620

  14. Effects of One Cycle of Recurrent Selection for Early Blight Resistance in a Diploid Hybrid Solanum phureja-S. stenotomum Population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early blight, caused by Alternaria solani, is the second most important foliar disease in potatoes, after late blight, around the world. Heritable early blight resistance was previously identified in a diploid hybrid population of Solanum phureja-S. stenotomum (phu-stn). Seventy-two clones, consis...

  15. Registration of 'Okfield' wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    'Okfield' (Reg. No. CV-_______, PI 643087) is a hard red winter (HRW) wheat (Triticum aestivum L.) cultivar developed and released cooperatively by the Oklahoma Agric. Exp. Stn. (AES) and the USDA-ARS in 2005. It is recommended for dryland wheat production using either grain-only and dual-purpose m...

  16. Registration of ‘OK Bullet’ Wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    ‘OK Bullet’ (Reg. No. CV-999, PI 642415) is a hard red winter (HRW) wheat (Triticum aestivum L.) cultivar developed cooperatively by the Oklahoma Agric. Exp. Stn. (AES), USDA-ARS, and the Texas AES and released by the Oklahoma AES and the USDA-ARS in 2005. OK Bullet is recommended for grain-only and...

  17. Two cycles of recurrent maternal half-sib selection reduce foliar late blight in a diploid hybrid Solanum phureja-S. stenotomum population by two-thirds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foliar late blight, caused by Phytophthora infestans, is an important disease problem worldwide. Foliar resistance to late blight was found in a hybrid population of the cultivated diploid species Solanum phureja-S. stenotomum (phu-stn). The objective of this study was to determine if resistance t...

  18. Chemical Substructure Searching: Comparing Three Commercially Available Databases.

    ERIC Educational Resources Information Center

    Wagner, A. Ben

    1986-01-01

    Compares the differences in coverage and utility of three substructure databases--Chemical Abstracts, Index Chemicus, and Chemical Information System's Nomenclature Search System. The differences between Chemical Abstracts with two different vendors--STN International and Questel--are described and a summary guide for choosing between databases is…

  19. Mode coupling in glass optical fibers and liquid-core optical fibers by three methods

    NASA Astrophysics Data System (ADS)

    Djordjevich, Alexandar; Savović, Svetislav

    2015-12-01

    We test Slemon and Wells's function and recently reported Hurand et al.'s (Appl. Opt., 50, 492-499, 2011) function for calculation of coupling characteristics in step-index optical fibers against experimental measurements and against calculations by a related method that is based on the power flow equation. Compared are the coupling length Lc (which is the fiber length where the equilibrium mode distribution is achieved) and length zs (where steady-state distribution is achieved) in three step index glass optical fibers as well as a liquid core optical fiber. The two functions, while simpler to apply being just algebraic formulas, are less accurate over a wide range of numerical apertures. It is also shown that fibers with same coupling coefficient can have much different coupling characteristics.

  20. Subthalamic deep brain stimulation improves smooth pursuit and saccade performance in patients with Parkinson’s disease

    PubMed Central

    2013-01-01

    Background Deep brain stimulation (DBS) in the subthalamic nucleus (STN) significantly reduces symptoms of Parkinson’s disease (PD) such as bradykinesia, tremor and rigidity. It also reduces the need for anti-PD medication, and thereby potential side-effects of L-Dopa. Although DBS in the STN is a highly effective therapeutic intervention in PD, its mechanism and effects on oculomotor eye movement control and particularly smooth pursuit eye movements have to date rarely been investigated. Furthermore, previous reports provide conflicting information. The aim was to investigate how DBS in STN affected oculomotor performance in persons with PD using novel analysis techniques. Methods Twenty-five patients were eligible (22 males, 3 females) according to the clinical inclusion criteria: idiopathic PD responsive to L-Dopa and having had bilateral STN stimulation for at least one year to ensure stable DBS treatment. Fifteen patients were excluded due to the strict inclusion criteria applied to avoid interacting and confounding factors when determining the effects of DBS applied alone without PD medication. One patient declined participation. Nine PD patients (median age 63, range 59–69 years) were assessed after having their PD medications withdrawn overnight. They were examined with DBS ON and OFF, with the ON/OFF order individually randomized. Results DBS ON increased smooth pursuit velocity accuracy (p < 0.001) and smooth pursuit gain (p = 0.005), especially for faster smooth pursuits (p = 0.034). DBS ON generally increased saccade amplitude accuracy (p = 0.007) and tended to increase peak saccade velocity also (p = 0.087), specifically both saccade velocity and amplitude accuracy for the 20 and 40 degree saccades (p < 0.05). Smooth pursuit latency tended to be longer (p = 0.090) approaching normal with DBS ON. Saccade latency was unaffected. Conclusions STN stimulation from DBS alone significantly improved both smooth pursuit and

  1. Abnormal Protein Glycosylation and Activated PI3K/Akt/mTOR Pathway: Role in Bladder Cancer Prognosis and Targeted Therapeutics

    PubMed Central

    Lima, Luís; Peixoto, Andreia; Fernandes, Elisabete; Neves, Diogo; Neves, Manuel; Gaiteiro, Cristiana; Tavares, Ana; Gil da Costa, Rui M.; Cruz, Ricardo; Amaro, Teresina; Oliveira, Paula A.; Ferreira, José Alexandre; Santos, Lúcio L.

    2015-01-01

    Muscle invasive bladder cancer (MIBC, stage ≥T2) is generally associated with poor prognosis, constituting the second most common cause of death among genitourinary tumours. Due to high molecular heterogeneity significant variations in the natural history and disease outcome have been observed. This has also delayed the introduction of personalized therapeutics, making advanced stage bladder cancer almost an orphan disease in terms of treatment. Altered protein glycosylation translated by the expression of the sialyl-Tn antigen (STn) and its precursor Tn as well as the activation of the PI3K/Akt/mTOR pathway are cancer-associated events that may hold potential for patient stratification and guided therapy. Therefore, a retrospective design, 96 bladder tumours of different stages (Ta, T1-T4) was screened for STn and phosphorylated forms of Akt (pAkt), mTOR (pmTOR), S6 (pS6) and PTEN, related with the activation of the PI3K/Akt/mTOR pathway. In our series the expression of Tn was residual and was not linked to stage or outcome, while STn was statically higher in MIBC when compared to non-muscle invasive tumours (p = 0.001) and associated decreased cancer-specific survival (log rank p = 0.024). Conversely, PI3K/Akt/mTOR pathway intermediates showed an equal distribution between non-muscle invasive bladder cancer (NMIBC) and MIBC and did not associate with cancer-specif survival (CSS) in any of these groups. However, the overexpression of pAKT, pmTOR and/or pS6 allowed discriminating STn-positive advanced stage bladder tumours facing worst CSS (p = 0.027). Furthermore, multivariate Cox regression analysis revealed that overexpression of PI3K/Akt/mTOR pathway proteins in STn+ MIBC was independently associated with approximately 6-fold risk of death by cancer (p = 0.039). Mice bearing advanced stage chemically-induced bladder tumours mimicking the histological and molecular nature of human tumours were then administrated with mTOR-pathway inhibitor sirolimus (rapamycin

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

    PubMed

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

    2010-03-01

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

  3. Human subthalamic nucleus-medial frontal cortex theta phase coherence is involved in conflict and error related cortical monitoring.

    PubMed

    Zavala, Baltazar; Tan, Huiling; Ashkan, Keyoumars; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Zaghloul, Kareem; Brown, Peter

    2016-08-15

    The medial prefrontal cortex (mPFC) is thought to control the shift from automatic to controlled action selection when conflict is present or when mistakes have been recently committed. Growing evidence suggests that this process involves frequency specific communication in the theta (4-8Hz) band between the mPFC and the subthalamic nucleus (STN), which is the main target of deep brain stimulation (DBS) for Parkinson's disease. Key in this hypothesis is the finding that DBS can lead to impulsivity by disrupting the correlation between higher mPFC oscillations and slower reaction times during conflict. In order to test whether theta band coherence between the mPFC and the STN underlies adjustments to conflict and to errors, we simultaneously recorded mPFC and STN electrophysiological activity while DBS patients performed an arrowed flanker task. These recordings revealed higher theta phase coherence between the two sites during the high conflict trials relative to the low conflict trials. These differences were observed soon after conflicting arrows were displayed, but before a response was executed. Furthermore, trials that occurred after an error was committed showed higher phase coherence relative to trials that followed a correct trial, suggesting that mPFC-STN connectivity may also play a role in error related adjustments in behavior. Interestingly, the phase coherence we observed occurred before increases in theta power, implying that the theta phase and power may influence behavior at separate times during cortical monitoring. Finally, we showed that pre-stimulus differences in STN theta power were related to the reaction time on a given trial, which may help adjust behavior based on the probability of observing conflict during a task. PMID:27181763

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

    PubMed

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

    2013-08-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. D2 dopamine receptors modulate neuronal resonance in subthalamic nucleus and cortical high-voltage spindles through HCN channels.

    PubMed

    Yang, Chen; Yan, Zhiqiang; Zhao, Bo; Wang, Julei; Gao, Guodong; Zhu, Junling; Wang, Wenting

    2016-06-01

    The high-voltage spindles (HVSs), one of the characteristic oscillations that include theta frequencies in the basal ganglia (BG)-cortical system, are involved in immobile behavior and show increasing power in Parkinson's disease (PD). Our previous results suggested that the D2 dopamine receptor might be involved in HVSs modulations in a rat model of PD. Membrane resonance is one of the cellular mechanisms of network oscillation; therefore, we investigated how dopamine modulates the theta frequency membrane resonance of neurons in the subthalamic nucleus (STN), a central pacemaker of BG, and whether such changes in STN neurons subsequently alter HVSs in the BG-cortical system. In particular, we tested whether dopamine modulates HVSs through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels-dependent membrane resonance in STN neurons. We found that an antagonist of D2 receptors, but not of D1 receptors, inhibited membrane resonance and HCN currents of STN neurons through a G-protein activity in acute brain slices. Our further in vivo experiments using local injection of a D2 receptor antagonist or an HCN blocker in STNs of free-moving rats showed an increase in HVSs power and correlation in the BG-cortical system. Local injection of lamotrigine, an HCN agonist, counteracted the effect induced by the D2 antagonist. Taken together, our results revealed a potential cellular mechanism underlying HVSs activity modulation in the BG-cortical system, i.e. tuning HCN activities in STN neurons through dopamine D2 receptors. Our findings might lead to a new direction in PD treatment by providing promising new drug targets for HVSs activity modulation. PMID:26808313

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

    PubMed

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

    2003-12-01

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

  8. Releasing metal catalysts via phase transition: (NiO)0.05-(SrTi0.8Nb0.2O3)0.95 as a redox stable anode material for solid oxide fuel cells.

    PubMed

    Xiao, Guoliang; Wang, Siwei; Lin, Ye; Zhang, Yanxiang; An, Ke; Chen, Fanglin

    2014-11-26

    Donor-doped perovskite-type SrTiO3 experiences stoichiometric changes at high temperatures in different Po2 involving the formation of Sr or Ti-rich impurities. NiO is incorporated into the stoichiometric strontium titanate, SrTi0.8Nb0.2O3-δ (STN), to form an A-site deficient perovskite material, (NiO)0.05-(SrTi0.8Nb0.2O3)0.95 (Ni-STN), for balancing the phase transition. Metallic Ni nanoparticles can be released upon reduction instead of forming undesired secondary phases. This material design introduces a simple catalytic modification method with good compositional control of the ceramic backbones, by which transport property and durability of solid oxide fuel cell anodes are largely determined. Using Ni-STN as anodes for solid oxide fuel cells, enhanced catalytic activity and remarkable stability in redox cycling have been achieved. Electrolyte-supported cells with the cell configuration of Ni-STN-SDC anode, La0.8Sr0.2Ga0.87Mg0.13O3 (LSGM) electrolyte, and La0.6Sr0.4Co0.2Fe0.8O3 (LSCF) cathode produce peak power densities of 612, 794, and 922 mW cm(-2) at 800, 850, and 900 °C, respectively, using H2 as the fuel and air as the oxidant. Minor degradation in fuel cell performance resulted from redox cycling can be recovered upon operating the fuel cells in H2. Such property makes Ni-STN a promising regenerative anode candidate for solid oxide fuel cells. PMID:25333295

  9. Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

    PubMed

    Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

    2012-11-01

    Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. PMID:22845853

  10. Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

    PubMed

    Yágüez, Lidia; Costello, Angela; Moriarty, John; Hulse, Natasha; Selway, Richard; Clough, Chris; Samuel, Michael; Ashkan, Keyoumars

    2014-03-01

    The beneficial effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the motor symptoms in advanced Parkinson's disease (PD) are well established. Early in PD, mild cognitive impairment is present in a proportion of patients. Hence, it can also be present in PD patients considered for DBS. The potential impact of even a modest decline post-surgically is a concern because it could result in impaired cognitive function. Therefore, attempts to determine which pre-operative cognitive measures predict post-operative cognitive change warrant further attention. We report our findings in a cohort of 30 routinely operated non-demented patients who underwent detailed neuropsychological assessments on average 7.1 months before and 9.4 months after STN DBS. We report the individual and group differences pre- and post-DBS. Stepwise regression analysis was used to analyse the best cognitive predictors of post-operative cognitive changes. We describe our data in relation to published normative data. Post-STN DBS, the immediate story recall component of verbal memory was the most affected cognitive function showing a significant decline in its group mean with a large effect size. The best predictors for this change were pre-surgical list learning and Full Scale Intelligence Quotient. These results suggest that non-demented patients, with even mild impairments in both general intellectual functions and list learning, may be at greater risk of decline in other aspects of verbal memory after STN DBS. Pre-existing mild executive dysfunction was not influenced post-operatively. These findings may help selection and consent for STN DBS. PMID:24231557

  11. Parkinson subtype-specific Granger-causal coupling and coherence frequency in the subthalamic area.

    PubMed

    Florin, Esther; Pfeifer, Johannes; Visser-Vandewalle, Veerle; Schnitzler, Alfons; Timmermann, Lars

    2016-09-22

    Previous work on Parkinson's disease (PD) has indicated a predominantly afferent coupling between affected arm muscle activity and electrophysiological activity within the subthalamic nucleus (STN). So far, no information is available indicating which frequency components drive the afferent information flow in PD patients. Non-directional coupling e.g. by measuring coherence is primarily established in the beta band as well as at tremor frequency. Based on previous evidence it is likely that different subtypes of the disease are associated with different connectivity patterns. Therefore, we determined coherence and causality between local field potentials (LFPs) in the STN and surface electromyograms (EMGs) from the contralateral arm in 18 akinetic-rigid (AR) PD patients and 8 tremor-dominant (TD) PD patients. During the intraoperative recording, patients were asked to lift their forearm contralateral to the recording side. Significantly more afferent connections were detected for the TD patients for tremor-periods and non-tremor-periods combined as well as for only tremor periods. Within the STN 74% and 63% of the afferent connections are associated with coherence from 4-8Hz and 8-12Hz, respectively. However, when considering only tremor-periods significantly more afferent than efferent connections were associated with coherence from 12 to 20Hz across all recording heights. No difference between efferent and afferent connections is seen in the frequency range from 4 to 12Hz for all recording heights. For the AR patients, no significant difference in afferent and efferent connections within the STN was found for the different frequency bands. Still, for the AR patients dorsal of the STN significantly more afferent than efferent connections were associated with coherence in the frequency range from 12 to 16Hz. These results provide further evidence for the differential pathological oscillations and pathways present in AR and TD Parkinson patients. PMID:27393252

  12. The combined depletion of monoamines alters the effectiveness of subthalamic deep brain stimulation.

    PubMed

    Faggiani, Emilie; Delaville, Claire; Benazzouz, Abdelhamid

    2015-10-01

    Non-motor symptoms of Parkinson's disease are under-studied and therefore not well treated. Here, we investigated the role of combined depletions of dopamine, norepinephrine and/or serotonin in the manifestation of motor and non-motor deficits in the rat. Then, we studied the impact of these depletions on the efficacy of deep brain stimulation of the subthalamic nucleus (STN-DBS). We performed selective depletions of dopamine, norepinephrine and serotonin, and the behavioral effects of different combined depletions were investigated using the open field, the elevated plus maze and the forced swim test. Bilateral dopamine depletion alone induced locomotor deficits associated with anxiety and mild "depressive-like" behaviors. Although additional depletions of norepinephrine and/or serotonin did not potentiate locomotor and anxiety disorders, combined depletions of the three monoamines dramatically exacerbated "depressive-like" behavior. STN-DBS markedly reversed locomotor deficits and anxiety behavior in animals with bilateral dopamine depletion alone. However, these improvements were reduced or lost by the additional depletion of norepinephrine and/or serotonin, indicating that the depletion of these monoamines may interfere with the antiparkinsonian efficacy of STN-DBS. Furthermore, our results showed that acute STN-DBS improved "depressive-like" disorder in animals with bilateral depletion of dopamine and also in animals with combined depletions of the three monoamines, which induced severe immobility in the forced swim test. Our data highlight the key role of monoamine depletions in the pathophysiology of anxiety and depressive-like disorders and provide the first evidence of their negative consequences on the efficacy of STN-DBS upon the motor and anxiety disorders in the context of Parkinson's disease. PMID:26206409

  13. Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus

    PubMed Central

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

    2015-01-01

    Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory–motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing. PMID:26594626

  14. Subthalamic Nucleus Deep Brain Stimulation Impacts Language in Early Parkinson's Disease

    PubMed Central

    Phillips, Lara; Litcofsky, Kaitlyn A.; Pelster, Michael; Gelfand, Matthew

    2012-01-01

    Although deep brain stimulation (DBS) of the basal ganglia improves motor outcomes in Parkinson's disease (PD), its effects on cognition, including language, remain unclear. This study examined the impact of subthalamic nucleus (STN) DBS on two fundamental capacities of language, grammatical and lexical functions. These functions were tested with the production of regular and irregular past-tenses, which contrast aspects of grammatical (regulars) and lexical (irregulars) processing while controlling for multiple potentially confounding factors. Aspects of the motor system were tested by contrasting the naming of manipulated (motor) and non-manipulated (non-motor) objects. Performance was compared between healthy controls and early-stage PD patients treated with either DBS/medications or medications alone. Patients were assessed on and off treatment, with controls following a parallel testing schedule. STN-DBS improved naming of manipulated (motor) but not non-manipulated (non-motor) objects, as compared to both controls and patients with just medications, who did not differ from each other across assessment sessions. In contrast, STN-DBS led to worse performance at regulars (grammar) but not irregulars (lexicon), as compared to the other two subject groups, who again did not differ. The results suggest that STN-DBS negatively impacts language in early PD, but may be specific in depressing aspects of grammatical and not lexical processing. The finding that STN-DBS affects both motor and grammar (but not lexical) functions strengthens the view that both depend on basal ganglia circuitry, although the mechanisms for its differential impact on the two (improved motor, impaired grammar) remain to be elucidated. PMID:22880117

  15. Activation of caspase-3 and its correlation with shear force in bovine skeletal muscles during postmortem conditioning.

    PubMed

    Cao, J-X; Ou, C-R; Zou, Y-F; Ye, K-P; Zhang, Q-Q; Khan, M A; Pan, D-D; Zhou, G

    2013-09-01

    The study was aimed at exploring the mechanism of tenderization by establishing a correlation between caspase-3 activity and shear force, verifying the activation occurring by analyzing active caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) fragments, and understanding the pathways involved in activation of caspase-3 by evaluating its correlation with caspase-8 and -9 activities in LM, semitendinosus (STN), and psoas minor (PM) muscles. The results indicated that shear force decreased at 48 h in PM (P < 0.01), LM (P < 0.01), and STN (P < 0.05). We detected p22, p23, p20, and p18 caspase fragments as well as distinctive PARP fragments of 24 kDa by caspase-3 and 36 kDa by µ-calpain. Caspase-3 activity correlated with shear force negatively at 24 and 48 h in STN (P < 0.01 at 24 h; P < 0.01 at 48 h), PM (P < 0.001 at 24 h; P < 0.01 at 48 h), and LM muscles (P < 0.05 at 24 h; P < 0.01 at 48 h). The greatest activities of caspase-8 (P < 0.001 in PM and STN; P < 0.01 in LM) and caspase-9 (P < 0.001 in muscles) appeared at 4 h whereas that of caspase-3 was at 24 h (P < 0.001 in muscles). Caspase-9 activity correlated positively with caspase-3 at 4, 24, and 48 h in STN (P < 0.01 at 4 h; P < 0.05 at 24 h; P < 0.001 at 48 h) and at 4 and 96 h in PM (P < 0.001 at 4 h; P < 0.05 at 96 h) and LM muscles (P < 0.001 at 4 h; P < 0.001 at 96 h). The caspase-8 activity correlated with caspase-3 at 4, 48, and 96 h in STN (P < 0.05 at 4 h; P < 0.001 at 48 h; P < 0.05 at 96 h), at 4 and 24 h in PM (P < 0.001 at 4 h; P < 0.05 at 24 h), and at 4 and 96 h in LM (P < 0.001 at 4 h; P < 0.01 at 96 h). We concluded that caspase-3 was associated with the decline of shear force; the activation of caspase-3 was mediated by caspases -8 and -9 in muscles. However, more detailed studies are needed to define the precise mechanism for the cleavage of pro-caspases -8 and -9 during conditioning. PMID:23893998

  16. Novel driving scheme for FLCD

    NASA Astrophysics Data System (ADS)

    Wu, Jiin-chuan; Wang, Chi-Chang

    1996-03-01

    A frame change data driving scheme (FCDDS) for ferroelectric LCD(FLCD) of matrix- addressing is developed which uses only positive voltages for the row and column waveforms to achieve bipolar driving waveforms on the FLCD pixels. Thus the required supply voltage for the driver chips is half that of the conventional driving scheme. Each scan line is addressed in only twice the switching time (tau) (minimum response time of FLC) so that this scheme is suitable for high duty ratio panels. In order to meet this bistable electro-optic effect of FLCD and zero net dc voltage across each pixel of the liquid crystal, turning on and turning off pixels are done at different time slots and frame slots. This driving scheme can be easily implemented using commercially available STN LCD drivers plus a small external circuit or by making an ASIC which is a slight modification of the STN driver. Both methods are discussed.

  17. Sensitivity of inverse estimation of 2004 elemental carbon emissions inventory in the United States to the choice of observational networks

    NASA Astrophysics Data System (ADS)

    Hu, Yongtao; Napelenok, Sergey L.; Odman, M. Talat; Russell, Armistead G.

    2009-08-01

    Choice of observational networks for inverse re-estimation of elemental carbon (EC) emissions in the United States impacts results. We convert the Thermal Optical Transmittance (TOT) EC measurements to the Thermal Optical Reflectance (TOR) equivalents to make full utilization of available networks in inverse modeling of EC using regional air quality model. Results show that using the Interagency Monitoring of Protected Visual Environments (IMPROVE) network gives significantly lower emissions estimate compared to using the Speciation Trends Network (STN) and other networks or using all available networks together. The re-estimate obtained by using IMPROVE sites alone made overall model performance worse compared to the bottom-up estimate of EC emissions, while both re-estimates, using STN (and others) sites and using all sites together, significantly improved the performance, showing higher robustness. Further analysis suggests that site density with respect to geographical location (downwind of source) impacts the robustness of a network's inverse re-estimate.

  18. Temperature dependence of the deformation behavior of 316 stainless steel after low temperature neutron irradiation

    SciTech Connect

    Pawel-Robertson, J.E.; Rowcliffe, A.F.; Grossbeck, M.L.

    1996-10-01

    The effects of low temperature neutron irradiation on the tensile behavior of 316 stainless steel have been investigated. A single heat of solution annealed 316 was irradiated to 7 and 18 dpa at 60, 200, 330, and 400{degrees}C. The tensile properties as a function of dose and as a function of temperature were examined. Large changes in yield strength, deformation mode, strain to necking, and strain hardening capacity were seen in this irradiation experiment. The magnitudes of the changes are dependent on both irradiation temperature and neutron dose. Irradiation can more than triple the yield strength over the unirradiated value and decrease the strain to necking (STN) to less than 0.5% under certain conditions. A maximum increase in yield strength and a minimum in the STN occur after irradiation at 330{degrees}C but the failure mode remains ductile.

  19. Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation on gait kinematics in Parkinson's disease: a randomized, blinded study.

    PubMed

    Lizarraga, Karlo J; Jagid, Jonathan R; Luca, Corneliu C

    2016-08-01

    Gait dysfunction in Parkinson's disease (PD) does not always respond to bilateral subthalamic nucleus deep brain stimulation (STN-DBS). Since right hemisphere motor networks may be dominant for gait control, identical stimulation of asymmetric circuits could account for gait dysfunction. We compared the effects of bilateral and unilateral STN-DBS on gait kinematics in PD patients who developed gait impairment after STN-DBS. Twenty-two PD patients with >50 % improvement in motor scores, but dopamine-resistant gait dysfunction 6-12 months after bilateral STN-DBS were blindly tested off dopaminergic effects in four randomly assigned DBS conditions: bilateral, right-sided, left-sided and off stimulation. Motor scores (MDS-UPDRS III), gait scores (MDS-UPRDS 2.11-2.13 + 3.9-3.13), turning time (seconds), stride length (meters) and velocity (meters/second) were measured 1 h after DBS changes. Motor and gait scores significantly improved with bilateral versus unilateral STN-DBS. Stride length and velocity (0.95 ± 0.06, 0.84 ± 0.07) significantly improved with bilateral (1.09 ± 0.04, 0.95 ± 0.05), right-sided (1.06 ± 0.04, 0.92 ± 0.05) and left-sided stimulation (1.01 ± 0.05, 0.90 ± 0.05) (p < 0.05). Stride length significantly improved with right-sided versus left-sided (0.05 ± 0.02) and bilateral versus left-sided stimulation (0.07 ± 0.02) (p < 0.05). Turning time (4.89 ± 0.6) tended to improve with bilateral (4.13 ± 0.5) (p = 0.15) and right-sided (4.27 ± 0.6) (p = 0.2) more than with left STN-DBS (4.69 ± 0.5) (p = 0.5). Bilateral STN-DBS yields greater improvement in motor and gait scores in PD patients. Yet, unilateral stimulation has similar effects on gait kinematics. Particularly, right-sided stimulation might produce slightly greater improvements. Although the clinical relevance of differential programming of right versus left-sided STN-DBS is unclear, this approach could be considered in the management of

  20. Randomness switches the dynamics in a biophysical model for Parkinson Disease

    NASA Astrophysics Data System (ADS)

    Spiliotis, Konstantinos G.; Radhakrishnan, Hari; Georgiou, George C.

    2012-09-01

    The interpallidal network of the two areas, the Globus Pallidus External (GPE) and the Subthalamic nucleus, (STN) plays an important role for controlling the movement. Changes in the dynamics of this network are closed related with the Parkinson Disease (PD) symptoms. In this paper we show how the connectivity between these two areas affects the dynamics of a biophysical-based neuronal-model. By changing the kind of interconnection from local (or lattice) to random structure between the two areas, the system switches the dynamics from correlated and clustered firing state (associated with PD) to a relatively quietness and less correlate state. In addition, the synchronization of the GPE and STN with respect to the connectivity distribution is examined by using the phase synchronization index.

  1. Altitudinal gradients of soil and vegetation carbon and nitrogen in a high altitude nature reserve of Karakoram ranges.

    PubMed

    Shedayi, Arshad Ali; Xu, Ming; Naseer, Iqnaa; Khan, Babar

    2016-01-01

    This study aimed to investigate the correlation of carbon and nitrogen in soil and leaves with the altitude, vegetation type, herbaceous biomass (HB), litter mass (LM) and with each other. Soil and leaf samples collected from different forest types along altitudinal gradients in the Karakoram Mountains. Dry and gas law methods were used for the chemical analysis. Regression models used for correlation analysis and T test for comparison. The correlation of soil total carbon (STC) and soil total nitrogen (STN) along altitudinal gradients and correlation between soil organic carbon (SOC) and STN was significantly positive with the values R(2) = 0.1684, p = 0.01, R(2) = 0.1537, p = 0.009 and R(2) = 0.856, p = 7.31E-10 respectively, while it was non-significant between soil inorganic carbon (SIC) and altitude and also between SIC and STN. The concentration of SOC and STN was highest in the broad leaved Betula utilis forest (22.31, 1.6 %) and least in the mixed (Pinus, Juniper, Betula) forest soil (0.85, 0.09 %) respectively. In the tree species leaf total carbon (LTC) and leaf total nitrogen (LTN) were highest in the Pinus wallichiana (PW) (632.54, 19.77), and least in the Populus alba (87.59, 4.06). In the shrub species LTC and LTN nitrogen were highest in the Rosa webiana (235.64, 7.45) and least in the Astragalus gilgitensis (43.45, 1.60) respectively. Total carbon and total nitrogen showed a slightly decreasing and increasing trend with altitude in the leaf and soil samples, respectively. The mean nitrogen and carbon was higher in the leaves of trees (3, 97.95) than in the shrubs (2.725, 74.24) and conifers (2.26, 76.46) than in the leaves of the deciduous (2, 46.36) trees. The correlation between LTC and STN was non-significant. Strong significant (R(2) = 0.608, p = 0.003) and weak non-significant (R(2) = 0.04, p = 0.32) relationships were found in STN and STC with LM and HB respectively. SOC (75.15 %) was found to be the main contributor to

  2. Parkinsonian beta oscillations in the external globus pallidus and their relationship with subthalamic nucleus activity.

    PubMed

    Mallet, Nicolas; Pogosyan, Alek; Márton, László F; Bolam, J Paul; Brown, Peter; Magill, Peter J

    2008-12-24

    Inappropriately synchronized beta (beta) oscillations (15-30 Hz) in the subthalamic nucleus (STN) accompany movement difficulties in idiopathic Parkinson's disease (PD). The cellular and network substrates underlying these exaggerated beta oscillations are unknown but activity in the external globus pallidus (GP), which forms a candidate pacemaker network with STN, might be of particular importance. Using a clinically relevant rat model of PD, we demonstrate that oscillatory activity in GP neuronal networks becomes excessively and selectively synchronized at beta frequencies in a spatially widespread and brain state-dependent manner after lesion of dopamine neurons. Although synchronization of GP unit activity increased by almost 100-fold during beta oscillations, the mean firing rate of GP neurons decreased compared with controls. Importantly, in parkinsonian animals, two main types of GP neuron were identified according to their distinct and inversely related firing rates and patterns. Moreover, neurons of the same type tended to fire together, with small phase differences, whereas different types of neuron tended not to do so. This functional dichotomy in temporal coupling persisted across extreme brain states, suggesting that maladaptive interactions are dominated by hardwiring. Finally, the precisely timed discharges of GP and STN neurons indicated that rhythmic sequences of recurrent excitation and inhibition in the STN-GP network, and lateral inhibition between GP neurons, could actively support abnormal beta oscillations. We propose that GP neurons, by virtue of their spatiotemporal synchronization, widespread axon collaterals and feed-back/feed-forward mechanisms, are well placed to orchestrate and propagate exaggerated beta oscillations throughout the entire basal ganglia in PD. PMID:19109506

  3. Effects of Subthalamic Nucleus Stimulation on Emotional Prosody Comprehension in Parkinson's Disease

    PubMed Central

    Kreifelts, Benjamin; Krüger, Rejko; Wächter, Tobias

    2011-01-01

    Background Although impaired decoding of emotional prosody has frequently been associated with Parkinson's disease (PD), to date only few reports have sought to explore the effect of Parkinson's treatment on disturbances of prosody decoding. In particular, little is known about how surgical treatment approaches such as high frequency deep brain stimulation (DBS) affect emotional speech perception in patients with PD. Accordingly, the objective of this study was to evaluate the effect of subthalamic nucleus (STN) stimulation on prosody processing. Methodology/Principal Findings To this end the performance of 13 PD patients on three tasks requiring the decoding of emotional speech was assessed and subsequently compared to the performance of healthy control individuals. To delineate the effect of STN-DBS, all patients were tested with stimulators turned on as well as with stimulators turned off. Results revealed that irrespective of whether assessments were made “on” or “off” stimulation, patients' performance was less accurate as compared to healthy control participants on all tasks employed in this study. However, while accuracy appeared to be unaffected by stimulator status, a facilitation of reactions specific to highly conflicting emotional stimulus material (i.e. stimulus material presenting contradicting emotional messages on a verbal and non-verbal prosodic level) was observed during “on” stimulation assessments. Conclusion In sum, presented results suggest that the processing of emotional speech is indeed modulated by STN-DBS. Observed alterations might, on the one hand, reflect a more efficient processing of highly conflicting stimulus material following DBS. However, on the other hand, given the lack of an improvement in accuracy, increased impulsivity associated with STN stimulation needs to be taken into consideration. PMID:21552518

  4. Altered Neuronal Firing Pattern of the Basal Ganglia Nucleus Plays a Role in Levodopa-Induced Dyskinesia in Patients with Parkinson’s Disease

    PubMed Central

    Li, Xiaoyu; Zhuang, Ping; Li, Yongjie

    2015-01-01

    Background: Levodopa therapy alleviates the symptoms of Parkinson’s disease (PD), but long-term treatment often leads to motor complications such as levodopa-induced dyskinesia (LID). Aim: To explore the neuronal activity in the basal ganglia nuclei in patients with PD and LID. Methods: Thirty patients with idiopathic PD (age, 55.1 ± 11.0 years; disease duration, 8.7 ± 5.6 years) were enrolled between August 2006 and August 2013 at the Xuanwu Hospital, Capital Medical University, China. Their Hoehn and Yahr (1967) scores ranged from 2–4 and their UPDRS III scores were 28.5 ± 5.2. Fifteen of them had severe LID (UPDRS IV scores of 6.7 ± 1.6). Microelectrode recording was performed in the globus pallidus internus (GPi) and subthalamic nucleus (STN) during pallidotomy (n = 12) or STN deep brain stimulation (DBS; bilateral, n = 12; unilateral, n = 6). The firing patterns and frequencies of various cell types were analyzed by assessing single cell interspike intervals (ISIs) and the corresponding coefficient of variation (CV). Results: A total of 295 neurons were identified from the GPi (n = 12) and STN (n = 18). These included 26 (8.8%) highly grouped discharge, 30 (10.2%) low frequency firing, 78 (26.4%) rapid tonic discharge, 103 (34.9%) irregular activity, and 58 (19.7%) tremor-related activity. There were significant differences between the two groups (p < 0.05) for neurons with irregular firing, highly irregular cluster-like firing, and low-frequency firing. Conclusion: Altered neuronal activity was observed in the basal ganglia nucleus of GPi and STN, and may play important roles in the pathophysiology of PD and LID. PMID:26635583

  5. Chemical mass balance source apportionment for combined PM 2.5 measurements from U.S. non-urban and urban long-term networks

    NASA Astrophysics Data System (ADS)

    Antony Chen, L.-W.; Watson, John G.; Chow, Judith C.; DuBois, David W.; Herschberger, Lisa

    2010-12-01

    The Minnesota Particulate Matter 2.5 (PM 2.5) Source Apportionment Study was undertaken to explore the utility of PM 2.5 mass, element, ion, and carbon measurements from long-term speciation networks for pollution source attribution. Ambient monitoring data at eight sites across the state were retrieved from the archives of the Interagency Monitoring of Protected Visual Environments (IMPROVE) and the Speciation Trends Network (STN; part of the Chemical Speciation Network [CSN]) and analyzed by an Effective Variance - Chemical Mass Balance (EV-CMB) receptor model with region-specific geological source profiles developed in this study. PM 2.5 was apportioned into contributions of fugitive soil dust, calcium-rich dust, taconite (low grade iron ore) dust, road salt, motor vehicle exhaust, biomass burning, coal-fired utility, and secondary aerosol. Secondary sulfate and nitrate contributed strongly (49-71% of PM 2.5) across all sites and was dominant (≥60%) at IMPROVE sites. Vehicle exhausts accounted for 20-70% of the primary PM 2.5 contribution, largely exceeding the proportion in the primary PM 2.5 emission inventory. The diesel exhaust contribution was separable from the gasoline engine exhaust contribution at the STN sites. Higher detection limits for several marker elements in the STN resulted in non-detectable coal-fired boiler contributions which were detected in the IMPROVE data. Despite the different measured variables, analytical methods, and detection limits, EV-CMB results from a nearby IMPROVE-STN non-urban/urban sites showed similar contributions from regional sources - including fugitive dust and secondary aerosol. Seasonal variations of source contributions were examined and extreme PM 2.5 episodes were explained by both local and regional pollution events.

  6. Understanding the impact of deep brain stimulation on ambulatory activity in advanced Parkinson's disease.

    PubMed

    Rochester, Lynn; Chastin, Sebastien Francois Martin; Lord, Sue; Baker, Katherine; Burn, David John

    2012-06-01

    Whilst deep brain stimulation of the subthalamic nucleus (DBS-STN) improves the motor symptoms of Parkinson's disease (PD), its effect on daily activity is unknown. We aimed to quantify changes in ambulatory activity following DBS-STN in advanced PD using novel accelerometry based measures that describe changes to the volume and pattern of walking. Seventeen participants with advanced PD were measured over a 7-day period using an activPAL (™) activity monitor. Data were collected 6 weeks before and 6 months after surgery and included measures that describe the volume and pattern of ambulatory activity (number of steps per day, accumulation, diversity and variability of walking time), alongside standard measures for disease severity, freezing of gait, gait speed, and extended activities of daily living. Activity outcomes were compared pre- and 6 months post-surgery using linear mixed models and correlated with standard outcomes. The results of this study are despite significant improvements in motor symptoms after surgery, the volume of ambulatory activity (total number of steps per day) did not change (P = 0.468). However, significant increases in length and variability of walking bouts emerged, suggesting improvements in diversity and flexibility of walking patterns. Motor severity and extended activities of daily living scores were significantly correlated with walking bout variability but not with volume of walking. Thus, the conclusions are reduction in motor symptom severity after DBS-STN translated into selective improvements in daily activity. Novel measures derived from accelerometry provide a discrete measure of performance and allow closer interpretation of the impact of DBS-STN on real-world activity. PMID:22086738

  7. A spiking Basal Ganglia model of synchrony, exploration and decision making

    PubMed Central

    Mandali, Alekhya; Rengaswamy, Maithreye; Chakravarthy, V. Srinivasa; Moustafa, Ahmed A.

    2015-01-01

    To make an optimal decision we need to weigh all the available options, compare them with the current goal, and choose the most rewarding one. Depending on the situation an optimal decision could be to either “explore” or “exploit” or “not to take any action” for which the Basal Ganglia (BG) is considered to be a key neural substrate. In an attempt to expand this classical picture of BG function, we had earlier hypothesized that the Indirect Pathway (IP) of the BG could be the subcortical substrate for exploration. In this study we build a spiking network model to relate exploration to synchrony levels in the BG (which are a neural marker for tremor in Parkinson's disease). Key BG nuclei such as the Sub Thalamic Nucleus (STN), Globus Pallidus externus (GPe) and Globus Pallidus internus (GPi) were modeled as Izhikevich spiking neurons whereas the Striatal output was modeled as Poisson spikes. The model is cast in reinforcement learning framework with the dopamine signal representing reward prediction error. We apply the model to two decision making tasks: a binary action selection task (similar to one used by Humphries et al., 2006) and an n-armed bandit task (Bourdaud et al., 2008). The model shows that exploration levels could be controlled by STN's lateral connection strength which also influenced the synchrony levels in the STN-GPe circuit. An increase in STN's lateral strength led to a decrease in exploration which can be thought as the possible explanation for reduced exploratory levels in Parkinson's patients. Our simulations also show that on complete removal of IP, the model exhibits only Go and No-Go behaviors, thereby demonstrating the crucial role of IP in exploration. Our model provides a unified account for synchronization, action section, and explorative behavior. PMID:26074761

  8. Enhanced expression of glutamate decarboxylase 65 improves symptoms of rat parkinsonian models.

    PubMed

    Lee, B; Lee, H; Nam, Y R; Oh, J H; Cho, Y H; Chang, J W

    2005-08-01

    In this study, we report the amelioration of parkinsonian symptoms in rat Parkinson's disease (PD) models, as a result of the expression of glutamate decarboxylase (GAD) 65 with a modified cytomegalovirus (CMV) promoter. The transfer of the gene for gamma-amino butryic acid (GAD), the rate-limiting enzyme in gama-amino butrylic acid (GABA) production, has been investigated as a means to increase inhibitory synaptic activity. Electrophysiological evidence suggests that the transfer of the GAD65 gene to the subthalamic nucleus (STN) can change the excitatory output of this nucleus to inhibitory output. Our in vitro results also demonstrated higher GAD65 expression in cells transfected with the JDK promoter, as compared to cells transfected with the CMV promoter. Also, a rat PD model in which recombinant adeno-associated virus-2 (rAAV2)-JDK-GAD65 was delivered into the STN exhibited significant behavioral improvements, as compared to the saline-injected group. Interestingly, we observed that these behavioral improvements were more obvious in rat PD models in which rAAV2-JDK-GAD65 was injected into the STN than in rat PD models in which rAAV2-CMV-GAD65 was injected into the STN. Moreover, according to electrophysiological data, the rAAV2-JDK-GAD65-injected group exhibited more constant improvements in firing rates than did the rAAV2-CMV-GAD65-injected group. These data indicate that the JDK promoter, when coupled with GAD65 expression, is more effective with regard to parkinsonian symptoms than is the CMV promoter. PMID:15829994

  9. Preserved dichotomy but highly irregular and burst discharge in the basal ganglia in alert dystonic rats at rest.

    PubMed

    Kumbhare, Deepak; Chaniary, Kunal D; Baron, Mark S

    2015-10-22

    Despite its prevalence, the underlying pathophysiology of dystonia remains poorly understood. Using our novel tri-component classification algorithm, extracellular neuronal activity in the globus pallidus (GP), STN, and the entopeduncular nucleus (EP) was characterized in 34 normal and 25 jaundiced dystonic Gunn rats with their heads restrained while at rest. In normal rats, neurons in each nucleus were similarly characterized by two physiologically distinct types: regular tonic with moderate discharge frequencies (mean rates in GP, STN and EP ranging from 35-41 spikes/s) or irregular at slower frequencies (17-20 spikes/s), with a paucity of burst activity. In dystonic rats, these nuclei were also characterized by two distinct principal neuronal patterns. However, in marked difference, in the dystonic rats, neurons were primarily slow and highly irregular (12-15 spikes/s) or burst predominant (14-17 spikes/s), with maintained modest differences between nuclei. In GP and EP, with increasing severity of dystonia, burstiness was moderately further increased, irregularity mildly further increased, and discharge rates mildly further reduced. In contrast, these features did not appreciably change in STN with worsening dystonia. Findings of a lack of bursting in GP, STN and EP in normal rats in an alert resting state and prominent bursting in dystonic Gunn rats suggest that cortical or other external drive is normally required for bursting in these nuclei and that spontaneous bursting, as seen in dystonia and Parkinson's disease, is reflective of an underlying pathophysiological state. Moreover, the extent of burstiness appears to most closely correlate with the severity of the dystonia. PMID:26210616

  10. Deep Brain Stimulation in Early Stage Parkinson’s Disease: Operative Experience from a Prospective, Randomized Clinical Trial

    PubMed Central

    Kahn, Elyne; D'Haese, Pierre-Francois; Dawant, Benoit; Allen, Laura; Kao, Chris; Charles, P. David; Konrad, Peter

    2013-01-01

    Background Recent evidence suggests that STN-DBS may have a disease-modifying effect in early PD. A randomized, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable. Objectives / Methods Fifteen of thirty early PD patients were randomized to receive STN-DBS implants in an IRB-approved protocol. Operative technique, location of DBS leads, and perioperative adverse events are reported. Active contact used for stimulation in these patients were compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon. Results Fourteen of the 15 patients did not sustain any long-term (> 3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior −1.1±1.7mm, lateral 10.7±1.7mm, superior −3.3±2.5mm (AC-PC coordinates). This location is statistically no different (0.77mm, p> 0.05) than the optimal contact used in treatment of 47 advanced PD patients. Conclusions The perioperative adverse events in this trial of subjects with early stage PD are comparable to that reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomized, surgical-versus-best-medical-therapy trial for the early treatment of Parkinson’s disease. PMID:21890575

  11. Interaction of Reinforced Elastomeric Bearings in Bridge Construction

    NASA Astrophysics Data System (ADS)

    Nittmannová, Ľubica; Magura, Martin

    2016-03-01

    The aim of this paper is to demonstrate the behavior of reinforced elastomeric bearings under various loads. They are made of special types of bearings. The experimental verification of these special bearings has been tested on various types of loading. The results of the experimental measurements are compared with the results of the numerical modeling and calculations according to the standard assumptions in STN EN 1337-3. In the conclusion, the results are summarized for the selected types of bearings.

  12. Subthalamic Nucleus Discharge Patterns during Movement in the Normal Monkey and Parkinsonian Patient

    PubMed Central

    Gale, John T.; Shields, Donald C.; Jain, Felipe A.; Amirnovin, Ramin; Eskandar, Emad N.

    2009-01-01

    The pathophysiology of Parkinson disease (PD) is characterized by derangements in the discharge rates, bursting patterns, and oscillatory activity of basal ganglia (BG) neurons. In this study, subthalamic nucleus (STN) neuronal activity patterns in humans with PD was compared with that in the normal monkey during performance of similar volitional movements. Single-unit STN recordings were collected while PD patients and animals moved a joystick in the direction of targets presented on a monitor. When discharge rates in all PD human and normal monkey neurons were compared, no significant differences were observed. However, when neurons were classified by peri-movement response type (i.e., excited, inhibited, or unresponsive to movement) statistical differences were demonstrated – most significantly among PD excited neurons. Analysis of burst activity demonstrated inter- and intra-burst activities were greater in the PD human compared to the monkey irrespective of neuronal response type. Moreover, simultaneously recorded neurons in the human demonstrated consistent oscillatory synchronization at restricted frequency bands, whereas synchronized oscillatory neurons in the monkey were not restricted to distinct frequencies. During movement, discharge and burst rates were positively correlated, independent of subject or neuronal response type; however, rates and oscillatory activity were more strongly correlated in the PD human than the normal monkey. Interestingly, across all domains of analysis, STN neurons in PD demonstrated reduced response variability when compared to STN neurons in the normal monkey brain. Thus, the net effect of PD may be a reduction in the physiological degrees of freedom of BG neurons with diminished information carrying capacity. PMID:19167367

  13. The network of causal interactions for beta oscillations in the pedunculopontine nucleus, primary motor cortex, and subthalamic nucleus of walking parkinsonian rats.

    PubMed

    Li, Min; Zhou, Ming; Wen, Peng; Wang, Qiang; Yang, Yong; Xiao, Hu; Xie, Zhengyuan; Li, Xing; Wang, Ning; Wang, Jinyan; Luo, Fei; Chang, Jingyu; Zhang, Wangming

    2016-08-01

    Oscillatory activity has been well-studied in many structures within cortico-basal ganglia circuits, but it is not well understood within the pedunculopontine nucleus (PPN), which was recently introduced as a potential target for the treatment of gait and postural impairments in advanced stages of Parkinson's disease (PD). To investigate oscillatory activity in the PPN and its relationship with oscillatory activity in cortico-basal ganglia circuits, we simultaneously recorded local field potentials in the PPN, primary motor cortex (M1), and subthalamic nucleus (STN) of 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats during resting and walking. After analysis of power spectral density, coherence, and partial Granger causality, three major findings emerged: 1) after 6-OHDA lesions, beta band oscillations were enhanced in all three regions during walking; 2) the direction of information flow for beta oscillations among the three structures was STN→M1, STN→PPN, and PPN→M1; 3) after the treatment of levodopa, beta activity in the three regions was reduced significantly and the flow of beta band was also abrogated. Our results suggest that beta activity in the PPN is transmitted from the basal ganglia and probably comes from the STN, and the STN plays a dominant role in the network of causal interactions for beta activity. Thus, the STN may be a potential source of aberrant beta band oscillations in PD. Levodopa can inhibit beta activity in the PPN of parkinsonian rats but cannot relieve parkinsonian patients' axial symptoms clinically. Therefore, beta oscillations may not be the major cause of axial symptoms. PMID:27163550

  14. Cortico-striatal connections predict control over speed and accuracy in perceptual decision making

    PubMed Central

    Forstmann, Birte U.; Anwander, Alfred; Schäfer, Andreas; Neumann, Jane; Brown, Scott; Wagenmakers, Eric-Jan; Bogacz, Rafal; Turner, Robert

    2010-01-01

    When people make decisions they often face opposing demands for response speed and response accuracy, a process likely mediated by response thresholds. According to the striatal hypothesis, people decrease response thresholds by increasing activation from cortex to striatum, releasing the brain from inhibition. According to the STN hypothesis, people decrease response thresholds by decreasing activation from cortex to subthalamic nucleus (STN); a decrease in STN activity is likewise thought to release the brain from inhibition and result in responses that are fast but error-prone. To test these hypotheses—both of which may be true—we conducted two experiments on perceptual decision making in which we used cues to vary the demands for speed vs. accuracy. In both experiments, behavioral data and mathematical model analyses confirmed that instruction from the cue selectively affected the setting of response thresholds. In the first experiment we used ultra-high-resolution 7T structural MRI to locate the STN precisely. We then used 3T structural MRI and probabilistic tractography to quantify the connectivity between the relevant brain areas. The results showed that participants who flexibly change response thresholds (as quantified by the mathematical model) have strong structural connections between presupplementary motor area and striatum. This result was confirmed in an independent second experiment. In general, these findings show that individual differences in elementary cognitive tasks are partly driven by structural differences in brain connectivity. Specifically, these findings support a cortico-striatal control account of how the brain implements adaptive switches between cautious and risky behavior. PMID:20733082

  15. Subthalamic Nucleus Deep Brain Stimulation May Reduce Medication Costs in Early Stage Parkinson’s Disease

    PubMed Central

    Hacker, Mallory L.; Currie, Amanda D.; Molinari, Anna L.; Turchan, Maxim; Millan, Sarah M.; Heusinkveld, Lauren E.; Roach, Jonathon; Konrad, Peter E.; Davis, Thomas L.; Neimat, Joseph S.; Phibbs, Fenna T.; Hedera, Peter; Byrne, Daniel W.; Charles, David

    2016-01-01

    Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is well-known to reduce medication burden in advanced stage Parkinson’s disease (PD). Preliminary data from a prospective, single blind, controlled pilot trial demonstrated that early stage PD subjects treated with STN-DBS also required less medication than those treated with optimal drug therapy (ODT). Objective: The purpose of this study was to analyze medication cost and utilization from the pilot trial of DBS in early stage PD and to project 10 year medication costs. Methods: Medication data collected at each visit were used to calculate medication costs. Medications were converted to levodopa equivalent daily dose, categorized by medication class, and compared. Medication costs were projected to advanced stage PD, the time when a typical patient may be offered DBS. Results: Medication costs increased 72% in the ODT group and decreased 16% in the DBS+ODT group from baseline to 24 months. This cost difference translates into a cumulative savings for the DBS+ODT group of $7,150 over the study period. Projected medication cost savings over 10 years reach $64,590. Additionally, DBS+ODT subjects were 80% less likely to require polypharmacy compared with ODT subjects at 24 months (p <  0.05; OR = 0.2; 95% CI: 0.04–0.97). Conclusions: STN-DBS in early PD reduced medication cost over the two-year study period. DBS may offer substantial long-term reduction in medication cost by maintaining a simplified, low dose medication regimen. Further study is needed to confirm these findings, and the FDA has approved a pivotal, multicenter clinical trial evaluating STN-DBS in early PD. PMID:26967937

  16. Task specific inter-hemispheric coupling in human subthalamic nuclei

    PubMed Central

    Darvas, Felix; Hebb, Adam O.

    2014-01-01

    Cortical networks and quantitative measures of connectivity are integral to the study of brain function. Despite lack of direct connections between left and right subthalamic nuclei (STN), there are apparent physiological connections. During clinical examination of patients with Parkinson’s disease (PD), this connectivity is exploited to enhance signs of PD, yet our understanding of this connectivity is limited. We hypothesized that movement leads to synchronization of neural oscillations in bilateral STN, and we implemented phase coherence, a measure of phase-locking between cortical sites in a narrow frequency band, to demonstrate this synchronization. We analyzed task specific phase synchronization and causality between left and right STN local field potentials (LFPs) recorded from both hemispheres simultaneously during a cued movement task in four subjects with PD who underwent Deep Brain Stimulation (DBS) surgery. We used a data driven approach to determine inter-hemispheric channel pairs and frequencies with a task specific increase in phase locking.We found significant phase locking between hemispheres in alpha frequency (8–12 Hz) in all subjects concurrent with movement of either hand. In all subjects, phase synchronization increased over baseline upon or prior to hand movement onset and lasted until the motion ceased. Left and right hand movement showed similar patterns. Granger causality (GC) at the phase-locking frequencies between synchronized electrodes revealed a unidirectional causality from right to left STN regardless of which side was moved.Phase synchronization across hemispheres between basal ganglia supports existence of a bilateral network having lateralized regions of specialization for motor processing. Our results suggest this bilateral network is activated by a unilateral motor program. Understanding phase synchronization in natural brain functions is critical to development of future DBS systems that augment goal directed behavioral

  17. Effects of subthalamic nucleus stimulation on motor cortex plasticity in Parkinson disease

    PubMed Central

    Kim, Sang Jin; Udupa, Kaviraja; Ni, Zhen; Moro, Elena; Gunraj, Carolyn; Mazzella, Filomena; Lozano, Andres M.; Hodaie, Mojgan; Lang, Anthony E.

    2015-01-01

    Objective: We hypothesized that subthalamic nucleus (STN) deep brain stimulation (DBS) will improve long-term potentiation (LTP)-like plasticity in motor cortex in Parkinson disease (PD). Methods: We studied 8 patients with PD treated with STN-DBS and 9 age-matched healthy controls. Patients with PD were studied in 4 sessions in medication (Med) OFF/stimulator (Stim) OFF, Med-OFF/Stim-ON, Med-ON/Stim-OFF, and Med-ON/Stim-ON states in random order. Motor evoked potential amplitude and cortical silent period duration were measured at baseline before paired associated stimulation (PAS) and at 3 different time intervals (T0, T30, T60) up to 60 minutes after PAS in the abductor pollicis brevis and abductor digiti minimi muscles. Results: Motor evoked potential size significantly increased after PAS in controls (+67.7% of baseline at T30) and in patients in the Med-ON/Stim-ON condition (+55.8% of baseline at T30), but not in patients in the Med-OFF/Stim-OFF (−0.4% of baseline at T30), Med-OFF/Stim-ON (+10.3% of baseline at T30), and Med-ON/Stim-OFF conditions (+17.3% of baseline at T30). Cortical silent period duration increased after PAS in controls but not in patients in all test conditions. Conclusions: Our findings suggest that STN-DBS together with dopaminergic medications restore LTP-like plasticity in motor cortex in PD. Restoration of cortical plasticity may be one of the mechanisms of how STN-DBS produces clinical benefit. PMID:26156511

  18. Long-term impact on quality of life of subthalamic nucleus stimulation in Parkinson's disease.

    PubMed

    Lezcano, Elena; Gómez-Esteban, Juan Carlos; Tijero, Beatriz; Bilbao, Gaizka; Lambarri, Imanol; Rodriguez, Olivia; Villoria, Rafael; Dolado, Ainara; Berganzo, Koldo; Molano, Ana; de Gopegui, Edurne Ruiz; Pomposo, Iñigo; Gabilondo, Iñigo; Zarranz, Juan José

    2016-05-01

    Long-term impact of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on health-related quality of life (HRQOL) and associated factors in patients with Parkinson's disease (PD) are not clear. In this prospective study, we included 69 PD patients (64 % men, mean age 61.3 ± 7.4 and disease duration 13.2 ± 5.7 years) undergoing STN-DBS. They were evaluated preoperatively (baseline), 1 and 5 years postoperatively assessing 39-item Parkinson's Disease Questionnaire (PDQ-39), Schwab and England Activities of Daily Living Scale (SEADL), Unified Parkinson's Disease Rating Scale (UPDRS) off- and on-medication, patient diaries, dopaminergic treatment, mortality and surgical complications. Five years postoperatively, off-medication, there were improvements from baseline in UPDRS-II and III total (27.2 and 26.7 %, respectively) and SEADL (18.6 % more completely independent patients) (p < 0.05) scores, while on-medication, there was a deterioration in UPDRS-III (37.8 %, mainly axial signs) (p < 0.05) and minor improvements in SEADL (3.7 %). While at 1 year PDQ-39, the summary index improved substantially (36.5 %) (p < 0.05), at 5 years patients regressed (only 8.8 %) (p < 0.05), though changes in PDQ-39 subscores remained significant, with improvements in ADL (18.8 %), emotional well-being (19.0 %), stigma (36.4 %) and discomfort (20.6 %), despite worsening in communication (47.8 %) (p < 0.05). Lower preoperative PDQ-39 summary index and greater 1-year UPDRS-III-off total score gain predicted better long-term HRQOL. STN-DBS produces long-term improvements in HRQOL in PD. Preoperative HRQOL and short-term postoperative changes in off-medication motor status may predict long-term HRQOL in PD following STN-DBS. PMID:26964542

  19. BREVEL: a Franco/German reconnaissance and target-localization UAV system

    NASA Astrophysics Data System (ADS)

    Schlenkrich, Volker; Stahl, Karl-Hermann

    1993-12-01

    At the end of 1992 Eurodrone, a jointly owned company by MATRA DEFENSE in France and STN in Germany were awarded a contract by the french and german government to develop a reconnaissance and target localization system based on UAV. This article describes the rationale for the chosen design of the system and its performance. The system provides realtime reconnaissance and target localization with high accuracy.

  20. Estimation of organic carbon blank values and error structures of the speciation trends network data for source apportionment

    SciTech Connect

    Eugene Kim; Philip K. Hopke; Youjun Qin

    2005-08-01

    Because the particulate organic carbon (OC) concentrations reported in U.S. Environment Protection Agency Speciation Trends Network (STN) data were not blank corrected, the OC blank concentrations were estimated using the intercept in particulate matter {lt} 2.5 {mu}m in aerodynamic diameter (PM2.5) regression against OC concentrations. The estimated OC blank concentrations ranged from 1 to 2.4 {mu}g/m{sup 3} showing higher values in urban areas for the 13 monitoring sites in the northeastern United States. In the STN data, several different samplers and analyzers are used, and various instruments show different method detection limit (MDL) values, as well as errors. A comprehensive set of error structures that would be used for numerous source apportionment studies of STN data was estimated by comparing a limited set of measured concentrations and their associated uncertainties. To examine the estimated error structures and investigate the appropriate MDL values, PM2.5 samples collected at a STN site in Burlington, VT, were analyzed through the application of the positive matrix factorization. A total of 323 samples that were collected between December 2000 and December 2003 and 49 species based on several variable selection criteria were used, and eight sources were successfully identified in this study with the estimated error structures and min values among different MDL values from the five instruments: secondary sulfate aerosol (41%) identified as the result of emissions from coal-fired power plants, secondary nitrate aerosol (20%), airborne soil (15%), gasoline vehicle emissions (7%), diesel emissions (7%), aged sea salt (4%), copper smelting (3%), and ferrous smelting (2%). Time series plots of contributions from airborne soil indicate that the highly elevated impacts from this source were likely caused primarily by dust storms.

  1. Dissecting Human Skeletal Muscle Troponin Proteoforms by Top-down Mass Spectrometry

    PubMed Central

    Chen, Yi-Chen; Sumandea, Marius P.; Larsson, Lars; Moss, Richard L.; Ge, Ying

    2015-01-01

    Skeletal muscles are the most abundant tissues in the human body. They are composed of a heterogeneous collection of muscle fibers that perform various functions. Skeletal muscle troponin (sTn) regulates skeletal muscle contraction and relaxation. sTn consists of 3 subunits, troponin I (TnI), troponin T (TnT), and troponin C (TnC). TnI inhibits the actomyosin Mg2+-ATPase, TnC binds Ca2+, and TnT is the tropomyosin (Tm)-binding subunit. The cardiac and skeletal isoforms of Tn share many similarities but the roles of modifications of Tn in the two muscles may differ. The modifications of cardiac Tn are known to alter muscle contractility and have been well-characterized. However, the modification status of sTn remains unclear. Here, we have employed top-down mass spectrometry (MS) to decipher the modifications of human sTnT and sTnI. We have extensively characterized sTnT and sTnI proteoforms, including alternatively spliced isoforms and post-translationally modified forms, found in human skeletal muscle with high mass accuracy and comprehensive sequence coverage. Moreover, we have localized the phosphorylation site of slow sTnT isoform III to Ser1 by tandem MS with electron capture dissociation. This is the first study to comprehensively characterize human sTn and also the first to identify the basal phosphorylation site for human sTnT by top-down MS. PMID:25613324

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

    PubMed

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

    2012-07-01

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

  3. Simple solution for preventing cerebrospinal fluid loss and brain shift during multitrack deep brain stimulation surgery in the semisupine position: polyethylene glycol hydrogel dural sealant capping: rapid communication.

    PubMed

    Takumi, Ichiro; Mishina, Masahiro; Hironaka, Kohei; Oyama, Kenichi; Yamada, Akira; Adachi, Koji; Hamamoto, Makoto; Kitamura, Shin; Yoshida, Daizo; Teramoto, Akira

    2013-01-01

    This study evaluated preliminary findings on the efficacy of polyethylene glycol (PEG) hydrogel dural sealant capping for the prevention of cerebrospinal fluid (CSF) leakage and pneumocephalus during deep brain stimulation (DBS) surgery in the semisupine position. Group A consisted of 5 patients who underwent bilateral subthalamic nucleus (STN)-DBS surgery without PEG hydrogel dural sealant capping. Group B consisted of 5 patients who underwent bilateral STN-DBS surgery with PEG hydrogel dural sealant capping. The immediate postoperative intracranial air volume was measured in all patients and compared between the 2 groups using the Welch test. Adverse effects were also examined in both groups. The intracranial air volume in Group A was 32.3 ± 12.3 ml (range 19.1-42.5 ml), whereas that in Group B was 1.3 ± 1.5 ml (range 0.0-3.5 ml), showing a significant difference (p < 0.005). No hemorrhage or venous air embolisms were observed in either group. The effect of brain shift was discriminated by STN recordings in Group B. These preliminary findings indicate that PEG hydrogel dural sealant capping may reduce adverse effects related to CSF leakage and brain shift during DBS surgery. PMID:23358161

  4. Transplantation of mouse embryonic stem cell-derived neurons into the striatum, subthalamic nucleus and substantia nigra, and behavioral recovery in hemiparkinsonian rats.

    PubMed

    Inden, Masatoshi; Kim, Do-hoon; Qi, Meirigeng; Kitamura, Yoshihisa; Yanagisawa, Daijiro; Nishimura, Kaneyasu; Tsuchiya, Daiju; Takata, Kazuyuki; Hayashi, Kousuke; Taniguchi, Takashi; Yoshimoto, Kanji; Shimohama, Shun; Sumi, Shoichiro; Inoue, Kazutomo

    2005-10-28

    Usefulness of the in vitro and in vivo generation of neural precursors from embryonic stem (ES) cells has been widely discussed, but functional recovery in animal models of Parkinson's disease (PD) is not fully understood. The aim of this study was to investigate a transplantation strategy for PD by assessing whether double-transplants in the striatum (ST) and substantia nigra (SN), or ST and subthalamic nucleus (STN) induce functional recovery in 6-hydroxydopamine-lesioned rats. Methamphetamine-induced rotation was significantly reduced by transplantation of mouse ES cell-derived neurons into the ST, but not the STN or SN alone. Double-transplantation was also effective at recovering rotational behavior. Although immunoreactivity for tyrosine hydroxylase (TH) was almost completely lost in the ipsilateral striatum in hemiparkinsonian rats, TH immunoreactivity was detected in transplanted cells and sprouting fibers in the ST, STN and SN. These results suggest that both the involvement of ST as a place of transplantation and the number of ES cell-derived neurons are essential factors for efficacy on hemiparkinsonian behaviors. PMID:16023291

  5. Surprise disrupts cognition via a fronto-basal ganglia suppressive mechanism.

    PubMed

    Wessel, Jan R; Jenkinson, Ned; Brittain, John-Stuart; Voets, Sarah H E M; Aziz, Tipu Z; Aron, Adam R

    2016-01-01

    Surprising events markedly affect behaviour and cognition, yet the underlying mechanism is unclear. Surprise recruits a brain mechanism that globally suppresses motor activity, ostensibly via the subthalamic nucleus (STN) of the basal ganglia. Here, we tested whether this suppressive mechanism extends beyond skeletomotor suppression and also affects cognition (here, verbal working memory, WM). We recorded scalp-EEG (electrophysiology) in healthy participants and STN local field potentials in Parkinson's patients during a task in which surprise disrupted WM. For scalp-EEG, surprising events engage the same independent neural signal component that indexes action stopping in a stop-signal task. Importantly, the degree of this recruitment mediates surprise-related WM decrements. Intracranially, STN activity is also increased post surprise, especially when WM is interrupted. These results suggest that surprise interrupts cognition via the same fronto-basal ganglia mechanism that interrupts action. This motivates a new neural theory of how cognition is interrupted, and how distraction arises after surprising events. PMID:27088156

  6. Intensive Voice Treatment (LSVT®LOUD) for Parkinson’s disease following Deep Brain Stimulation of the Subthalamic Nucleus

    PubMed Central

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

    2011-01-01

    Purpose Intensive voice therapy (LSVT®LOUD) can effectively manage voice and speech symptoms associated with idiopathic Parkinson disease (PD). This small-group study evaluated voice and speech in individuals with and without deep brain stimulation of the subthalamic nucleus (STN-DBS) before and after LSVT LOUD, to determine whether outcomes for surgical subjects were comparable to non-surgical cohorts. Methods Eight subjects with PD (four with STN-DBS and four without) received LSVT LOUD four times a week for four weeks. Four additional subjects with PD remained untreated. Voice intensity (SPL), Vowel Articulation Index (VAI), the Voice Handicap Index (VHI), and a structured interview were evaluated before and after treatment and again six months later. Results Both treated groups showed significant increases in SPL from pre to post and six-month follow up. VAI was significantly higher for the treated groups compared to the untreated subjects at follow up. Several treated individuals had significant clinical improvement in VHI scores, particularly within the LSVT-DBS group. Treated individuals reported improvements in voice and speech in structured interviews; however, answers suggest more variable long-term maintenance within the LSVT-DBS group. The untreated group exhibited no significant changes in any measure throughout the study. Conclusions Results support LSVT LOUD for treating voice and speech in individuals with PD following STN-DBS surgery. However, modifications may be required to maintain functional improvements. PMID:21724193

  7. The subthalamic nucleus contributes to post-error slowing.

    PubMed

    Cavanagh, James F; Sanguinetti, Joseph L; Allen, John J B; Sherman, Scott J; Frank, Michael J

    2014-11-01

    pFC is proposed to implement cognitive control via directed "top-down" influence over behavior. But how is this feat achieved? The virtue of such a descriptive model is contingent on a mechanistic understanding of how motor execution is altered in specific circumstances. In this report, we provide evidence that the well-known phenomenon of slowed RTs following mistakes (post-error slowing) is directly influenced by the degree of subthalamic nucleus (STN) activity. The STN is proposed to act as a brake on motor execution following conflict or errors, buying time so a more cautious response can be made on the next trial. STN local field potentials from nine Parkinson disease patients undergoing deep brain stimulation surgery were recorded while they performed a response conflict task. In a 2.5- to 5-Hz frequency range previously associated with conflict and error processing, the degree phase consistency preceding the response was associated with increasingly slower RTs specifically following errors. These findings provide compelling evidence that post-error slowing is in part mediated by a corticosubthalamic "hyperdirect" pathway for increased response caution. PMID:24800632

  8. Virulence genes detection of Salmonella serovars isolated from pork and slaughterhouse environment in Ahmedabad, Gujarat

    PubMed Central

    Chaudhary, J. H.; Nayak, J. B.; Brahmbhatt, M. N.; Makwana, P. P.

    2015-01-01

    Aim: The aim was to detect virulence gene associated with the Salmonella serovars isolated from pork and Slaughterhouse environment. Materials and Methods: Salmonella isolates (n=37) used in this study were isolated from 270 pork and slaughter house environmental samples collected from the Ahmedabad Municipal Corporation Slaughter House, Ahmedabad, Gujarat, India. Salmonella serovars were isolated and identified as per BAM USFDA method and serotyped at National Salmonella and Escherichia Centre, Central Research Institute, Kasauli (Himachal Pradesh, India). Polymerase chain reaction technique was used for detection of five genes, namely invA, spvR, spvC, fimA and stn among different serovars of Salmonella. Results: Out of a total of 270 samples, 37 (13.70%) Salmonella were isolated with two serovars, namely Enteritidis and Typhimurium. All Salmonella serovars produced 284 bp invA gene, 84 bp fimA and 260 bp amplicon for enterotoxin (stn) gene whereas 30 isolates possessed 310 bp spvR gene, but no isolate possessed spvC gene. Conclusion: Presence of invA, fimA and stn gene in all isolates shows that they are the specific targets for Salmonella identification and are capable of producing gastroenteric illness to humans, whereas 20 Typhimurium serovars and 10 Enteritidis serovars can able to produce systemic infection. PMID:27047008

  9. Alterations in Brain Connectivity Underlying Beta Oscillations in Parkinsonism

    PubMed Central

    Moran, Rosalyn J.; Mallet, Nicolas; Litvak, Vladimir; Dolan, Raymond J.; Magill, Peter J.; Friston, Karl J.; Brown, Peter

    2011-01-01

    Cortico-basal ganglia-thalamocortical circuits are severely disrupted by the dopamine depletion of Parkinson's disease (PD), leading to pathologically exaggerated beta oscillations. Abnormal rhythms, found in several circuit nodes are correlated with movement impairments but their neural basis remains unclear. Here, we used dynamic causal modelling (DCM) and the 6-hydroxydopamine-lesioned rat model of PD to examine the effective connectivity underlying these spectral abnormalities. We acquired auto-spectral and cross-spectral measures of beta oscillations (10–35 Hz) from local field potential recordings made simultaneously in the frontal cortex, striatum, external globus pallidus (GPe) and subthalamic nucleus (STN), and used these data to optimise neurobiologically plausible models. Chronic dopamine depletion reorganised the cortico-basal ganglia-thalamocortical circuit, with increased effective connectivity in the pathway from cortex to STN and decreased connectivity from STN to GPe. Moreover, a contribution analysis of the Parkinsonian circuit distinguished between pathogenic and compensatory processes and revealed how effective connectivity along the indirect pathway acquired a strategic importance that underpins beta oscillations. In modelling excessive beta synchrony in PD, these findings provide a novel perspective on how altered connectivity in basal ganglia-thalamocortical circuits reflects a balance between pathogenesis and compensation, and predicts potential new therapeutic targets to overcome dysfunctional oscillations. PMID:21852943

  10. Globus Pallidus Externus Neurons Expressing parvalbumin Interconnect the Subthalamic Nucleus and Striatal Interneurons

    PubMed Central

    Saunders, Arpiar; Huang, Kee Wui; Sabatini, Bernardo Luis

    2016-01-01

    The globus pallidus externus (GP) is a nucleus of the basal ganglia (BG), containing GABAergic projection neurons that arborize widely throughout the BG, thalamus and cortex. Ongoing work seeks to map axonal projection patterns from GP cell types, as defined by their electrophysiological and molecular properties. Here we use transgenic mice and recombinant viruses to characterize parvalbumin expressing (PV+) GP neurons within the BG circuit. We confirm that PV+ neurons 1) make up ~40% of the GP neurons 2) exhibit fast-firing spontaneous activity and 3) provide the major axonal arborization to the STN and substantia nigra reticulata/compacta (SNr/c). PV+ neurons also innervate the striatum. Retrograde labeling identifies ~17% of pallidostriatal neurons as PV+, at least a subset of which also innervate the STN and SNr. Optogenetic experiments in acute brain slices demonstrate that the PV+ pallidostriatal axons make potent inhibitory synapses on low threshold spiking (LTS) and fast-spiking interneurons (FS) in the striatum, but rarely on spiny projection neurons (SPNs). Thus PV+ GP neurons are synaptically positioned to directly coordinate activity between BG input nuclei, the striatum and STN, and thalamic-output from the SNr. PMID:26905595

  11. The serendipity case of the pedunculopontine nucleus low-frequency brain stimulation: chasing a gait response, finding sleep, and cognition improvement.

    PubMed

    Stefani, Alessandro; Peppe, Antonella; Galati, Salvatore; Bassi, Mario Stampanoni; D'Angelo, Vincenza; Pierantozzi, Mariangela

    2013-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an efficacious therapy for Parkinson's disease (PD) but its effects on non-motor facets may be detrimental. The low-frequency stimulation (LFS) of the pedunculopontine nucleus (PPN or the nucleus tegmenti pedunculopontini - PPTg-) opened new perspectives. In our hands, PPTg-LFS revealed a modest influence on gait but increased sleep quality and degree of attentiveness. At odds with potential adverse events following STN-DBS, executive functions, under PPTg-ON, ameliorated. A recent study comparing both targets found that only PPTg-LFS improved night-time sleep and daytime sleepiness. Chances are that different neurosurgical groups influence either the PPN sub-portion identified as pars dissipata (more interconnected with GPi/STN) or the caudal PPN region known as pars compacta, preferentially targeting intralaminar and associative nucleus of the thalamus. Yet, the wide electrical field delivered affects a plethora of en passant circuits, and a fine distinction on the specific pathways involved is elusive. This review explores our angle of vision, by which PPTg-LFS activates cholinergic and glutamatergic ascending fibers, influencing non-motor behaviors. PMID:23761781

  12. Morphological changes of glutamatergic synapses in animal models of Parkinson’s disease

    PubMed Central

    Villalba, Rosa M.; Mathai, Abraham; Smith, Yoland

    2015-01-01

    The striatum and the subthalamic nucleus (STN) are the main entry doors for extrinsic inputs to reach the basal ganglia (BG) circuitry. The cerebral cortex, thalamus and brainstem are the key sources of glutamatergic inputs to these nuclei. There is anatomical, functional and neurochemical evidence that glutamatergic neurotransmission is altered in the striatum and STN of animal models of Parkinson’s disease (PD) and that these changes may contribute to aberrant network neuronal activity in the BG-thalamocortical circuitry. Postmortem studies of animal models and PD patients have revealed significant pathology of glutamatergic synapses, dendritic spines and microcircuits in the striatum of parkinsonians. More recent findings have also demonstrated a significant breakdown of the glutamatergic corticosubthalamic system in parkinsonian monkeys. In this review, we will discuss evidence for synaptic glutamatergic dysfunction and pathology of cortical and thalamic inputs to the striatum and STN in models of PD. The potential functional implication of these alterations on synaptic integration, processing and transmission of extrinsic information through the BG circuits will be considered. Finally, the significance of these pathological changes in the pathophysiology of motor and non-motor symptoms in PD will be examined. PMID:26441550

  13. Deep brain stimulation of the subthalamic nucleus facilitates coordination of hand preshaping in Parkinson's disease.

    PubMed

    Schettino, L F; Van Erp, E; Hening, W; Lessig, S; Song, D; Barba, D; Poizner, H

    2009-01-01

    Several studies have found that Parkinson's disease (PD) disrupts the organization of complex motor sequences regardless of the influence of parkinsonian medications. A clear candidate for the neural bases of such deficits, which we term "coordinative," is the failure to integrate propioceptive and visual information by cortico-striatal circuits in a timed fashion. Recent reports, however, have indicated that deep-brain stimulation of the subthalamic nucleus (STN DBS) may result in an improvement in coordinative deficits beyond the amelioration of "intensive deficits" such as bradykinesia and scaling errors. The present study examined the spatio-temporal organization underlying the shaping of the hand during reaching to grasp objects differing in shape. Six PD patients ON and OFF their STN DBS when OFF their concomitant medications and six age-matched controls participated in this study. STN DBS improved the coordination involved in preshaping the hand while grasping. We discuss these results in light of our earlier work with PD patients on and off dopamine replacement therapy. PMID:19922392

  14. Interactions between Cortical Rhythms and Spiking Activity of Single Basal Ganglia Neurons in the Normal and Parkinsonian State

    PubMed Central

    Gatev, Plamen

    2009-01-01

    In order to evaluate the specific interactions between cortical oscillations and basal ganglia–spiking activity under normal and parkinsonian conditions, we examined the relationship between frontal cortex electroencephalographic (EEG) signals and simultaneously recorded neuronal activity in the internal and external segments of the pallidum or the subthalamic nucleus (STN) in 3 rhesus monkeys. After we made recordings in the normal state, hemiparkinsonism was induced with intracarotid injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in one animal, followed by additional recordings. Spiking activity in the pallidum and STN was associated with significant shifts in the level of EEG synchronization. We also found that the spectral power of beta- and gamma-band EEG rhythms covaried positively before the basal ganglia spikes but did not covary or covaried negatively thereafter. In parkinsonism, changes in cortical synchronization and phase coherence were reduced in EEG segments aligned to STN spikes, whereas both were increased in data segments aligned to pallidal spikes. Spiking-related changes in beta/gamma-band covariance were reduced. The findings indicate that basal ganglia and cortex interact in the processing of cortical rhythms that contain oscillations across a broad range of frequencies and that this interaction is severely disrupted in parkinsonism. PMID:18842667

  15. Manganese-Induced Atypical Parkinsonism Is Associated with Altered Basal Ganglia Activity and Changes in Tissue Levels of Monoamines in the Rat

    PubMed Central

    Bouabid, Safa; Delaville, Claire; De Deurwaerdère, Philippe; Lakhdar-Ghazal, Nouria; Benazzouz, Abdelhamid

    2014-01-01

    Manganese neurotoxicity is associated with motor and cognitive disturbances known as Manganism. However, the mechanisms underlying these deficits remain unknown. Here we investigated the effects of manganese intoxication on motor and non-motor parkinsonian-like deficits such as locomotor activity, motor coordination, anxiety and “depressive-like” behaviors. Then, we studied the impact of this intoxication on the neuronal activity, the globus pallidus (GP) and subthalamic nucleus (STN). At the end of experiments, post-mortem tissue level of the three monoamines (dopamine, norepinephrine and serotonin) has been determined. The experiments were carried out in adult Sprague-Dawley rats, daily treated with MnCl2 (10 mg/kg/, i.p.) for 5 weeks. We show that manganese progressively reduced locomotor activity as well as motor coordination in parallel with the manifestation of anxiety and “depressive-like” behaviors. Electrophysiological results show that, while majority of GP and STN neurons discharged regularly in controls, manganese increased the number of GP and STN neurons discharging irregularly and/or with bursts. Biochemical results show that manganese significantly decreased tissue levels of norepinephrine and serotonin with increased metabolism of dopamine in the striatum. Our data provide evidence that manganese intoxication is associated with impaired neurotransmission of monoaminergic systems, which is at the origin of changes in basal ganglia neuronal activity and the manifestation of motor and non-motor deficits similar to those observed in atypical Parkinsonism. PMID:24896650

  16. Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection

    PubMed Central

    Bogacz, Rafal; Martin Moraud, Eduardo; Abdi, Azzedine; Magill, Peter J.; Baufreton, Jérôme

    2016-01-01

    The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes’ equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called ‘prototypic’ and ‘arkypallidal’ neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions. PMID:27389780

  17. Inclusion of Cocoa as a Dietary Supplement Represses Expression of Inflammatory Proteins in Spinal Trigeminal Nucleus in Response to Chronic Trigeminal Nerve Stimulation

    PubMed Central

    Cady, Ryan J.; Denson, Jennifer E.; Durham, Paul L.

    2013-01-01

    Scope Central sensitization is implicated in the pathology of temporomandibular joint disorder (TMD) and other types of orofacial pain. We investigated the effects of dietary cocoa on expression of proteins involved in the development of central sensitization in the spinal trigeminal nucleus (STN) in response to inflammatory stimulation of trigeminal nerves. Methods and results Male Sprague Dawley rats were fed either a control diet or an isocaloric diet consisting of 10% cocoa powder 14 days prior to bilateral injection of complete Freund’s adjuvant (CFA) into the temporomandibular joint to promote prolonged activation of trigeminal ganglion neurons and glia. While dietary cocoa stimulated basal expression of GLAST and MKP-1 when compared to animals on a normal diet, cocoa suppressed basal calcitonin gene-related peptide levels in the STN. CFA-stimulated levels of protein kinase A, P2X3, P-p38, GFAP, and OX-42, whose elevated levels in the STN are implicated in central sensitization, were repressed to near control levels in animals on a cocoa enriched diet. Similarly, dietary cocoa repressed CFA-stimulated inflammatory cytokine expression. Conclusion Based on our findings, we speculate that cocoa enriched diets could be beneficial as a natural therapeutic option for TMD and other chronic orofacial pain conditions. PMID:23576361

  18. Human CST Facilitates Genome-wide RAD51 Recruitment to GC-Rich Repetitive Sequences in Response to Replication Stress.

    PubMed

    Chastain, Megan; Zhou, Qing; Shiva, Olga; Whitmore, Leanne; Jia, Pingping; Dai, Xueyu; Huang, Chenhui; Fadri-Moskwik, Maria; Ye, Ping; Chai, Weihang

    2016-08-01

    The telomeric CTC1/STN1/TEN1 (CST) complex has been implicated in promoting replication recovery under replication stress at genomic regions, yet its precise role is unclear. Here, we report that STN1 is enriched at GC-rich repetitive sequences genome-wide in response to hydroxyurea (HU)-induced replication stress. STN1 deficiency exacerbates the fragility of these sequences under replication stress, resulting in chromosome fragmentation. We find that upon fork stalling, CST proteins form distinct nuclear foci that colocalize with RAD51. Furthermore, replication stress induces physical association of CST with RAD51 in an ATR-dependent manner. Strikingly, CST deficiency diminishes HU-induced RAD51 foci formation and reduces RAD51 recruitment to telomeres and non-telomeric GC-rich fragile sequences. Collectively, our findings establish that CST promotes RAD51 recruitment to GC-rich repetitive sequences in response to replication stress to facilitate replication restart, thereby providing insights into the mechanism underlying genome stability maintenance. PMID:27487043

  19. High-Frequency Stimulation of the Rat Entopeduncular Nucleus Does Not Provide Functional or Morphological Neuroprotection from 6-Hydroxydopamine

    PubMed Central

    Fischer, D. Luke; Collier, Timothy J.; Cole-Strauss, Allyson; Wohlgenant, Susan L.; Lipton, Jack W.; Steece-Collier, Kathy; Manfredsson, Fredric P.; Kemp, Christopher J.; Sortwell, Caryl E.

    2015-01-01

    Deep brain stimulation (DBS) is the most common neurosurgical treatment for Parkinson’s disease (PD). Whereas the globus pallidus interna (GPi) has been less commonly targeted than the subthalamic nucleus (STN), a recent clinical trial suggests that GPi DBS may provide better outcomes for patients with psychiatric comorbidities. Several laboratories have demonstrated that DBS of the STN provides neuroprotection of substantia nigra pars compacta (SNpc) dopamine neurons in preclinical neurotoxin models of PD and increases brain-derived neurotrophic factor (BDNF). However, whether DBS of the entopeduncular nucleus (EP), the homologous structure to the GPi in the rat, has similar neuroprotective potential in preclinical models has not been investigated. We investigated the impact of EP DBS on forelimb use asymmetry and SNpc degeneration induced by 6-hydroxydopamine (6-OHDA) and on BDNF levels. EP DBS in male rats received unilateral, intrastriatal 6-OHDA and ACTIVE or INACTIVE stimulation continuously for two weeks. Outcome measures included quantification of contralateral forelimb use, stereological assessment of SNpc neurons and BDNF levels. EP DBS 1) did not ameliorate forelimb impairments induced by 6-OHDA, 2) did not provide neuroprotection for SNpc neurons and 3) did not significantly increase BDNF levels in any of the structures examined. These results are in sharp contrast to the functional improvement, neuroprotection and BDNF-enhancing effects of STN DBS under identical experimental parameters in the rat. The lack of functional response to EP DBS suggests that stimulation of the rat EP may not represent an accurate model of clinical GPi stimulation. PMID:26222442

  20. Surprise disrupts cognition via a fronto-basal ganglia suppressive mechanism

    PubMed Central

    Wessel, Jan R.; Jenkinson, Ned; Brittain, John-Stuart; Voets, Sarah H. E. M.; Aziz, Tipu Z.; Aron, Adam R.

    2016-01-01

    Surprising events markedly affect behaviour and cognition, yet the underlying mechanism is unclear. Surprise recruits a brain mechanism that globally suppresses motor activity, ostensibly via the subthalamic nucleus (STN) of the basal ganglia. Here, we tested whether this suppressive mechanism extends beyond skeletomotor suppression and also affects cognition (here, verbal working memory, WM). We recorded scalp-EEG (electrophysiology) in healthy participants and STN local field potentials in Parkinson's patients during a task in which surprise disrupted WM. For scalp-EEG, surprising events engage the same independent neural signal component that indexes action stopping in a stop-signal task. Importantly, the degree of this recruitment mediates surprise-related WM decrements. Intracranially, STN activity is also increased post surprise, especially when WM is interrupted. These results suggest that surprise interrupts cognition via the same fronto-basal ganglia mechanism that interrupts action. This motivates a new neural theory of how cognition is interrupted, and how distraction arises after surprising events. PMID:27088156

  1. Successful subthalamic stimulation in genetic Parkinson's disease caused by duplication of the α-synuclein gene.

    PubMed

    Antonini, Angelo; Pilleri, Manuela; Padoan, Angelo; Landi, Andrea; Ferla, Salvatore; Biundo, Roberta; D'Avella, Domenico

    2012-01-01

    The α-synuclein gene (SNCA) multiplication causes autosomal dominant Parkinson's disease (PD). Particularly triplication, but also duplication, of the SNCA is associated with early-onset rapidly progressing parkinsonism with increased risk of cognitive impairment. There is no report about the effect and safety of Deep Brain Stimulation (DBS) in carriers of this mutation and, in general, data in patients with genetic parkinsonism are scarce. We report a one-year prospective follow-up of subthalamic nucleus (STN) DBS in a 46-year old female carrier of SNCA duplication who developed PD at the age of 41 years, and rapidly showed disabling motor fluctuations and dyskinesias refractory to pharmacological strategies. One year after surgery there was a clinically relevant improvement in motor features with a reduction of 64% in UPDRS III in "off medication" and a complete abolition of peak dose dyskinesias. Patient did not report procedure-related adverse events following STN-DBS except for stimulation-induced right foot dystonia relieved by modulating stimulation parameters. Postoperative cognitive testing showed a decline in executive functions, mostly verbal fluency and attention shifting, compared with presurgical assessment. STN-DBS is safe and effective in patients with SNCA duplication showing a clinical pattern similar to idiopathic PD. Our case suggests that clinical phenotype rather genotype is the main predictor for DBS outcome. PMID:21761143

  2. CDX2 homeoprotein is involved in the regulation of ST6GalNAc-I gene in intestinal metaplasia.

    PubMed

    Pinto, Rita; Barros, Rita; Pereira-Castro, Isabel; Mesquita, Patricia; da Costa, Luis T; Bennett, Eric P; Almeida, Raquel; David, Leonor

    2015-07-01

    De novo expression of Sialyl-Tn (STn) antigen is one of the most common features of intestinal metaplasia (IM) and gastric carcinomas, and its biosynthesis has been mostly attributed to ST6GalNAc-I activity. However, the regulation of this glycosyltransferase expression is not elucidated. In IM lesions and in the intestine, CDX2 homeobox transcription factor is co-expressed with STn and ST6GalNAc-I. We therefore hypothesized that CDX2 might induce STn expression by positive regulation of ST6GalNAc-I. We showed that ST6GalNAc-I transcript levels and CDX2 have a coordinated expression upon Caco-2 in vitro differentiation, and overexpression of CDX2 in MKN45 gastric cells increases ST6GalNAc-I transcript levels. Nine putative CDX-binding sites in the ST6GalNAc-I-regulatory sequence were identified and analyzed by chromatin immunoprecipitation in Caco-2 cells and in IM. The results showed that CDX2 protein is recruited to all regions, being the most proximal sites preferentially occupied in vivo. Luciferase assays demonstrated that CDX2 is able to transactivate ST6GalNac-I-regulatory region. The induction was stronger for the regions mapped in the neighbourhood of ATG start codon and site-directed mutagenesis of these sites confirmed their importance. In conclusion, we show that CDX2 transcriptionally regulates ST6GalNAc-I gene expression, specifically in the preneoplastic IM lesion. PMID:25867765

  3. The influence of bilateral subthalamic nucleus deep brain stimulation on impulsivity and prepulse inhibition in Parkinson’s disease patients

    PubMed Central

    Gee, Lucy; Smith, Heather; Cruz, Priscilla De La; Campbell, Joannalee; Fama, Chris; Haller, Jessica; Ramirez-Zamora, Adolfo; Durphy, Jennifer; Hanspal, Era; Molho, Eric; Barba, Anne; Shin, Damian; Pilitsis, Julie G.

    2015-01-01

    Background At least 14% of Parkinson disease (PD) patients develop impulse control disorders (ICDs). The pathophysiology behind these behaviors and the impact of deep brain stimulation in a real-life setting remains unclear. Objectives We prospectively examined the impact of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on ICDs in PD patients, as well as the relationship between impaired sensorimotor gaiting and impulsivity. Methods Patients undergoing bilateral STN-DBS were assessed for ICDs preoperatively and 1-year postoperatively using a validated questionnaire (QUIP-RS). A subset of patients completed the Balloon Analog Risk Task (BART) and auditory pre-pulse inhibition (PPI) testing. Results Analysis revealed 12 patients had an improvement in score assessing ICDs (“good responders” – GR; p = 0.006) while 4 had a worse or stable score (“poor responders” – PR; p > 0.05). GR further exemplified a significant decrease in hypersexual behavior (p = 0.005) and binge eating (p = 0.01). Impaired PPI responses also significantly correlated with impulsivity in BART (r = −0.72, p = 0.044). Discussion Following bilateral STN-DBS 75% of our cohort had a reduction in ICDs, thus suggesting deep brain stimulation effectively manages ICDs in PD. The role of impaired PPI in predisposition to ICDs in PD warrants further investigation. PMID:26066569

  4. Manganese-induced atypical parkinsonism is associated with altered Basal Ganglia activity and changes in tissue levels of monoamines in the rat.

    PubMed

    Bouabid, Safa; Delaville, Claire; De Deurwaerdère, Philippe; Lakhdar-Ghazal, Nouria; Benazzouz, Abdelhamid

    2014-01-01

    Manganese neurotoxicity is associated with motor and cognitive disturbances known as Manganism. However, the mechanisms underlying these deficits remain unknown. Here we investigated the effects of manganese intoxication on motor and non-motor parkinsonian-like deficits such as locomotor activity, motor coordination, anxiety and "depressive-like" behaviors. Then, we studied the impact of this intoxication on the neuronal activity, the globus pallidus (GP) and subthalamic nucleus (STN). At the end of experiments, post-mortem tissue level of the three monoamines (dopamine, norepinephrine and serotonin) has been determined. The experiments were carried out in adult Sprague-Dawley rats, daily treated with MnCl2 (10 mg/kg/, i.p.) for 5 weeks. We show that manganese progressively reduced locomotor activity as well as motor coordination in parallel with the manifestation of anxiety and "depressive-like" behaviors. Electrophysiological results show that, while majority of GP and STN neurons discharged regularly in controls, manganese increased the number of GP and STN neurons discharging irregularly and/or with bursts. Biochemical results show that manganese significantly decreased tissue levels of norepinephrine and serotonin with increased metabolism of dopamine in the striatum. Our data provide evidence that manganese intoxication is associated with impaired neurotransmission of monoaminergic systems, which is at the origin of changes in basal ganglia neuronal activity and the manifestation of motor and non-motor deficits similar to those observed in atypical Parkinsonism. PMID:24896650

  5. Seasonal variation in the biochemical composition of red seaweed ( Catenella repens) from Gangetic delta, northeast coast of India

    NASA Astrophysics Data System (ADS)

    Banerjee, Kakoli; Ghosh, Rajrupa; Homechaudhuri, Sumit; Mitra, Abhijit

    2009-10-01

    The biochemical composition of red seaweeds, Catenella repens was investigated in this present study along with subsequent analysis of relevant physico-chemical variables. In this study, the relationship between the nutritive components of this species and the ambient environmental parameters was established. Protein content varied from 2.78 ± 0.30% of dry weight (stn.3) to 16.03 ± 0.96% of dry weight (stn.1) with highest values during monsoon. The protein levels were positively correlated with dissolved nitrate content and negatively correlated with water temperature (except stn.3) and salinity. Carbohydrate content of this species varied significantly ( p < 0.05) during pre-monsoon between stations and the values showed positive relationship with salinity and surface water temperature. In contrast to carbohydrate, lipid concentration was lowest in values and varied very slightly between seasons and stations. Astaxanthin content of the seaweed species was greater in pre-monsoon than monsoon and post-monsoon in all the selected stations. Compared with the three seasons, samples of red seaweed collected in pre-monsoon has high carbohydrate-astaxanthin in contrast to protein-lipid which showed high values during monsoon. Statistical analysis computed among the environmental and biochemical parameters suggests the potential role played by the abiotic parameters on biosynthetic pathways of seaweed. This paper also highlights the influence of the nutritional quality of water that can be used for mass cultivation of Catenella repens.

  6. Critical reappraisal of DBS targeting for movement disorders.

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2011-01-01

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

  8. Fine particulate matter source apportionment for the chemical speciation trends network site at Birmingham, Alabama, using positive matrix factorization

    SciTech Connect

    Baumann, K.; Jayanty, R.K.; Flanagan, J.B.

    2008-01-15

    The Positive Matrix Factorization (PMF) receptor model version 1.1 was used with data from the fine particulate matter (PM2.5) Chemical Speciation Trends Network (STN) to estimate source contributions to ambient PM2.5 in a highly industrialized urban setting in the southeastern United States. Model results consistently resolved 10 factors that are interpreted as two secondary, five industrial, one motor vehicle, one road dust, and one biomass burning sources. It was found that most PMF factors did not cleanly represent single source types and instead are 'contaminated' by other sources. Secondary particulate matter formed by atmospheric processes, such as sulfate and secondary OC, contribute the majority of ambient PM2.5 and exhibit strong seasonality 37 {+-} 10% winter vs. 55 {+-} 16% summer average. Motor vehicle emissions constitute the biggest primary PM2.5 mass contribution. In summary, this study demonstrates the utility of the EC tracer method to effectively blank-correct the OC concentrations in the STN dataset. In addition, examination of the effect of input uncertainty estimates on model results indicates that the estimated uncertainties currently being provided with the STN data may be somewhat lower than the levels needed for optimum modeling results. An appendix , available to members on the website www.awma lists stationary sources of PM2.5 within 10 km of the NHBM site and PM2.5 emissions greater than 1 ton per year. 71 refs., 7 figs., 9 tabs.

  9. Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection.

    PubMed

    Bogacz, Rafal; Martin Moraud, Eduardo; Abdi, Azzedine; Magill, Peter J; Baufreton, Jérôme

    2016-07-01

    The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes' equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called 'prototypic' and 'arkypallidal' neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions. PMID:27389780

  10. Aerosol-cloud interactions studied with the chemistry-climate model EMAC

    NASA Astrophysics Data System (ADS)

    Chang, D. Y.; Tost, H.; Steil, B.; Lelieveld, J.

    2014-08-01

    This study uses the EMAC atmospheric chemistry-climate model to simulate cloud properties and estimate cloud radiative effects induced by aerosols. We have tested two prognostic cloud droplet nucleation parameterizations, i.e., the standard STN (osmotic coefficient model) and hybrid (HYB, replacing the osmotic coefficient by the κ hygroscopicity parameter) schemes to calculate aerosol hygroscopicity and critical supersaturation, and consider aerosol-cloud feedbacks with a focus on warm clouds. Both prognostic schemes (STN and HYB) account for aerosol number, size and composition effects on droplet nucleation, and are tested in combination with two different cloud cover parameterizations, i.e., a relative humidity threshold and a statistical cloud cover scheme (RH-CLC and ST-CLC). The use of either STN and HYB leads to very different cloud radiative effects, particularly over the continents. The STN scheme predicts highly effective CCN activation in warm clouds and hazes/fogs near the surface. The enhanced CCN activity increases the cloud albedo effect of aerosols and cools the Earth's surface. The cooler surface enhances the hydrostatic stability of the lower continental troposphere and thereby reduces convection and convective precipitation. In contrast, the HYB simulations calculate lower, more realistic CCN activation and consequent cloud albedo effect, leading to relatively stronger convection and high cloud formation. The enhanced high clouds increase greenhouse warming and moderate the cooling effect of the low clouds. With respect to the cloud radiative effects, the statistical ST-CLC scheme shows much higher sensitivity to aerosol-cloud coupling for all continental regions than the RH-CLC threshold scheme, most pronounced for low clouds but also for high clouds. Simulations of the short wave cloud radiative effect at the top of the atmosphere in ST-CLC are a factor of 2-8 more sensitive to aerosol coupling than the RH-CLC configurations. The long wave

  11. Deep brain stimulation of pallidal versus subthalamic for patients with Parkinson’s disease: a meta-analysis of controlled clinical trials

    PubMed Central

    Xu, Fan; Ma, Wenbin; Huang, Yongmin; Qiu, Zhihai; Sun, Lei

    2016-01-01

    Background Parkinson’s disease (PD) is a common neurodegenerative disorder that affects many people every year. Deep brain stimulation (DBS) is an effective nonpharmacological method to treat PD motor symptoms. This meta-analysis was conducted to evaluate the efficacy of subthalamic nucleus (STN)-DBS versus globus pallidus internus (GPi)-DBS in treating advanced PD. Methods Controlled clinical trials that compared STN-DBS to GPi-DBS for short-term treatment of PD in adults were researched up to November 2015. The primary outcomes were the Unified Parkinson’s Disease Rating Scale Section (UPDRS) III score and the levodopa-equivalent dosage (LED) after DBS. The secondary outcomes were the UPDRS II score and the Beck Depression Inventory (BDI) score. Results Totally, 13 studies containing 1,148 PD patients were included in this meta-analysis to compare STN-DBS versus GPi-DBS. During the off-medication state, the pooled weighted mean difference (WMD) of UPDRS III and II scores were −2.18 (95% CI =−5.11 to 0.74) and −1.96 (95% CI =−3.84 to −0.08), respectively. During the on-medication state, the pooled WMD of UPDRS III and II scores were 0.15 (95% CI =−1.14 to 1.44) and 1.01 (95% CI =0.12 to 1.89), respectively. After DBS, the pooled WMD of LED and BDI were −254.48 (95% CI =−341.66) and 2.29 (95% CI =0.83 to 3.75), respectively. Conclusion These results indicate that during the off-medication state, the STN-DBS might be superior to GPi-DBS in improving the motor function and activities of daily living for PD patients; but during the on-medication state, the opposite result is observed. Meanwhile, the STN-DBS is superior at reducing the LED, whereas the GPi-DBS shows a significantly greater reduction in BDI score after DBS. PMID:27382286

  12. Chronic L-DOPA administration increases the firing rate but does not reverse enhanced slow frequency oscillatory activity and synchronization in substantia nigra pars reticulata neurons from 6-hydroxydopamine-lesioned rats.

    PubMed

    Aristieta, A; Ruiz-Ortega, J A; Miguelez, C; Morera-Herreras, T; Ugedo, L

    2016-05-01

    The pathophysiology of Parkinson's disease (PD) and of L-DOPA-induced dyskinesia (LID) is associated with dysfunctional neuronal activity in several nuclei of the basal ganglia. Moreover, high levels of oscillatory activity and synchronization have also been described in both intra- and inter-basal ganglia nuclei and the cerebral cortex. However, the relevance of these alterations in the motor symptomatology related to Parkinsonism and LID is not fully understood. Recently, we have shown that subthalamic neuronal activity correlates with axial abnormal movements and that a subthalamic nucleus (STN) lesion partially reduces LID severity as well as the expression of some striatal molecular modifications. The aim of the present study was to assess, through single-unit extracellular recording techniques under urethane anaesthesia, neuronal activity of the substantia nigra pars reticulata (SNr) and its relationship with LID and STN hyperactivity together with oscillatory and synchronization between these nuclei and the cerebral cortex in 6-OHDA-lesioned and dyskinetic rats. Twenty-four hours after the last injection of L-DOPA the firing rate and the inhibitory response to an acute challenge of L-DOPA of SNr neurons from dyskinetic animals were increased with respect to those found in intact and 6-OHDA-lesioned rats. Moreover, there was a significant correlation between the mean firing rate of SNr neurons and the severity of the abnormal movements (limb and orolingual subtypes). There was also a significant correlation between the firing activity of SNr and STN neurons recorded from dyskinetic rats. In addition, low frequency band oscillatory activity and synchronization both within the SNr or STN and with the cerebral cortex were enhanced in 6-OHDA-lesioned animals and not or slightly affected by chronic treatment with L-DOPA. Altogether, these results indicate that neuronal SNr firing activity is relevant in dyskinesia and may be driven by STN hyperactivity. Conversely

  13. Efficacies of globus pallidus stimulation and subthalamic nucleus stimulation for advanced Parkinson’s disease: a meta-analysis of randomized controlled trials

    PubMed Central

    Tan, Zhi-Gang; Zhou, Qian; Huang, Tao; Jiang, Yugang

    2016-01-01

    Objectives Deep brain stimulation (DBS) is the surgical procedure for patients with advanced Parkinson’s disease. Globus pallidus internus (GPi) and subthalamic nucleus (STN) are the most targeted locations for the procedure. To investigate the variable efficiencies for the two different locations, we conducted a meta-analysis to compare both stimulation sites. Materials and methods A systematic search was performed in PubMed, Embase, and the Cochrane Library databases. Randomized controlled trials comparing the efficacies of GPi and STN DBS were included. Clinical outcomes of motor function, nonmotor function, and quality of life (QOL) were collected for the meta-analysis. Results Ten eligible trials with 1,034 patients were included in the analysis. Unified Parkinson’s disease rating scale III (UPDRS-III) scores were collected at 6, 12, and 24 months postsurgery separately to assess the motor function of the patients. A statistically significant effect in favor of the GPi DBS was obtained in the off-medication/on-stimulation phase of UPDRS-III at 12 months (mean difference [MD] =6.87, 95% confidence interval [95% CI]: 3.00–10.74, P=0.57, I2=0%). However, GPi DBS showed an opposite result at 24 months (MD =−2.46, 95% CI: −4.91 to −0.02, P=0.05, I2=0%). In the on-medication/on-stimulation phase, GPi DBS obtained a worse outcome compared with STN DBS (MD =−2.90, 95% CI: −5.71 to −0.09, P=0.05, I2=0%). Compared with STN DBS, increased dosage of levodopa equivalent doses was needed in GPi DBS (standardized MD =0.60, 95% CI: 0.46–0.74, P<0.00001, I2=24%). Meanwhile, Beck Depression Inventory II scores demonstrated that STN has a better performance (standardized MD =−0.31, 95% CI: −0.51 to −0.12, P=0.002, I2=0%). As for neurocognitive phase postsurgery, GPi DBS showed better performance in three of the nine tests, especially in verbal fluency. Use of GPi DBS was associated with a greater effect in eight of the nine subscales of QOL. Conclusion

  14. Brine shrimp cytotoxicity of crude methanol extract and antispasmodic activity of α-amyrin acetate from Tylophora hirsuta Wall

    PubMed Central

    2013-01-01

    Background We have previously reported that aerial parts of Tylophora hirsuta have antispasmodic profile. The current work is an attempt for isolation of pharmacologically active compound(s) that contribute for its antispasmodic activity. Methods Preliminary phytochemical screening for crude methanol extract of Tylophora hirsuta (Th.Cr) is performed. Brine shrimp cytotoxicity of crude methanol extract is performed. Column chromatography was used for isolation of compounds. Mass spectroscopy, H1 NMR and C13 NMR were used for structural determination of compounds. α-amyrin acetate was tried for possible spasmolytic activity in rabbit’s jejunal preparations and KCl-induced contractions. Results Th.Cr tested positive for saponins, alkaloids, flavonoids and terpenoids. Compound 1 was isolated as α-amyrin acetate. Compound 2 was heptaeicosanol. Crude methanol extract tested positive for brine shrimp cytotoxicity with LC50 492.33± 8.08 mg/ml. Compound 1 tested positive for antispasmodic activity on spontaneous rabbits’ jejunum preparations with EC50 (60 ± 2) × 10-5M. The compound also tested positive on KCl induced contractions with EC50 (72 ± 3) × 10-5M. Conclusions The present work confirms that α-amyrin acetate is has antispasmodic profile and the relaxant effect may be attributed to α-amyrin acetate which is a major compound. PMID:23773697

  15. Outbred genome sequencing and CRISPR/Cas9 gene editing in butterflies

    PubMed Central

    Li, Xueyan; Fan, Dingding; Zhang, Wei; Liu, Guichun; Zhang, Lu; Zhao, Li; Fang, Xiaodong; Chen, Lei; Dong, Yang; Chen, Yuan; Ding, Yun; Zhao, Ruoping; Feng, Mingji; Zhu, Yabing; Feng, Yue; Jiang, Xuanting; Zhu, Deying; Xiang, Hui; Feng, Xikan; Li, Shuaicheng; Wang, Jun; Zhang, Guojie; Kronforst, Marcus R.; Wang, Wen

    2015-01-01

    Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system. PMID:26354079

  16. Local field potential recordings in a non-human primate model of Parkinsons disease using the Activa PC + S neurostimulator

    NASA Astrophysics Data System (ADS)

    Connolly, Allison T.; Muralidharan, Abirami; Hendrix, Claudia; Johnson, Luke; Gupta, Rahul; Stanslaski, Scott; Denison, Tim; Baker, Kenneth B.; Vitek, Jerrold L.; Johnson, Matthew D.

    2015-12-01

    Objective. Using the Medtronic Activa® PC + S system, this study investigated how passive joint manipulation, reaching behavior, and deep brain stimulation (DBS) modulate local field potential (LFP) activity in the subthalamic nucleus (STN) and globus pallidus (GP). Approach. Five non-human primates were implanted unilaterally with one or more DBS leads. LFPs were collected in montage recordings during resting state conditions and during motor tasks that facilitate the expression of parkinsonian motor signs. These recordings were made in the naïve state in one subject, in the parkinsonian state in two subjects, and in both naïve and parkinsonian states in two subjects. Main results. LFPs measured at rest were consistent over time for a given recording location and parkinsonian state in a given subject; however, LFPs were highly variable between subjects, between and within recording locations, and across parkinsonian states. LFPs in both naïve and parkinsonian states across all recorded nuclei contained a spectral peak in the beta band (10-30 Hz). Moreover, the spectral content of recorded LFPs was modulated by passive and active movement of the subjects’ limbs. LFPs recorded during a cued-reaching task displayed task-related beta desynchronization in STN and GP. The bidirectional capabilities of the Activa® PC + S also allowed for recording LFPs while delivering DBS. The therapeutic effect of STN DBS on parkinsonian rigidity outlasted stimulation for 30-60 s, but there was no correlation with beta band power. Significance. This study emphasizes (1) the variability in spontaneous LFPs amongst subjects and (2) the value of using the Activa® PC + S system to record neural data in the context of behavioral tasks that allow one to evaluate a subject’s symptomatology.

  17. Steady-state phosphorylation of light-harvesting complex II proteins preserves photosystem I under fluctuating white light.

    PubMed

    Grieco, Michele; Tikkanen, Mikko; Paakkarinen, Virpi; Kangasjärvi, Saijaliisa; Aro, Eva-Mari

    2012-12-01

    According to the "state transitions" theory, the light-harvesting complex II (LHCII) phosphorylation in plant chloroplasts is essential to adjust the relative absorption cross section of photosystem II (PSII) and PSI upon changes in light quality. The role of LHCII phosphorylation upon changes in light intensity is less thoroughly investigated, particularly when changes in light intensity are too fast to allow the phosphorylation/dephosphorylation processes to occur. Here, we demonstrate that the Arabidopsis (Arabidopsis thaliana) stn7 (for state transition7) mutant, devoid of the STN7 kinase and LHCII phosphorylation, shows a growth penalty only under fluctuating white light due to a low amount of PSI. Under constant growth light conditions, stn7 acquires chloroplast redox homeostasis by increasing the relative amount of PSI centers. Thus, in plant chloroplasts, the steady-state LHCII phosphorylation plays a major role in preserving PSI upon rapid fluctuations in white light intensity. Such protection of PSI results from LHCII phosphorylation-dependent equal distribution of excitation energy to both PSII and PSI from the shared LHCII antenna and occurs in cooperation with nonphotochemical quenching and the proton gradient regulation5-dependent control of electron flow, which are likewise strictly regulated by white light intensity. LHCII phosphorylation is concluded to function both as a stabilizer (in time scales of seconds to minutes) and a dynamic regulator (in time scales from tens of minutes to hours and days) of redox homeostasis in chloroplasts, subject to modifications by both environmental and metabolic cues. Exceeding the capacity of LHCII phosphorylation/dephosphorylation to balance the distribution of excitation energy between PSII and PSI results in readjustment of photosystem stoichiometry. PMID:23033142

  18. Probing the O-Glycoproteome of Gastric Cancer Cell Lines for Biomarker Discovery*

    PubMed Central

    Campos, Diana; Freitas, Daniela; Gomes, Joana; Magalhães, Ana; Steentoft, Catharina; Gomes, Catarina; Vester-Christensen, Malene B.; Ferreira, José Alexandre; Afonso, Luis P.; Santos, Lúcio L.; Pinto de Sousa, João; Mandel, Ulla; Clausen, Henrik; Vakhrushev, Sergey Y.; Reis, Celso A.

    2015-01-01

    Circulating O-glycoproteins shed from cancer cells represent important serum biomarkers for diagnostic and prognostic purposes. We have recently shown that selective detection of cancer-associated aberrant glycoforms of circulating O-glycoprotein biomarkers can increase specificity of cancer biomarker assays. However, the current knowledge of secreted and circulating O-glycoproteins is limited. Here, we used the COSMC KO “SimpleCell” (SC) strategy to characterize the O-glycoproteome of two gastric cancer SimpleCell lines (AGS, MKN45) as well as a gastric cell line (KATO III) which naturally expresses at least partially truncated O-glycans. Overall, we identified 499 O-glycoproteins and 1236 O-glycosites in gastric cancer SimpleCells, and a total 47 O-glycoproteins and 73 O-glycosites in the KATO III cell line. We next modified the glycoproteomic strategy to apply it to pools of sera from gastric cancer and healthy individuals to identify circulating O-glycoproteins with the STn glycoform. We identified 37 O-glycoproteins in the pool of cancer sera, and only nine of these were also found in sera from healthy individuals. Two identified candidate O-glycoprotein biomarkers (CD44 and GalNAc-T5) circulating with the STn glycoform were further validated as being expressed in gastric cancer tissue. A proximity ligation assay was used to show that CD44 was expressed with the STn glycoform in gastric cancer tissues. The study provides a discovery strategy for aberrantly glycosylated O-glycoproteins and a set of O-glycoprotein candidates with biomarker potential in gastric cancer. PMID:25813380

  19. Why do Parkinson's Disease Patients Sometimes Make Wrong Decisions?

    PubMed

    Damier, Philippe

    2015-01-01

    Our knowledge of the cerebral bases of decision making has grown considerably in the past decade. The dopamine system is closely involved in many aspects of the decisional process. It is therefore not surprising that the dysfunctions that occur in Parkinson's disease (PD) can alter some patients' decisions. Put simply, a decision is the final step of a process in which a subject weighs up the potential benefits and costs associated with each of the different options available for a given choice. The option that appears to have the best ratio of benefits to costs is chosen. In some PD patients, dopamine agonists destabilize the balance: the benefits are given an inappropriately high weighting relative to the costs, leading patients to take decisions they would not otherwise have taken. This might be one of the explanations for impulse control disorders observed in some PD patients. Dysfunction of the subthalamic nucleus (STN) induced by dopamine replacement or by deep brain stimulation is another mechanism that can alter decision making. The STN plays an active role in the decisional process, especially by slowing down the process when the difference between the options to be considered in a given choice is small (e.g. a win-win choice). Deep brain stimulation applied to the STN may interfere with its monitoring role and lead to an impulsive choice. Attention disorders and frontal lobe dysfunction, highly prevalent in the course of PD, are other factors that may alter a patient's decision making. Patients and caregivers need to be aware of this, since the consequences can sometimes be detrimental. PMID:26406144

  20. Neuronal activity (c-Fos) delineating interactions of the cerebral cortex and basal ganglia

    PubMed Central

    Qiu, Mei-Hong; Chen, Michael C.; Huang, Zhi-Li; Lu, Jun

    2014-01-01

    The cerebral cortex and basal ganglia (BG) form a neural circuit that is disrupted in disorders such as Parkinson’s disease. We found that neuronal activity (c-Fos) in the BG followed cortical activity, i.e., high in arousal state and low in sleep state. To determine if cortical activity is necessary for BG activity, we administered atropine to rats to induce a dissociative state resulting in slow-wave electroencephalography but hyperactive motor behaviors. Atropine blocked c-Fos expression in the cortex and BG, despite high c-Fos expression in the sub-cortical arousal neuronal groups and thalamus, indicating that cortical activity is required for BG activation. To identify which glutamate receptors in the BG that mediate cortical inputs, we injected ketamine [N-methyl-d-aspartate (NMDA) receptor antagonist] and 6-cyano-nitroquinoxaline-2, 3-dione (CNQX, a non-NMDA receptor antagonist). Systemic ketamine and CNQX administration revealed that NMDA receptors mediated subthalamic nucleus (STN) input to internal globus pallidus (GPi) and substantia nigra pars reticulata (SNr), while non-NMDA receptor mediated cortical input to the STN. Both types of glutamate receptors were involved in mediating cortical input to the striatum. Dorsal striatal (caudoputamen, CPu) dopamine depletion by 6-hydroxydopamine resulted in reduced activity of the CPu, globus pallidus externa (GPe), and STN but increased activity of the GPi, SNr, and putative layer V neurons in the motor cortex. Our results reveal that the cortical activity is necessary for BG activity and clarifies the pathways and properties of the BG-cortical network and their putative role in the pathophysiology of BG disorders. PMID:24723855

  1. Transient and state modulation of beta power in human subthalamic nucleus during speech production and finger movement.

    PubMed

    Hebb, A O; Darvas, F; Miller, K J

    2012-01-27

    Signs of Parkinson's disease (PD) are augmented by speech and repetitive motor tasks. The neurophysiological basis for this phenomenon is unknown, but may involve augmentation of β (13-30 Hz) oscillations within the subthalamic nucleus (STN). We hypothesized that speech and motor tasks increase β power in STN and propose a mechanism for clinical observations of worsening motor state during such behaviors. Subjects undergoing deep brain stimulation (DBS) surgery performed tasks while STN local field potential (LFP) data were collected. Power in the β frequency range was analyzed across the entire recording to observe slow shifts related to block design and during time epochs synchronized to behavior to evaluate immediate fluctuations related to task execution. Bilaterally symmetric β event related desynchronization was observed in analysis time-locked to subject motor and speech tasks. We also observed slow shifts of β power associated with blocks of tasks. Repetitive combined speech and motor, and isolated motor blocks were associated with the highest bilateral β power state. Overt speech alone and imagined speech were associated with a low bilateral β power state. Thus, changing behavioral tasks is associated with bilateral switching of β power states. This offers a potential neurophysiologic correlate of worsened PD motor signs experienced during clinical examination with provocative tasks: switching into a high β power state may be responsible for worsening motor states in PD patients when performing unilateral repetitive motor tasks and combined speech and motor tasks. Beta state changes could be chronically measured and potentially used to control closed loop neuromodulatory devices in the future. PMID:22173017

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

    PubMed Central

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

    2015-01-01

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

  3. Physiological brainstem mechanisms of trigeminal nociception: An fMRI study at 3T.

    PubMed

    Schulte, Laura H; Sprenger, Christian; May, Arne

    2016-01-01

    The brainstem is a major site of processing and modulation of nociceptive input and plays a key role in the pathophysiology of various headache disorders. However, human imaging studies on brainstem function following trigeminal nociceptive stimulation are scarce as brainstem specific imaging approaches have to address multiple challenges such as magnetic field inhomogeneities and an enhanced level of physiological noise. In this study we used a viable protocol for brainstem fMRI of standardized trigeminal nociceptive stimulation to achieve detailed insight into physiological brainstem mechanisms of trigeminal nociception. We conducted a study of 21 healthy participants using a nociceptive ammonia stimulation of the left nasal mucosa with an optimized MR acquisition protocol for high resolution brainstem echoplanar imaging in combination with two different noise correction techniques. Significant BOLD responses to noxious ammonia stimulation were observed in areas typically involved in trigeminal nociceptive processing such as the spinal trigeminal nuclei (sTN), thalamus, secondary somatosensory cortex, insular cortex and cerebellum as well as in a pain modulating network including the periaqueductal gray area, hypothalamus (HT), locus coeruleus and cuneiform nucleus (CNF). Activations of the left CNF were positively correlated with pain intensity ratings. Employing psychophysiological interaction (PPI) analysis we found enhanced functional connectivity of the sTN with the contralateral sTN and HT following trigeminal nociception. We also observed enhanced functional connectivity of the CNF with the RVM during painful stimulation thus implying an important role of these two brainstem regions in central pain processing. The chosen approach to study trigeminal nociception with high-resolution fMRI offers new insight into human pain processing and might thus lead to a better understanding of headache pathophysiology. PMID:26388554

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

    PubMed Central

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

    2015-01-01

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

  5. Deep Brain Stimulation for Parkinson’s Disease: Recent Trends and Future Direction

    PubMed Central

    FUKAYA, Chikashi; YAMAMOTO, Takamitsu

    2015-01-01

    To date, deep brain stimulation (DBS) has already been performed on more than 120,000 patients worldwide and in more than 7,000 patients in Japan. However, fundamental understanding of DBS effects on the pathological neural circuitry remains insufficient. Recent studies have specifically shown the importance of cortico-striato-thalamo-cortical (CSTC) loops, which were identified as functionally and anatomically discrete units. Three main circuits exist in the CSTC loops, namely, the motor, associative, and limbic circuits. From these theoretical backgrounds, it is determined that DBS sometimes influences not only motor functions but also the cognitive and affective functions of Parkinson’s disease (PD) patients. The main targets of DBS for PD are subthalamic nucleus (STN) and globus pallidus interna (GPi). Ventralis intermedius (Vim)-DBS was found to be effective in improving tremor. However, Vim-DBS cannot sufficiently improve akinesia and rigidity. Therefore, Vim-DBS is seldom carried out for the treatment of PD. In this article, we review the present state of DBS, mainly STN-DBS and GPi-DBS, for PD. In the first part of the article, appropriate indications and practical effects established in previous studies are discussed. The findings of previous investigations on the complications caused by the surgical procedure and on the adverse events induced by DBS itself are reviewed. In the second part, we discuss target selection (GPi vs. STN) and the effect of DBS on nonmotor symptoms. In the final part, as issues that should be resolved, the suitable timing of surgery, symptoms unresponsive to DBS such as on-period axial symptoms, and the related postoperative programing of stimulation parameters, are discussed. PMID:25925761

  6. Long-term Efficacy of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A 5-year Follow-up Study in China

    PubMed Central

    Jiang, Lu-Lu; Liu, Jin-Long; Fu, Xiao-Li; Xian, Wen-Biao; Gu, Jing; Liu, Yan-Mei; Ye, Jing; Chen, Jie; Qian, Hao; Xu, Shao-Hua; Pei, Zhong; Chen, Ling

    2015-01-01

    Background: Subthalamic nucleus deep brain stimulation (STN DBS) is effective against advanced Parkinson's disease (PD), allowing dramatic improvement of Parkinsonism, in addition to a significant reduction in medication. Here we aimed to investigate the long-term effect of STN DBS in Chinese PD patients, which has not been thoroughly studied in China. Methods: Ten PD patients were assessed before DBS and followed up 1, 3, and 5 years later using Unified Parkinson's Disease Rating Scale Part III (UPDRS III), Parkinson's Disease Questionnatire-39, Parkinson's Disease Sleep Scale-Chinese Version, Mini-mental State Examination, Montreal Cognitive Assessment, Hamilton Anxiety Scale and Hamilton Depression Scale. Stimulation parameters and drug dosages were recorded at each follow-up. Data were analyzed using the ANOVA for repeated measures. Results: In the “off” state (off medication), DBS improved UPDRS III scores by 35.87% in 5 years, compared with preoperative baseline (P < 0.001). In the “on” state (on medication), motor scores at 5 years were similar to the results of preoperative levodopa challenge test. The quality of life is improved by 58.18% (P < 0.001) from baseline to 3 years and gradually declined afterward. Sleep, cognition, and emotion were mostly unchanged. Levodopa equivalent daily dose was reduced from 660.4 ± 210.1 mg at baseline to 310.6 ± 158.4 mg at 5 years (by 52.96%, P < 0.001). The average pulse width, frequency and amplitude at 5 years were 75.0 ± 18.21 μs, 138.5 ± 19.34 Hz, and 2.68 ± 0.43 V, respectively. Conclusions: STN DBS is an effective intervention for PD, although associated with a slightly diminished efficacy after 5 years. Compared with other studies, patients in our study required lower voltage and medication for satisfactory symptom control. PMID:26365958

  7. Resiliency in adolescents at high-risk for substance abuse: flexible adaptation via subthalamic nucleus and linkage to drinking and drug use in early adulthood

    PubMed Central

    Weiland, Barbara J.; Nigg, Joel T.; Welsh, Robert C.; Yau, Wai-Ying Wendy; Zubieta, Jon-Kar; Zucker, Robert A.; Heitzeg, Mary M.

    2012-01-01

    Introduction The personality trait resiliency is the ability to flexibly adapt impulse control relative to contextual demand. Low resiliency has been linked to later alcohol/drug problems. The underlying psychological and neural mechanisms are unknown but neurocomputational models suggested relations between resiliency and working memory. Cortical-striatal connectivity has been proposed to underlie adaptive switches between cautious and risky behaviors. Methods Working memory was probed in sixty-seven 18–22 year olds from a larger community study of alcoholism, using the n-back task during functional magnetic resonance imaging. Functional connectivity between task-related regions was investigated with psychophysiological interaction analysis. Resiliency was measured in early teen years and related to early adulthood measures of drinking/drug use, task activation and connectivity. Relationships with risk factors, including family history, age of drinking onset and number of alcohol problems were also investigated. Results Higher resiliency was related to lower levels of substance use, fewer alcohol problems and better working memory performance. Whole brain regression revealed resiliency negatively correlated with activation of subthalamic nucleus (STN) and pallidum during the n-back. High and Low resiliency quartile groups (n=17 each) differed in coupling strength between STN and median cingulate cortex, a region of reduced activation during working memory. The High resiliency group had later onset of drinking, fewer alcohol problems, had used fewer illicit drugs and were less likely to smoke cigarettes than their Low resiliency counterparts, Conclusions These findings suggest that resiliency in early adolescence may protect against alcohol problems and drug use, though the direction of this effect is currently unknown. This protective factor may relate to executive functioning as supported by the finding of a neural link shared between resiliency and working

  8. Deep Brain Stimulation Reduces Neuronal Entropy in the MPTP-Primate Model of Parkinson's Disease

    PubMed Central

    Dorval, Alan D.; Russo, Gary S.; Hashimoto, Takao; Xu, Weidong; Grill, Warren M.; Vitek, Jerrold L.

    2008-01-01

    High-frequency stimulation (HFS) of the subthalamic nucleus (STN) or internal segment of the globus pallidus is a clinically successful treatment for the motor symptoms of Parkinson's disease. However, the mechanisms by which HFS alleviates these symptoms are not understood. Whereas initial studies focused on HFS-induced changes in neuronal firing rates, recent studies suggest that changes in patterns of neuronal activity may correlate with symptom alleviation. We hypothesized that effective STN HFS reduces the disorder of neuronal firing patterns in the basal ganglia thalamic circuit, minimizing the pathological activity associated with parkinsonism. Stimulating leads were implanted in the STN of two rhesus monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Action potentials were recorded from neurons of the internal and external globus pallidus and the motor thalamus (ventralis anterior, ventralis lateralis pars oralis, and ventralis posterior lateralis pars oralis) during HFS that reduced motor symptoms and during clinically ineffective low-frequency stimulation (LFS). Firing pattern entropy was calculated from the recorded spike times to quantify the disorder of the neuronal activity. The firing pattern entropy of neurons within each region of the pallidum and motor thalamus decreased in response to HFS (n ≥ 18 and P ≤ 0.02 in each region), whereas firing rate changes were specific to pallidal neurons only. In response to LFS, firing rates were unchanged, but firing pattern entropy increased throughout the circuit (n ≥ 24 and P ≤ 10−4 in each region). These data suggest that the clinical effectiveness of HFS is correlated with, and potentially mediated by, a regularization of the pattern of neuronal activity throughout the basal ganglia thalamic circuit. PMID:18784271

  9. Movement-Related Discharge in the Macaque Globus Pallidus during High-Frequency Stimulation of the Subthalamic Nucleus

    PubMed Central

    Zimnik, Andrew J.; Nora, Gerald J.; Desmurget, Michel

    2015-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) has largely replaced ablative therapies for Parkinson's disease. Because of the similar efficacies of the two treatments, it has been proposed that DBS acts by creating an “informational lesion,” whereby pathologic neuronal firing patterns are replaced by low-entropy, stimulus-entrained firing patterns. The informational lesion hypothesis, in its current form, states that DBS blocks the transmission of all information from the basal ganglia, including both pathologic firing patterns and normal, task-related modulations in activity. We tested this prediction in two healthy rhesus macaques by recording single-unit spiking activity from the globus pallidus (232 neurons) while the animals completed choice reaction time reaching movements with and without STN-DBS. Despite strong effects of DBS on the activity of most pallidal cells, reach-related modulations in firing rate were equally prevalent in the DBS-on and DBS-off states. This remained true even when the analysis was restricted to cells affected significantly by DBS. In addition, the overall form and timing of perimovement modulations in firing rate were preserved between DBS-on and DBS-off states in the majority of neurons (66%). Active movement and DBS had largely additive effects on the firing rate of most neurons, indicating an orthogonal relationship in which both inputs contribute independently to the overall firing rate of pallidal neurons. These findings suggest that STN-DBS does not act as an indiscriminate informational lesion but rather as a filter that permits task-related modulations in activity while, presumably, eliminating the pathological firing associated with parkinsonism. PMID:25740526

  10. Intraoperative MRI for optimizing electrode placement for deep brain stimulation of the subthalamic nucleus in Parkinson disease.

    PubMed

    Cui, Zhiqiang; Pan, Longsheng; Song, Huifang; Xu, Xin; Xu, Bainan; Yu, Xinguang; Ling, Zhipei

    2016-01-01

    OBJECT The degree of clinical improvement achieved by deep brain stimulation (DBS) is largely dependent on the accuracy of lead placement. This study reports on the evaluation of intraoperative MRI (iMRI) for adjusting deviated electrodes to the accurate anatomical position during DBS surgery and acute intracranial changes. METHODS Two hundred and six DBS electrodes were implanted in the subthalamic nucleus (STN) in 110 patients with Parkinson disease. All patients underwent iMRI after implantation to define the accuracy of lead placement. Fifty-six DBS electrode positions in 35 patients deviated from the center of the STN, according to the result of the initial postplacement iMRI scans. Thus, we adjusted the electrode positions for placement in the center of the STN and verified this by means of second or third iMRI scans. Recording was performed in adjusted parameters in the x-, y-, and z-axes. RESULTS Fifty-six (27%) of 206 DBS electrodes were adjusted as guided by iMRI. Electrode position was adjusted on the basis of iMRI 62 times. The sum of target coordinate adjustment was -0.5 mm in the x-axis, -4 mm in the y-axis, and 15.5 mm in the z-axis; the total of distance adjustment was 74.5 mm in the x-axis, 88 mm in the y-axis, and 42.5 mm in the z-axis. After adjustment with the help of iMRI, all electrodes were located in the center of the STN. Intraoperative MRI revealed 2 intraparenchymal hemorrhages in 2 patients, brain shift in all patients, and leads penetrating the lateral ventricle in 3 patients. CONCLUSIONS The iMRI technique can guide surgeons as they adjust deviated electrodes to improve the accuracy of implanting the electrodes into the correct anatomical position. The iMRI technique can also immediately demonstrate acute changes such as hemorrhage and brain shift during DBS surgery. PMID:26274983

  11. Tenth anniversary of CAS ONLINE service : What CAS services should be in the new era of chemical information

    NASA Astrophysics Data System (ADS)

    Kostakos, Charles N.

    Chemical Abstracts Service celebrated 10th anniversary of CAS online information service in 1990. A speech given on the occasion reviewed history of the CAS ONLINE, in relation to its most important benefits for scientists and engineers. The development of STN international, the network through which CAS ONLINE is accessible around the world, was also discussed in the speech. The CAS ONLINE now contains a wide variety of files relating to chemical field including CA file, Registry file. CA previews,. CASREACT, CIN. MARPAT, etc for supplying chemical information worldwide.

  12. Abrasion Resistance of as-Cast High-Chromium Cast Iron

    NASA Astrophysics Data System (ADS)

    Pokusová, Marcela; Berta, Igor; Šooš, Ľubomír

    2014-12-01

    High chromium cast irons are widely used as abrasion resistant materials. Their properties and wear resistance depend on carbides and on the nature of the matrix supporting these carbides. The paper presents test results of irons which contain (in wt.%) 18-22 Cr and 2-5 C, and is alloyed by 1.7 Mo + 5 Ni + 2 Mn to improve the toughness. Tests showed as-cast irons with mostly austenitic matrix achieved hardness 36-53 HRC but their relative abrasion-resistance was higher than the tool steel STN 19436 heat treated on hardness 60 HRC.

  13. Improvement of sleep architecture in PD with subthalamic nucleus stimulation.

    PubMed

    Arnulf, I; Bejjani, B P; Garma, L; Bonnet, A M; Houeto, J L; Damier, P; Derenne, J P; Agid, Y

    2000-12-12

    High-frequency stimulation of the subthalamic nucleus (STN) was used to investigate the relationship of sleep disorders with motor handicap in PD. In 10 insomniac patients with PD, stimulation reduced nighttime akinesia by 60% and completely suppressed axial and early morning dystonia, but did not alleviate periodic leg movements (n = 3) or REM sleep behavior disorders (n = 5). Total sleep time increased by 47%; wakefulness after sleep onset decreased by 51 minutes. Insomnia in patients with PD may predominantly result from nighttime motor disability. PMID:11113233

  14. Comparative evaluation of the impact of WRF/NMM and WRF/ARW meteorology on CMAQ simulations for PM2.5 and its related precursors during the 2006 TexAQS/GoMACCS study

    NASA Astrophysics Data System (ADS)

    Yu, S.; Mathur, R.; Pleim, J.; Pouliot, G.; Wong, D.; Eder, B.; Schere, K.; Gilliam, R.; Rao, S. T.

    2012-05-01

    This study presents a comparative evaluation of the impact of WRF-NMM and WRF-ARW meteorology on CMAQ simulations of PM2.5, its composition and related precursors over the eastern United States with the intensive observations obtained by aircraft (NOAA WP-3), ship and surface monitoring networks (AIRNow, IMPROVE, CASTNet and STN) during the 2006 TexAQS/GoMACCS study. The results at the AIRNow surface sites show that both ARW-CMAQ and NMM-CMAQ reproduced day-to-day variations of observed PM2.5 and captured the majority of observed PM2.5 within a factor of 2 with a NMB value of -0.4% for ARW-CMAQ and -18% for NMM-CMAQ. Both models performed much better at the urban sites than at the rural sites, with greater underpredictions at the rural sites. Both models consistently underestimated the observed PM2.5 at the rural IMPROVE sites by -1% for the ARW-CMAQ and -19% for the NMM-CMAQ. The greater underestimations of SO42-, OC and EC by the NMM-CMAQ contributed to increased underestimation of PM2.5 at the IMPROVE sites. The NMB values for PM2.5 at the STN urban sites are 15% and -16% for the ARW-CMAQ and NMM-CMAQ, respectively. The underestimation of PM2.5 at the STN sites by the NMM-CMAQ mainly results from the underestimations of the SO42-, NH4+ and TCM components, whereas the overestimation of PM2.5 at the STN sites by the ARW-CMAQ results from the overestimations of SO42-, NO3-, and NH4+. The Comparison with WP-3 aircraft measurements reveals that both ARW-CMAQ and NMM-CMAQ have very similar model performance for vertical profiles for PM2.5 chemical components (SO42-, NH4+) and related gaseous species (HNO3, SO2, NH3, isoprene, toluene, terpenes) as both models used the same chemical mechanisms and emissions. The results of ship along the coast of southeastern Texas over the Gulf of Mexico show that both models captured the temporal variations and broad synoptic change seen in the observed HCHO and acetaldehyde with the means NMB <30% most of the time but they

  15. Bilateral subthalamic stimulation impairs cognitive–motor performance in Parkinson's disease patients

    PubMed Central

    Voelcker-Rehage, Claudia; Hallahan, Katie; Vitek, Megan; Bamzai, Rashi; Vitek, Jerrold L.

    2008-01-01

    Deep brain stimulation (DBS) is a surgical procedure that has been shown effective in improving the cardinal motor signs of advanced Parkinson's disease, however, declines in cognitive function have been associated with bilateral subthalamic nucleus (STN) DBS. Despite the fact that most activities of daily living clearly have motor and cognitive components performed simultaneously, postoperative assessments of cognitive and motor function occur, in general, in isolation of one another. The primary aim of this study was to determine the effects of unilateral and bilateral STN DBS on upper extremity motor function and cognitive performance under single- and dual-task conditions in advanced Parkinson's disease patients. Data were collected from eight advanced Parkinson's disease patients between the ages of 48 and 70 years (mean 56.5) who had bilaterally placed STN stimulators. Stimulation parameters for DBS devices were optimized clinically and were stable for at least 6 months prior to study participation. Data were collected while patients were Off anti-parkinsonian medications under three stimulation conditions: Off stimulation, unilateral DBS and bilateral DBS. In each stimulation condition patients performed a cognitive (n-back task) and motor (force tracking) task under single- and dual-task conditions. During dual-task conditions, patients performed the n-back and force-maintenance task simultaneously. Under relatively simple dual-task conditions there were no differences in cognitive or motor performance under unilateral and bilateral stimulation. As dual-task complexity increased, cognitive and motor performance was significantly worse with bilateral compared with unilateral stimulation. In the most complex dual-task condition (i.e. 2-back + force tracking), bilateral stimulation resulted in a level of motor performance that was similar to the Off stimulation condition. Significant declines in cognitive and motor function under modest dual-task conditions

  16. Cellerator: extending a computer algebra system to include biochemical arrows for signal transduction simulations

    NASA Technical Reports Server (NTRS)

    Shapiro, Bruce E.; Levchenko, Andre; Meyerowitz, Elliot M.; Wold, Barbara J.; Mjolsness, Eric D.

    2003-01-01

    Cellerator describes single and multi-cellular signal transduction networks (STN) with a compact, optionally palette-driven, arrow-based notation to represent biochemical reactions and transcriptional activation. Multi-compartment systems are represented as graphs with STNs embedded in each node. Interactions include mass-action, enzymatic, allosteric and connectionist models. Reactions are translated into differential equations and can be solved numerically to generate predictive time courses or output as systems of equations that can be read by other programs. Cellerator simulations are fully extensible and portable to any operating system that supports Mathematica, and can be indefinitely nested within larger data structures to produce highly scaleable models.

  17. Analysis of Indoor Environment in Classroom Based on Hygienic Requirements

    NASA Astrophysics Data System (ADS)

    Javorček, Miroslav; Sternová, Zuzana

    2016-06-01

    The article contains the analysis of experimental ventilation measurement in selected classrooms of the Elementary School Štrba. Mathematical model of selected classroom was prepared according to in-situ measurements and air exchange was calculated. Interior air temperature and quality influences the students ´ comfort. Evaluated data were compared to requirements of standard (STN EN 15251,2008) applicable to classroom indoor environment during lectures, highlighting the difference between required ambiance quality and actually measured values. CO2 concentration refers to one of the parameters indicating indoor environment quality.

  18. Spatial distance between anatomically- and physiologically-identified targets in subthalamic nucleus deep brain stimulation in Parkinson’s disease

    PubMed Central

    Parvaresh-Rizi, Mansour; Tabibkhoei, Alireza; Shahidi, Gholamali; Vaidyanathan, Janardan; Tabibkhoei, Amirreza; Rohani, Mohammad

    2016-01-01

    Background: Subthalamic nucleus (STN) stimulation is the treatment of choice for carefully chosen patients with idiopathic Parkinson's disease (PD) and refractory motor fluctuations. We evaluated the value of intraoperative electrophysiology during STN deep brain stimulation (DBS) procedures in refining the anatomically-defined target. Methods: We determined the spatial distance between the anatomical and physiological targets along x, y and z axes in 50 patients with PD who underwent bilateral subthalamic nucleus DBS surgery. Results: The mean spatial distance between anatomical and functional targets was 1.84 ± 0.88 mm and the least distances in different methods were 0.66 mm [standard error (SE): 0.07], 1.07 mm (SE: 0.08) and 1.01 mm (SE: 0.08) on x, y and z axes, respectively, for the combined method. Conclusion: The most physiologically-accurate anatomical targeting was achieved via a combination of multiple independent methods. There was a statistically significant difference between the anatomical and functional targets in all methods (even the combined) on the y coordinate, emphasizing the need for intra-operative electrophysiological monitoring to refine the anatomico-radiologically-defined target. PMID:27141275

  19. How does environmental enrichment reduce repetitive motor behaviors? Neuronal activation and dendritic morphology in the indirect basal ganglia pathway of a mouse model.

    PubMed

    Bechard, Allison R; Cacodcar, Nadia; King, Michael A; Lewis, Mark H

    2016-02-15

    Repetitive motor behaviors are observed in many neurodevelopmental and neurological disorders (e.g., autism spectrum disorders, Tourette syndrome, fronto-temporal dementia). Despite their clinical importance, the neurobiology underlying these highly stereotyped, apparently functionless behaviors is poorly understood. Identification of mechanisms that mediate the development of repetitive behaviors will aid in the discovery of new therapeutic targets and treatment development. Using a deer mouse model, we have shown that decreased indirect basal ganglia pathway activity is associated with high levels of repetitive behavior. Environmental enrichment (EE) markedly attenuates the development of such aberrant behaviors in mice, although mechanisms driving this effect are unknown. We hypothesized that EE would reduce repetitive motor behaviors by increasing indirect basal ganglia pathway function. We assessed neuronal activation and dendritic spine density in basal ganglia of adult deer mice reared in EE and standard housing. Significant increases in neuronal activation and dendritic spine densities were observed only in the subthalamic nucleus (STN) and globus pallidus (GP), and only for those mice that exhibited an EE-induced decrease in repetitive motor behavior. As the STN and GP lie within the indirect pathway, these data suggest that EE-induced attenuation of repetitive motor behaviors is associated with increased functional activation of the indirect basal ganglia pathway. These results are consistent with our other findings highlighting the importance of the indirect pathway in mediating repetitive motor behaviors. PMID:26620495

  20. Neuronal discharge patterns in the globus pallidus pars interna in a patient with Parkinson's disease and hemiballismus secondary to subthalamotomy.

    PubMed

    Cerquetti, Daniel; Obeso, José Angel; Merello, Marcelo

    2011-09-01

    Alterations in the basal ganglia-thalamocortical "motor" circuit activity, have been proposed to explain many features associated with hypokinetic and hyperkinetic movement disorders. We describe the firing pattern of the globus pallidus pars interna in a Parkinson disease's patient who developed Hemichorea-Ballismus subsequent to ipsilateral subthalamotomy, and compare findings to those from PD patients submitted to pallidotomy while in the OFF-medication state. Single units obtained from extracellular recordings were extracted and mean discharge frequency, interspike interval and coefficient of variation (defined as Tonicity Score) were computed. Discharge density histograms, analysis of distribution and spectral analysis were also performed. Mean firing frequency showed no significant difference between PD patients in the OFF state and the patient we report. However, a significant difference in tonicity was found for this patient characterized by a regular, non-bursting firing pattern. The findings indicate that in HB caused by lesions to STN in the parkinsonian state, GPi firing rates can be similar to and firing pattern more regular than those observed in GPi of PD patients OFF-medication with intact STN. PMID:21786135

  1. Glutamate and GABA concentration changes in the globus pallidus internus of Parkinson's patients during performance of implicit and declarative memory tasks: a report of two subjects.

    PubMed

    Buchanan, Robert J; Gjini, Klevest; Darrow, David; Varga, Georgeta; Robinson, Jennifer L; Nadasdy, Zoltan

    2015-03-01

    The basal ganglia, typically associated with motor function, are involved in human cognitive processes, as demonstrated in behavioral, lesion, and noninvasive functional neuroimaging studies. Here we report task-contingent changes in concentrations of the neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) in the globus pallidus internus (GPi) of two patients with Parkinson's disease undergoing deep brain stimulation surgery by utilizing in-vivo microdialysis measurements during performance of implicit and declarative memory tasks. Performance of an implicit memory task (weather prediction task-WPT) was associated with increased levels of glutamate and GABA in the GPi compared to their concentrations at baseline. On the other hand, performance of a declarative memory task (verbal learning task-VLT) was associated with decreased levels of glutamate and GABA in GPi compared to baseline during the encoding and immediate recall phase with less conclusive results during the delayed recall phase. These results are in line with hypothesized changes in these neurotransmitter levels: an increase of excitatory (Glu) input from subthalamic nucleus (STN) to GPi during implicit memory task performance and a decrease of inhibitory inputs (GABA) from globus pallidus externus (GPe) and striatum to GPi during declarative memory performance. Consistent with our previous report on in-vivo neurotransmitter changes during tasks in STN, these data provide corroborative evidence for the direct involvement of basal ganglia in cognitive functions and complements our model of the functional circuitry of basal ganglia in the healthy and Parkinson's disease affected brain. PMID:25596441

  2. Deep Brain Stimulation Significantly Decreases Disability from Low Back Pain in Patients with Advanced Parkinson's Disease

    PubMed Central

    Smith, Heather; Gee, Lucy; Kumar, Vignessh; Ramirez-Zamora, Adolfo; Durphy, Jennifer; Hanspal, Era; Barba, Anne; Molho, Eric; Shin, Damian; Pilitsis, Julie G.

    2015-01-01

    Background Up to 60% of Parkinson's patients suffer from low back pain (LBP) during the course of their disease. How LBP affects daily functional status and how to manage this aspect of PD has not been adequately explored. Methods We examined sixteen patients undergoing bilateral subthalamic nucleus deep brain stimulation (STN DBS) who met inclusion criteria for moderate disability from LBP, as classified by the Oswestry Low Back Pain Disability Index (OLBPD). Results Thirteen of 16 patients had attempted additional treatments for LBP including medical management, massage, chiropractic, epidural steroid injections and/or surgery and with minimal relief. Following DBS, there was a significant improvement in OLBPD at both the 6-month and 1-year time points (p < 0.02, p < 0.005 respectively). A mean improvement of 31.7% on OLBPD score was noted. Visual Analogue Scale (VAS) similarly decreased significantly at 1 year (p = 0.015). There was no correlation between OLBPD score and other measures including UPDRS, age, and other non-motor symptoms. Conclusion Given the prevalent yet undertreated disability associated with LBP in PD, these results are novel in that they show STN DBS has a significant positive effect on disability associated with LBP. PMID:25895600

  3. An update on the treatment of Parkinson's disease.

    PubMed

    Jankovic, Joseph

    2006-07-01

    Although levodopa remains the most effective symptomatic drug for Parkinson's disease (PD), its use is limited by the emergence of motor fluctuations and dyskinesias, particularly in young-onset patients. Dopamine agonists, catechol-O-methyltransferasee inhibitors and other anti-parkinsonian drugs have been found to diminish or prevent these complications and possibly to exert disease-modifying effects. The finding that the subthalamic nucleus (STN) and the globus pallidum internus (GPi) are abnormally active in PD has led to effective surgical treatments designed to improve patients' quality of life. The relative benefits of targeting STN or GPi with high-frequency stimulation are still being debated. Experimental therapeutics of PD include novel delivery systems, anti-apoptotic strategies and implantation of genetically engineered cells, and stem cells. Despite encouraging results from early pre-clinical and clinical studies, trials of human fetal grafts and intraventricular and intraparenchymal infusion of glial cell-line-derived neurotrophic factor have not shown clinically meaningful benefits. Future therapeutic strategies should focus not only on ameliorating the symptoms of PD, but also on neuroprotective or neurorescue therapies that can favorably modify the natural course of the disease and slow the progression of both motor and nonmotor manifestations of PD. PMID:16878274

  4. Extrastriatal Dopaminergic Circuits of the Basal Ganglia

    PubMed Central

    Rommelfanger, Karen S.; Wichmann, Thomas

    2010-01-01

    The basal ganglia are comprised of the striatum, the external and internal segment of the globus pallidus (GPe and GPi, respectively), the subthalamic nucleus (STN), and the substantia nigra pars compacta and reticulata (SNc and SNr, respectively). Dopamine has long been identified as an important modulator of basal ganglia function in the striatum, and disturbances of striatal dopaminergic transmission have been implicated in diseases such as Parkinson's disease (PD), addiction and attention deficit hyperactivity disorder. However, recent evidence suggests that dopamine may also modulate basal ganglia function at sites outside of the striatum, and that changes in dopaminergic transmission at these sites may contribute to the symptoms of PD and other neuropsychiatric disorders. This review summarizes the current knowledge of the anatomy, functional effects and behavioral consequences of the dopaminergic innervation to the GPe, GPi, STN, and SNr. Further insights into the dopaminergic modulation of basal ganglia function at extrastriatal sites may provide us with opportunities to develop new and more specific strategies for treating disorders of basal ganglia dysfunction. PMID:21103009

  5. Reduced levodopa-induced complications after 5 years of subthalamic stimulation in Parkinson's disease: a second honeymoon.

    PubMed

    Simonin, Clemence; Tir, M; Devos, D; Kreisler, A; Dujardin, K; Salleron, J; Delval, A; Blond, S; Defebvre, L; Destée, A; Krystkowiak, P

    2009-10-01

    The purpose of this paper is to describe the effect of 5 years of subthalamic nucleus deep brain stimulation (STN DBS) on levodopa-induced complications, both in everyday life and during an acute challenge with levodopa. Thirty three patients were evaluated during an acute levodopa challenge before surgery and then 1 and 5 years afterwards (both off stim and on stim), using the UPDRS III scale and the CAPSIT-PD scales for dystonia and peak-dose dyskinesia. The UPDRS IV scale was used to assess motor complications in everyday life. The levodopa daily dose and DBS parameters were also recorded. Levodopa-induced complications in everyday life (UPDRS IV) and during an acute levodopa challenge had improved markedly after 1 year (both on and off stim) and still further at 5 years. Peak-dose dyskinesia decreased between the 1- and 5-year measurements. STN DBS decreases levodopa-induced motor complications over the long term. This phenomenon may be explained by (a) overall stabilization of the basal ganglia network and (b) striatal synaptic changes. Our results suggest that DBS leads to both qualitative and quantitative modulations in the corticostriatal loops. PMID:19536584

  6. Role of the indirect pathway of the basal ganglia in perceptual decision making.

    PubMed

    Wei, Wei; Rubin, Jonathan E; Wang, Xiao-Jing

    2015-03-01

    The basal ganglia (BG) play an important role in motor control, reinforcement learning, and perceptual decision making. Modeling and experimental evidence suggest that, in a speed-accuracy tradeoff, the corticostriatal pathway can adaptively adjust a decision threshold (the amount of information needed to make a choice). In this study, we go beyond the focus of previous works on the direct and hyperdirect pathways to examine the contribution of the indirect pathway of the BG system to decision making in a biophysically based spiking network model. We find that the mechanism of adjusting the decision threshold by plasticity of the corticostriatal connections is effective, provided that the indirect pathway counterbalances the direct pathway in their projections to the output nucleus. Furthermore, in our model, changes within basal ganglia connections similar to those that arise in parkinsonism give rise to strong beta oscillations. Specifically, beta oscillations are produced by an abnormal enhancement of the interactions between the subthalamic nucleus (STN) and the external segment of globus pallidus (GPe) in the indirect pathway, with an oscillation frequency that depends on the excitatory cortical input to the STN and the inhibitory input to the GPe from the striatum. In a parkinsonian state characterized by pronounced beta oscillations, the mean reaction time and range of threshold variation (a measure of behavioral flexibility) are significantly reduced compared with the normal state. Our work thus reveals a specific circuit mechanism for impairments of perceptual decision making associated with Parkinson's disease. PMID:25740532

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

    PubMed Central

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

    2016-01-01

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

  8. Role of the Indirect Pathway of the Basal Ganglia in Perceptual Decision Making

    PubMed Central

    Wei, Wei; Rubin, Jonathan E.

    2015-01-01

    The basal ganglia (BG) play an important role in motor control, reinforcement learning, and perceptual decision making. Modeling and experimental evidence suggest that, in a speed–accuracy tradeoff, the corticostriatal pathway can adaptively adjust a decision threshold (the amount of information needed to make a choice). In this study, we go beyond the focus of previous works on the direct and hyperdirect pathways to examine the contribution of the indirect pathway of the BG system to decision making in a biophysically based spiking network model. We find that the mechanism of adjusting the decision threshold by plasticity of the corticostriatal connections is effective, provided that the indirect pathway counterbalances the direct pathway in their projections to the output nucleus. Furthermore, in our model, changes within basal ganglia connections similar to those that arise in parkinsonism give rise to strong beta oscillations. Specifically, beta oscillations are produced by an abnormal enhancement of the interactions between the subthalamic nucleus (STN) and the external segment of globus pallidus (GPe) in the indirect pathway, with an oscillation frequency that depends on the excitatory cortical input to the STN and the inhibitory input to the GPe from the striatum. In a parkinsonian state characterized by pronounced beta oscillations, the mean reaction time and range of threshold variation (a measure of behavioral flexibility) are significantly reduced compared with the normal state. Our work thus reveals a specific circuit mechanism for impairments of perceptual decision making associated with Parkinson's disease. PMID:25740532

  9. Impulsivities and Parkinson's disease: delay aversion is not worsened by Deep Brain Stimulation of the subthalamic nucleus.

    PubMed

    Torta, Diana M E; Vizzari, Vincenzo; Castelli, Lorys; Zibetti, Maurizio; Lanotte, Michele; Lopiano, Leonardo; Geminiani, Giuliano

    2012-01-01

    Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) improves motor symptoms in Parkinson's disease (PD), but can exert detrimental effects on impulsivity. These effects are especially related to the inability to slow down when high-conflict choices have to be made. However, the influence that DBS has on delay aversion is still under-investigated. Here, we tested a group of 21 PD patients on and off stimulation (off medication) by using the Cambridge Gamble Task (CGT), a computerized task that allows the investigation of risk-related behaviours and delay aversion, and psychological questionnaires such as the Barratt Impulsiveness Scale (BIS), the Sensitivity to Punishment and to Reward Questionnaire (SPSRQ), and the Quick Delay Questionnaire (QDQ). We found that delay aversion scores on the CGT were no higher when patients were on stimulation as compared to when they were off stimulation. In contrast, PD patients reported feeling more impulsive in the off stimulation state, as revealed by significantly higher scores on the BIS. Higher scores on the sensitivity to punishment subscale of the SPSRQ highlighted that possible punishments influence patients' behaviours more than possible rewards. Significant correlations between delay aversion scores on the CGT and QDQ delay aversion subscale suggest that these two instruments can be used in synergy to reach a convergent validity. In conclusion, our results show that not all impulsivities are detrimentally affected by DBS of the STN and that the joint use of experimental paradigms and psychological questionnaires can provide useful insights in the study of impulsivity. PMID:22984415

  10. The effect of cholesterol on the long-range network of interactions established among sea anemone Sticholysin II residues at the water-membrane interface.

    PubMed

    García-Linares, Sara; Alm, Ida; Maula, Terhi; Gavilanes, José G; Slotte, Johan Peter; Martínez-Del-Pozo, Álvaro

    2015-04-01

    Actinoporins are α-pore forming proteins with therapeutic potential, produced by sea anemones. Sticholysin II (StnII) from Stichodactyla helianthus is one of its most extensively characterized members. These proteins remain stably folded in water, but upon interaction with lipid bilayers, they oligomerize to form a pore. This event is triggered by the presence of sphingomyelin (SM), but cholesterol (Chol) facilitates pore formation. Membrane attachment and pore formation require changes involving long-distance rearrangements of residues located at the protein-membrane interface. The influence of Chol on membrane recognition, oligomerization, and/or pore formation is now studied using StnII variants, which are characterized in terms of their ability to interact with model membranes in the presence or absence of Chol. The results obtained frame Chol not only as an important partner for SM for functional membrane recognition but also as a molecule which significantly reduces the structural requirements for the mentioned conformational rearrangements to occur. However, given that the DOPC:SM:Chol vesicles employed display phase coexistence and have domain boundaries, the observed effects could be also due to the presence of these different phases on the membrane. In addition, it is also shown that the Arg51 guanidinium group is strictly required for membrane recognition, independently of the presence of Chol. PMID:25815890

  11. Therapeutic stimulation versus ablation.

    PubMed

    Hariz, Marwan I; Hariz, Gun-Marie

    2013-01-01

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

  12. Functional localization and visualization of the subthalamic nucleus from microelectrode recordings acquired during DBS surgery with unsupervised machine learning

    NASA Astrophysics Data System (ADS)

    Wong, S.; Baltuch, G. H.; Jaggi, J. L.; Danish, S. F.

    2009-04-01

    Microelectrode recordings are a useful adjunctive method for subthalamic nucleus localization during deep brain stimulation surgery for Parkinson's disease. Attempts to quantitate and standardize this process, using single computational measures of neural activity, have been limited by variability in patient neurophysiology and recording conditions. Investigators have suggested that a multi-feature approach may be necessary for automated approaches to perform within acceptable clinical standards. We present a novel data visualization algorithm and several unique features that address these shortcomings. The algorithm extracts multiple computational features from the microelectrode neurophysiology and integrates them with tools from unsupervised machine learning. The resulting colour-coded map of neural activity reveals activity transitions that correspond to the anatomic boundaries of subcortical structures. Using these maps, a non-neurophysiologist is able to achieve sensitivities of 90% and 95% for STN entry and exit, respectively, to within 0.5 mm accuracy of the current gold standard. The accuracy of this technique is attributed to the multi-feature approach. This activity map can simplify and standardize the process of localizing the subthalamic nucleus (STN) for neurostimulation. Because this method does not require a stationary electrode for careful recording of unit activity for spike sorting, the length of the operation may be shortened.

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

    PubMed

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

    2014-08-13

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

  14. Efficient ceramic anodes infiltrated with binary and ternary electrocatalysts for SOFCs operating at low temperatures

    NASA Astrophysics Data System (ADS)

    Hussain, A. Mohammed; Høgh, Jens V. T.; Zhang, Wei; Bonanos, Nikolaos

    2012-10-01

    Electrocatalyst precursor of various combinations: Pt, Ru, Pd, Ni and Gd-doped CeO2 (CGO) were infiltrated into a porous Sr0.94Ti0.9Nb0.1O3 (STN) backbone, to study the electrode performance of infiltrated ceramic anodes at low temperature ranges of 400-600 °C. The performance of the binary electrocatalyst infiltrated ceramic backbones are Pt-CGO>Ru-CGO>Pd-CGO>Ni-CGO. Ternary electrocatalyst of Ni-Pd-CGO and Ni-Pt-CGO showed the lowest polarization resistance of 0.31 and 0.11 Ωcm2, respectively at 600 °C in H2/3% H2O. The average particle size of the ternary electrocatalyst was larger than the binary Pd-CGO and Pt-CGO due to the particle coarsening of Ni nanoparticles. High resolution transmission electron microscopic analysis on the best performing Ni-Pt-CGO electrocatalyst infiltrated anode reveals the formation of Ni-Pt nanocrystalline alloy and a homogenous distribution of nanoparticles on STN backbone.

  15. Diffuse reflectance spectroscopy measurements for tissue-type discrimination during deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Antonsson, Johan; Eriksson, Ola; Blomstedt, Patric; Bergenheim, A. Tommy; Hariz, Marwan I.; Richter, Johan; Zsigmond, Peter; Wårdell, Karin

    2008-06-01

    Diffuse reflectance spectroscopy as a method for improving intracerebral guidance during functional neurosurgery has been investigated. An optical probe was developed for measurements during stereotactic and functional neurosurgery in man. The aim of the study was to investigate the spectral differences between white and grey matter and between white matter and functional targets. Diffuse reflectance spectroscopy measurements in ten patients were recorded at incremental steps towards and in three different functional targets (STN, GPi and Zi). The recorded spectra along the trajectory were sorted into white or grey matter, based on preoperative MRI images or the recorded spectral shape and intensity. The difference between tissue types was calculated as a quotient. Significant intensity differences between white and grey matter were found to be at least 14% (p < 0.05) and 20% (p < 0.0001) for MRI and spectral-sorted data respectively. The reflectance difference between white matter and the functional targets of GPi was higher than for STN and Zi. The results indicate that diffuse reflectance spectroscopy has a potential to be developed to a suitable complement to other intracerebral guidance methods.

  16. ACTS Satellite Telemammography Network Experiments

    NASA Technical Reports Server (NTRS)

    Kachmar, Brian A.; Kerczewski, Robert J.

    2000-01-01

    The Satellite Networks and Architectures Branch of NASA's Glenn Research Center has developed and demonstrated several advanced satellite communications technologies through the Advanced Communications Technology Satellite (ACTS) program. One of these technologies is the implementation of a Satellite Telemammography Network (STN) encompassing NASA Glenn, the Cleveland Clinic Foundation. the University of Virginia, and the Ashtabula County Medical Center. This paper will present a look at the STN from its beginnings to the impact it may have on future telemedicine applications. Results obtained using the experimental ACTS satellite demonstrate the feasibility of Satellite Telemammography. These results have improved teleradiology processes and mammography image manipulation, and enabled advances in remote screening methodologies. Future implementation of satellite telemammography using next generation commercial satellite networks will be explored. In addition, the technical aspects of the project will be discussed, in particular how the project has evolved from using NASA developed hardware and software to commercial off the shelf (COTS) products. Development of asymmetrical link technologies was an outcome of this work. Improvements in the display of digital mammographic images, better understanding of end-to-end system requirements, and advances in radiological image compression were achieved as a result of the research. Finally, rigorous clinical medical studies are required for new technologies such as digital satellite telemammography to gain acceptance in the medical establishment. These experiments produced data that were useful in two key medical studies that addressed the diagnostic accuracy of compressed satellite transmitted digital mammography images. The results of these studies will also be discussed.

  17. Determination Of The Maximum Explosion Pressure And The Maximum Rate Of Pressure Rise During Explosion Of Wood Dust Clouds

    NASA Astrophysics Data System (ADS)

    Kuracina, Richard; Szabová, Zuzana; Čekan, Pavol

    2015-06-01

    The article deals with the measurement of maximum explosion pressure and the maximum rate of exposure pressure rise of wood dust cloud. The measurements were carried out according to STN EN 14034-1+A1:2011 Determination of explosion characteristics of dust clouds. Part 1: Determination of the maximum explosion pressure pmax of dust clouds and the maximum rate of explosion pressure rise according to STN EN 14034-2+A1:2012 Determination of explosion characteristics of dust clouds - Part 2: Determination of the maximum rate of explosion pressure rise (dp/dt)max of dust clouds. The wood dust cloud in the chamber is achieved mechanically. The testing of explosions of wood dust clouds showed that the maximum value of the pressure was reached at the concentrations of 450 g / m3 and its value is 7.95 bar. The fastest increase of pressure was observed at the concentrations of 450 g / m3 and its value was 68 bar / s.

  18. New targets for DBS.

    PubMed

    Benabid, Alim Louis; Torres, Napoleon

    2012-01-01

    The specific effect of DBS at high frequency, discovered during a VIM thalamotomy, was extended to the older targets of ablative neurosurgery such as the pallidum, for tremor in Parkinson's disease (PD), dyskinesias, essential tremor, as well as the internal capsule to treat psychiatric disorders (OCD). A second wave of targets came from basic research, enabled by the low morbidity, reversibility, and adaptability of DBS. This was the case for the subthalamic nucleus (STN) which improves the triad of dopaminergic symptoms, and the pedunculopontine nucleus (PPN) for gait disorders in PD. The new concepts of the role of basal ganglia in psychiatric disorders indicate the subgenual cortex CG 25 for severe resistant depression, the accumbens nucleus for depression, anorexia nervosa, and addiction, and the thalamus intralaminar nuclei for minimally conscious states. Serendipity and a scientific approach have provided several instances where targets have produced unexpected effects (such as STN in OCD), as well as limbic effects observed during attempts at VMH stimulation for obesity: this might offer a novel way to treat mild cognitive impairment, or memory deficits reported in Alzheimer's disease. While these might provide solutions for as yet unsolved problems, attention must be paid to ethical considerations. PMID:22166437

  19. Defining the neurocircuitry of exercise hyperpnoea

    PubMed Central

    Paterson, David J

    2014-01-01

    One hundred years ago in this journal, Krogh and Lindhard published a seminal paper highlighting the importance of the brain in the control of breathing during exercise. This symposium report reviews the historical developments that have taken place since 1913, and attempts to place the detailed neurocircuitry thought to underpin exercise hyperpnoea into context by focusing on key structures that might form the command network. With the advent of enhanced neuroimaging and functional neurosurgical techniques, a unique window of opportunity has recently arisen to target potential circuits in humans. Animal studies have identified a priori sites of interest in mid-brain structures, in particular the subthalamic locomotor region (subthalamic nucleus, STN) and the periaqueductal grey (PAG), which have now been recorded from in humans during exercise. When all data are viewed in an integrative manner, the PAG, in particular the lateral PAG, and aspects of the dorsal lateral PAG, appear to be key communicating circuitry for ‘central command’. Moreover, the PAG also fulfils many requirements of a command centre. It has functional connectivity to higher centres (dorsal lateral prefrontal cortex) and the basal ganglia (in particular, the STN), and receives a sensory input from contracting muscle, but, importantly, it sends efferent information to brainstem nuclei involved in cardiorespiratory control. PMID:23918772

  20. A combined approach of VNTR and MLST analysis: improving molecular typing of Argentinean isolates of Leptospira interrogans.

    PubMed

    Caimi, Karina; Varni, Vanina; Melendez, Yamil; Koval, Ariel; Brihuega, Bibiana; Ruybal, Paula

    2012-08-01

    Leptospirosis is an emerging infectious disease that has been identified as both a human and animal health problem worldwide. Regular outbreaks associated with specific risk factors have been reported in Argentina. However, there are no available data concerning the genetic population level for this pathogen. Therefore, the aim of this work was to describe the genetic diversity of Leptospira interrogans through the application of two molecular typing strategies: variable number of tandem repeats (VNTR) and multilocus sequence typing (MLST). For this purpose, seven reference strains and 18 non-epidemiologically related isolates from diverse hosts and Argentinean regions were analysed. Among them, nine genotypes and seven sequence types (STs), including three unreported STs, were described using VNTR and MLST, respectively. eBURST analysis demonstrated that ST37 was the most frequent and founder genotype of a clonal complex (CCs) containing STN1 and STN3, suggesting the importance of studying the serovars belonging to this CC in Argentina. The data from maximum parsimony analysis, which combined both techniques, achieved intra-serovar discrimination, surmounted microscopic agglutination test discrepancies and increased the discriminatory power of each technique applied separately. This study is the first to combine both strategies for L. interrogans typing to generate a more comprehensive molecular genotyping of isolates from Argentina in a global context. PMID:22850955

  1. Neuronal Complexity in Subthalamic Nucleus is Reduced in Parkinson's Disease.

    PubMed

    Vyas, Saurabh; Huang, He; Gale, John T; Sarma, Sridevi V; Montgomery, Erwin B

    2016-01-01

    Several theories posit increased Subthalamic Nucleus (STN) activity is causal to Parkinsonism, yet in our previous study we showed that activity from 113 STN neurons from two epilepsy patients and 103 neurons from nine Parkinson's disease (PD) patients demonstrated no significant differences in frequencies or in the coefficients of variation of mean discharge frequencies per 1-s epochs. We continued our analysis using point process modeling to capture higher order temporal dynamics; in particular, bursting, beta-band oscillations, excitatory and inhibitory ensemble interactions, and neuronal complexity. We used this analysis as input to a logistic regression classifier and were able to differentiate between PD and epilepsy neurons with an accuracy of 92%. We also found neuronal complexity, i.e., the number of states in a neuron's point process model, and inhibitory ensemble dynamics, which can be interpreted as a reduction in complexity, to be the most important features with respect to classification accuracy. Even in a dataset with no significant differences in firing rate, we observed differences between PD and epilepsy for other single-neuron measures. Our results suggest PD comes with a reduction in neuronal "complexity," which translates to a neuron's ability to encode information; the more complexity, the more information the neuron can encode. This is also consistent with studies correlating disease to loss of variability in neuronal activity, as the lower the complexity, the less variability. PMID:26168436

  2. The PPH1 phosphatase is specifically involved in LHCII dephosphorylation and state transitions in Arabidopsis

    PubMed Central

    Shapiguzov, Alexey; Ingelsson, Björn; Samol, Iga; Andres, Charles; Kessler, Felix; Rochaix, Jean-David; Vener, Alexander V.; Goldschmidt-Clermont, Michel

    2010-01-01

    The ability of plants to adapt to changing light conditions depends on a protein kinase network in the chloroplast that leads to the reversible phosphorylation of key proteins in the photosynthetic membrane. Phosphorylation regulates, in a process called state transition, a profound reorganization of the electron transfer chain and remodeling of the thylakoid membranes. Phosphorylation governs the association of the mobile part of the light-harvesting antenna LHCII with either photosystem I or photosystem II. Recent work has identified the redox-regulated protein kinase STN7 as a major actor in state transitions, but the nature of the corresponding phosphatases remained unknown. Here we identify a phosphatase of Arabidopsis thaliana, called PPH1, which is specifically required for the dephosphorylation of light-harvesting complex II (LHCII). We show that this single phosphatase is largely responsible for the dephosphorylation of Lhcb1 and Lhcb2 but not of the photosystem II core proteins. PPH1, which belongs to the family of monomeric PP2C type phosphatases, is a chloroplast protein and is mainly associated with the stroma lamellae of the thylakoid membranes. We demonstrate that loss of PPH1 leads to an increase in the antenna size of photosystem I and to a strong impairment of state transitions. Thus phosphorylation and dephosphorylation of LHCII appear to be specifically mediated by the kinase/phosphatase pair STN7 and PPH1. These two proteins emerge as key players in the adaptation of the photosynthetic apparatus to changes in light quality and quantity. PMID:20176943

  3. Pallidal gap junctions-triggers of synchrony in Parkinson's disease?

    PubMed Central

    Schwab, Bettina C; Heida, Tjitske; Zhao, Yan; van Gils, Stephan A; van Wezel, Richard J A

    2014-01-01

    Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin-36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin-36 spots in PD tissues increased by 50% in the putamen, 43% in the GPe, and 109% in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin-36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia. PMID:25124148

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

    PubMed

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

    2005-03-01

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

  5. Electrochemical characterisation of solid oxide cell electrodes for hydrogen production

    NASA Astrophysics Data System (ADS)

    Bernuy-Lopez, Carlos; Knibbe, Ruth; He, Zeming; Mao, Xiaojian; Hauch, Anne; Nielsen, Karsten A.

    Oxygen electrodes and steam electrodes are designed and tested to develop improved solid oxide electrolysis cells for H 2 production with the cell support on the oxygen electrode. The electrode performance is evaluated by impedance spectroscopy testing of symmetric cells at open circuit voltage (OCV) in a one-atmosphere set-up. For the oxygen electrode, nano-structured La 0.75Sr 0.25MnO 3 (LSM25) is impregnated into a LSM25/yttria stabilised zirconia (YSZ) composite, whereas for the steam electrode, nano-structured Ni and Ce 0.8Gd 0.2O 2- δ (CGO) is impregnated into a Sr 0.94Ti 0.9Nb 0.10O 3- δ (STN) backbone. In the present study, the best performing oxygen electrode is a LSM25-YSZ composite with 20% porosity and impregnated with a LSM25 solution measuring a polarisation resistance (R p) of 0.12 Ω cm 2 at 850 °C in oxygen. For the steam electrode, the best performance is obtained for a STN backbone, sintered at 1200 °C and impregnated with CGO/Ni, with an R p of 0.08 Ω cm 2 at 850 °C in 3% H 2O/H 2.

  6. Pallidal gap junctions-triggers of synchrony in Parkinson's disease?

    PubMed

    Schwab, Bettina C; Heida, Tjitske; Zhao, Yan; van Gils, Stephan A; van Wezel, Richard J A

    2014-10-01

    Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin-36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin-36 spots in PD tissues increased by 50% in the putamen, 43% in the GPe, and 109% in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin-36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia. PMID:25124148

  7. The causal relationship between subcortical local field potential oscillations and Parkinsonian resting tremor

    NASA Astrophysics Data System (ADS)

    Tass, Peter; Smirnov, Dmitry; Karavaev, Anatoly; Barnikol, Utako; Barnikol, Thomas; Adamchic, Ilya; Hauptmann, Christian; Pawelcyzk, Norbert; Maarouf, Mohammad; Sturm, Volker; Freund, Hans-Joachim; Bezruchko, Boris

    2010-02-01

    To study the dynamical mechanism which generates Parkinsonian resting tremor, we apply coupling directionality analysis to local field potentials (LFP) and accelerometer signals recorded in an ensemble of 48 tremor epochs in four Parkinsonian patients with depth electrodes implanted in the ventro-intermediate nucleus of the thalamus (VIM) or the subthalmic nucleus (STN). Apart from the traditional linear Granger causality method we use two nonlinear techniques: phase dynamics modelling and nonlinear Granger causality. We detect a bidirectional coupling between the subcortical (VIM or STN) oscillation and the tremor, in the theta range (around 5 Hz) as well as broadband (>2 Hz). In particular, we show that the theta band LFP oscillations definitely play an efferent role in tremor generation, while beta band LFP oscillations might additionally contribute. The brain→tremor driving is a complex, nonlinear mechanism, which is reliably detected with the two nonlinear techniques only. In contrast, the tremor→brain driving is detected with any of the techniques including the linear one, though the latter is less sensitive. The phase dynamics modelling (applied to theta band oscillations) consistently reveals a long delay in the order of 1-2 mean tremor periods for the brain→tremor driving and a small delay, compatible with the neural transmission time, for the proprioceptive feedback. Granger causality estimation (applied to broadband signals) does not provide reliable estimates of the delay times, but is even more sensitive to detect the brain→tremor influence than the phase dynamics modelling.

  8. The PPH1 phosphatase is specifically involved in LHCII dephosphorylation and state transitions in Arabidopsis.

    PubMed

    Shapiguzov, Alexey; Ingelsson, Björn; Samol, Iga; Andres, Charles; Kessler, Felix; Rochaix, Jean-David; Vener, Alexander V; Goldschmidt-Clermont, Michel

    2010-03-01

    The ability of plants to adapt to changing light conditions depends on a protein kinase network in the chloroplast that leads to the reversible phosphorylation of key proteins in the photosynthetic membrane. Phosphorylation regulates, in a process called state transition, a profound reorganization of the electron transfer chain and remodeling of the thylakoid membranes. Phosphorylation governs the association of the mobile part of the light-harvesting antenna LHCII with either photosystem I or photosystem II. Recent work has identified the redox-regulated protein kinase STN7 as a major actor in state transitions, but the nature of the corresponding phosphatases remained unknown. Here we identify a phosphatase of Arabidopsis thaliana, called PPH1, which is specifically required for the dephosphorylation of light-harvesting complex II (LHCII). We show that this single phosphatase is largely responsible for the dephosphorylation of Lhcb1 and Lhcb2 but not of the photosystem II core proteins. PPH1, which belongs to the family of monomeric PP2C type phosphatases, is a chloroplast protein and is mainly associated with the stroma lamellae of the thylakoid membranes. We demonstrate that loss of PPH1 leads to an increase in the antenna size of photosystem I and to a strong impairment of state transitions. Thus phosphorylation and dephosphorylation of LHCII appear to be specifically mediated by the kinase/phosphatase pair STN7 and PPH1. These two proteins emerge as key players in the adaptation of the photosynthetic apparatus to changes in light quality and quantity. PMID:20176943

  9. Amniotic fluid embolism: pathophysiology and new strategies for management.

    PubMed

    Kanayama, Naohiro; Tamura, Naoaki

    2014-06-01

    The registry program of amniotic fluid embolism (AFE) in Japan started in 2003. More than 400 hundred clinical diagnosed amniotic fluid embolism has been accumulated. Those data showed that there were two etiologies of AFE: the fetal materials create physical obstructions in the maternal microvessels in various organs, such as the lung; and (ii) the liquids cause an anaphylactoid reaction that leads to pulmonary vasospasm and activation of platelets, white blood cells and/or complements. The clinical findings showed that AFE was characterized mainly by cardiopulmonary collapse, the other involves the presence of disseminated intravascular coagulation (DIC) and atonic bleeding. Zinc coproporphyrin-1, sialyl Tn antigen (STN), complement C3, C4 and interleukin-8 have been used as serum markers of AFE. The levels of zinc coproporphyrin-1 and STN were increased in cardiopulmonary collapse type AFE, and a marked reduction of C3 and C4 was observed in DIC type AFE. At the primary medical institution, initial treatments for shock airway management, vascular management, fluid replacement, administration of anti-DIC therapy such as antithrombin, and administration of fresh frozen plasma should be provided. C1 esterase inhibitor activity in AFE cases was significantly lower than those of normal pregnant women. C1 esterase inhibitor may be a promising candidate of treatment of AFE. PMID:24888909

  10. The Effect of Cholesterol on the Long-Range Network of Interactions Established among Sea Anemone Sticholysin II Residues at the Water-Membrane Interface

    PubMed Central

    García-Linares, Sara; Alm, Ida; Maula, Terhi; Gavilanes, José G.; Slotte, Johan Peter; Martínez-del-Pozo, Álvaro

    2015-01-01

    Actinoporins are α-pore forming proteins with therapeutic potential, produced by sea anemones. Sticholysin II (StnII) from Stichodactyla helianthus is one of its most extensively characterized members. These proteins remain stably folded in water, but upon interaction with lipid bilayers, they oligomerize to form a pore. This event is triggered by the presence of sphingomyelin (SM), but cholesterol (Chol) facilitates pore formation. Membrane attachment and pore formation require changes involving long-distance rearrangements of residues located at the protein-membrane interface. The influence of Chol on membrane recognition, oligomerization, and/or pore formation is now studied using StnII variants, which are characterized in terms of their ability to interact with model membranes in the presence or absence of Chol. The results obtained frame Chol not only as an important partner for SM for functional membrane recognition but also as a molecule which significantly reduces the structural requirements for the mentioned conformational rearrangements to occur. However, given that the DOPC:SM:Chol vesicles employed display phase coexistence and have domain boundaries, the observed effects could be also due to the presence of these different phases on the membrane. In addition, it is also shown that the Arg51 guanidinium group is strictly required for membrane recognition, independently of the presence of Chol. PMID:25815890

  11. Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase [alpha

    SciTech Connect

    Sun, Jia; Yang, Yuting; Wan, Ke; Mao, Ninghui; Yu, Tai-Yuan; Lin, Yi-Chien; DeZwaan, Diane C.; Freeman, Brian C.; Lin, Jing-Jer; Lue, Neal F.; Lei, Ming

    2011-08-24

    Budding yeast Cdc13-Stn1-Ten1 (CST) complex plays an essential role in telomere protection and maintenance, and has been proposed to be a telomere-specific replication protein A (RPA)-like complex. Previous genetic and structural studies revealed a close resemblance between Stn1-Ten1 and RPA32-RPA14. However, the relationship between Cdc13 and RPA70, the largest subunit of RPA, has remained unclear. Here, we report the crystal structure of the N-terminal OB (oligonucleotide/oligosaccharide binding) fold of Cdc13. Although Cdc13 has an RPA70-like domain organization, the structures of Cdc13 OB folds are significantly different from their counterparts in RPA70, suggesting that they have distinct evolutionary origins. Furthermore, our structural and biochemical analyses revealed unexpected dimerization by the N-terminal OB fold and showed that homodimerization is probably a conserved feature of all Cdc13 proteins. We also uncovered the structural basis of the interaction between the Cdc13 N-terminal OB fold and the catalytic subunit of DNA polymerase {alpha} (Pol1), and demonstrated a role for Cdc13 dimerization in Pol1 binding. Analysis of the phenotypes of mutants defective in Cdc13 dimerization and Cdc13-Pol1 interaction revealed multiple mechanisms by which dimerization regulates telomere lengths in vivo. Collectively, our findings provide novel insights into the mechanisms and evolution of Cdc13.

  12. Sensory contribution to vocal emotion deficit in Parkinson's disease after subthalamic stimulation.

    PubMed

    Péron, Julie; Cekic, Sezen; Haegelen, Claire; Sauleau, Paul; Patel, Sona; Drapier, Dominique; Vérin, Marc; Grandjean, Didier

    2015-02-01

    Subthalamic nucleus (STN) deep brain stimulation in Parkinson's disease induces modifications in the recognition of emotion from voices (or emotional prosody). Nevertheless, the underlying mechanisms are still only poorly understood, and the role of acoustic features in these deficits has yet to be elucidated. Our aim was to identify the influence of acoustic features on changes in emotional prosody recognition following STN stimulation in Parkinson's disease. To this end, we analysed the performances of patients on vocal emotion recognition in pre-versus post-operative groups, as well as of matched controls, entering the acoustic features of the stimuli into our statistical models. Analyses revealed that the post-operative biased ratings on the Fear scale when patients listened to happy stimuli were correlated with loudness, while the biased ratings on the Sadness scale when they listened to happiness were correlated with fundamental frequency (F0). Furthermore, disturbed ratings on the Happiness scale when the post-operative patients listened to sadness were found to be correlated with F0. These results suggest that inadequate use of acoustic features following subthalamic stimulation has a significant impact on emotional prosody recognition in patients with Parkinson's disease, affecting the extraction and integration of acoustic cues during emotion perception. PMID:25282055

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

    PubMed

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

    2013-09-01

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

  14. Neural integrity is maintained by dystrophin in C. elegans

    PubMed Central

    Zhou, Shan

    2011-01-01

    The dystrophin protein complex (DPC), composed of dystrophin and associated proteins, is essential for maintaining muscle membrane integrity. The link between mutations in dystrophin and the devastating muscle failure of Duchenne’s muscular dystrophy (DMD) has been well established. Less well appreciated are the accompanying cognitive impairment and neuropsychiatric disorders also presented in many DMD patients, which suggest a wider role for dystrophin in membrane–cytoskeleton function. This study provides genetic evidence of a novel role for DYS-1/dystrophin in maintaining neural organization in Caenorhabditis elegans. This neuronal function is distinct from the established role of DYS-1/dystrophin in maintaining muscle integrity and regulating locomotion. SAX-7, an L1 cell adhesion molecule (CAM) homologue, and STN-2/γ-syntrophin also function to maintain neural integrity in C. elegans. This study provides biochemical data that show that SAX-7 associates with DYS-1 in an STN-2/γ-syntrophin–dependent manner. These results reveal a recruitment of L1CAMs to the DPC to ensure neural integrity is maintained. PMID:21242290

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

    Devergnas, Annaelle; Wichmann, Thomas

    2011-01-01

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

  17. Teaching Chemical Information in a Liberal Arts Curriculum

    NASA Astrophysics Data System (ADS)

    Ricker, Alison Scott; Thompson, Robert Q.

    1999-11-01

    We first offered Chemical Information as a one-credit, semester-long course in 1993 and have continued to team-teach it each fall. We offer this summary of our course as a model that might be adapted in other settings, acknowledging that no single course can adequately prepare chemists for the many challenges involved in finding, evaluating, and utilizing chemical information. The focus on information retrieval, evaluation, and presentation in a separate course has worked well for us, successfully integrating concepts of information literacy in a chemical context. We cover a wide array of topics, beginning with print and electronic resources on our campus and moving quickly to databases and other sources on the Internet. Searching CA Online via STN Express and STN Easy is emphasized more than any other single source. We have described the course in some detail elsewhere and give here a synopsis of our current approach and significant changes in the course over the last two years.

  18. Motor task event detection using Subthalamic Nucleus Local Field Potentials.

    PubMed

    Niketeghad, Soroush; Hebb, Adam O; Nedrud, Joshua; Hanrahan, Sara J; Mahoor, Mohammad H

    2015-08-01

    Deep Brain Stimulation (DBS) provides significant therapeutic benefit for movement disorders such as Parkinson's disease. Current DBS devices lack real-time feedback (thus are open loop) and stimulation parameters are adjusted during scheduled visits with a clinician. A closed-loop DBS system may reduce power consumption and DBS side effects. In such systems, DBS parameters are adjusted based on patient's behavior, which means that behavior detection is a major step in designing such systems. Various physiological signals can be used to recognize the behaviors. Subthalamic Nucleus (STN) Local Field Potential (LFP) is a great candidate signal for the neural feedback, because it can be recorded from the stimulation lead and does not require additional sensors. A practical behavior detection method should be able to detect behaviors asynchronously meaning that it should not use any prior knowledge of behavior onsets. In this paper, we introduce a behavior detection method that is able to asynchronously detect the finger movements of Parkinson patients. As a result of this study, we learned that there is a motor-modulated inter-hemispheric connectivity between LFP signals recorded bilaterally from STN. We used non-linear regression method to measure this connectivity and use it to detect the finger movements. Performance of this method is evaluated using Receiver Operating Characteristic (ROC). PMID:26737550

  19. Frequency-Specific Synchronization in the Bilateral Subthalamic Nuclei Depending on Voluntary Muscle Contraction and Relaxation in Patients with Parkinson’s Disease

    PubMed Central

    Kato, Kenji; Yokochi, Fusako; Iwamuro, Hirokazu; Kawasaki, Takashi; Hamada, Kohichi; Isoo, Ayako; Kimura, Katsuo; Okiyama, Ryoichi; Taniguchi, Makoto; Ushiba, Junichi

    2016-01-01

    The volitional control of muscle contraction and relaxation is a fundamental component of human motor activity, but how the processing of the subcortical networks, including the subthalamic nucleus (STN), is involved in voluntary muscle contraction (VMC) and voluntary muscle relaxation (VMR) remains unclear. In this study, local field potentials (LFPs) of bilateral STNs were recorded in patients with Parkinson’s disease (PD) while performing externally paced VMC and VMR tasks of the unilateral wrist extensor muscle. The VMC- or VMR-related oscillatory activities and their functional couplings were investigated over the theta (4–7 Hz), alpha (8–13 Hz), beta (14–35 Hz), and gamma (40–100 Hz) frequency bands. Alpha and beta desynchronizations were observed in bilateral STNs at the onset of both VMC and VMR tasks. On the other hand, theta and gamma synchronizations were prominent in bilateral STNs specifically at the onset of the VMC task. In particular, just after VMC, theta functional coupling between the bilateral STNs increased, and the theta phase became coupled to the gamma amplitude within the contralateral STN in a phase-amplitude cross-frequency coupled manner. On the other hand, the prominent beta-gamma cross-frequency couplings observed in the bilateral STNs at rest were reduced by the VMC and VMR tasks. These results suggest that STNs are bilaterally involved in the different performances of muscle contraction and relaxation through the theta-gamma and beta-gamma networks between bilateral STNs in patients with PD. PMID:27064969

  20. Detection of Cell Surface Hydrophobicity, Biofilm and Fimbirae Genes in Salmonella Isolated from Tunisian Clinical and Poultry Meat

    PubMed Central

    BEN ABDALLAH, Fethi; LAGHA, Rihab; SAID, Khaled; KALLEL, Héla; GHARBI, Jawhar

    2014-01-01

    Abstract Background The aim of this study was to evaluate the ability of 15 serotypes of Salmonella to form biofilm on polystyrene, polyvinyl chloride (PVC) and glass surfaces. . Methods Initially slime production was assessed on CRA agar and hydrophobicity of 20 Salmonella strains isolated from poultry and human and two Salmonella enterica serovar Typhimurium references strains was achieved by microbial adhesion to n-hexadecane. In addition, biofilm formation on polystyrene, PVC and glass surfaces was also investigated by using MTT and XTT colorimetric assay. Further, distribution of Salmonella enterotoxin (stn), Salmonella Enteritidis fimbrial (sef) and plasmid encoded fimbrial (pef) genes among tested strains was achieved by PCR. Results Salmonella strains developed red and white colonies on CRA and they are considered as hydrophilic with affinity values to n-hexadecane ranged between 0.29% and 29.55%. Quantitative biofilm assays showed that bacteria are able to form biofilm on polystyrene with different degrees and 54.54% of strains produce a strong biofilm on glass. In addition, all the strains form only a moderate (54.54%) and weak (40.91%) biofilm on PVC. PCR detection showed that only S. Enteritidis harbour Sef gene, whereas Pef and stn genes were detected in S. Kentucky, S. Amsterdam, S. Hadar, S. Enteritidis and S. Typhimurium. Conclusion Salmonella serotypes are able to form biofilm on hydrophobic and hydrophilic industrial surfaces. Biofilm formation of Salmonella on these surfaces has an increased potential to compromise food safety and potentiate public health risk. PMID:26005652

  1. An Assessment of Stakeholder Perceptions and Management of Noxious Alien Plants in Spain

    NASA Astrophysics Data System (ADS)

    Andreu, Jara; Vilà, Montserrat; Hulme, Philip E.

    2009-06-01

    Despite biological invasions being a worldwide phenomenon causing significant ecological, economic, and human welfare impacts, there is limited understanding regarding how environmental managers perceive the problem and subsequently manage alien species. Spanish environmental managers were surveyed using questionnaires to (1) analyze the extent to which they perceive plant invasions as a problem; (2) identify the status, occurrence, and impacts of noxious alien plant species; (3) assess current effort and expenditure targeting alien plant management; and, finally, (4) identify the criteria they use to set priorities for management. In comparison to other environmental concerns, plant invasions are perceived as only moderately problematic and mechanical control is the most valued and frequently used strategy to cope with plant invasions in Spain. Based on 70 questionnaires received, 193 species are considered noxious, 109 of which have been the subject of management activities. More than 90% of species are found in at least one protected area. According to respondents, the most frequently managed species are the most widespread across administrative regions and the ones perceived as causing the highest impacts. The perception of impact seems to be independent of their invasion status, since only half of the species identified as noxious are believed to be invasive in Spain, while 43% of species thought to only be casual aliens are causing a high impact. Records of management costs are poor and the few data indicate that the total actual expenditure amounted to 50,492,437 € in the last decade. The majority of respondents stated that management measures are insufficient to control alien plants due to limited economic resources, lack of public awareness and support, and an absence of coordination among different public administrations. Managers also expressed their concern about the fact that much scientific research is concerned with the ecology of alien plants

  2. [Polychlorinated biphenyls and their methylsulfonyl metabolites in fish from an electronic waste recycling site in south China: tissue distribution and human dietary exposure].

    PubMed

    Tang, Bin; Luo, Xiao-Jun; Zeng, Yan-Hong; Mai, Bi-Xian

    2014-12-01

    In the present study, we determined polychlorinated biphenyls and their methylsulfonyl metabolites (MeSO2-PCBs) in the tissues of two fish species-mud carp and northern snakehead-from a natural pond in an electronic waste recycling site in the Pearl River Delta, Southern China. The mean concentrations of PCBs (Σ PCBs )varied from 560 to 10 462 ng x g(-1) wet weight, and from 580 to 50 492 ng x g(-1) wet weight in the tissues of mud carp and northern snakehead, respectively, with the highest levels found in the liver. Lipid contents played an important role in the determination of tissue distribution of PCBs. The mean concentrations of Σ MeSO2-PCBs varied between 0.44 and 53 ng x g(-1) wet weight in tissues of mud carp, while varied between 1.86 and 132 ng x g(-1) wet weight in northern snakehead. These levels were one order of magnitude greater than the highest levels of MeSO2-PCBs previously reported in fish. The EF values of chiral PCBs in mud carp were lower than those in the sediments, with an exception of PCB149. However, the declined EFs in mud carp were rebounded in northern snakehead, and some values were even higher than those in the sediment. This result may suggest that the mud carp and the northern snakehead preferred to biotransform different enantiomers of PCB congeners. The elevated levels of Σ PCBs and Σ MeSO2-PCBs detected in the present study indicated a high exposure risk to the local residents. Restricting the consumption of these fish in the local markets is important and essential for reducing the health risks to local residents. PMID:25826938

  3. Soil Carbon and Nitrogen Fractions and Crop Yields Affected by Residue Placement and Crop Types

    PubMed Central

    Wang, Jun; Sainju, Upendra M.

    2014-01-01

    Soil labile C and N fractions can change rapidly in response to management practices compared to non-labile fractions. High variability in soil properties in the field, however, results in nonresponse to management practices on these parameters. We evaluated the effects of residue placement (surface application [or simulated no-tillage] and incorporation into the soil [or simulated conventional tillage]) and crop types (spring wheat [Triticum aestivum L.], pea [Pisum sativum L.], and fallow) on crop yields and soil C and N fractions at the 0–20 cm depth within a crop growing season in the greenhouse and the field. Soil C and N fractions were soil organic C (SOC), total N (STN), particulate organic C and N (POC and PON), microbial biomass C and N (MBC and MBN), potential C and N mineralization (PCM and PNM), NH4-N, and NO3-N concentrations. Yields of both wheat and pea varied with residue placement in the greenhouse as well as in the field. In the greenhouse, SOC, PCM, STN, MBN, and NH4-N concentrations were greater in surface placement than incorporation of residue and greater under wheat than pea or fallow. In the field, MBN and NH4-N concentrations were greater in no-tillage than conventional tillage, but the trend reversed for NO3-N. The PNM was greater under pea or fallow than wheat in the greenhouse and the field. Average SOC, POC, MBC, PON, PNM, MBN, and NO3-N concentrations across treatments were higher, but STN, PCM and NH4-N concentrations were lower in the greenhouse than the field. The coefficient of variation for soil parameters ranged from 2.6 to 15.9% in the greenhouse and 8.0 to 36.7% in the field. Although crop yields varied, most soil C and N fractions were greater in surface placement than incorporation of residue and greater under wheat than pea or fallow in the greenhouse than the field within a crop growing season. Short-term management effect on soil C and N fractions were readily obtained with reduced variability under controlled soil and

  4. Rates of N2 production and diversity and abundance of functional genes associated with denitrification and anaerobic ammonium oxidation in the sediment of the Amundsen Sea Polynya, Antarctica

    NASA Astrophysics Data System (ADS)

    Choi, Ayeon; Cho, Hyeyoun; Kim, Sung-Han; Thamdrup, Bo; Lee, SangHoon; Hyun, Jung-Ho

    2016-01-01

    A combination of molecular microbiological analyses and metabolic rate measurements was conducted to elucidate the diversity and abundance of denitrifying and anaerobic ammonium oxidation (anammox) bacteria and the nitrogen gas (N2) production rates in sediment underlying the highly productive polynya (Stns. 10 and 17) and the sea-ice zone on the outer shelf (Stn. 83) of the Amundsen Sea, Antarctica. Despite the high water column productivity, the N2 production rates by denitrification (0.04-0.31 nmol N cm-3sed. h-1) and anammox (0.13-0.26 nmol N cm-3 sed. h-1) were lower than those measured in other polar regions. In contrast, gene copy number (106-107 copies cm-3 of nirS and nosZ genes targeting denitirifiers and 105-107 copies cm-3 of 16S rRNA genes related to anammox bacteria) of the two bacterial groups at Stn. 17 was similar compared to those of other organic-rich environments. The majority of the nirS sequences were affiliated with Gammaproteobacteria (54% and 61% of the total nirS gene at Stns. 17 and 83, respectively), which were closely related to Pseudomonas aeruginosa. Most nosZ sequences (92% and 72% of the total nosZ genes at Stns. 17 and 83, respectively) were related to the Alphaproteobacteria, which were closely related to Ruegeria pomeroyi and Roseobacter denitrificans. Most (98%) of the sequences related to anammox bacteria were affiliated with Candidatus Scalindua at Stn. 17. Consequently, despite the low metabolic activity, the abundance and composition of most denitrifying and anammox bacteria detected from the ASP were similar to those reported from a variety of marine environments. Our results further imply that increased labile organic matter production resulting from a shift of the phytoplankton community from Phaeocystis to diatoms in response to rapid melting of sea ice stimulates metabolic activities of the denitrifying and anammox bacteria, thereby enhancing the N removal process in the ASP.

  5. Atlas-based identification of targets for functional radiosurgery

    SciTech Connect

    Stancanello, Joseph; Romanelli, Pantaleo; Modugno, Nicola; Cerveri, Pietro; Ferrigno, Giancarlo; Uggeri, Fulvio; Cantore, Giampaolo

    2006-06-15

    Functional disorders of the brain, such as Parkinson's disease, dystonia, epilepsy, and neuropathic pain, may exhibit poor response to medical therapy. In such cases, surgical intervention may become necessary. Modern surgical approaches to such disorders include radio-frequency lesioning and deep brain stimulation (DBS). The subthalamic nucleus (STN) is one of the most useful stereotactic targets available: STN DBS is known to induce substantial improvement in patients with end-stage Parkinson's disease. Other targets include the Globus Pallidus pars interna (GPi) for dystonia and Parkinson's disease, and the centromedian nucleus of the thalamus (CMN) for neuropathic pain. Radiosurgery is an attractive noninvasive alternative to treat some functional brain disorders. The main technical limitation to radiosurgery is that the target can be selected only on the basis of magnetic resonance anatomy without electrophysiological confirmation. The aim of this work is to provide a method for the correct atlas-based identification of the target to be used in functional neurosurgery treatment planning. The coordinates of STN, CMN, and GPi were identified in the Talairach and Tournoux atlas and transformed to the corresponding regions of the Montreal Neurological Institute (MNI) electronic atlas. Binary masks describing the target nuclei were created. The MNI electronic atlas was deformed onto the patient magnetic resonance imaging-T1 scan by applying an affine transformation followed by a local nonrigid registration. The first transformation was based on normalized cross correlation and the second on optimization of a two-part objective function consisting of similarity criteria and weighted regularization. The obtained deformation field was then applied to the target masks. The minimum distance between the surface of an implanted electrode and the surface of the deformed mask was calculated. The validation of the method consisted of comparing the electrode-mask distance to

  6. Soil carbon and nitrogen fractions and crop yields affected by residue placement and crop types.

    PubMed

    Wang, Jun; Sainju, Upendra M

    2014-01-01

    Soil labile C and N fractions can change rapidly in response to management practices compared to non-labile fractions. High variability in soil properties in the field, however, results in nonresponse to management practices on these parameters. We evaluated the effects of residue placement (surface application [or simulated no-tillage] and incorporation into the soil [or simulated conventional tillage]) and crop types (spring wheat [Triticum aestivum L.], pea [Pisum sativum L.], and fallow) on crop yields and soil C and N fractions at the 0-20 cm depth within a crop growing season in the greenhouse and the field. Soil C and N fractions were soil organic C (SOC), total N (STN), particulate organic C and N (POC and PON), microbial biomass C and N (MBC and MBN), potential C and N mineralization (PCM and PNM), NH4-N, and NO3-N concentrations. Yields of both wheat and pea varied with residue placement in the greenhouse as well as in the field. In the greenhouse, SOC, PCM, STN, MBN, and NH4-N concentrations were greater in surface placement than incorporation of residue and greater under wheat than pea or fallow. In the field, MBN and NH4-N concentrations were greater in no-tillage than conventional tillage, but the trend reversed for NO3-N. The PNM was greater under pea or fallow than wheat in the greenhouse and the field. Average SOC, POC, MBC, PON, PNM, MBN, and NO3-N concentrations across treatments were higher, but STN, PCM and NH4-N concentrations were lower in the greenhouse than the field. The coefficient of variation for soil parameters ranged from 2.6 to 15.9% in the greenhouse and 8.0 to 36.7% in the field. Although crop yields varied, most soil C and N fractions were greater in surface placement than incorporation of residue and greater under wheat than pea or fallow in the greenhouse than the field within a crop growing season. Short-term management effect on soil C and N fractions were readily obtained with reduced variability under controlled soil and

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

    NASA Astrophysics Data System (ADS)

    Fan, Denggui; Wang, Zhihui; Wang, Qingyun

    2016-07-01

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

  8. Variations in speciated emissions from spark-ignition and compression-ignition motor vehicles in California's south coast air basin.

    PubMed

    Fujita, Eric M; Zielinska, Barbara; Campbell, David E; Arnott, W Patrick; Sagebiel, John C; Mazzoleni, Lynn; Chow, Judith C; Gabele, Peter A; Crews, William; Snow, Richard; Clark, Nigel N; Wayne, W Scott; Lawson, Douglas R

    2007-06-01

    The U.S. Department of Energy Gasoline/Diesel PM Split Study examined the sources of uncertainties in using an organic compound-based chemical mass balance receptor model to quantify the contributions of spark-ignition (SI) and compression-ignition (CI) engine exhaust to ambient fine particulate matter (PM2.5). This paper presents the chemical composition profiles of SI and CI engine exhaust from the vehicle-testing portion of the study. Chemical analysis of source samples consisted of gravimetric mass, elements, ions, organic carbon (OC), and elemental carbon (EC) by the Interagency Monitoring of Protected Visual Environments (IMPROVE) and Speciation Trends Network (STN) thermal/optical methods, polycyclic aromatic hydrocarbons (PAHs), hopanes, steranes, alkanes, and polar organic compounds. More than half of the mass of carbonaceous particles emitted by heavy-duty diesel trucks was EC (IMPROVE) and emissions from SI vehicles contained predominantly OC. Although total carbon (TC) by the IMPROVE and STN protocols agreed well for all of the samples, the STN/IMPROVE ratios for EC from SI exhaust decreased with decreasing sample loading. SI vehicles, whether low or high emitters, emitted greater amounts of high-molecular-weight particulate PAHs (benzo[ghi]perylene, indeno[1,2,3-cd]pyrene, and coronene) than did CI vehicles. Diesel emissions contained higher abundances of two- to four-ring semivolatile PAHs. Diacids were emitted by CI vehicles but are also prevalent in secondary organic aerosols, so they cannot be considered unique tracers. Hopanes and steranes were present in lubricating oil with similar composition for both gasoline and diesel vehicles and were negligible in gasoline or diesel fuels. CI vehicles emitted greater total amounts of hopanes and steranes on a mass per mile basis, but abundances were comparable to SI exhaust normalized to TC emissions within measurement uncertainty. The combustion-produced high-molecular-weight PAHs were found in used

  9. Tuning the Brake While Raising the Stake: Network Dynamics during Sequential Decision-Making

    PubMed Central

    Meder, David; Haagensen, Brian Numelin; Hulme, Oliver; Morville, Tobias; Gelskov, Sofie; Herz, Damian Marc; Diomsina, Beata; Christensen, Mark Schram; Madsen, Kristoffer Hougaard

    2016-01-01

    When gathering valued goods, risk and reward are often coupled and escalate over time, for instance, during foraging, trading, or gambling. This escalating frame requires agents to continuously balance expectations of reward against those of risk. To address how the human brain dynamically computes these tradeoffs, we performed whole-brain fMRI while healthy young individuals engaged in a sequential gambling task. Participants were repeatedly confronted with the option to continue with throwing a die to accumulate monetary reward under escalating risk, or the alternative option to stop to bank the current balance. Within each gambling round, the accumulation of gains gradually increased reaction times for “continue” choices, indicating growing uncertainty in the decision to continue. Neural activity evoked by “continue” choices was associated with growing activity and connectivity of a cortico-subcortical “braking” network that positively scaled with the accumulated gains, including pre-supplementary motor area (pre-SMA), inferior frontal gyrus, caudate, and subthalamic nucleus (STN). The influence of the STN on continue-evoked activity in the pre-SMA was predicted by interindividual differences in risk-aversion attitudes expressed during the gambling task. Furthermore, activity in dorsal anterior cingulate cortex (ACC) reflected individual choice tendencies by showing increased activation when subjects made nondefault “continue” choices despite an increasing tendency to stop, but ACC activity did not change in proportion with subjective choice uncertainty. Together, the results implicate a key role of dorsal ACC, pre-SMA, inferior frontal gyrus, and STN in computing the trade-off between escalating reward and risk in sequential decision-making. SIGNIFICANCE STATEMENT Using a paradigm where subjects experienced increasing potential rewards coupled with increasing risk, this study addressed two unresolved questions in the field of decision

  10. Early spawning of Antarctic krill in the Scotia Sea is fuelled by “superfluous” feeding on non-ice associated phytoplankton blooms

    NASA Astrophysics Data System (ADS)

    Schmidt, Katrin; Atkinson, Angus; Venables, Hugh J.; Pond, David W.

    2012-01-01

    The spawning success of Antarctic krill ( Euphausia superba) is generally assumed to depend on substantial winter sea ice extent, as ice biota can serve as a food source during winter/spring and the seasonal ice melt conditions the upper water column for extensive phytoplankton blooms. However, direct observations during spring are rare. Here we studied krill body condition and maturity stage in relation to feeding (i.e. stomach fullness, diet, absorption of individual fatty acids and defecation rate) across the Scotia Sea in November 2006. The phytoplankton concentrations were low at the marginal ice zone (MIZ) in the southern Scotia Sea (Stn. 1, 2, and 3), high in open waters of the Southern Antarctic Circumpolar Current Front (SACCF) in the central Scotia Sea (Stn. 5), and moderate further north (Stn. 6 and 7). Krill had low lipid reserves (˜6.5% of dry mass, DM), low mass:length ratios (˜1.7 mg DM mm -1), and small digestive glands (˜7% of total DM) near the ice edge. The stomachs contained lithogenic particles, diatom debris, and bacterial fatty acids, but low proportions of diatom-indicating fatty acids, which suggest that these krill were feeding on detritus rather than on fresh ice algae. In the SACCF, krill had higher lipid reserves (˜10% of DM), high mass:length ratios (˜2.2 mg DM mm -1), and large digestive glands (˜16% of total DM). Stomach content and tissue composition indicate feeding on diatoms. In the north, moderate food concentrations co-occurred with low lipid reserves in krill, and moderate mass:length ratios and digestive gland sizes. Only in the phytoplankton bloom in the SACCF had the mating season already started and some females were about to spawn. Based on the way krill processed their food at the different stations, we indicate two mechanisms that can lead to fast regeneration of body reserves and oocyte maturation in E. superba. One is "superfluous" feeding at high food concentrations, which maximises the overall nutrient gain

  11. A computational model of Parkinsonian handwriting that highlights the role of the indirect pathway in the basal ganglia.

    PubMed

    Gangadhar, G; Joseph, D; Srinivasan, A V; Subramanian, D; Shivakeshavan, R G; Shobana, N; Chakravarthy, V S

    2009-10-01

    Parkinsonian handwriting is typically characterized by micrographia, jagged line contour, and unusual fluctuations in pen velocity. In this paper we present a computational model of handwriting generation that highlights the role of the basal ganglia, particularly the indirect pathway. Whereas reduced dopamine levels resulted in reduced letter size, transition of STN-GPe dynamics from desynchronized (normal) to synchronized (PD) condition resulted in increased fluctuations in velocity in the model. We also present handwriting data from PD patients (n=34) who are at various stages of disease and had taken medication various lengths of time before the handwriting sessions. The patient data are compared with those of age-matched controls. PD handwriting statistically exhibited smaller size and larger velocity fluctuation compared to normal handwriting. PMID:19720411

  12. Format( )MEDIC( )Input

    NASA Astrophysics Data System (ADS)

    Foster, K.

    1994-09-01

    This document is a description of a computer program called Format( )MEDIC( )Input. The purpose of this program is to allow the user to quickly reformat wind velocity data in the Model Evaluation Database (MEDb) into a reasonable 'first cut' set of MEDIC input files (MEDIC.nml, StnLoc.Met, and Observ.Met). The user is cautioned that these resulting input files must be reviewed for correctness and completeness. This program will not format MEDb data into a Problem Station Library or Problem Metdata File. A description of how the program reformats the data is provided, along with a description of the required and optional user input and a description of the resulting output files. A description of the MEDb is not provided here but can be found in the RAS Division Model Evaluation Database Description document.

  13. Globus pallidus internal segment.

    PubMed

    Nambu, Atsushi

    2007-01-01

    The internal segment of the globus pallidus (GP(i)) gathers many bits of information including movement-related activity from the striatum, external segment of the globus pallidus (GP(e)), and subthalamic nucleus (STN), and integrates them. The GP(i) receives rich GABAergic inputs from the striatum and GP(e), and gamma-aminobutyric acid (GABA) receptors are distributed in the GP(i) in a specific manner. Thus, inputs from the striatum and GP(e) may control GP(i) activity in a different way. The GP(i) finally conveys processed information outside the basal ganglia. Changes in GABAergic neurotransmission have been reported in movement disorders and suggested to play an important role in the pathophysiology of the symptoms. PMID:17499112

  14. The Evaluation of Flammability Properties Regarding Testing Methods

    NASA Astrophysics Data System (ADS)

    Osvaldová, Linda Makovická; Gašpercová, Stanislava

    2015-12-01

    In this paper, we address the historical comparison methods with current methods for the assessment of flammability characteristics for materials an especially for wood, wood components and wooden buildings. Nowadays in European Union brings harmonization in evaluated of standards into each European country and try to make one concept of evaluated the flammability properties. In each European country to the one standard level which will be used by evaluation of materials regarding flammability. In our article we focused mainly on improving the evaluation methods in terms of flammability characteristics of using materials at building industry. In the article we present examples of different assessment methods at their own test methods in terms of fire prevention. On the base of old compared of materials by STN, BS and DIN methods for testing materials on fire and new methods of evaluating the flammability properties regarding EU standards before and after starting the flash over.

  15. Twiddler syndrome in a patient with tremor dominant Parkinson's disease. A case report and literature review.

    PubMed

    Sobstyl, Michał; Ząbek, Mirosław; Górecki, Wojciech; Brzuszkiewicz-Kuźmicka, Grażyna

    2015-01-01

    Twiddler syndrome is described as a spontaneous rotation or intentional external manipulation of implanted cardiac or occasionally deep brain stimulation (DBS) devices. We report this hardware related complication in a patient with tremor dominant Parkinson's disease (PD), who underwent unilateral subthalamic nucleus (STN) DBS and subsequently developed twiddler syndrome. The clinical course of twiddler syndrome in this patient is described. Some surgical nuances which may prevent its occurrence are suggested. Our case report indicates that twiddler syndrome occurs in DBS patients. Impedance check of DBS hardware, plain chest X-ray, or palpation for a knobbly extension lead through the skin above the IPG allows the correct diagnosis and subsequently a prompt surgical revision. Our subsequent literature review revealed only 10 patients with twiddler syndrome in DBS patient population worldwide. This number may suggest that this syndrome may be unrecognized or underreported, given the number of patients with movement disorders implanted with DBS hardware worldwide. PMID:26652885

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

    PubMed Central

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

    2015-01-01

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

  17. Synchronizing microelectrode and electronic goniometer data using a pseudo-random binary signal.

    PubMed

    Moore, Tyler Robert; Jacobs, Rennie Underwood; Yang, Alexander Cheung; Richter, Erich Oscar

    2013-04-01

    Intra-operative investigation of the subthalamic nucleus (STN) requires concurrent measurement of microelectrode voltage, electrode depth and joint movement during deep brain stimulation (DBS) surgery. Commercial solutions to this problem exist but are more expensive. Multiple instruments from different manufacturers can collect the same data, but data from incompatible instruments are collected on disparate clocks, precluding quantitative analysis. A pseudo-random binary signal recorded simultaneously by each set of instruments allows for chronological reconciliation. A custom program collects microelectrode data while simultaneously sending a pseudo-random binary signal to instruments measuring joint movement. The record of this signal is later used to express microelectrode voltage and joint position in a single chronological frame of reference. ClockSynch was used in 15 DBS procedures. After each surgery, records of microelectrode and joint movement were successfully chronologically reconciled. In conclusion, a pseudo-random binary signal integrates disparate systems of instrumentation at a significantly decreased cost. PMID:23547750

  18. Thermal/Optical Methods for Elemental Carbon Quantification in Soils and Urban Dusts: Equivalence of Different Analysis Protocols

    PubMed Central

    Han, Yongming; Chen, Antony; Cao, Junji; Fung, Kochy; Ho, Fai; Yan, Beizhan; Zhan, Changlin; Liu, Suixin; Wei, Chong; An, Zhisheng

    2013-01-01

    Quantifying elemental carbon (EC) content in geological samples is challenging due to interferences of crustal, salt, and organic material. Thermal/optical analysis, combined with acid pretreatment, represents a feasible approach. However, the consistency of various thermal/optical analysis protocols for this type of samples has never been examined. In this study, urban street dust and soil samples from Baoji, China were pretreated with acids and analyzed with four thermal/optical protocols to investigate how analytical conditions and optical correction affect EC measurement. The EC values measured with reflectance correction (ECR) were found always higher and less sensitive to temperature program than the EC values measured with transmittance correction (ECT). A high-temperature method with extended heating times (STN120) showed the highest ECT/ECR ratio (0.86) while a low-temperature protocol (IMPROVE-550), with heating time adjusted for sample loading, showed the lowest (0.53). STN ECT was higher than IMPROVE ECT, in contrast to results from aerosol samples. A higher peak inert-mode temperature and extended heating times can elevate ECT/ECR ratios for pretreated geological samples by promoting pyrolyzed organic carbon (PyOC) removal over EC under trace levels of oxygen. Considering that PyOC within filter increases ECR while decreases ECT from the actual EC levels, simultaneous ECR and ECT measurements would constrain the range of EC loading and provide information on method performance. Further testing with standard reference materials of common environmental matrices supports the findings. Char and soot fractions of EC can be further separated using the IMPROVE protocol. The char/soot ratio was lower in street dusts (2.2 on average) than in soils (5.2 on average), most likely reflecting motor vehicle emissions. The soot concentrations agreed with EC from CTO-375, a pure thermal method. PMID:24358286

  19. Predicting In vitro Culture Medium Macro-Nutrients Composition for Pear Rootstocks Using Regression Analysis and Neural Network Models

    PubMed Central

    Jamshidi, S.; Yadollahi, A.; Ahmadi, H.; Arab, M. M.; Eftekhari, M.

    2016-01-01

    Two modeling techniques [artificial neural network-genetic algorithm (ANN-GA) and stepwise regression analysis] were used to predict the effect of medium macro-nutrients on in vitro performance of pear rootstocks (OHF and Pyrodwarf). The ANN-GA described associations between investigating eight macronutrients (NO3-, NH4+, Ca2+, K+, Mg2+, PO42-, SO42-, and Cl−) and explant growth parameters [proliferation rate (PR), shoot length (SL), shoot tip necrosis (STN), chlorosis (Chl), and vitrification (Vitri)]. ANN-GA revealed a substantially higher accuracy of prediction than for regression models. According to the ANN-GA results, among the input variables concentrations (mM), NH4+ (301.7), and NO3-, NH4+ (64), SO42- (54.1), K+ (40.4), and NO3- (35.1) in OHF and Ca2+ (23.7), NH4+ (10.7), NO3- (9.1), NH4+ (317.6), and NH4+ (79.6) in Pyrodwarf had the highest values of VSR in data set, respectively, for PR, SL, STN, Chl, and Vitri. The ANN-GA showed that media containing (mM) 62.5 NO3-, 5.7 NH4+, 2.7 Ca2+, 31.5 K+, 3.3 Mg2+, 2.6 PO42-, 5.6 SO42-, and 3.5 Cl− could lead to optimal PR for OHF and optimal PR for Pyrodwarf may be obtained with media containing 25.6 NO3-, 13.1 NH4+, 5.5 Ca2+, 35.7 K+, 1.5 Mg2+, 2.1 PO42-, 3.6 SO42-, and 3 Cl−. PMID:27066013

  20. A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson’s disease—a pilot study

    NASA Astrophysics Data System (ADS)

    Gmel, Gerrit E.; Hamilton, Tara J.; Obradovic, Milan; Gorman, Robert B.; Single, Peter S.; Chenery, Helen J.; Coyne, Terry; Silburn, Peter A.; Parker, John L.

    2015-12-01

    Objective. Deep brain stimulation (DBS) has become the standard treatment for advanced stages of Parkinson’s disease (PD) and other motor disorders. Although the surgical procedure has improved in accuracy over the years thanks to imaging and microelectrode recordings, the underlying principles that render DBS effective are still debated today. The aim of this paper is to present initial findings around a new biomarker that is capable of assessing the efficacy of DBS treatment for PD which could be used both as a research tool, as well as in the context of a closed-loop stimulator. Approach. We have used a novel multi-channel stimulator and recording device capable of measuring the response of nervous tissue to stimulation very close to the stimulus site with minimal latency, rejecting most of the stimulus artefact usually found with commercial devices. We have recorded and analyzed the responses obtained intraoperatively in two patients undergoing DBS surgery in the subthalamic nucleus (STN) for advanced PD. Main results. We have identified a biomarker in the responses of the STN to DBS. The responses can be analyzed in two parts, an initial evoked compound action potential arising directly after the stimulus onset, and late responses (LRs), taking the form of positive peaks, that follow the initial response. We have observed a morphological change in the LRs coinciding with a decrease in the rigidity of the patients. Significance. These initial results could lead to a better characterization of the DBS therapy, and the design of adaptive DBS algorithms that could significantly improve existing therapies and help us gain insights into the functioning of the basal ganglia and DBS.

  1. Interactions between HIF-1α and AMPK in the regulation of cellular hypoxia adaptation in chronic kidney disease.

    PubMed

    Li, Hui; Satriano, Joseph; Thomas, Joanna L; Miyamoto, Satoshi; Sharma, Kumar; Pastor-Soler, Núria M; Hallows, Kenneth R; Singh, Prabhleen

    2015-09-01

    Renal hypoxia contributes to chronic kidney disease (CKD) progression, as validated in experimental and human CKD. In the early stages, increased oxygen consumption causes oxygen demand/supply mismatch, leading to hypoxia. Hence, early targeting of the determinants and regulators of oxygen consumption in CKD may alter the disease course before permanent damage ensues. Here, we focus on hypoxia inducible factor-1α (HIF-1α) and AMP-activated protein kinase (AMPK) and on the mechanisms by which they may facilitate cellular hypoxia adaptation. We found that HIF-1α activation in the subtotal nephrectomy (STN) model of CKD limits protein synthesis, inhibits apoptosis, and activates autophagy, presumably for improved cell survival. AMPK activation was diminished in the STN kidney and was remarkably restored by HIF-1α activation, demonstrating a novel role for HIF-1α in the regulation of AMPK activity. We also investigated the independent and combined effects of HIF-1α and AMPK on cell survival and death pathways by utilizing pharmacological and knockdown approaches in cell culture models. We found that the effect of HIF-1α activation on autophagy is independent of AMPK, but on apoptosis it is partially AMPK dependent. The effects of HIF-1α and AMPK activation on inhibiting protein synthesis via the mTOR pathway appear to be additive. These various effects were also observed under hypoxic conditions. In conclusion, HIF-1α and AMPK appear to be linked at a molecular level and may act as components of a concerted cellular response to hypoxic stress in the pathophysiology of CKD. PMID:26136559

  2. Dopamine-dependent non-linear correlation between subthalamic rhythms in Parkinson's disease

    PubMed Central

    Marceglia, S; Foffani, G; Bianchi, A M; Baselli, G; Tamma, F; Egidi, M; Priori, A

    2006-01-01

    The basic information architecture in the basal ganglia circuit is under debate. Whereas anatomical studies quantify extensive convergence/divergence patterns in the circuit, suggesting an information sharing scheme, neurophysiological studies report an absence of linear correlation between single neurones in normal animals, suggesting a segregated parallel processing scheme. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and in parkinsonian patients single neurones become linearly correlated, thus leading to a loss of segregation between neurones. Here we propose a possible integrative solution to this debate, by extending the concept of functional segregation from the cellular level to the network level. To this end, we recorded local field potentials (LFPs) from electrodes implanted for deep brain stimulation (DBS) in the subthalamic nucleus (STN) of parkinsonian patients. By applying bispectral analysis, we found that in the absence of dopamine stimulation STN LFP rhythms became non-linearly correlated, thus leading to a loss of segregation between rhythms. Non-linear correlation was particularly consistent between the low-beta rhythm (13–20 Hz) and the high-beta rhythm (20–35 Hz). Levodopa administration significantly decreased these non-linear correlations, therefore increasing segregation between rhythms. These results suggest that the extensive convergence/divergence in the basal ganglia circuit is physiologically necessary to sustain LFP rhythms distributed in large ensembles of neurones, but is not sufficient to induce correlated firing between neurone pairs. Conversely, loss of dopamine generates pathological linear correlation between neurone pairs, alters the patterns within LFP rhythms, and induces non-linear correlation between LFP rhythms operating at different frequencies. The pathophysiology of information processing in the human basal ganglia therefore involves not only activities of individual rhythms, but also

  3. Photosystem II Function and Dynamics in Three Widely Used Arabidopsis thaliana Accessions

    PubMed Central

    Yin, Lan; Fristedt, Rikard; Vener, Alexander V.; Schoefs, Benoît; Spetea, Cornelia

    2012-01-01

    Columbia-0 (Col-0), Wassilewskija-4 (Ws-4), and Landsberg erecta-0 (Ler-0) are used as background lines for many public Arabidopsis mutant collections, and for investigation in laboratory conditions of plant processes, including photosynthesis and response to high-intensity light (HL). The photosystem II (PSII) complex is sensitive to HL and requires repair to sustain its function. PSII repair is a multistep process controlled by numerous factors, including protein phosphorylation and thylakoid membrane stacking. Here we have characterized the function and dynamics of PSII complex under growth-light and HL conditions. Ws-4 displayed 30% more thylakoid lipids per chlorophyll and 40% less chlorophyll per carotenoid than Col-0 and Ler-0. There were no large differences in thylakoid stacking, photoprotection and relative levels of photosynthetic complexes among the three accessions. An increased efficiency of PSII closure was found in Ws-4 following illumination with saturation flashes or continuous light. Phosphorylation of the PSII D1/D2 proteins was reduced by 50% in Ws-4 as compared to Col-0 and Ler-0. An increase in abundance of the responsible STN8 kinase in response to HL treatment was found in all three accessions, but Ws-4 displayed 50% lower levels than Col-0 and Ler-0. Despite this, the HL treatment caused in Ws-4 the lagest extent of PSII inactivation, disassembly, D1 protein degradation, and the largest decrease in the size of stacked thylakoids. The dilution of chlorophyll-protein complexes with additional lipids and carotenoids in Ws-4 may represent a mechanism to facilitate lateral protein traffic in the membrane, thus compensating for the lack of a full complement of STN8 kinase. Nevertheless, additional PSII damage occurs in Ws-4, which exceeds the D1 protein synthesis capacity, thus leading to enhanced photoinhibition. Our findings are valuable for selection of appropriate background line for PSII characterization in Arabidopsis mutants, and also

  4. Anaerobiosis Induced State Transition: A Non Photochemical Reduction of PQ Pool Mediated by NDH in Arabidopsis thaliana

    PubMed Central

    Tirupathi, Malavath; Subramanyam, Rajagopal

    2012-01-01

    Background Non photochemical reduction of PQ pool and mobilization of LHCII between PSII and PSI are found to be linked under abiotic stress conditions. The interaction of non photochemical reduction of PQ pool and state transitions associated physiological changes are critically important under anaerobic condition in higher plants. Methodology/Findings The present study focused on the effect of anaerobiosis on non-photochemical reduction of PQ pool which trigger state II transition in Arabidopsis thaliana. Upon exposure to dark-anaerobic condition the shape of the OJIP transient rise is completely altered where as in aerobic treated leaves the rise is unaltered. Rise in Fo and FJ was due to the loss of oxidized PQ pool as the PQ pool becomes more reduced. The increase in Fo′ was due to the non photochemical reduction of PQ pool which activated STN7 kinase and induced LHCII phosphorylation under anaerobic condition. Further, it was observed that the phosphorylated LHCII is migrated and associated with PSI supercomplex increasing its absorption cross-section. Furthermore, evidences from crr2-2 (NDH mutant) and pgr5 mutants (deficient in non NDH pathway of cyclic electron transport) have indicated that NDH is responsible for non photochemical reduction of the PQ pool. We propose that dark anaerobic condition accelerates production of reducing equivalents (such as NADPH by various metabolic pathways) which reduce PQ pool and is mediated by NDH leading to state II transition. Conclusions/Significance Anaerobic condition triggers non photochemical reduction of PQ pool mediated by NDH complex. The reduced PQ pool activates STN7 kinase leading to state II transition in A. thaliana. PMID:23185453

  5. Subthalamic nucleus deep brain stimulation in elderly patients – analysis of outcome and complications

    PubMed Central

    Vesper, Jan; Haak, Susanne; Ostertag, Christoph; Nikkhah, Guido

    2007-01-01

    Background There is an ongoing discussion about age limits for deep brain stimulation (DBS). Current indications for DBS are tremor-dominant disorders, Parkinson's disease, and dystonia. Electrode implantation for DBS with analgesia and sedation makes surgery more comfortable, especially for elderly patients. However, the value of DBS in terms of benefit-risk ratio in this patient population is still uncertain. Methods Bilateral electrode implantation into the subthalamic nucleus (STN) was performed in a total of 73 patients suffering from Parkinson's disease. Patients were analyzed retrospectively. For this study they were divided into two age groups: group I (age <65 years, n = 37) and group II (age ≥ 65 years, n = 36). Examinations were performed preoperatively and at 6-month follow-up intervals for 24 months postoperatively. Age, UPDRS motor score (part III) on/off, Hoehn & Yahr score, Activity of Daily Living (ADL), L-dopa medication, and complications were determined. Results Significant differences were found in overall performance determined as ADL scores (group I: 48/71 points, group II: 41/62 points [preoperatively/6-month postoperatively]) and in the rate of complications (group I: 4 transient psychosis, 4 infections in a total of 8 patients, group II: 2 deaths [unrelated to surgery], 1 intracerebral hemorrhage, 7 transient psychosis, 3 infections, 2 pneumonia in a total of 13 patients), (p < 0.05). Interestingly, changes in UPDRS scores, Hoehn & Yahr scores, and L-dopa medication were not statistically different between the two groups. Conclusion DBS of the STN is clinically as effective in elderly patients as it is in younger ones. However, a more careful selection and follow-up of the elderly patients are required because elderly patients have a higher risk of surgery-related complications and a higher morbidity rate. PMID:17367531

  6. Nitric Oxide-Mediated Modulation of Central Network Dynamics during Olfactory Perception.

    PubMed

    Watanabe, Satoshi; Takanashi, Fumihito; Ishida, Kohei; Kobayashi, Suguru; Kitamura, Yoshiichiro; Hamasaki, Yuuta; Saito, Minoru

    2015-01-01

    Nitric oxide (NO) modulates the dynamics of central olfactory networks and has been implicated in olfactory processing including learning. Land mollusks have a specialized olfactory lobe in the brain called the procerebral (PC) lobe. The PC lobe produces ongoing local field potential (LFP) oscillation, which is modulated by olfactory stimulation. We hypothesized that NO should be released in the PC lobe in response to olfactory stimulation, and to prove this, we applied an NO electrode to the PC lobe of the land slug Limax in an isolated tentacle-brain preparation. Olfactory stimulation applied to the olfactory epithelium transiently increased the NO concentration in the PC lobe, and this was blocked by the NO synthase inhibitor L-NAME at 3.7 mM. L-NAME at this concentration did not block the ongoing LFP oscillation, but did block the frequency increase during olfactory stimulation. Olfactory stimulation also enhanced spatial synchronicity of activity, and this response was also blocked by L-NAME. Single electrical stimulation of the superior tentacle nerve (STN) mimicked the effects of olfactory stimulation on LFP frequency and synchronicity, and both of these effects were blocked by L-NAME. L-NAME did not block synaptic transmission from the STN to the nonbursting (NB)-type PC lobe neurons, which presumably produce NO in an activity-dependent manner. Previous behavioral experiments have revealed impairment of olfactory discrimination after L-NAME injection. The recording conditions in the present work likely reproduce the in vivo brain state in those behavioral experiments. We speculate that the dynamical effects of NO released during olfactory perception underlie precise odor representation and memory formation in the brain, presumably through regulation of NB neuron activity. PMID:26360020

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

  8. Postmortem titin proteolysis is influenced by sarcomere length in bovine muscle.

    PubMed

    England, E M; Fisher, K D; Wells, S J; Mohrhauser, D A; Gerrard, D E; Weaver, A D

    2012-03-01

    The calpain protease system, in particular, μ-calpain is involved in the disassembly of specific myofibrillar proteins, resulting in tenderization of meat postmortem. Given the size, complexity, and integral nature of titin to the structure of the sarcomere, it is plausible that the length of a sarcomere may alter the susceptibility of various domains of titin to cleavage by the calpains. Therefore, we hypothesized titin degradation differs in a sarcomere-length-dependent manner in beef. After slaughter, beef carcasses were split and sides were either suspended by the Achilles tendon (normal suspension, NS) or by the aitchbone (hip suspension, HS). Immediately after suspension, samples were dissected from the LM, psoas major (PM), and semitendinosus (STN) muscles to serve as 0-d controls. After 24 h, 4 steaks were removed from each muscle and randomly assigned to 1-, 4-, 7-, or 10-d aging treatments. After the assigned aging period, myofibrils were purified for determination of sarcomere length. Warner-Bratzler shear force analysis was also performed to evaluate differences in tenderness. Muscle proteins were solubilized and subjected to SDS-VAGE (vertical agarose gel electrophoresis) to evaluate titin degradation. Sarcomere lengths differed (P < 0.0001) between contralateral muscles of NS and HS carcasses. Quantification of SDS-VAGE gels revealed less (P < 0.05) intact titin in the PM muscle of NS carcasses at each aging period compared with the PM of HS carcasses. No significant differences (P > 0.05) were detected in the disappearance of intact titin among suspension methods in the LM or STN. These data demonstrate that suspension method alters proteolysis of titin and suggest an increase in sarcomere length may contribute to the susceptibility of titin to postmortem proteolysis in beef. PMID:21984717

  9. Systems genetics of the nuclear factor-κB signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging.

    PubMed

    Diego, Vincent P; Curran, Joanne E; Charlesworth, Jac; Peralta, Juan M; Voruganti, V Saroja; Cole, Shelley A; Dyer, Thomas D; Johnson, Matthew P; Moses, Eric K; Göring, Harald H H; Williams, Jeff T; Comuzzie, Anthony G; Almasy, Laura; Blangero, John; Williams-Blangero, Sarah

    2012-01-01

    A theory of aging holds that senescence is caused by a dysregulated nuclear factor kappa B (NF-κB) signal transduction network (STN). We adopted a systems genetics approach in our study of the NF-κB STN. Ingenuity Pathways Analysis (IPA) was used to identify gene/gene product interactions between NF-κB and the genes in our transcriptional profiling array. Principal components factor analysis (PCFA) was performed on a sub-network of 19 genes, including two initiators of the toll-like receptor (TLR) pathway, myeloid differentiation primary response gene (88) (MyD88) and TIR (Toll/interleukin-1 receptor)-domain-containing adapter-inducing interferon-β (TRIF). TLR pathways are either MyD88-dependent or TRIF-dependent. Therefore, we also performed PCFA on a subset excluding the MyD88 transcript, and on another subset excluding two TRIF transcripts. Using linkage analysis we found that each set gave rise to at least one factor with a logarithm of the odds (LOD) score greater than 3, two on chromosome 15 at 15q12 and 15q22.2, and another two on chromosome 17 at 17p13.3 and 17q25.3. We also found several suggestive signals (2

  10. Yeast telomere maintenance is globally controlled by programmed ribosomal frameshifting and the nonsense-mediated mRNA decay pathway

    PubMed Central

    Advani, Vivek M.; Belew, Ashton T.; Dinman, Jonathan D.

    2013-01-01

    We have previously shown that ~10% of all eukaryotic mRNAs contain potential programmed -1 ribosomal frameshifting (-1 PRF) signals and that some function as mRNA destabilizing elements through the Nonsense-Mediated mRNA Decay (NMD) pathway by directing translating ribosomes to premature termination codons. Here, the connection between -1 PRF, NMD and telomere end maintenance are explored. Functional -1 PRF signals were identified in the mRNAs encoding two components of yeast telomerase, EST1 and EST2, and in mRNAs encoding proteins involved in recruiting telomerase to chromosome ends, STN1 and CDC13. All of these elements responded to mutants and drugs previously known to stimulate or inhibit -1 PRF, further supporting the hypothesis that they promote -1 PRF through the canonical mechanism. All affected the steady-state abundance of a reporter mRNA and the wide range of -1 PRF efficiencies promoted by these elements enabled the determination of an inverse logarithmic relationship between -1 PRF efficiency and mRNA accumulation. Steady-state abundances of the endogenous EST1, EST2, STN1 and CDC13 mRNAs were similarly inversely proportional to changes in -1 PRF efficiency promoted by mutants and drugs, supporting the hypothesis that expression of these genes is post-transcriptionally controlled by -1 PRF under native conditions. Overexpression of EST2 by ablation of -1 PRF signals or inhibition of NMD promoted formation of shorter telomeres and accumulation of large budded cells at the G2/M boundary. A model  is presented describing how limitation and maintenance of correct stoichiometries of telomerase components by -1 PRF is used to maintain yeast telomere length. PMID:24563826

  11. Emotion recognition in early Parkinson’s disease patients undergoing deep brain stimulation or dopaminergic therapy: a comparison to healthy participants

    PubMed Central

    McIntosh, Lindsey G.; Mannava, Sishir; Camalier, Corrie R.; Folley, Bradley S.; Albritton, Aaron; Konrad, Peter E.; Charles, David; Park, Sohee; Neimat, Joseph S.

    2015-01-01

    Parkinson’s disease (PD) is traditionally regarded as a neurodegenerative movement disorder, however, nigrostriatal dopaminergic degeneration is also thought to disrupt non-motor loops connecting basal ganglia to areas in frontal cortex involved in cognition and emotion processing. PD patients are impaired on tests of emotion recognition, but it is difficult to disentangle this deficit from the more general cognitive dysfunction that frequently accompanies disease progression. Testing for emotion recognition deficits early in the disease course, prior to cognitive decline, better assesses the sensitivity of these non-motor corticobasal ganglia-thalamocortical loops involved in emotion processing to early degenerative change in basal ganglia circuits. In addition, contrasting this with a group of healthy aging individuals demonstrates changes in emotion processing specific to the degeneration of basal ganglia circuitry in PD. Early PD patients (EPD) were recruited from a randomized clinical trial testing the safety and tolerability of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) in early-staged PD. EPD patients were previously randomized to receive optimal drug therapy only (ODT), or drug therapy plus STN-DBS (ODT + DBS). Matched healthy elderly controls (HEC) and young controls (HYC) also participated in this study. Participants completed two control tasks and three emotion recognition tests that varied in stimulus domain. EPD patients were impaired on all emotion recognition tasks compared to HEC. Neither therapy type (ODT or ODT + DBS) nor therapy state (ON/OFF) altered emotion recognition performance in this study. Finally, HEC were impaired on vocal emotion recognition relative to HYC, suggesting a decline related to healthy aging. This study supports the existence of impaired emotion recognition early in the PD course, implicating an early disruption of fronto-striatal loops mediating emotional function. PMID:25653616

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

    PubMed

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

    2016-01-01

    The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson's disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target. PMID:27070317

  13. Functional Reorganization of the Locomotor Network in Parkinson Patients with Freezing of Gait

    PubMed Central

    Fling, Brett W.; Cohen, Rajal G.; Mancini, Martina; Carpenter, Samuel D.; Fair, Damien A.; Nutt, John G.; Horak, Fay B.

    2014-01-01

    Freezing of gait (FoG) is a transient inability to initiate or maintain stepping that often accompanies advanced Parkinson’s disease (PD) and significantly impairs mobility. The current study uses a multimodal neuroimaging approach to assess differences in the functional and structural locomotor neural network in PD patients with and without FoG and relates these findings to measures of FoG severity. Twenty-six PD patients and fifteen age-matched controls underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging along with self-reported and clinical assessments of FoG. After stringent movement correction, fifteen PD patients and fourteen control participants were available for analysis. We assessed functional connectivity strength between the supplementary motor area (SMA) and the following locomotor hubs: 1) subthalamic nucleus (STN), 2) mesencephalic and 3) cerebellar locomotor region (MLR and CLR, respectively) within each hemisphere. Additionally, we quantified structural connectivity strength between locomotor hubs and assessed relationships with metrics of FoG. FoG+ patients showed greater functional connectivity between the SMA and bilateral MLR and between the SMA and left CLR compared to both FoG− and controls. Importantly, greater functional connectivity between the SMA and MLR was positively correlated with i) clinical, ii) self-reported and iii) objective ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural compensation. The current findings demonstrate a re-organization of functional communication within the locomotor network in FoG+ patients whereby the higher-order motor cortex (SMA) responsible for gait initiation communicates with the MLR and CLR to a greater extent than in FoG− patients and controls. The observed pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS to compensate for the loss of connectivity between the STN and SMA and may reflect a loss

  14. PM2.5 source apportionment: reconciling receptor models for U.S. nonurban and urban long-term networks.

    PubMed

    Chen, L W Antony; Watson, John G; Chow, Judith C; DuBois, Dave W; Herschberger, Lisa

    2011-11-01

    Chemical mass balance (CMB) and trajectory receptor models were applied to speciated particulate matter with aerodynamic diameter < or =2.5 microm (PM2.5) measurements from Speciation Trends Network (STN; part of the Chemical Speciation Network [CSN]) and Interagency Monitoring of Protected Visual Environments (IMPROVE) monitoring network across the state of Minnesota as part of the Minnesota PM2.5 Source Apportionment Study (MPSAS). CMB equations were solved by the Unmix, positive matrix factorization (PMF), and effective variance (EV) methods, giving collective source contribution and uncertainty estimates. Geological source profiles developed from local dust materials were either incorporated into the EV-CMB model or used to verify factors derived from Unmix and PMF. Common sources include soil dust, calcium (Ca)-rich dust, diesel and gasoline vehicle exhausts, biomass burning, secondary sulfate, and secondary nitrate. Secondary sulfate and nitrate aerosols dominate PM2.5 mass (50-69%). Mobile sources outweigh area sources at urban sites, and vice versa at rural sites due to traffic emissions. Gasoline and diesel contributions can be separated using data from the STN, despite significant uncertainties. Major differences between MPSAS and earlier studies on similar environments appear to be the type and magnitude of stationary sources, but these sources are generally minor (<7%) in this and other studies. Ensemble back-trajectory analysis shows that the lower Midwestern states are the predominant source region for secondary ammoniated sulfate in Minnesota. It also suggests substantial contributions of biomass burning and soil dust from out-of-state on occasions, although a quantitative separation of local and regional contributions was not achieved in the current study. Supplemental materials are available for this article. Go to the publisher's online edition of the Journal of the Air & Waste Management Association for a summary of input data, Unmix and PMF

  15. Prototypic and Arkypallidal Neurons in the Dopamine-Intact External Globus Pallidus

    PubMed Central

    Abdi, Azzedine; Mallet, Nicolas; Mohamed, Foad Y.; Sharott, Andrew; Dodson, Paul D.; Nakamura, Kouichi C.; Suri, Sana; Avery, Sophie V.; Larvin, Joseph T.; Garas, Farid N.; Garas, Shady N.; Vinciati, Federica; Morin, Stéphanie; Bezard, Erwan

    2015-01-01

    Studies in dopamine-depleted rats indicate that the external globus pallidus (GPe) contains two main types of GABAergic projection cell; so-called “prototypic” and “arkypallidal” neurons. Here, we used correlative anatomical and electrophysiological approaches in rats to determine whether and how this dichotomous organization applies to the dopamine-intact GPe. Prototypic neurons coexpressed the transcription factors Nkx2-1 and Lhx6, comprised approximately two-thirds of all GPe neurons, and were the major GPe cell type innervating the subthalamic nucleus (STN). In contrast, arkypallidal neurons expressed the transcription factor FoxP2, constituted just over one-fourth of GPe neurons, and innervated the striatum but not STN. In anesthetized dopamine-intact rats, molecularly identified prototypic neurons fired at relatively high rates and with high regularity, regardless of brain state (slow-wave activity or spontaneous activation). On average, arkypallidal neurons fired at lower rates and regularities than prototypic neurons, and the two cell types could be further distinguished by the temporal coupling of their firing to ongoing cortical oscillations. Complementing the activity differences observed in vivo, the autonomous firing of identified arkypallidal neurons in vitro was slower and more variable than that of prototypic neurons, which tallied with arkypallidal neurons displaying lower amplitudes of a “persistent” sodium current important for such pacemaking. Arkypallidal neurons also exhibited weaker driven and rebound firing compared with prototypic neurons. In conclusion, our data support the concept that a dichotomous functional organization, as actioned by arkypallidal and prototypic neurons with specialized molecular, structural, and physiological properties, is fundamental to the operations of the dopamine-intact GPe. PMID:25926446

  16. Long-range correlation properties in timing of skilled piano performance: the influence of auditory feedback and deep brain stimulation

    PubMed Central

    Herrojo Ruiz, María; Hong, Sang Bin; Hennig, Holger; Altenmüller, Eckart; Kühn, Andrea A.

    2014-01-01

    Unintentional timing deviations during musical performance can be conceived of as timing errors. However, recent research on humanizing computer-generated music has demonstrated that timing fluctuations that exhibit long-range temporal correlations (LRTC) are preferred by human listeners. This preference can be accounted for by the ubiquitous presence of LRTC in human tapping and rhythmic performances. Interestingly, the manifestation of LRTC in tapping behavior seems to be driven in a subject-specific manner by the LRTC properties of resting-state background cortical oscillatory activity. In this framework, the current study aimed to investigate whether propagation of timing deviations during the skilled, memorized piano performance (without metronome) of 17 professional pianists exhibits LRTC and whether the structure of the correlations is influenced by the presence or absence of auditory feedback. As an additional goal, we set out to investigate the influence of altering the dynamics along the cortico-basal-ganglia-thalamo-cortical network via deep brain stimulation (DBS) on the LRTC properties of musical performance. Specifically, we investigated temporal deviations during the skilled piano performance of a non-professional pianist who was treated with subthalamic-deep brain stimulation (STN-DBS) due to severe Parkinson's disease, with predominant tremor affecting his right upper extremity. In the tremor-affected right hand, the timing fluctuations of the performance exhibited random correlations with DBS OFF. By contrast, DBS restored long-range dependency in the temporal fluctuations, corresponding with the general motor improvement on DBS. Overall, the present investigations demonstrate the presence of LRTC in skilled piano performances, indicating that unintentional temporal deviations are correlated over a wide range of time scales. This phenomenon is stable after removal of the auditory feedback, but is altered by STN-DBS, which suggests that cortico

  17. Long-range correlation properties in timing of skilled piano performance: the influence of auditory feedback and deep brain stimulation.

    PubMed

    Herrojo Ruiz, María; Hong, Sang Bin; Hennig, Holger; Altenmüller, Eckart; Kühn, Andrea A

    2014-01-01

    Unintentional timing deviations during musical performance can be conceived of as timing errors. However, recent research on humanizing computer-generated music has demonstrated that timing fluctuations that exhibit long-range temporal correlations (LRTC) are preferred by human listeners. This preference can be accounted for by the ubiquitous presence of LRTC in human tapping and rhythmic performances. Interestingly, the manifestation of LRTC in tapping behavior seems to be driven in a subject-specific manner by the LRTC properties of resting-state background cortical oscillatory activity. In this framework, the current study aimed to investigate whether propagation of timing deviations during the skilled, memorized piano performance (without metronome) of 17 professional pianists exhibits LRTC and whether the structure of the correlations is influenced by the presence or absence of auditory feedback. As an additional goal, we set out to investigate the influence of altering the dynamics along the cortico-basal-ganglia-thalamo-cortical network via deep brain stimulation (DBS) on the LRTC properties of musical performance. Specifically, we investigated temporal deviations during the skilled piano performance of a non-professional pianist who was treated with subthalamic-deep brain stimulation (STN-DBS) due to severe Parkinson's disease, with predominant tremor affecting his right upper extremity. In the tremor-affected right hand, the timing fluctuations of the performance exhibited random correlations with DBS OFF. By contrast, DBS restored long-range dependency in the temporal fluctuations, corresponding with the general motor improvement on DBS. Overall, the present investigations demonstrate the presence of LRTC in skilled piano performances, indicating that unintentional temporal deviations are correlated over a wide range of time scales. This phenomenon is stable after removal of the auditory feedback, but is altered by STN-DBS, which suggests that cortico

  18. Viewing angle compensation of various LCD modes by using a liquid crystalline polymer film

    NASA Astrophysics Data System (ADS)

    Matsumoto, Takuya; Nishimura, Suzushi

    2013-09-01

    The authors have developed liquid crystalline retardation films to improve certain aspects of LCD image quality such as viewing angle performance and coloration. We have successfully created several types of optical retardation films using a rod-like liquid crystalline polymer. The resulting liquid crystalline polymer films have several advantages over conventional uni- or biaxially stretched retardation films. Precisely controlled structures such as twisted nematic, homogeneous nematic, hybrid nematic and homeotropic structures can provide ideal compensation of various LCD types, such as STN, TN, ECB, VA and IPS-LCDs. Twisted nematic film effectively prevents coloration of STN-LCDs, which is a critical flaw affecting color representation. Short pitch cholesteric film, which utilizes said rod-like liquid crystalline polymer and is the optical equivalent of a negative C-plate, can expand the viewing angle of VA-LCDs. Hybrid nematic film is quite unique in that the film functions not only as a wave plate but also as a viewing angle compensator for TN and ECB-LCDs. Homeotropic film, which acts as a positive-C plate, greatly improves the viewing angle performance of IPS and CPVA-LCDs. Our homeotropically aligned liquid crystalline film, called "NV film", is the world's thinnest retardation film. The thickness of the liquid crystalline layer is a mere 1 micrometer. Homeotropic film can be used to expand the viewing angle not only of LCDs but also OLED displays. And NV film, when used in in combination with a quarter wavelength plate, can expand the viewing angles of the circular polarizers used to prevent reflection in OLED displays.

  19. Development of efficient amine-modified mesoporous silica SBA-15 for CO{sub 2} capture

    SciTech Connect

    Zhang, Xiaoyun; Qin, Hongyan; Zheng, Xiuxin; Wu, Wei

    2013-10-15

    Graphical abstract: - Highlights: • A secondary amine AN-TEPA is used to modify the SBA-15. • CO{sub 2} adsorption capacity (180.1 mg g{sup −1}-adsorbent for 70% amine loading) is high. • The sorbent exhibits a high stability after 12 cycling runs. • The modified SBA-15 achieves complete desorption at low temperature (100 °C). - Abstract: A novel CO{sub 2} sorbent was prepared by impregnating mesoporous silica, SBA-15, with acrylonitrile (AN)-modified tetraethylenepentamine (TEPA) in order to increase CO{sub 2} adsorption capacity and improve cycling stability. The mesoporous silica with pre- and post-surface modification was investigated by X-ray diffraction characterization (XRD), N{sub 2} adsorption–desorption test (N{sub 2}-BET), transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). The adsorption/desorption performance of S-TN (TN: AN modified TEPA) and S-TEPA was studied by dynamic adsorption. Test results showed that the solid base-impregnated SBA-15 demonstrated high CO{sub 2} adsorption capacity (180.1 mg g{sup −1}-adsorbent for 70% amine loading level). Compared to S-TEPA (24.1% decrease of initial capacity), S-TN with 50% amine loading exhibited improved cycling stability, 99.9% activity reserved (from initial 153.0 mg g{sup −1} to 151.3 mg g{sup −1}) after 12 cycles of adsorption/desorption at 100 °C. A mechanism of molecular structure of the loaded amine was attributed to the improved performance.

  20. Mucins MUC16 and MUC1 are major carriers of SLe(a) and SLe(x) in borderline and malignant serous ovarian tumors.

    PubMed

    Ricardo, Sara; Marcos-Silva, Lara; Valente, Cristina; Coelho, Ricardo; Gomes, Rosa; David, Leonor

    2016-06-01

    Mucins are heavily glycosylated proteins overexpressed and associated with truncated or sialylated glycans upon malignant transformation. We previously identified a panel of four glyco-mucin profiles (MUC16/Tn, MUC16/STn, MUC1/Tn, and MUC1/STn) with 100 % specificity and 100 % positive predictive value for detection of borderline/malignant serous tumors of the ovary, using proximity ligation assay (PLA). In the present work, using the same method, we studied other mucin glycosylation profiles that might add relevant information for diagnostic purposes. We used PLA probes to MUC16, MUC1, sialyl Lewis(a) (SLe(a)), and sialyl Lewis(x) (SLe(x)) to study a series of 39 ovarian serous tumors (14 adenocarcinomas, 10 borderline ovarian tumors (BOTs), and 15 cystadenomas). Our results demonstrated that, in adenocarcinomas and BOTs, the major carriers of SLe(a) and SLe(x) are MUC16 and/or MUC1 (100 and 92 % for SLe(a) and 64 and 70 % for SLe(x), respectively). In cystadenomas, SLe(a) and SLe(x) are mainly carried by unidentified proteins (85 and 78 %, respectively). Our study identified, for the first time, the major protein carriers of SLe(a) and SLe(x) in ovarian adenocarcinomas and BOTs, MUC1 and MUC16, and also that distinct unidentified carriers are involved in cystadenomas. These results emphasize the relevance of multiple biomarker recognition provided by multiplex assays, such as PLA, to enhance sensitivity and specificity of serum and tissue assays. PMID:27003157

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

    PubMed Central

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

    2016-01-01

    The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson’s disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target. PMID:27070317

  2. Supporting clinical decision making during deep brain stimulation surgery by means of a stochastic dynamical model

    NASA Astrophysics Data System (ADS)

    Karamintziou, Sofia D.; Tsirogiannis, George L.; Stathis, Pantelis G.; Tagaris, George A.; Boviatsis, Efstathios J.; Sakas, Damianos E.; Nikita, Konstantina S.

    2014-10-01

    Objective. During deep brain stimulation (DBS) surgery for the treatment of advanced Parkinson's disease (PD), microelectrode recording (MER) in conjunction with functional stimulation techniques are commonly applied for accurate electrode implantation. However, the development of automatic methods for clinical decision making has to date been characterized by the absence of a robust single-biomarker approach. Moreover, it has only been restricted to the framework of MER without encompassing intraoperative macrostimulation. Here, we propose an integrated series of novel single-biomarker approaches applicable to the entire electrophysiological procedure by means of a stochastic dynamical model. Approach. The methods are applied to MER data pertinent to ten DBS procedures. Considering the presence of measurement noise, we initially employ a multivariate phase synchronization index for automatic delineation of the functional boundaries of the subthalamic nucleus (STN) and determination of the acceptable MER trajectories. By introducing the index into a nonlinear stochastic model, appropriately fitted to pre-selected MERs, we simulate the neuronal response to periodic stimuli (130 Hz), and examine the Lyapunov exponent as an indirect indicator of the clinical effectiveness yielded by stimulation at the corresponding sites. Main results. Compared with the gold-standard dataset of annotations made intraoperatively by clinical experts, the STN detection methodology demonstrates a false negative rate of 4.8% and a false positive rate of 0%, across all trajectories. Site eligibility for implantation of the DBS electrode, as implicitly determined through the Lyapunov exponent of the proposed stochastic model, displays a sensitivity of 71.43%. Significance. The suggested comprehensive method exhibits remarkable performance in automatically determining both the acceptable MER trajectories and the optimal stimulation sites, thereby having the potential to accelerate precise

  3. Ceftriaxone prevents the neurodegeneration and decreased neurogenesis seen in a Parkinson's disease rat model: An immunohistochemical and MRI study.

    PubMed

    Weng, Jun-Cheng; Tikhonova, Maria A; Chen, Jian-Horng; Shen, Mei-Shiuan; Meng, Wan-Yun; Chang, Yen-Ting; Chen, Ke-Hsin; Liang, Keng-Chen; Hung, Ching-Sui; Amstislavskaya, Tamara G; Ho, Ying-Jui

    2016-05-15

    Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique for detecting neuronal activity in the brain of a living animal. Ceftriaxone (CEF) has been shown to have neuroprotective effects in neurodegenerative diseases. The present study was aimed at clarifying whether, in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) rat model, the known CEF-induced neuronal protection was accompanied by neurogenesis and decreased loss of neuronal activity. After MPTP lesioning (day 0), the rats were treated with CEF (100mg/kg/day, i.p.) or saline for 15 days. They were then injected with MnCl2 (40mg/kg, i.p.) on day 13 and underwent a brain MRI scan on day 14, then the brain was taken for histological evaluation on day 15. The results showed that MPTP lesioning resulted in decreased neuronal activity and density in the nigrostriatal dopaminergic (DAergic) system and the hippocampal CA1, CA3, and dentate gyrus (DG) areas and reduced neurogenesis in the DG, but in hyperactivity in the subthalamic nucleus (STN). These neuronal changes were prevented by CEF treatment. Positive correlations between MEMRI R1 values and neuronal density in the hippocampus were evidenced. Neuronal densities in the hippocampus and SNc were positively correlated. In addition, the R1 value of the STN showed a positive correlation with its neuronal activity but showed a negative correlation with the density of DAergic neurons in the SNc. Therefore, MEMRI R1 value may serve as a good indicator for PD severity and the effect of treatment. To our knowledge, this is the first study showing that CEF prevents loss of neuronal activity and neurogenesis in the brain of PD rats. CEF may therefore have clinical potential in the treatment of PD. PMID:26940602

  4. The sensitivity of health effect estimates from time-series studies to fine particulate matter component sampling schedule.

    PubMed

    Kim, Sun-Young; Sheppard, Lianne; Hannigan, Michael P; Dutton, Steven J; Peel, Jennifer L; Clark, Maggie L; Vedal, Sverre

    2013-01-01

    The US Environmental Protection Agency air pollution monitoring data have been a valuable resource commonly used for investigating the associations between short-term exposures to PM2.5 chemical components and human health. However, the temporally sparse sampling on every third or sixth day may affect health effect estimation. We examined the impact of non-daily monitoring data on health effect estimates using daily data from the Denver Aerosol Sources and Health (DASH) study. Daily concentrations of four PM2.5 chemical components (elemental and organic carbon, sulfate, and nitrate) and hospital admission counts from 2003 through 2007 were used. Three every-third-day time series were created from the daily DASH monitoring data, imitating the US Speciation Trend Network (STN) monitoring schedule. A fourth, partly irregular, every-third-day time series was created by matching existing sampling days at a nearby STN monitor. Relative risks (RRs) of hospital admissions for PM2.5 components at lags 0-3 were estimated for each data set, adjusting for temperature, relative humidity, longer term temporal trends, and day of week using generalized additive models, and compared across different sampling schedules. The estimated RRs varied somewhat between the non-daily and daily sampling schedules and between the four non-daily schedules, and in some instances could lead to different conclusions. It was not evident which features of the data or analysis were responsible for the variation in effect estimates, although seeing similar variability in resampled data sets with relaxation of the every-third-day constraint suggests that limited power may have had a role. The use of non-daily monitoring data can influence interpretation of estimated effects of PM2.5 components on hospital admissions in time-series studies. PMID:23673462

  5. Nitric Oxide-Mediated Modulation of Central Network Dynamics during Olfactory Perception

    PubMed Central

    Kobayashi, Suguru; Kitamura, Yoshiichiro; Hamasaki, Yuuta; Saito, Minoru

    2015-01-01

    Nitric oxide (NO) modulates the dynamics of central olfactory networks and has been implicated in olfactory processing including learning. Land mollusks have a specialized olfactory lobe in the brain called the procerebral (PC) lobe. The PC lobe produces ongoing local field potential (LFP) oscillation, which is modulated by olfactory stimulation. We hypothesized that NO should be released in the PC lobe in response to olfactory stimulation, and to prove this, we applied an NO electrode to the PC lobe of the land slug Limax in an isolated tentacle-brain preparation. Olfactory stimulation applied to the olfactory epithelium transiently increased the NO concentration in the PC lobe, and this was blocked by the NO synthase inhibitor L-NAME at 3.7 mM. L-NAME at this concentration did not block the ongoing LFP oscillation, but did block the frequency increase during olfactory stimulation. Olfactory stimulation also enhanced spatial synchronicity of activity, and this response was also blocked by L-NAME. Single electrical stimulation of the superior tentacle nerve (STN) mimicked the effects of olfactory stimulation on LFP frequency and synchronicity, and both of these effects were blocked by L-NAME. L-NAME did not block synaptic transmission from the STN to the nonbursting (NB)-type PC lobe neurons, which presumably produce NO in an activity-dependent manner. Previous behavioral experiments have revealed impairment of olfactory discrimination after L-NAME injection. The recording conditions in the present work likely reproduce the in vivo brain state in those behavioral experiments. We speculate that the dynamical effects of NO released during olfactory perception underlie precise odor representation and memory formation in the brain, presumably through regulation of NB neuron activity. PMID:26360020

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

    PubMed Central

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

    2016-01-01

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

  7. Cognitive impairment and dementia in Parkinson's disease: practical issues and management.

    PubMed

    Emre, Murat; Ford, Paul J; Bilgiç, Başar; Uç, Ergun Y

    2014-04-15

    Cognitive impairment and dementia pose particular challenges in the management of patients with Parkinson's disease (PD). Decision-making capacity can render patients vulnerable in a way that requires careful ethical considerations by clinicians with respect to medical decision making, research participation, and public safety. Clinicians should discuss how future decisions will be made as early in the disease course as possible. Because of cognitive, visual, and motor impairments, PD may be associated with unsafe driving, leading to early driving cessation in many. DBS of the STN and, to a lesser degree, globus pallidus interna (GPi) has consistently been associated with decreased verbal fluency, but significant global cognitive decline is usually not observed in patients who undergo rigorous selection. There are some observations suggesting lesser cognitive decline in GPi DBS than STN DBS, but further research is required. Management of PD dementia (PDD) patients involves both pharmacological and nonpharmacological measures. Patients with PDD should be offered treatment with a cholinesterase inhibitor taking into account expected benefits and potential risks. Treatment with neuroleptics may be necessary to treat psychosis; classical neuroleptics, as well as risperidone and olanzapine, should be avoided. Quetiapine might be considered first-line treatment because it does not need special monitoring, although the strongest evidence for efficacy exists for clozapine. Evidence from randomized, controlled studies in the PDD population is lacking; selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors may be used to treat depressive features. Clonazepam or melatonin may be useful in the treatment of rapid eye movement behavior disorder. PMID:24757114

  8. Moving Forward: Advances in the Treatment of Movement Disorders with Deep Brain Stimulation

    PubMed Central

    Schiefer, Terry K.; Matsumoto, Joseph Y.; Lee, Kendall H.

    2011-01-01

    The modern era of stereotactic and functional neurosurgery has ushered in state of the art technologies for the treatment of movement disorders, particularly Parkinson’s disease (PD), tremor, and dystonia. After years of experience with various surgical therapies, the eventual shortcomings of both medical and surgical treatments, and several serendipitous discoveries, deep brain stimulation (DBS) has risen to the forefront as a highly effective, safe, and reversible treatment for these conditions. Idiopathic advanced PD can be treated with thalamic, globus pallidus internus (GPi), or subthalamic nucleus (STN) DBS. Thalamic DBS primarily relieves tremor while GPi and STN DBS alleviate a wide range of Parkinsonian symptoms. Thalamic DBS is also used in the treatment of other types of tremor, particularly essential tremor, with excellent results. Both primary and various types of secondary dystonia can be treated very effectively with GPi DBS. The variety of anatomical targets for these movement disorders is indicative of the network-level dysfunction mediating these movement disturbances. Despite an increasing understanding of the clinical benefits of DBS, little is known about how DBS can create such wide sweeping neuromodulatory effects. The key to improving this therapeutic modality and discovering new ways to treat these and other neurologic conditions lies in better understanding the intricacies of DBS. Here we review the history and pertinent clinical data for DBS treatment of PD, tremor, and dystonia. While multiple regions of the brain have been targeted for DBS in the treatment of these movement disorders, this review article focuses on those that are most commonly used in current clinical practice. Our search criteria for PubMed included combinations of the following terms: DBS, neuromodulation, movement disorders, PD, tremor, dystonia, and history. Dates were not restricted. PMID:22084629

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  10. Plants Actively Avoid State Transitions upon Changes in Light Intensity: Role of Light-Harvesting Complex II Protein Dephosphorylation in High Light1[OPEN

    PubMed Central

    Suorsa, Marjaana; Rantala, Marjaana; Aro, Eva-Mari

    2015-01-01

    Photosystem II (PSII) core and light-harvesting complex II (LHCII) proteins in plant chloroplasts undergo reversible phosphorylation upon changes in light intensity (being under control of redox-regulated STN7 and STN8 kinases and TAP38/PPH1 and PSII core phosphatases). Shift of plants from growth light to high light results in an increase of PSII core phosphorylation, whereas LHCII phosphorylation concomitantly decreases. Exactly the opposite takes place when plants are shifted to lower light intensity. Despite distinct changes occurring in thylakoid protein phosphorylation upon light intensity changes, the excitation balance between PSII and photosystem I remains unchanged. This differs drastically from the canonical-state transition model induced by artificial states 1 and 2 lights that concomitantly either dephosphorylate or phosphorylate, respectively, both the PSII core and LHCII phosphoproteins. Analysis of the kinase and phosphatase mutants revealed that TAP38/PPH1 phosphatase is crucial in preventing state transition upon increase in light intensity. Indeed, tap38/pph1 mutant revealed strong concomitant phosphorylation of both the PSII core and LHCII proteins upon transfer to high light, thus resembling the wild type under state 2 light. Coordinated function of thylakoid protein kinases and phosphatases is shown to secure balanced excitation energy for both photosystems by preventing state transitions upon changes in light intensity. Moreover, PROTON GRADIENT REGULATION5 (PGR5) is required for proper regulation of thylakoid protein kinases and phosphatases, and the pgr5 mutant mimics phenotypes of tap38/pph1. This shows that there is a close cooperation between the redox- and proton gradient-dependent regulatory mechanisms for proper function of the photosynthetic machinery. PMID:25902812

  11. Subthalamic and Cortical Local Field Potentials Associated with Pilocarpine-Induced Oral Tremor in the Rat

    PubMed Central

    Long, Lauren L.; Podurgiel, Samantha J.; Haque, Aileen F.; Errante, Emily L.; Chrobak, James J.; Salamone, John D.

    2016-01-01

    Tremulous jaw movements (TJMs) are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rodents, TJMs are induced by neurochemical conditions that parallel those seen in human Parkinsonism, including neurotoxic or pharmacological depletion of striatal dopamine (DA), DA antagonism, and cholinomimetic administration. Moreover, TJMs in rodents can be attenuated by antiparkinsonian agents, including levodopa (L-DOPA), DA agonists, muscarinic antagonists, and adenosine A2A antagonists. In human Parkinsonian patients, exaggerated physiological synchrony is seen in the beta frequency band in various parts of the cortical/basal ganglia/thalamic circuitry, and activity in the tremor frequency range (3–7 Hz) also has been recorded. The present studies were undertaken to determine if tremor-related local field potential (LFP) activity could be recorded from motor cortex (M1) or subthalamic nucleus (STN) during the TJMs induced by the muscarinic agonist pilocarpine, which is a well-known tremorogenic agent. Pilocarpine induced a robust TJM response that was marked by rhythmic electromyographic (EMG) activity in the temporalis muscle. Compared to periods with no tremor activity, TJM epochs were characterized by increased LFP activity in the tremor frequency range in both neocortex and STN. Tremor activity was not associated with increased synchrony in the beta frequency band. These studies identified tremor-related LFP activity in parts of the cortical/basal ganglia circuitry that are involved in the pathophysiology of Parkinsonism. This research may ultimately lead to identification of the oscillatory neural mechanisms involved in the generation of tremulous activity, and promote development of novel treatments for tremor disorders. PMID:27378874

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

    PubMed

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

    2015-09-23

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

  13. Evaluation of real-time PM2.5 forecasts and process analysis for PM2.5 formation over the eastern United States using the Eta-CMAQ forecast model during the 2004 ICARTT study

    NASA Astrophysics Data System (ADS)

    Yu, Shaocai; Mathur, Rohit; Schere, Kenneth; Kang, Daiwen; Pleim, Jonathan; Young, Jeffrey; Tong, Daniel; Pouliot, George; McKeen, Stuart A.; Rao, S. T.

    2008-03-01

    The performance of the Eta-Community Multiscale Air Quality (CMAQ) modeling system in forecasting PM2.5 and chemical species is assessed over the eastern United States with the observations obtained by aircraft (NOAA P-3 and NASA DC-8) and four surface monitoring networks (AIRNOW, IMPROVE, CASTNet and STN) during the 2004 International Consortium for Atmospheric Research on Transport and Transformation (ICARTT) study. The results of the statistical analysis at the AIRNOW sites show that the model was able to reproduce the day-to-day and spatial variations of observed PM2.5 and captured a majority (73%) of PM2.5 observations within a factor of 2, with normalized mean bias of -21%. The consistent underestimations in regional PM2.5 forecast at other networks (IMPROVE and STN) were mainly due to the underestimation of total carbonaceous aerosols at both urban and rural sites. The significant underestimation of the "other" category, which predominantly is composed of primary emitted trace elements in the current model configuration, is also one of the reasons leading to the underestimation of PM2.5 at rural sites. The systematic overestimations of SO42- both at the surface sites and aloft, in part, suggest too much SO2 cloud oxidation due to the overestimation of SO2 and H2O2 in the model. The underestimation of NH4+ at the rural sites and aloft may be attributed to the exclusion of some sources of NH3 in the emission inventory. The systematic underestimations of NO3- may result from the general overestimations of SO42-. Note that there are compensating errors among the underestimation of PM2.5 species (such as total carbonaceous aerosols) and overestimation of PM2.5 species (such as SO42-), leading to generally better performance of PM2.5 mass. The systematic underestimation of biogenic isoprene (by ˜30%) and terpene (by a factor of 4) suggests that their biogenic emissions may have been biased low, whereas the consistent overestimations of toluene by the model under

  14. Dopamine and the Biology of Creativity: Lessons from Parkinson’s Disease

    PubMed Central

    Lhommée, Eugénie; Batir, Alina; Quesada, Jean-Louis; Ardouin, Claire; Fraix, Valérie; Seigneuret, Eric; Chabardès, Stéphan; Benabid, Alim-Louis; Pollak, Pierre; Krack, Paul

    2014-01-01

    Background: Parkinson’s disease (PD) is characterized by reduced flexibility, conceptualization, and visuo-spatial abilities. Although these are essential to creativity, case studies show emergence of creativity during PD. Knowledge about the role of dopamine in creativity so far only stems from a few case reports. We aim at demonstrating that creativity can be induced by dopaminergic treatments in PD, and tends to disappear after withdrawal of dopamine agonists. Methods: Eleven consecutive creative PD patients were selected from candidates for subthalamic nucleus deep brain stimulation (STN DBS) surgery, and compared to 22 non-creative control PD patients. Motor disability (UPDRS III), cognition (Frontal score, Mattis scale), and behavior (Ardouin scale) were assessed before surgery and 1 year after. Results: Before surgery, whereas cognitive and motor assessments were similar between groups, dopamine agonist (but not levodopa) dosages were higher in creative patients (p = 0.01). The Ardouin scale revealed also a specific psycho-behavioral profile of creative patients which had higher scores for mania (p < 0.001), hobbyism (p = 0.001), nocturnal hyperactivity (p = 0.041), appetitive functioning (p = 0.003), and ON euphoria (p = 0.007) and lower scores for apathy and OFF dysphoria (p = 0.04 for each). Post-operative motor, cognitive, and behavioral scores as dopaminergic treatment dosages were equivalent between groups. Motor improvement allowed for a 68.6% decrease in dopaminergic treatment. Only 1 of the 11 patients remained creative after surgery. Reduction of dopamine agonist was significantly correlated to the decrease in creativity in the whole population of study (Spearman correlation coefficient ρ = 0.47 with confidence index of 95% = 0.16; 0.70, p = 0.0053). Conclusion: Creativity in PD is linked to dopamine agonist therapy, and tends to disappear after STN DBS in parallel to reduction of dopamine agonists

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

    PubMed

    Sharma, Mayur; Deogaonkar, Milind

    2016-05-01

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

  16. The response of nitrifying microbial assemblages to ammonium (NH4+) enrichment from salmon farm activities in a northern Chilean Fjord

    NASA Astrophysics Data System (ADS)

    Elizondo-Patrone, Claudia; Hernández, Klaudia; Yannicelli, Beatriz; Olsen, Lasse Mork; Molina, Verónica

    2015-12-01

    The consequences of aquaculture include alterations in nitrogen cycling in aquatic environments that may lead to ecosystem degradation. Herein salmon aquaculture release of ammonium (NH4+) to the water column and its effects on natural archaea and bacteria ammonia-oxidizers (AOA and AOB) and nitrite-oxidizing bacteria (NOB) community structure were studied in the Comau fjord using molecular approaches, such as: cloning (AOA and AOB richness), qPCR for C. Nitrosopumilus maritimus (AOA) and Nitrospina sp. (NOB) abundance (DNA) and RT-qPCR only for Nitrospina sp activity (RNA). Sampling was carried out in brackish (0.7-25 salinity, <5 m depth) and marine (>30 salinity, 25 m depth) waters during contrasting salmon production periods: rest (winter 2012), growth and harvest (summer and winter 2013). During the rest period, the highest NH4+ concentration was observed at Vodudahue River, whereas during productive periods NH4+ accumulated in the brackish layer inside salmon cages and in the vicinty (up to 700 m distance from the cages). The nitrifier community from the fjord reference station (Stn-C) was characterized by C. N. maritimus (AOA) and Nitrosomonas sp. (AOB) sequences affiliated with cosmopolitan ecotypes (e.g., marine, freshwater, hydrothermal), maxima abundances of C. N. maritimus (AOA) and Nitrospina sp. and extreme ranges of Nitrospina sp. activity occurred in the brackish layer. During productive periods, abundances of C. N. maritimus were co-varied with NH4+ concentrations inside salmon cages (summer) and the adjacent areas (winter). Productive periods were characterized by lower abundances but more homogeneity between brackish and marine areas than for the Stn-C nitrifiers. The physiological state of Nitrospina sp. estimated from cDNA:DNA ratios indicated higher growth during winter 2013 associated with NH4+ enrichment derived from production and river input. Our results suggest that in Comau Fjord, NH4+ enrichment events occur during salmon production and

  17. The Evaluation of PM2.5 Forecasts from Several Regional Air Quality Models Using Data from the ICARTT/NEAQS-2K4 Field Study

    NASA Astrophysics Data System (ADS)

    McKeen, S. A.; Hsie, E.; Grell, G.; Peckham, S.; Mathur, R.; Yu, S.; Gong, W.; Bouchet, V.; Menard, S.; Tang, Y.; Carmichael, G.

    2005-12-01

    Real-time air quality forecasts of aerosol PM2.5 for the Eastern U.S. and Southern Canada are currently available through a number forecast offices and research centers. This study presents results from an evaluation of six regional air quality models compared to surface data from the U.S. EPA AIRNow PM2.5 network and Speciation Trends Network (STN), as well as data collected during the ICARTT/NEAQS-2K4 field campaign from the NOAA WP-3 aircraft and Ronald H. Brown research vessel. The forecast models include two versions of the NOAA/FSL WRF/Chem model, a developmental version of the NWS/NCEP CMAQ/ETA model, the Canadian Meteorological Services CHRONOS and AURAMS models, and the University of Iowa STEM-2K3 model. Statistical evaluations of each model with the AIRNow PM2.5 network characterize the models' ability to forecast surface PM2.5 over a large region of Eastern North America for a seven-week period during the summer of 2004. The composition of aerosol PM2.5 is statistically evaluated by comparing model predicted PM2.5 sulfate, nitrate, ammonium, organic carbon and elemental carbon with aerosol compositional data from the aircraft, ship, and STN surface network. Several important conclusions have emerged from the analysis completed to date. Comparisons of model forecasts with surface AIRNow PM2.5 network data show that all models possess some skill in predicting daytime average PM2.5 levels when compared to simple persistence forecasts. An ensemble PM2.5 forecast, constructed by taking the geometric mean of the six forecasts, shows significant statistical improvement over any individual forecast. Comparisons of model forecasts with aerosol composition measurements from the W-P3 aircraft show that all models under-predict the organic carbon fraction of aerosol. SO2 oxidation rates downwind of urban centers are examined by comparing SO2/SO4 ratios between the models and WP-3 observations, and those models that include SO2 conversion to SO4 by cloud oxidation

  18. Mesozooplankton biomass and grazing responses to Cyclone Opal, a subtropical mesoscale eddy

    NASA Astrophysics Data System (ADS)

    Landry, Michael R.; Decima, Moira; Simmons, Melinda P.; Hannides, Cecelia C. S.; Daniels, Emy

    2008-05-01

    As part of E-Flux III cruise studies in March 2005, plankton net collections were made to assess the effects of a cyclonic cold-core eddy (Cyclone Opal) on the biomass and grazing of mesozooplankton. Mesozooplankton biomass in the central region of Cyclone Opal, an area of uplifted nutricline and a subsurface diatom bloom, averaged 0.80±0.24 and 1.51±0.59 g DW m -2, for day and night tows, respectively. These biomass estimates were about 80% higher than control (OUT) stations, with increases more or less proportionately distributed among size classes from 0.2 to >5 mm. Though elevated relative to surrounding waters south of the Hawaiian Islands (Hawai'i lee), total biomass and size distribution in Cyclone Opal were almost exactly the same as contemporary measurements made at Stn. ALOHA, 100 km north of the islands, by the HOT (Hawaii Ocean Time-series) Program. Mesozooplankton biomass and community composition at the OUT stations were also similar to ALOHA values from 1994 to 1996, preceding a recent decadal increase. These comparisons may therefore provide insight into production characteristics or biomass gradients associated with decadal changes at Stn. ALOHA. Gut fluorescence estimates were higher in Opal than in ambient waters, translating to grazing impacts of 0.11±0.02 d -1 (IN) versus 0.03±0.01 d -1 (OUT). Over the depth-integrated euphotic zone, mesozooplankton accounted for 30% of the combined grazing losses of phytoplankton to micro- and meso-herbivores in Opal, as compared to 13% at control stations. Estimates of active export flux by migrating zooplankton averaged 0.81 mmol C m -2 d -1 in Cyclone Opal and 0.37 mmol C m -2 d -1 at OUT stations, 53% and 24%, respectively, of the carbon export measured by passive sediment traps. Migrants also exported 0.18 mmol N m -2 d -1 (117% of trap N flux) in Cyclone Opal compared to 0.08 mmol N m -2 d -1 (51% of trap flux) at control stations. Overall, the food-web importance of mesozooplankton increased in

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

    PubMed Central

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

    2015-01-01

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

  20. Denitrification controls in urban riparian soils: implications for reducing urban nonpoint source nitrogen pollution.

    PubMed

    Li, Yangjie; Chen, Zhenlou; Lou, Huanjie; Wang, Dongqi; Deng, Huanguang; Wang, Chu

    2014-09-01

    The purpose of this research was to thoroughly analyze the influences of environmental factors on denitrification processes in urban riparian soils. Besides, the study was also carried out to identify whether the denitrification processes in urban riparian soils could control nonpoint source nitrogen pollution in urban areas. The denitrification rates (DR) over 1 year were measured using an acetylene inhibition technique during the incubation of intact soil cores from six urban riparian sites, which could be divided into three types according to their vegetation. The soil samples were analyzed to determine the soil organic carbon (SOC), soil total nitrogen (STN), C/N ratio, extractable NO3 (-)-N and NH4 (+)-N, pH value, soil water content (SWC), and the soil nitrification potential to evaluate which of these factors determined the final outcome of denitrification. A nitrate amendment experiment further indicated that the riparian DR was responsive to added nitrate. Although the DRs were very low (0.099 ~ 33.23 ng N2O-N g(-1) h(-1)) due to the small amount of nitrogen moving into the urban riparian zone, the spatial and temporal patterns of denitrification differed significantly. The extractable NO3 (-)-N proved to be the dominant factor influencing the spatial distribution of denitrification, whereas the soil temperature was a determinant of the seasonal DR variation. The six riparian sites could also be divided into two types (a nitrate-abundant and a nitrate-stressed riparian system) according to the soil NO3 (-)-N concentration. The DR in nitrate-abundant riparian systems was significantly higher than that in the nitrate-stressed riparian systems. The DR in riparian zones that were covered with bushes and had adjacent cropland was higher than in grass-covered riparian sites. Furthermore, the riparian DR decreased with soil depth, which was mainly attributed to the concentrated nitrate in surface soils. The DR was not associated with the SOC, STN, C/N ratio, and

  1. Predicting In vitro Culture Medium Macro-Nutrients Composition for Pear Rootstocks Using Regression Analysis and Neural Network Models.

    PubMed

    Jamshidi, S; Yadollahi, A; Ahmadi, H; Arab, M M; Eftekhari, M

    2016-01-01

    Two modeling techniques [artificial neural network-genetic algorithm (ANN-GA) and stepwise regression analysis] were used to predict the effect of medium macro-nutrients on in vitro performance of pear rootstocks (OHF and Pyrodwarf). The ANN-GA described associations between investigating eight macronutrients (NO[Formula: see text], NH[Formula: see text], Ca(2+), K(+), Mg(2+), PO[Formula: see text], SO[Formula: see text], and Cl(-)) and explant growth parameters [proliferation rate (PR), shoot length (SL), shoot tip necrosis (STN), chlorosis (Chl), and vitrification (Vitri)]. ANN-GA revealed a substantially higher accuracy of prediction than for regression models. According to the ANN-GA results, among the input variables concentrations (mM), NH[Formula: see text] (301.7), and NO[Formula: see text], NH[Formula: see text] (64), SO[Formula: see text] (54.1), K(+) (40.4), and NO[Formula: see text] (35.1) in OHF and Ca(2+) (23.7), NH[Formula: see text] (10.7), NO[Formula: see text] (9.1), NH[Formula: see text] (317.6), and NH[Formula: see text] (79.6) in Pyrodwarf had the highest values of VSR in data set, respectively, for PR, SL, STN, Chl, and Vitri. The ANN-GA showed that media containing (mM) 62.5 NO[Formula: see text], 5.7 NH[Formula: see text], 2.7 Ca(2+), 31.5 K(+), 3.3 Mg(2+), 2.6 PO[Formula: see text], 5.6 SO[Formula: see text], and 3.5 Cl(-) could lead to optimal PR for OHF and optimal PR for Pyrodwarf may be obtained with media containing 25.6 NO[Formula: see text], 13.1 NH[Formula: see text], 5.5 Ca(2+), 35.7 K(+), 1.5 Mg(2+), 2.1 PO[Formula: see text], 3.6 SO[Formula: see text], and 3 Cl(-). PMID:27066013

  2. Changes in GABA and glutamate concentrations during memory tasks in patients with Parkinson's disease undergoing DBS surgery.

    PubMed

    Buchanan, Robert J; Darrow, David P; Meier, Kevin T; Robinson, Jennifer; Schiehser, Dawn M; Glahn, David C; Nadasdy, Zoltan

    2014-01-01

    Until now direct neurochemical measurements during memory tasks have not been accomplished in the human basal ganglia. It has been proposed, based on both functional imaging studies and psychometric testing in normal subjects and in patients with Parkinson's disease (PD), that the basal ganglia is responsible for the performance of feedback-contingent implicit memory tasks. To measure neurotransmitters, we used in vivo microdialysis during deep brain stimulation (DBS) surgery. We show in the right subthalamic nucleus (STN) of patients with PD a task-dependent change in the concentrations of glutamate and GABA during an implicit memory task relative to baseline, while no difference was found between declarative memory tasks. The five patients studied had a significant decrease in the percent concentration of GABA and glutamate during the performance of the weather prediction task (WPT). We hypothesize, based on current models of basal ganglia function, that this decrease in the concentration is consistent with expected dysfunction in basal ganglia networks in patients with PD. PMID:24639638

  3. Sources of fine urban particulate matter in Detroit, MI.

    PubMed

    Gildemeister, Amy E; Hopke, Philip K; Kim, Eugene

    2007-10-01

    Data from the speciation trends network (STN) was used to evaluate the amount and temporal patterns of particulate matter originating from local industrial sources and long-range transport at two sites in Detroit, MI: Allen Park, MI, southwest of both Detroit and the areas of heavy industrial activity; Dearborn, MI, located on the south side of Detroit near the most heavily industrialized region. Using positive matrix factorization (PMF) and comparing source contributions at Allen Park to those in Dearborn, contributions made by local industrial sources (power plants, coke refineries, iron smelting, waste incineration), local area sources (automobile and diesel truck) and long range sources of PM(2.5) can be distinguished in greater Detroit. Overall, the mean mass concentration measured at Dearborn was 19% higher than that measured at Allen Park. The mass at Allen Park was apportioned as: secondary sulfate 31%, secondary nitrate 28%, soil 8%, mixed aged sea and road salts 4%, gasoline 15%, diesel 4%, and biomass burning 3%. At Dearborn the mass was apportioned as: secondary sulfate 25%, secondary nitrate 20%, soil 12%, mixed aged sea and road salts 4%, gasoline 20%, diesel 8%, iron and steel, 5%, and mixed industrial 7%. The impact of the iron and steel, soil, and mixed aged sea and road salt was much higher at the Dearborn site than at the Allen Park site, suggesting that close proximity to a local industrial complex has a direct negative impact on local air quality. PMID:17537480

  4. A probabilistic atlas of the basal ganglia using 7 T MRI

    PubMed Central

    Keuken, Max C.; Forstmann, Birte U.

    2015-01-01

    A common localization procedure in functional imaging studies includes the overlay of statistical parametric functional magnetic resonance imaging (fMRI) maps or coordinates with neuroanatomical atlases in standard space, e.g., MNI-space. This procedure allows the identification of specific brain regions. Most standard MRI software packages include a wide range of atlases but have a poor coverage of the subcortex. We estimated that approximately 7% of the known subcortical structures are mapped in standard MRI-compatible atlases [1]. Here we provide a data description of a subcortical probabilistic atlas based on ultra-high resolution in-vivo anatomical imaging using 7 T (T) MRI. The atlas includes six subcortical nuclei: the striatum (STR), the globus pallidus internal and external segment (GPi/e), the subthalamic nucleus (STN), the substantia nigra (SN), and the red nucleus (RN). These probabilistic atlases are shared on freely available platforms such as NITRC and NeuroVault and are published in NeuroImage “Quantifying inter-individual anatomical variability in the subcortex using 7 T structural MRI” [2]. PMID:26322322

  5. Report on twisted nematic and supertwisted nematic device characterization program

    NASA Technical Reports Server (NTRS)

    1995-01-01

    In this study we measured the optical characteristics of normally white twisted nematic (NWTN) and super twisted nematic (STN ) cells. Though no dynamic computer model was available, the static observations were compared with computer simulated behavior. The measurements were taken as a function of both viewing angle and applied voltage and included in the static case not only luminance but also contrast ratio and chromaticity . We employed the computer model Twist Cell Optics, developed at Kent State in conjunction with this study, and whose optical modeling foundation, Iike the ViDEOS program, is the 4 x 4 matrix method of Berreman. In order to resolve discrepancies between the experimental and modeled data the optical parameters of the individual cell components, where not known, were determined using refractometry, profilometry, and various forms of ellipsometry. The resulting agreement between experiment and model is quite good due primarily to a better understanding of the structure and optics of dichroic sheet polarizers. A description of the model and test cells employed are given in section 2. Section 3 contains the experimental data gathered and section 4 gives examples of the fit between model and experiment. Also included with this report are a pair of papers which resulted from the research and which detail the polarizer properties and some of the cell characterization methods.

  6. Preliminary Ecotoxicity and Biodegradability Assessment of Metalworking Fluids

    NASA Astrophysics Data System (ADS)

    Gerulová, Kristína; Amcha, Peter; Filická, Slávka

    2010-01-01

    The main aim of this study was to evaluate the potential of activated sludge from sewage treatment plant to degrade selected MWFs (ecotoxicity to bacterial consortium) and to evaluate the ecotoxicity by Lemna minor-higher plant. After evaluating the ecotoxicity, biodegradations rate with activated sludge was assessed on the basis of COD measurement. Preliminary study of measuring the ecotoxicity according to OECD 221 by Lemna minor shows effective concentration of Emulzin H at the rate of 81.6 mg l-1, for Ecocool 82.9 mg l-1, for BC 25 about 99.3 mg l-1, and for Dasnobor about 97.3 mg l-1. Preliminary study of measuring the ecotoxicity by bacterial consortium according to OECD 209 (STN EN ISO 8192) shows effective concentration of Blasocut BC 25 at the rate 227.4 mg l-1. According to OECD 302B, the biodegradations level of Emulzin H, Ecocool and BC 25 achieved 80% in 10 days. It can be stated that these MWFs have potential to ultimate degradation, but the statement has to be confirmed by a biodegradability test with other parameters than COD, which exhibits some disadvantages in testing O/W emulsions.

  7. Colorless and transparent copolyimide nanocomposites.

    PubMed

    Bae, Hye-Jin; Kim, Yong Seok; Chang, Jin-Hae

    2014-12-01

    Copolyimides (Co-PIs) were synthesized from 2,2'-bis(trifluoromethyl) benzidine (TFB) and different ratios of 4,4'-(hexafluoroisopropylidene) diphthalic anhydride (6FDA) and pyromellitic dianhydride (PMDA). The Co-PI films were obtained from poly(amic acid) (PAA) by solution-casting through typical chemical and thermal imidizations. The thermal properties and optical transparency of the Co-PI films with various PMDA monomer contents were investigated. It was found that with increasing PMDA content, the thermal transition temperatures of the Co-PI films increased. Co-PI nanocomposites were prepared with various amounts of organically modified hectorite (STN) on a TFB:6FDA:PMDA = 1.0:0.9:0.1 mole ratio Co-PI hybrid film to examine the thermal properties, morphology, and optical transparency. The thermo-optical properties of the Co-PI hybrid films deteriorated with increasing clay content. However, the coefficient of thermal expansion (CTE) and oxygen barrier properties of the PI hybrid films improved with increasing clay content. PMID:25971113

  8. Putative virulence genes of Vibrio cholerae from seafoods and the coastal environment of Southwest India.

    PubMed

    Saravanan, V; Sanath Kumar, H; Karunasagar, Indrani; Karunasagar, Iddya

    2007-11-01

    Shrimp, clam and oysters were obtained at two fish markets and at a fish landing dock, and plankton, water and sediment samples were obtained from four river estuaries, in southern India. The samples were analyzed for Vibrio cholerae by conventional isolation techniques and by polymerase chain reaction (PCR) procedures. V. cholerae was isolated from 2 of 5 shrimp, 2 of 5 clam and 5 of 20 water samples. All biochemically confirmed isolates of V. cholerae were positive for toxR. For direct detection of V. cholerae in enrichment broths, PCR was performed using lysates from 0 and 6 h enrichments. All the V. cholerae isolates and enrichment broth lysates were subjected to PCR analysis for the detection of the genes toxR, ctxA, tcpA, ompU, hly, ace, Nag-ST (stn/sto), and ompU. Enrichment broths of all the samples which yielded V. cholerae were positive for toxR, OmpU and hlyA genes, while one of a fresh fish market sample was positive for the ace gene. Choleragenic V. cholerae were absent from all environmental samples and fresh fish from the markets, but one sample of shrimp was positive for V. cholerae O139. PMID:17900729

  9. International energy: Research organizations, 1988--1992. Revision 1

    SciTech Connect

    Hendricks, P.; Jordan, S.

    1993-06-01

    This publication contains the standardized names of energy research organizations used in energy information databases. Involved in this cooperative task are (1) the technical staff of the US DOE Office of Scientific and Technical Information (OSTI) in cooperation with the member countries of the Energy Technology Data Exchange (ETDE) and (2) the International Nuclear Information System (INIS). ETDE member countries are also members of the International Nuclear Information System (INIS). Nuclear organization names recorded for INIS by these ETDE member countries are also included in the ETDE Energy Database. Therefore, these organization names are cooperatively standardized for use in both information systems. This publication identifies current organizations doing research in all energy fields, standardizes the format for recording these organization names in bibliographic citations, assigns a numeric code to facilitate data entry, and identifies report number prefixes assigned by these organizations. These research organization names may be used in searching the databases ``Energy Science & Technology`` on DIALOG and ``Energy`` on STN International. These organization names are also used in USDOE databases on the Integrated Technical Information System. Research organizations active in the past five years, as indicated by database records, were identified to form this publication. This directory includes approximately 31,000 organizations that reported energy-related literature from 1988 to 1992 and updates the DOE Energy Data Base: Corporate Author Entries.

  10. International energy: Research organizations, 1986--1990

    SciTech Connect

    Hendricks, P.; Jordan, S. )

    1991-03-01

    The International Energy: Research Organizations publication contains the standardized names of energy research organizations used in energy information databases. Involved in this cooperative task are (1) the technical staff of the USDOE Office of Scientific and Technical Information (OSTI) in cooperation with the member countries of the Energy Technology Data Exchange (ETDE) and (2) the International Nuclear Information System (INIS). This publication identifies current organizations doing research in all energy fields, standardizes the format for recording these organization names in bibliographic citations, assigns a numeric code to facilitate data entry, and identifies report number prefixes assigned by these organizations. These research organization names may be used in searching the databases Energy Science Technology'' on DIALOG and Energy'' on STN International. These organization names are also used in USDOE databases on the Integrated Technical Information System. Research organizations active in the past five years, as indicated by database records, were identified to form this publication. This directory includes approximately 34,000 organizations that reported energy-related literature from 1986 to 1990 and updates the DOE Energy Data Base: Corporate Author Entries.

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

    SciTech Connect

    Kuttner-Hirshler, Y.; Biegon, A.; Kuttner-Hirshler, Y.; Polat, U.; Biegon, A.

    2009-12-21

    Deep brain stimulation (DBS) is an established treatment for advanced Parkinson's disease (PD). The procedure entails intracranial implantation of an electrode in a specific brain structure followed by chronic stimulation. Although the beneficial effects of DBS on motor symptoms in PD are well known, it is often accompanied by cognitive impairments, the origin of which is not fully understood. To explore the possible contribution of the surgical procedure itself, we studied the effect of electrode implantation in the subthalamic nucleus (STN) on regional neuroinflammation and memory function in rats implanted bilaterally with stainless steel electrodes. Age-matched sham and intact rats were used as controls. Brains were removed 1 or 8 weeks post-implantation and processed for in vitro autoradiography with [(3)H]PK11195, an established marker of microglial activation. Memory function was assessed by the novel object recognition test (ORT) before surgery and 2 and 8 weeks after surgery. Electrode implantation produced region-dependent changes in ligand binding density in the implanted brains at 1 as well as 8 weeks post-implantation. Cortical regions showed more intense and widespread neuroinflammation than striatal or thalamic structures. Furthermore, implanted animals showed deficits in ORT performance 2 and 8 weeks post-implantation. Thus, electrode implantation resulted in a widespread and persistent neuroinflammation and sustained memory impairment. These results suggest that the insertion and continued presence of electrodes in the brain, even without stimulation, may lead to inflammation-mediated cognitive deficits in susceptible individuals, as observed in patients treated with DBS.

  12. Observations of asexual reproductive strategies in Antarctic hexactinellid sponges from ROV video records

    NASA Astrophysics Data System (ADS)

    Teixidó, Núria; Gili, Josep-Maria; Uriz, María-J.; Gutt, Julian; Arntz, Wolf E.

    2006-04-01

    Hexactinellid sponges are one of the structuring taxa of benthic communities on the Weddell Sea shelf (Antarctica). However, little is known about their reproduction patterns (larval development, release, settlement, and recruitment), particularly in relation to sexual and asexual processes in sponge populations. Video stations obtained during several expeditions covering a wide depth range and different areas recorded a high frequency of asexual reproductive strategies (ARS) (bipartition and budding) among hexactinellids. Analysis of seabed video strips between 108 and 256 m depth, representing an area of 1400 m 2, showed that about 28% of these sponges exhibited ARS. The Rossella nuda type dominated most of the video stations and exhibited the highest proportion of budding (35%). This proportion increased with the size class. Size class >20 cm exhibited in all the stations a mean value of 8.3±0.7 (SE) for primary and of 2.5±0.2 (SE) for secondary propagules per sponge, respectively. Results from a shallow station (Stn 059, 117 m depth) showed the highest relative abundance of R. nuda type and budding (>20 cm ˜72%, 10-20 cm ˜60%, 5-10 cm ˜12%, and <5 cm ˜3%). A potential influence of iceberg scouring disturbance on the occurrence of budding and number of propagules also was investigated. We conclude that asexual reproduction in hexactinellid sponges may be more frequent than has been thought before and it may greatly influence the genetic structure of populations.

  13. International Energy: Subject Thesaurus. Revision 1

    SciTech Connect

    Not Available

    1993-11-01

    The International Energy Agency: Subject Thesaurus contains the standard vocabulary of indexing terms (descriptors) developed and structured to build and maintain energy information databases. Involved in this cooperative task are (1) the technical staff of the USDOE Office of Scientific and Technical Information (OSTI) in cooperation with the member countries of the International Energy Agency`s Energy Technology Data Exchange (ETDE) and (2) the International Atomic Energy Agency`s International Nuclear Information System (INIS) staff representing the more than 100 countries and organizations that record and index information for the international nuclear information community. ETDE member countries are also members of INIS. Nuclear information prepared for INIS by ETDE member countries is included in the ETDE Energy Database, which contains the online equivalent of the printed INIS Atomindex. Indexing terminology is therefore cooperatively standardized for use in both information systems. This structured vocabulary reflects thscope of international energy research, development, and technological programs. The terminology of this thesaurus aids in subject searching on commercial systems, such as ``Energy Science & Technology`` by DIALOG Information Services, ``Energy`` by STN International and the ``ETDE Energy Database`` by SilverPlatter. It is also the thesaurus for the Integrated Technical Information System (ITIS) online databases of the US Department of Energy.

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

    PubMed

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

    2016-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson's disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson's Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson's disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought. PMID:27624437

  15. NEUROZONE: on-line recognition of brain structures in stereotactic surgery--application to Parkinson's disease.

    PubMed

    Vargas Cardona, Hernán Darío; Padilla, Jose Bestier; Arango, Ramiro; Carmona, Hans; Álvarez, Mauricio A; Guijarro Estellés, Enrique; Orozco, Álvaro Ángel

    2012-01-01

    The success of stereotactic surgery for Deep Brain Stimulation depends critically on the exact positioning of a microelectrode recording in a target area of the brain. This paper presents the software system NEUROZONE composed of two main applications: first, it allows online recognition of brain structures by the analysis of signals from microelectrode recordings (MER), and second, it processes and analyses off-line databases allowing the inclusion of new trained classifiers for automatic identification. The software serves as a support to the analysis done by a medical specialist during surgery, and seeks to reduce the adverse side effects that may occur because of inadequate identification of the target areas. The software also allows the specialists to label recordings obtained during surgery, in order to generate a new off-line database or increase the amount of records in an already existing off-line database. NEUROZONE has been tested for Deep Brain Stimulation performed at the Institute for Epilepsy and Parkinson of the Eje Cafetero (Colombia), achieving positive identifications of the Subthalamic Nucleus (STN) over to 85% using a naive Bayes classifier. PMID:23366364

  16. Cortical plasticity in patients with Parkinson's disease a window for therapeutic non-invasive neuromodulation.

    PubMed

    Quartarone, Angelo; Rizzo, Vincenzo; Terranova, Carmen; Bruschetta, Daniele; Milardi, Demetrio; Girlanda, Paolo; Ghilardi, Maria Felice

    2014-12-01

    Several evidences in animal models have consistently an alteration of cortico-striatal plasticity, which is related to the degeneration of the substantia nigra. An alteration of plasticity have also been reported in humans by recording evoked field potentials in the substantia nigra pars reticulata of PD patients undergoing subthalamic nucleus (STN) stimulation where high-frequency (HF) in the OFF state did not induce a lasting change in field potential amplitude in the substantia nigra. In addition protocols of non-invasive brain stimulation, such as paired associative stimulation (PAS) and theta-burst stimulation (TBS), can be used to investigate cortical plasticity of the human primary motor cortex. Despite data reported in literature are apparently controversial with some studies showing a reduced or increased or even normal LTP and LTD like plasticity, recent evidences suggest the hypothesis that these different pat- terns of cortical plasticity likely depend on the stage of the disease and on the concomitant administration of L-DOPA. The current review will provide an up-to-date of these issues on cortical plasticity in PD discussing the clinical implications in rehabilitation. In addition in the last section we will review the state of art of non invasive neuro- modulation as adjuvant treatment in the advanced stage of the disease. PMID:25987183

  17. Cdc13 N-Terminal Dimerization DNA Binding and Telomere Length Regulation

    SciTech Connect

    M Mitchell; J Smith; M Mason; S Harper; D Speicher; F Johnson; E Skordalakes

    2011-12-31

    The essential yeast protein Cdc13 facilitates chromosome end replication by recruiting telomerase to telomeres, and together with its interacting partners Stn1 and Ten1, it protects chromosome ends from nucleolytic attack, thus contributing to genome integrity. Although Cdc13 has been studied extensively, the precise role of its N-terminal domain (Cdc13N) in telomere length regulation remains unclear. Here we present a structural, biochemical, and functional characterization of Cdc13N. The structure reveals that this domain comprises an oligonucleotide/oligosaccharide binding (OB) fold and is involved in Cdc13 dimerization. Biochemical data show that Cdc13N weakly binds long, single-stranded, telomeric DNA in a fashion that is directly dependent on domain oligomerization. When introduced into full-length Cdc13 in vivo, point mutations that prevented Cdc13N dimerization or DNA binding caused telomere shortening or lengthening, respectively. The multiple DNA binding domains and dimeric nature of Cdc13 offer unique insights into how it coordinates the recruitment and regulation of telomerase access to the telomeres.

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

    PubMed

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

    2016-06-01

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

  19. Analyses of Candida Cdc13 Orthologues Revealed a Novel OB Fold Dimer Arrangement, Dimerization-Assisted DNA Binding, and Substantial Structural Differences between Cdc13 and RPA70

    PubMed Central

    Yu, Eun Young; Sun, Jia

    2012-01-01

    The budding yeast Cdc13-Stn1-Ten1 complex is crucial for telomere protection and has been proposed to resemble the RPA complex structurally and functionally. The Cdc13 homologues in Candida species are unusually small and lack two conserved domains previously implicated in telomere regulation, thus raising interesting questions concerning the mechanisms and evolution of these proteins. In this report, we show that the unusually small Cdc13 homologue in Candida albicans is indeed a regulator of telomere lengths and that it associates with telomere DNA in vivo. We demonstrated high-affinity telomere DNA binding by C. tropicalis Cdc13 (CtCdc13) and found that dimerization of this protein through its OB4 domain is important for high-affinity DNA binding. Interestingly, CtCdc13-DNA complex formation appears to involve primarily recognition of multiple copies of a six-nucleotide element (GGATGT) that is shared by many Candida telomere repeats. We also determined the crystal structure of the OB4 domain of C. glabrata Cdc13, which revealed a novel mechanism of OB fold dimerization. The structure also exhibits marked differences to the C-terminal OB fold of RPA70, thus arguing against a close evolutionary kinship between these two proteins. Our findings provide new insights on the mechanisms and evolution of a critical telomere end binding protein. PMID:22025677

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

    PubMed

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

    2011-02-01

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

  1. Genome Destabilizing Mutator Alleles Drive Specific Mutational Trajectories in Saccharomyces cerevisiae

    PubMed Central

    Stirling, Peter C.; Shen, Yaoqing; Corbett, Richard; Jones, Steven J. M.; Hieter, Philip

    2014-01-01

    In addition to environmental factors and intrinsic variations in base substitution rates, specific genome-destabilizing mutations can shape the mutational trajectory of genomes. How specific alleles influence the nature and position of accumulated mutations in a genomic context is largely unknown. Understanding the impact of genome-destabilizing alleles is particularly relevant to cancer genomes where biased mutational signatures are identifiable. We first created a more complete picture of cellular pathways that impact mutation rate using a primary screen to identify essential Saccharomyces cerevisiae gene mutations that cause mutator phenotypes. Drawing primarily on new alleles identified in this resource, we measure the impact of diverse mutator alleles on mutation patterns directly by whole-genome sequencing of 68 mutation-accumulation strains derived from wild-type and 11 parental mutator genotypes. The accumulated mutations differ across mutator strains, displaying base-substitution biases, allele-specific mutation hotspots, and break-associated mutation clustering. For example, in mutants of POLα and the Cdc13–Stn1–Ten1 complex, we find a distinct subtelomeric bias for mutations that we show is independent of the target sequence. Together our data suggest that specific genome-instability mutations are sufficient to drive discrete mutational signatures, some of which share properties with mutation patterns seen in tumors. Thus, in a population of cells, genome-instability mutations could influence clonal evolution by establishing discrete mutational trajectories for genomes. PMID:24336748

  2. The light-harvesting chlorophyll a/b binding proteins Lhcb1 and Lhcb2 play complementary roles during state transitions in Arabidopsis.

    PubMed

    Pietrzykowska, Malgorzata; Suorsa, Marjaana; Semchonok, Dmitry A; Tikkanen, Mikko; Boekema, Egbert J; Aro, Eva-Mari; Jansson, Stefan

    2014-09-01

    Photosynthetic light harvesting in plants is regulated by phosphorylation-driven state transitions: functional redistributions of the major trimeric light-harvesting complex II (LHCII) to balance the relative excitation of photosystem I and photosystem II. State transitions are driven by reversible LHCII phosphorylation by the STN7 kinase and PPH1/TAP38 phosphatase. LHCII trimers are composed of Lhcb1, Lhcb2, and Lhcb3 proteins in various trimeric configurations. Here, we show that despite their nearly identical amino acid composition, the functional roles of Lhcb1 and Lhcb2 are different but complementary. Arabidopsis thaliana plants lacking only Lhcb2 contain thylakoid protein complexes similar to wild-type plants, where Lhcb2 has been replaced by Lhcb1. However, these do not perform state transitions, so phosphorylation of Lhcb2 seems to be a critical step. In contrast, plants lacking Lhcb1 had a more profound antenna remodeling due to a decrease in the amount of LHCII trimers influencing thylakoid membrane structure and, more indirectly, state transitions. Although state transitions are also found in green algae, the detailed architecture of the extant seed plant light-harvesting antenna can now be dated back to a time after the divergence of the bryophyte and spermatophyte lineages, but before the split of the angiosperm and gymnosperm lineages more than 300 million years ago. PMID:25194026

  3. Terminin: a protein complex that mediates epigenetic maintenance of Drosophila telomeres.

    PubMed

    Raffa, Grazia D; Ciapponi, Laura; Cenci, Giovanni; Gatti, Maurizio

    2011-01-01

    In most organisms, telomeres are extended by telomerase and contain GC-rich repeats. Drosophila telomeres are elongated by occasional transposition of specialized retroelements rather than telomerase activity, and are assembled independently of the sequence of the DNA termini. Recent work has shown that Drosophila telomeres are capped by a complex, we call terminin, which includes HOAP, HipHop, Moi and Ver; these are fast-evolving proteins that prevent telomere fusion, directly interact with each other, and appear to localize and function only at telomeres. With the possible exception of Ver that contains an OB fold domain structurally similar to the Stn1 OB fold, none of the terminin proteins is evolutionarily conserved outside the Drosophila species. Human telomeres are protected by the shelterin complex, which comprises six proteins that bind chromosome ends in a sequence-dependent manner. Shelterin subunits are not fast-evolving proteins and are not conserved in flies, but localize and function only at telomeres like the terminin components. Based on these findings, we propose that concomitant with telomerase loss Drosophila rapidly evolved terminin to bind chromosome ends in a sequence-independent fashion, and that terminin is functionally analogous to shelterin. PMID:21989238

  4. Coordination of transposon expression with DNA replication in the targeting of telomeric retrotransposons in Drosophila

    PubMed Central

    Zhang, Liang; Beaucher, Michelle; Cheng, Yan; Rong, Yikang S

    2014-01-01

    In Drosophila, a group of retrotransposons is mobilized exclusively to telomeres in a sequence-independent manner. How they target chromosome ends is not understood. Here, we focused on the telomeric element HeT-A and characterized the cell cycle expression and cytological distribution of its protein and RNA products. We determined the timing of telomere replication by creating a single lacO-marked telomere and provide evidence suggesting that transposon expression and recruitment to telomeres is linked to telomere replication. The HeT-A-encoded ORF1p protein is expressed predominantly in S phase, particularly in early S phase. Orf1p binds HeT-A transcripts and forms spherical structures at telomeres undergoing DNA replication. HeT-A sphere formation requires Verrocchio, a putative homolog of the conserved Stn1 telomeric protein. Our results suggest that coupling of telomere elongation and telomere replication is a universal feature, and raise the possibility that transposon recruitment to Drosophila telomeres is mechanistically related to telomerase recruitment in other organisms. Our study also supports a co-adaptive relationship between the Drosophila host and HeT-A mobile elements. PMID:24733842

  5. Comparison of PM2.5 carbon measurement methods in Hong Kong, China.

    PubMed

    Chow, Judith C; Watson, John G; Louie, Peter K K; Chen, L-W Antony; Sin, Della

    2005-09-01

    Samples from Hong Kong, China, were analyzed for organic carbon (OC), elemental carbon (EC), and total carbon (TC) by three thermal protocols (low-temperature IMPROVE and high-temperature STN and NIOSH) and two optical monitoring methods: reflectance and transmittance. Good agreement (+/-10%) for TC among the three protocols was observed for sample loadings of 1-55 microg m(-3). The two protocols using a reflectance pyrolysis correction showed best agreement for EC, with <20% differences found for approximately 80% of the samples. Hong Kong has a large diesel fleet, and for some heavily loaded samples the light transmittance was too low for quantitative detection, resulting in large uncertainties in the OC/EC split based on transmittance. Hong Kong experienced OC levels similar to those at US sites, but has much higher EC concentrations. OC/EC ratios range from 2 to 5 at two US sites and from 0.2 to 1.2 at three Hong Kong sites. PMID:15963372

  6. Anatomy of the ICDS series: A bibliometric analysis

    NASA Astrophysics Data System (ADS)

    Cardona, Manuel; Marxa, Werner

    2007-12-01

    In this article, the proceedings of the International Conferences on Defects in Semiconductors (ICDS) have been analyzed by bibliometric methods. The papers of these conferences have been published as articles in regular journals or special proceedings journals and in books with diverse publishers. The conference name/title changed several times. Many of the proceedings did not appear in the so-called “source journals” covered by the Thomson/ISI citation databases, in particular by the Science Citation Index (SCI). But the number of citations within these source journals can be determined using the Cited Reference Search mode under the Web of Science (WoS) and the SCI offered by the host STN International. The search functions of both systems were needed to select the papers published as different document types and to cover the full time span of the series. The most cited ICDS papers were identified, and the overall numbers of citations as well as the time-dependent impact of these papers, of single conferences, and of the complete series, was established. The complete of citing papers was analyzed with respect to the countries of the citing authors, the citing journals, and the ISI subject categories.

  7. Changes in GABA and glutamate concentrations during memory tasks in patients with Parkinson’s disease undergoing DBS surgery

    PubMed Central

    Buchanan, Robert J.; Darrow, David P.; Meier, Kevin T.; Robinson, Jennifer; Schiehser, Dawn M.; Glahn, David C.; Nadasdy, Zoltan

    2014-01-01

    Until now direct neurochemical measurements during memory tasks have not been accomplished in the human basal ganglia. It has been proposed, based on both functional imaging studies and psychometric testing in normal subjects and in patients with Parkinson’s disease (PD), that the basal ganglia is responsible for the performance of feedback-contingent implicit memory tasks. To measure neurotransmitters, we used in vivo microdialysis during deep brain stimulation (DBS) surgery. We show in the right subthalamic nucleus (STN) of patients with PD a task-dependent change in the concentrations of glutamate and GABA during an implicit memory task relative to baseline, while no difference was found between declarative memory tasks. The five patients studied had a significant decrease in the percent concentration of GABA and glutamate during the performance of the weather prediction task (WPT). We hypothesize, based on current models of basal ganglia function, that this decrease in the concentration is consistent with expected dysfunction in basal ganglia networks in patients with PD. PMID:24639638

  8. In Parkinson's disease pallidal deep brain stimulation speeds up response initiation but has no effect on reactive inhibition.

    PubMed

    Kohl, S; Aggeli, K; Obeso, I; Speekenbrink, M; Limousin, P; Kuhn, J; Jahanshahi, M

    2015-07-01

    The fronto-striatal circuits are considered to mediate inhibitory control over action. The aim of this study was to investigate the contribution of the internal segment of the pallidum (GPi), one of the final output pathways from the basal ganglia to the cortex, in inhibition. We examined the effect of deep brain stimulation (DBS) of the GPi (GPi-DBS) in patients with Parkinson's disease who performed a conditional stop signal task, with DBS on and off. Modulation of GPi activity was associated with significantly faster Go reaction times with DBS on than off, but stop signal reaction times were not altered. Application of the drift diffusion model indicated that GPi-DBS was associated with significantly lower response thresholds compared to GPi-DBS off. However, the drift rate was significantly lower than healthy controls with both GPi-DBS on and off. These results suggest that the GPi plays a crucial role in the 'Go' pathway, perhaps facilitating reaching the required threshold to initiate actions. However, GPi-DBS does not alter the functioning of the indirect 'NoGo' pathway, and other basal ganglia nuclei, such as the STN, may play a greater role in reactive response inhibition and conflict resolution. PMID:25963101

  9. Using on-line altered auditory feedback treating Parkinsonian speech

    NASA Astrophysics Data System (ADS)

    Wang, Emily; Verhagen, Leo; de Vries, Meinou H.

    2005-09-01

    Patients with advanced Parkinson's disease tend to have dysarthric speech that is hesitant, accelerated, and repetitive, and that is often resistant to behavior speech therapy. In this pilot study, the speech disturbances were treated using on-line altered feedbacks (AF) provided by SpeechEasy (SE), an in-the-ear device registered with the FDA for use in humans to treat chronic stuttering. Eight PD patients participated in the study. All had moderate to severe speech disturbances. In addition, two patients had moderate recurring stuttering at the onset of PD after long remission since adolescence, two had bilateral STN DBS, and two bilateral pallidal DBS. An effective combination of delayed auditory feedback and frequency-altered feedback was selected for each subject and provided via SE worn in one ear. All subjects produced speech samples (structured-monologue and reading) under three conditions: baseline, with SE without, and with feedbacks. The speech samples were randomly presented and rated for speech intelligibility goodness using UPDRS-III item 18 and the speaking rate. The results indicted that SpeechEasy is well tolerated and AF can improve speech intelligibility in spontaneous speech. Further investigational use of this device for treating speech disorders in PD is warranted [Work partially supported by Janus Dev. Group, Inc.].

  10. International energy: Research organizations, 1986 - 1990

    NASA Astrophysics Data System (ADS)

    Hendricks, P.; Jordan, S.

    1991-03-01

    The International Energy: Research Organizations publication contains the standardized names of energy research organizations used in energy information databases. Involved in this cooperative task are (1) the technical staff of the USDOE Office of Scientific and Technical Information (OSTI) in cooperation with the member countries of the Energy Technology Data Exchange (ETDE), and (2) the International Nuclear Information System (INIS). This publication identifies current organizations doing research in all energy fields, standardizes the format for recording these organization names in bibliographic citations, assigns a numeric code to facilitate data entry, and identifies report number prefixes assigned by these organizations. These research organization names may be used in searching the databases Energy Science and Technology on DIALOG and Energy on STN International. These organization names are also used in USDOE databases on the Integrated Technical Information System. Research organizations active in the past five years, as indicated by database records, were identified to form this publication. This directory includes approximately 34,000 organizations that reported energy-related literature from 1986 to 1990 and updates the DOE Energy Data Base: Corporate Author Entries.

  11. Neural substrates underlying effort, time, and risk-based decision making in motivated behavior.

    PubMed

    Bailey, Matthew R; Simpson, Eleanor H; Balsam, Peter D

    2016-09-01

    All mobile organisms rely on adaptive motivated behavior to overcome the challenges of living in an environment in which essential resources may be limited. A variety of influences ranging from an organism's environment, experiential history, and physiological state all influence a cost-benefit analysis which allows motivation to energize behavior and direct it toward specific goals. Here we review the substantial amount of research aimed at discovering the interconnected neural circuits which allow organisms to carry-out the cost-benefit computations which allow them to behave in adaptive ways. We specifically focus on how the brain deals with different types of costs, including effort requirements, delays to reward and payoff riskiness. An examination of this broad literature highlights the importance of the extended neural circuits which enable organisms to make decisions about these different types of costs. This involves Cortical Structures, including the Anterior Cingulate Cortex (ACC), the Orbital Frontal Cortex (OFC), the Infralimbic Cortex (IL), and prelimbic Cortex (PL), as well as the Baso-Lateral Amygdala (BLA), the Nucleus Accumbens (NAcc), the Ventral Pallidal (VP), the Sub Thalamic Nucleus (STN) among others. Some regions are involved in multiple aspects of cost-benefit computations while the involvement of other regions is restricted to information relating to specific types of costs. PMID:27427327