Sample records for well stimulation

  1. Geothermal Reservoir Well Stimulation Program: technology transfer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1980-05-01

    Each of the following types of well stimulation techniques are summarized and explained: hydraulic fracturing; thermal; mechanical, jetting, and drainhole drilling; explosive and implosive; and injection methods. Current stimulation techniques, stimulation techniques for geothermal wells, areas of needed investigation, and engineering calculations for various techniques. (MHR)

  2. An Independent Scientific Assessment of Well Stimulation in California Volume I

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jane C.S. Long; Laura C. Feinstein; Birkholzer, Jens

    In 2013, the California Legislature passed Senate Bill 4 (SB 4), setting the framework for regulation of well stimulation technologies in California, including hydraulic fracturing. SB 4 also requires the California Natural Resources Agency to conduct an independent scientific study of well stimulation technologies in California to assess current and potential future practices, including the likelihood that well stimulation technologies could enable extensive new petroleum production in the state, evaluate the impacts of well stimulation technologies and the gaps in data that preclude this understanding, identify risks associated with current practices, and identify alternative practices which might limit these risks.more » The study is issued in three volumes. This document, Volume I, provides the factual basis describing well stimulation technologies, how and where operators deploy these technologies for oil and gas production in California, and where they might enable production in the future. Volume II discusses how well stimulation affects water, the atmosphere, seismic activity, wildlife and vegetation, traffic, light and noise levels; it will also explore human health hazards, and identify data gaps and alternative practices. Volume III presents case studies to assess environmental issues and qualitative« less

  3. Impact to Underground Sources of Drinking Water and Domestic Wells from Production Well Stimulation and Completion Practices in the Pavillion, Wyoming, Field.

    PubMed

    DiGiulio, Dominic C; Jackson, Robert B

    2016-04-19

    A comprehensive analysis of all publicly available data and reports was conducted to evaluate impact to Underground Sources of Drinking Water (USDWs) as a result of acid stimulation and hydraulic fracturing in the Pavillion, WY, Field. Although injection of stimulation fluids into USDWs in the Pavillion Field was documented by EPA, potential impact to USDWs at the depths of stimulation as a result of this activity was not previously evaluated. Concentrations of major ions in produced water samples outside expected levels in the Wind River Formation, leakoff of stimulation fluids into formation media, and likely loss of zonal isolation during stimulation at several production wells, indicates that impact to USDWs has occurred. Detection of organic compounds used for well stimulation in samples from two monitoring wells installed by EPA, plus anomalies in major ion concentrations in water from one of these monitoring wells, provide additional evidence of impact to USDWs and indicate upward solute migration to depths of current groundwater use. Detections of diesel range organics and other organic compounds in domestic wells <600 m from unlined pits used prior to the mid-1990s to dispose diesel-fuel based drilling mud and production fluids suggest impact to domestic wells as a result of legacy pit disposal practices.

  4. Newberry Well 55-29 Stimulation Data

    DOE Data Explorer

    Trenton T. Cladouhos

    2012-12-08

    The Newberry Volcano EGS Demonstration in central Oregon, a 3 year project started in 2010, tests recent technological advances designed to reduce the cost of power generated by EGS in a hot, dry well (NWG 55-29) drilled in 2008. First, the stimulation pumps used were designed to run for weeks and deliver large volumes of water at moderate well-head pressure. Second, to stimulate multiple zones, AltaRock developed thermo-degradable zonal isolation materials (TZIMs) to seal off fractures in a geothermal well to stimulate secondary and tertiary fracture zones. The TZIMs degrade within weeks, resulting in an optimized injection/ production profile of the entire well. Third, the project followed a project-specific Induced Seismicity Mitigation Plan (ISMP) to evaluate, monitor for, and mitigate felt induced seismicity. Stimulation started October 17, 2012 and continued for 7 weeks, with over 41,000 m3 of water injected. Two TZIM treatments successfully shifted the depth of stimulation. Injectivity, DTS, and seismic analysis indicate that fracture permeability in well NWG 55-29 was enhanced by two orders of magnitude. This submission includes all of the files and reports associated with the geophysical exploration, stimulation, and monitoring included in the scope of the project.

  5. Stimulated emission in quantum well laser diodes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Blood, P.

    1989-07-03

    We observe that stimulated emission from inhomogeneously pumped quantum well laser diodes is shifted down in energy compared with the subband transition energy. Measured spontaneous emission spectra show that this stimulated emission is due to band-to-band transitions shifted by renormalization at high injected carrier densities, and we suggest that this same mechanism explains reported observations of stimulated emission from inhomogeneously photopumped structures which previously have been interpreted as evidence for longitudinal optic (LO) phonon participation. We show that LO phonon participation cannot account for the photon energy of stimulated emission from conventional homogeneously pumped quantum well laser diodes.

  6. 77 FR 27691 - Oil and Gas; Well Stimulation, Including Hydraulic Fracturing, on Federal and Indian Lands

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ...] RIN 1004-AE26 Oil and Gas; Well Stimulation, Including Hydraulic Fracturing, on Federal and Indian... stimulate production from oil and gas wells, has been a growing practice in recent years. Public awareness... oil and gas resources across the country, sometimes in areas that have not previously experienced...

  7. Newberry Well 55-29 Stimulation Data 2014

    DOE Data Explorer

    Trenton T. Cladouhos

    2015-09-03

    The Newberry Volcano EGS Demonstration in central Oregon, a 5 year project begun in 2010, tests recent technological advances designed to reduce the cost of power generated by EGS in a hot, dry well (NWG 55-29) drilled in 2008. First, the stimulation pumps used were designed to run for weeks and deliver large volumes of water at moderate well-head pressure. Second, to stimulate multiple zones, AltaRock developed thermo-degradable zonal isolation materials (TZIMs) to seal off fractures in a geothermal well to stimulate secondary and tertiary fracture zones. The TZIMs degrade within weeks, resulting in an optimized injection/ production profile of the entire well. Third, the project followed a project-specific Induced Seismicity Mitigation Plan (ISMP) to evaluate, monitor for, and mitigate felt induced seismicity. An initial stimulation was conducted in 2012 and continued for 7 weeks, with over 41,000 m3 of water injected. Further analysis indicated a shallow casing leak and an unstable formation in the open hole. The well was repaired with a shallow casing tieback and perforated liner in the open hole and re-stimulated in 2014. The second stimulation started September 23rd, 2014 and continued for 3 weeks with over 9,500 m3 of water injected. The well was treated with several batches of newly tested TZIM diverter materials and a newly designed Diverter Injection Vessel Assembly (DIVA), which was the main modification to the original injection system design used in 2012. A second round of stimulation that included two perforation shots and additional batches of TZIM was conducted on November 11th, 2014 for 9 days with an additional 4,000 m3 of water injected. The stimulations resulted in a 3-4 fold increase in injectivity, and PTS data indicates partial blocking and creation of flow zones near the bottom of the well.

  8. Cleanup/stimulation of a horizontal wellbore using propellants

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rougeot, J.E.; Lauterbach, K.A.

    1993-01-01

    This report documents the stimulation/cleanup of a horizontal well bore (Wilson 25) using propellants. The Wilson 25 is a Bartlesville Sand well located in the Flatrock Field, Osage County, Oklahoma. The Wilson 25 was drilled to determine if horizontal drilling could be used as a means to economically recover primary oil that had been left in place in a mostly abandoned oil field because of the adverse effects of water coning. Pump testing of the Wilson 25 horizontal well bore before cleanup or stimulation produced 6 barrels of oil and .84 barrels of water per day. The high percentage ofmore » daily oil production to total daily fluid production indicated that the horizontal well bore had accessed potentially economical oil reserves if the fluid production rate could be increased by performing a cleanup/stimulation treatment. Propellants were selected as an inexpensive means to stimulate and cleanup the near well bore area in a uniform manner. The ignition of a propellant creates a large volume of gas which penetrates the formation, creating numerous short cracks through which hydrocarbons can travel into the well bore. More conventional stimulation/cleanup techniques were either significantly more expensive, less likely to treat uniformly, or could not be confined to the near well bore area. Three different propellant torpedo designs were tested with a total of 304' of horizontal well bore being shot and producible. The initial test shot caused 400' of the horizontal well bore to become plugged off, and subsequently it could not be production tested. The second and third test shots were production tested, with the oil production being increased 458% and 349%, respectively, on a per foot basis. The Wilson 25 results indicate that a propellant shot treatment is an economically viable means to cleanup/stimulate a horizontal well bore.« less

  9. Non-intromissive mating stimuli are sufficient to enhance sexual behaviors in ovariectomized female rats.

    PubMed

    Blaustein, Jeffrey D; Farrell, Sara; Ghavami, Gila; Laroche, Julie; Mohan, Govini

    2009-03-01

    When ovariectomized/adrenalectomized female rats, injected with subthreshold doses of estradiol are given copulatory stimulation by a male rat at half hour intervals, the level of lordosis gradually increases over the course of a few hours. We tested the hypothesis that paracopulatory behaviors (behaviors that occur repetitively prior to and between mounts), also generally considered to be heavily dependent on progesterone, are enhanced by this stimulation as well. We have reported previously that the enhancement of copulatory behavior is dependent to a large extent on intromissive stimulation by the male. In the present study, mating stimulation induced high levels of paracopulatory behaviors, as well as lordosis. Surprisingly, though, and in contrast to previous findings, this increase was seen not only in rats receiving intromissive stimulation, but in those receiving non-intromissive stimulation as well. Furthermore, intromissive stimulation induced high levels of rejection behavior. In a subsequent experiment, experimenter-induced, mechanical stimulation increased only rejection behaviors, not copulatory behavior. The results collectively demonstrate that, under the conditions used in these experiments, non-intromissive stimulation is sufficient for inducing both copulatory and paracopulatory behaviors in estradiol-primed rats. However, under the conditions used in these studies, intromissive stimulation increases rejection behaviors.

  10. 18 CFR 270.305 - Determination of tight formation areas.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... pressure, of wells completed for production in such portion of such formation, without stimulation, is not...). Such expected stabilized, pre-stimulation production rate is to be determined through an arithmetic mean averaging of the known stabilized, pre-stimulation production rates obtained from the wells that...

  11. Transcranial magnetic stimulation (TMS) in Attention Deficit Hyperactivity Disorder (ADHD).

    PubMed

    Zaman, Rashid

    2015-09-01

    Attention Deficit Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder, which affects children as well as adults and leads to significant impairment in educational, social and occupational functioning and has associated personal and societal costs. Whilst there are effective medications (mostly stimulants) as well as some psychobehavioural treatments that help alleviate symptoms of ADHD, there is still need to improve our understanding of its neurobiology as well as explore other treatment options. Transcranial Magnetic Stimulation (TMS) and repetitive transcranial magnetic stimulation (rTMS) are safe and non-invasive investigative and therapeutic tools respectively. In this short article, I will explore their potential for improving our understanding of the neurobiology of ADHD as well consider its as a possible treatment option.

  12. Cleanup/stimulation of a horizontal wellbore using propellants. Final report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rougeot, J.E.; Lauterbach, K.A.

    1993-01-01

    This report documents the stimulation/cleanup of a horizontal well bore (Wilson 25) using propellants. The Wilson 25 is a Bartlesville Sand well located in the Flatrock Field, Osage County, Oklahoma. The Wilson 25 was drilled to determine if horizontal drilling could be used as a means to economically recover primary oil that had been left in place in a mostly abandoned oil field because of the adverse effects of water coning. Pump testing of the Wilson 25 horizontal well bore before cleanup or stimulation produced 6 barrels of oil and .84 barrels of water per day. The high percentage ofmore » daily oil production to total daily fluid production indicated that the horizontal well bore had accessed potentially economical oil reserves if the fluid production rate could be increased by performing a cleanup/stimulation treatment. Propellants were selected as an inexpensive means to stimulate and cleanup the near well bore area in a uniform manner. The ignition of a propellant creates a large volume of gas which penetrates the formation, creating numerous short cracks through which hydrocarbons can travel into the well bore. More conventional stimulation/cleanup techniques were either significantly more expensive, less likely to treat uniformly, or could not be confined to the near well bore area. Three different propellant torpedo designs were tested with a total of 304` of horizontal well bore being shot and producible. The initial test shot caused 400` of the horizontal well bore to become plugged off, and subsequently it could not be production tested. The second and third test shots were production tested, with the oil production being increased 458% and 349%, respectively, on a per foot basis. The Wilson 25 results indicate that a propellant shot treatment is an economically viable means to cleanup/stimulate a horizontal well bore.« less

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

    NASA Technical Reports Server (NTRS)

    Andrews, Russell J.

    2003-01-01

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

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

    PubMed

    Andrews, Russell J

    2003-05-01

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

  15. Performance of Surfactant Methyl Ester Sulphonate solution for Oil Well Stimulation in reservoir sandstone TJ Field

    NASA Astrophysics Data System (ADS)

    Eris, F. R.; Hambali, E.; Suryani, A.; Permadi, P.

    2017-05-01

    Asphaltene, paraffin, wax and sludge deposition, emulsion and water blocking are kinds ofprocess that results in a reduction of the fluid flow from the reservoir into formation which causes a decrease of oil wells productivity. Oil well Stimulation can be used as an alternative to solve oil well problems. Oil well stimulation technique requires applying of surfactant. Sodium Methyl Ester Sulphonate (SMES) of palm oil is an anionic surfactant derived from renewable natural resource that environmental friendly is one of potential surfactant types that can be used in oil well stimulation. This study was aimed at formulation SMES as well stimulation agent that can identify phase transitions to phase behavior in a brine-surfactant-oil system and altered the wettability of rock sandstone and limestone. Performance of SMES solution tested by thermal stability test, phase behavioral examination and rocks wettability test. The results showed that SMES solution (SMES 5% + xylene 5% in the diesel with addition of 1% NaCl at TJformation water and SMES 5% + xylene 5% in methyl ester with the addition of NaCl 1% in the TJ formation water) are surfactant that can maintain thermal stability, can mostly altered the wettability toward water-wet in sandstone reservoir, TJ Field.

  16. Impurity-assisted terahertz photoluminescence in quantum wells under conditions of interband stimulated emission

    NASA Astrophysics Data System (ADS)

    Makhov, I. S.; Panevin, V. Yu; Firsov, D. A.; Vorobjev, L. E.; Sofronov, A. N.; Vinnichenko, M. Ya; Maleev, N. A.; Vasil'ev, A. P.

    2018-03-01

    Terahertz and near-infrared photoluminescence under conditions of interband stimulated emission are studied in n-GaAs/AlGaAs quantum well laser structure. The observed terahertz emission is related to the optical transitions of nonequilibrium electrons from the first electron subband and excited donor states to donor ground states in quantum wells. The opportunity to increase the intensity of impurity-assisted terahertz emission due to interband stimulated emission with the participation of impurity centres is demonstrated.

  17. Deep Stimulation at Newberry Volcano EGS Demonstration

    NASA Astrophysics Data System (ADS)

    Grasso, K.; Cladouhos, T. T.; Petty, S.; Garrison, G. H.; Nordin, Y.; Uddenberg, M.; Swyer, M.

    2014-12-01

    The Newberry Volcano EGS Demonstration is a 5 year field project designed to demonstrate recent technological advances for engineered geothermal systems (EGS) development. Advances in reservoir stimulation, diverter, and monitoring are being tested in a hot (>300 C), dry well (NWG 55-29) drilled in 2008. These technologies could reduce the cost of electrical power generation. The project began in 2010 with two years of permitting, technical planning, and development of a project-specific Induced Seismicity Mitigation Plan (ISMP), and is funded in part by the Department of Energy. In 2012, the well was hydraulically stimulated with water at pressures below the principle stress for 7 weeks, resulting in hydroshearing. The depth of stimulation was successfully shifted by injection of two pills of Thermally-degradable Zonal Isolation Materials (TZIMs). Injectivity changes, thermal profiles and seismicity indicate that fracture permeability in well NWG 55-29 was enhanced during stimulation. This work successfully demonstrated the viability of large-volume (40,000 m3), low-pressure stimulation coupled with non-mechanical diverter technology, and microseismic monitoring for reservoir mapping. Further analysis and field testing in 2013 indicates further stimulation will be required in order to develop an economically viable reservoir, and is scheduled in 2014. The 2014 stimulation will use improved stimulation and monitoring equipment, better knowledge based on 2012 outcomes, and create a deep EGS reservoir in the hottest part of the wellbore.

  18. Theme 3: Mechanical Integrity - Pre & Post Well Integrity Methods for Hydraulically Fractured/Stimulated Wells

    EPA Pesticide Factsheets

    This presentation looks into wellbore design and monitoring techniques that are critical in assuring that wellbore integrity is maintained in conjunction with hydraulic fracturing/stimulation completion practices.

  19. Klamath Falls: High-Power Acoustic Well Stimulation Technology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Black, Brian

    Acoustic well stimulation (AWS) technology uses high-power sonic waves from specific frequency spectra in an attempt to stimulate production in a damaged or low-production wellbore. AWS technology is one of the most promising technologies in the oil and gas industry, but it has proven difficult for the industry to develop an effective downhole prototype. This collaboration between Klamath Falls Inc. and the Rocky Mountain Oilfield Testing Center (RMOTC) included a series of tests using high-power ultrasonic tools to stimulate oil and gas production. Phase I testing was designed and implemented to verify tool functionality, power requirements, and capacity of high-powermore » AWS tools. The purpose of Phase II testing was to validate the production response of wells with marginal production rates to AWS stimulation and to capture and identify any changes in the downhole environment after tool deployment. This final report presents methodology and results.« less

  20. Geomechanics of Hydraulic Stimulation in Geothermal Systems: Designing and Implementing a Successful Enhanced Geothermal System at Desert Peak, Nevada

    NASA Astrophysics Data System (ADS)

    Hickman, S. H.; Davatzes, N. C.; Zemach, E.; Chabora, E.; Lutz, S.; Rose, P.; Majer, E. L.; Robertson-Tait, A.

    2013-12-01

    Creation of an Enhanced Geothermal System (EGS) in hot but low-permeability rocks involves hydraulic stimulation of fracture permeability to develop a complex heat exchange system with low hydraulic impedance. An integrated study of stress, fractures and rock mechanical properties was conducted to develop the geomechanical framework for a multi-stage EGS stimulation in Desert Peak well 27-15, located at the low-permeability margins of an active geothermal field. The stimulation targeted silicified tuffs and metamorphosed mudstones at depths of 0.9 to 1.8 km and temperatures ~180 to 210° C. Drilling-induced tensile fractures in image logs from well 27-15 show that the least horizontal principal stress (Shmin) is consistent with normal faulting on ESE- and WNW-dipping fractures mapped at the surface and seen in the image logs. A hydraulic fracturing stress measurement indicates that the magnitude of Shmin at ~0.93 km depth is 0.61 of the calculated vertical stress. Coulomb failure calculations using these stresses together with measurements of friction and permeability on core predict that dilatant shear failure should be induced on pre-existing conjugate normal faults once pore pressures are increased ~2.5 MPa or more above ambient values, generating a zone of enhanced permeability elongated in the direction toward active geothermal wells ~0.5 km to the SSW. Hydraulic stimulation of well 27-15 began in September 2010 by injecting water into the open-hole interval between the casing shoe at 0.9 km depth and a temporary cement plug at 1.1 km. Stimulation was monitored by combined surface and down-hole seismic monitoring, inter-well tracer testing and periodic pressure-temperature-flowmeter logging. An initial stage of low-pressure (shear) stimulation was conducted for ~100 days at a series of pressure steps Shmin and injection rates up to 2800 l/min, resulting in an additional 6-fold increase in injectivity. Numerous microearthquakes induced during this high-pressure stage along with tracer testing demonstrated growth of the stimulated volume and establishment of a strong hydrologic connection between well 27-15 and geothermal production wells to the SSW. After drilling out the cement plug and opening up the stimulation zone to the total depth of the well (1.8 km), additional stages of low- and high-pressure stimulation were carried out in early 2013. This full-hole stimulation was characterized by continued growth of the microseismic cloud in the NNE - SSW direction and strong tracer returns to the main geothermal field. A cumulative 175-fold injectivity gain was achieved in well 27-15 over the entire EGS project, which exceeded project goals. The Desert Peak geomechanical model predicted both the approximate initiation criteria and directional characteristics of the injection-induced shear and tensile failure and resulting permeability gains that led to success of this EGS project.

  1. Seismic velocity variations at the EGS geothermal reservoir of Soultz-Sous-Forêts (France): Some observations for understanding stress regime changes during hydraulic stimulations using 4D tomography

    NASA Astrophysics Data System (ADS)

    Calo, M.; Dorbath, C.; Cornet, F.; Cuenot, N.

    2011-12-01

    During the last decade three deep wells (GPK2, GPK3, and GPK4) were drilled to a depth of about 5000 m at the Enhanced Geothermal System (EGS) site of Soultz-sous-Forêts (Alsace, France). All the wells were stimulated through high-pressure hydraulic injections. Several thousands of micro-earthquakes with Duration Magnitude ranging from -0.9 to 2.9 were produced. The induced earthquakes were located by downhole and surface seismic stations. The wells behaved differently during and after the stimulations, as shown by several authors. We present here a comparison between new 4D seismic tomographies performed for the above mentioned stimulation tests. The velocity models have been obtained using the Double-Difference tomographic method (Zhang and Thurber 2003) and have been further improved with the post-processing WAM technique (Calo' et al., 2009, 2011). For each stimulation test, the subsetting of the data was performed by taking into account injection parameters (the injected flow rate and the wellhead pressure). In this work we discuss some important steps observed during and after the injections. A first observation is that low velocity anomalies were centered around the wells when stimulations started and then disappeared just after strong changes in the injected flow rate. We interpret these changes in seismic properties as transient changes in the stress regime during the stimulations. Furthermore, as shown by the seismic velocity models, pre-existing fracture network played a fundamental role on the intensity and distribution of the observed velocity anomalies. Indeed we observe that low velocity anomalies are much less evident and moved away from the well when documented large pre-exiting fractures cross the openhole part of the well. In particular, we observed this pattern for the models calculated with the data of the GPK3 stimulation. Thanks to the improvement and the reliability of these new velocity models, new discussions about the mechanical processes that occurred during the stimulations has been opened.

  2. Ten minutes of 1 mA transcranial direct current stimulation was well tolerated by children and adolescents: Self-reports and resting state EEG analysis.

    PubMed

    Moliadze, Vera; Andreas, Saskia; Lyzhko, Ekaterina; Schmanke, Till; Gurashvili, Tea; Freitag, Christine M; Siniatchkin, Michael

    2015-10-01

    Transcranial direct current stimulation (tDCS) is a promising and well-tolerated method of non-invasive brain stimulation, by which cortical excitability can be modulated. However, the effects of tDCS on the developing brain are still unknown, and knowledge about its tolerability in children and adolescents is still lacking. Safety and tolerability of tDCS was assessed in children and adolescents by self-reports and spectral characteristics of electroencephalogram (EEG) recordings. Nineteen typically developing children and adolescents aged 11-16 years participated in the study. Anodal and cathodal tDCS as well as sham stimulation were applied for a duration of 10 min over the left primary motor cortex (M1), each with an intensity of 1 mA. Subjects were unable to identify whether they had received active or sham stimulation, and all participants tolerated the stimulation well with a low rate of adverse events in both groups and no serious adverse events. No pathological oscillations, in particular, no markers of epileptiform activity after 1mA tDCS were detected in any of the EEG analyses. In summary, our study demonstrates that tDCS with 1mA intensity over 10 min is well tolerated, and thus may be used as an experimental and treatment method in the pediatric population. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Creation of an Enhanced Geothermal System through Hydraulic and Thermal Stimulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rose, Peter Eugene

    2013-04-15

    This report describes a 10-year DOE-funded project to design, characterize and create an Engineered Geothermal System (EGS) through a combination of hydraulic, thermal and chemical stimulation techniques. Volume 1 describes a four-year Phase 1 campaign, which focused on the east compartment of the Coso geothermal field. It includes a description of the geomechanical, geophysical, hydraulic, and geochemical studies that were conducted to characterize the reservoir in anticipation of the hydraulic stimulation experiment. Phase 1 ended prematurely when the drill bit intersected a very permeable fault zone during the redrilling of target stimulation well 34-9RD2. A hydraulic stimulation was inadvertently achieved,more » however, since the flow of drill mud from the well into the formation created an earthquake swarm near the wellbore that was recorded, located, analyzed and interpreted by project seismologists. Upon completion of Phase 1, the project shifted focus to a new target well, which was located within the southwest compartment of the Coso geothermal field. Volume 2 describes the Phase 2 studies on the geomechanical, geophysical, hydraulic, and geochemical aspects of the reservoir in and around target-stimulation well 46A-19RD, which is the deepest and hottest well ever drilled at Coso. Its total measured depth exceeding 12,000 ft. It spite of its great depth, this well is largely impermeable below a depth of about 9,000 ft, thus providing an excellent target for stimulation. In order to prepare 46A-19RD for stimulation, however, it was necessary to pull the slotted liner. This proved to be unachievable under the budget allocated by the Coso Operating Company partners, and this aspect of the project was abandoned, ending the program at Coso. The program then shifted to the EGS project at Desert Peak, which had a goal similar to the one at Coso of creating an EGS on the periphery of an existing geothermal reservoir. Volume 3 describes the activities that the Coso team contributed to the Desert Peak project, focusing largely on a geomechanical investigation of the Desert Peak reservoir, tracer testing between injectors 21-2 and 22-22 and the field's main producers, and the chemical stimulation of target well 27-15.« less

  4. Creation of an Enhanced Geothermal System through Hydraulic and Thermal Stimulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rose, Peter Eugene

    This report describes a 10-year DOE-funded project to design, characterize and create an Engineered Geothermal System (EGS) through a combination of hydraulic, thermal and chemical stimulation techniques. Volume 1 describes a four-year Phase 1 campaign, which focused on the east compartment of the Coso geothermal field. It includes a description of the geomechanical, geophysical, hydraulic, and geochemical studies that were conducted to characterize the reservoir in anticipation of the hydraulic stimulation experiment. Phase 1 ended prematurely when the drill bit intersected a very permeable fault zone during the redrilling of target stimulation well 34-9RD2. A hydraulic stimulation was inadvertently achieved,more » however, since the flow of drill mud from the well into the formation created an earthquake swarm near the wellbore that was recorded, located, analyzed and interpreted by project seismologists. Upon completion of Phase 1, the project shifted focus to a new target well, which was located within the southwest compartment of the Coso geothermal field. Volume 2 describes the Phase 2 studies on the geomechanical, geophysical, hydraulic, and geochemical aspects of the reservoir in and around target-stimulation well 46A-19RD, which is the deepest and hottest well ever drilled at Coso. Its total measured depth exceeding 12,000 ft. It spite of its great depth, this well is largely impermeable below a depth of about 9,000 ft, thus providing an excellent target for stimulation. In order to prepare 46A-19RD for stimulation, however, it was necessary to pull the slotted liner. This proved to be unachievable under the budget allocated by the Coso Operating Company partners, and this aspect of the project was abandoned, ending the program at Coso. The program then shifted to the EGS project at Desert Peak, which had a goal similar to the one at Coso of creating an EGS on the periphery of an existing geothermal reservoir. Volume 3 describes the activities that the Coso team contributed to the Desert Peak project, focusing largely on a geomechanical investigation of the Desert Peak reservoir, tracer testing between injectors 21-2 and 22-22 and the field's main producers, and the chemical stimulation of target well 27-15.« less

  5. Microseismic monitoring during Hydraulic stimulation in Pohang (Korea) for EGS pilot project

    NASA Astrophysics Data System (ADS)

    Kim, M.; Yoon, B.; Lee, C.; Park, K. G.; Yoon, W. S.; Song, Y.; Lee, T. J.

    2017-12-01

    Since the geothermal anomaly in the Pohang area has been reported in 1960s, various geological and geophysical surveys have been conducted by Korea Institute of Geoscience and Mineral Resources (KIGAM) including gravity, seismic, airborne magnetic and magneto-telluric surveys. Based on these explorations, the Enhanced Geothermal System (EGS) pilot project has been carried out in Pohang since the end of 2010. One vertical well (PX-2, MD 4,348 m) and one deviated well (PX-1, MD 4,362 m) have been drilled in granite rock for the EGS. Microseismic (MS) monitoring is the best way to understand how the fracture grows during the hydraulic stimulation. KIGAM has set up 9 shallow borehole stations (100-130 m), 4 surface stations and two borehole geophones (1,350 and 1,550 m deep) within 5 km radius from injection well for the MS monitoring during hydraulic stimulation. The first hydraulic stimulation started on January 29th to February 20th, 2016 at PX-2 and the second stimulation was conducted in PX-1 from December 15th, 2016 to January 11th, 2017. Several hundreds of MS events occurred during stimulation and the biggest event was ML 2.3 during the shut in period of the second stimulation. Based on the results of the MS monitoring, a soft stimulation is scheduled at PX-1 in cooperation with one of the European Horizon2020 project, DESTRESS (Demonstration of soft stimulation treatments of geothermal reservoirs). We will present the MS monitoring system in Pohang and the data of the stimulation with the MS monitoring results. We believe that the data from Pohang will improve the understanding of seismic behavior due to hydraulic stimulation in crystalline rocks and also will contribute to success of the Pohang EGS project.

  6. Personal and perceived peer use and attitudes towards the use of nonmedical prescription stimulants to improve academic performance among university students in seven European countries.

    PubMed

    Helmer, S M; Pischke, C R; Van Hal, G; Vriesacker, B; Dempsey, R C; Akvardar, Y; Guillen-Grima, F; Salonna, F; Stock, C; Zeeb, H

    2016-11-01

    Overestimations of non-prescribed stimulant use of peers are well documented in the USA and have also been identified as predictive of personal stimulant consumption. This study aimed to examine whether overestimations of peer use and approval of the use are associated with personal use and attitude towards the use of non-prescribed stimulants among European university students. The EU funded 'Social Norms Intervention for the prevention of Polydrug usE (SNIPE)' study was conducted in seven European countries. In a web-based questionnaire, 4482 students were asked about their personal use and their attitude towards non-prescribed stimulant use, as well as the perceived peer use and peer attitude. 59% of students thought that the majority of their peers used non-prescribed stimulants more frequently than themselves, and only 4% thought that the use of the majority was lower than their personal use. The perception that the majority of peers had used non-prescribed stimulants at least once was significantly associated with higher odds for personal use of non-prescribed stimulants (OR: 3.30, 95% CI: 2.32-4.71). In addition, the perception that the majority of peers approved of the non-prescribed use of stimulants was associated with a 4.03 (95% CI: 3.35-4.84) times higher likelihood for personal approval. European university students generally perceived the non-prescribed use of stimulants of peers to be higher than their personal use. This perception, as well as a perception of higher approval in the peer group, was associated with a higher likelihood of personal non-prescribed stimulant medication use and approval. Copyright © 2016. Published by Elsevier Ireland Ltd.

  7. The coso EGS project - Recent developments

    USGS Publications Warehouse

    Rose, P.; Sheridan, J.; McCulloch, J.; Moore, J.N.; Kovac, K.; Weidler, R.; Hickman, S.

    2005-01-01

    An Enhanced Geothermal System (EGS) field experiment will be conducted to hydraulically stimulate injection well 34-9RD2, located on the east flank of the Coso geothermal reservoir, with the objective of increasing the injection rate of this well to 750 gpm at a wellhead pressure of 100 psi or less. The stimulation of this well is expected to create hydraulic communication with the recently drilled production well 38C-9, which is directly south of 34-9RD2. We summarize the results of fracture and stress analyses based upon borehole image logs of 38C-9; petrographic and petrologic analyses of cuttings from both the injection well 34-9RD2 and the production well 38C-9; and plans for the redrilling and stimulation of 34-9RD2.

  8. The Coso EGS project - Recent developments

    USGS Publications Warehouse

    Rose, P.; Sheridan, J.; McCulloch, J.; Moore, J.N.; Kovac, K.; Spielman, P.; Weidler, R.; Hickman, S.

    2004-01-01

    An Engineered Geothermal System (EGS) field experiment will be conducted to hydraulically stimulate injection well 34-9RD2, located on the east flank of the Coso geothermal reservoir, with the objective of increasing the injection rate of this well to 750 gpm at a wellhead pressure of 100 psi or less. The stimulation of this well is expected to create hydraulic communication with the recently drilled production well 38C-9, which is directly south of 34-9RD2. We summarize the results of fracture and stress analyses based upon borehole image logs of 38C-9; petrographic and petrologic analyses of cuttings from both the injection well 34-9RD2 and the production well 38C-9; and plans for the redrilling and stimulation of 34-9RD2.

  9. Background matters: Minor vibratory stimulation during motor skill acquisition selectively reduces off-line memory consolidation.

    PubMed

    Korman, Maria; Herling, Zohar; Levy, Ishay; Egbarieh, Nebal; Engel-Yeger, Batya; Karni, Avi

    2017-04-01

    Although a ubiquitous situation, it is not clear how effective is a learning experience when task-irrelevant, sensory noise occurs in the background. Here, young adults were trained on the finger opposition sequence task, in a well-established training and testing protocol affording measures for online as well as off-line learning. During the training session, one group experienced a minor background vibratory stimulation to the trunk by the means of vibrating cushion, while the second group experienced recorded sound vibrations. A control group was trained with no extra sensory stimulation. Sensory stimulation during training had no effect on the online within-session gains, but dampened the expression of the off-line, consolidation phase, gains in the two sensory stimulation groups. These results suggest that background sensory stimulation can selectively modify off-line, procedural memory consolidation processes, despite well-preserved on-line learning. Classical studies have shown that neural plasticity in sensory systems is modulated by motor input. The current results extend this notion and suggest that some types of task-irrelevant sensory stimulation, concurrent with motor training, may constitute a 'gating' factor - modulating the triggering of long-term procedural memory consolidation processes. Thus, vibratory stimulation may be considered as a behavioral counterpart of pharmacological interventions that do not interfere with short term neural plasticity but block long-term plasticity. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed

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

    2015-07-01

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

  11. High frequency oscillations evoked by peripheral magnetic stimulation.

    PubMed

    Biller, S; Simon, L; Fiedler, P; Strohmeier, D; Haueisen, J

    2011-01-01

    The analysis of somatosensory evoked potentials (SEP) and / or fields (SEF) is a well-established and important tool for investigating the functioning of the peripheral and central human nervous system. A standard technique to evoke SEPs / SEFs is the stimulation of the median nerve by using a bipolar electrical stimulus. We aim at an alternative stimulation technique enabling stimulation of deep nerve structures while reducing patient stress and error susceptibility. In the current study, we apply a commercial transcranial magnetic stimulation system for peripheral magnetic stimulation of the median nerve. We compare the results of simultaneously recorded EEG signals to prove applicability of our technique to evoke SEPs including low frequency components (LFC) as well as high frequency oscillations (HFO). Therefore, we compare amplitude, latency and time-frequency characteristics of the SEP of 14 healthy volunteers after electric and magnetic stimulation. Both low frequency components and high frequency oscillations were detected. The HFOs were superimposed onto the primary cortical response N20. Statistical analysis revealed significantly lower amplitudes and increased latencies for LFC and HFO components after magnetic stimulation. The differences indicate the inability of magnetic stimulation to elicit supramaximal responses. A psycho-perceptual evaluation showed that magnetic stimulation was less unpleasant for 12 out of the 14 volunteers. In conclusion, we showed that LFC and HFO components related to median nerve stimulation can be evoked by peripheral magnetic stimulation.

  12. Modeling of Oil Output Intensification in Porous Permeable Medium at Acoustical Stimulation from a Well

    NASA Astrophysics Data System (ADS)

    Maksimov, German A.; Radchenko, Aleksei V.

    2006-05-01

    Acoustical stimulation (AS) of oil production rate from a well is perspective technology for oil industry but physical mechanisms of acoustical action are not understood clear due to complex character of the phenomena. In practice the role of these mechanisms is appeared non-directly in the form of additional oil output. Thus the validity examination of any physical model has to be carried out as with account of mechanism of acoustic action by itself as well with account of previous and consequent stages dealt with fluid filtration into a well. The advanced model of physical processes taking place at acoustical stimulation is considered in the framework of heating mechanism of acoustical action, but for two-component fluid in porous permeable media. The porous fluid is considered as consisted of light and heavy hydrocarbonaceous phases, which are in a thermodynamic equilibrium. Filtration or acoustical stimulation can change equilibrium balance between phases so the heavy phase can be precipitated on pores walls or dissolved. The set of acoustical, heat and filtration tasks were solved numerically to describe oil output from a well — the final result of acoustical action, which can be compared with experimental data. It is shown that the suggested numerical model allows us to reproduce the basic features of fluid filtration in a well before during and after acoustical stimulation.

  13. Groundwater Monitoring and Engineered Geothermal Systems: The Newberry EGS Demonstration

    NASA Astrophysics Data System (ADS)

    Grasso, K.; Cladouhos, T. T.; Garrison, G.

    2013-12-01

    Engineered Geothermal Systems (EGS) represent the next generation of geothermal energy development. Stimulation of multiple zones within a single geothermal reservoir could significantly reduce the cost of geothermal energy production. Newberry Volcano in central Oregon represents an ideal location for EGS research and development. As such, the goals of the Newberry EGS Demonstration, operated by AltaRock Energy, Inc., include stimulation of a multiple-zone EGS reservoir, testing of single-well tracers and a demonstration of EGS reservoir viability through flow-back and circulation tests. A shallow, local aquifer supplied the approximately 41,630 m3 (11 million gals) of water used during stimulation of NWG 55-29, a deep geothermal well on the western flank of Newberry Volcano. Protection of the local aquifer is of primary importance to both the Newberry EGS Demonstration and the public. As part of the Demonstration, AltaRock Energy, Inc. has developed and implemented a groundwater monitoring plan to characterize the geochemistry of the local aquifer before, during and after stimulation. Background geochemical conditions were established prior to stimulation of NWG 55-29, which was completed in 2012. Nine sites were chosen for groundwater monitoring. These include the water supply well used during stimulation of NWG 55-29, three monitoring wells, three domestic water wells and two hot seeps located in the Newberry Caldera. Together, these nine monitoring sites represent up-, down- and cross-gradient locations. Groundwater samples are analyzed for 25 chemical constituents, stable isotopes, and geothermal tracers used during stimulation. In addition, water level data is collected at three monitoring sites in order to better characterize the effects of stimulation on the shallow aquifer. To date, no significant geochemical changes and no geothermal tracers have been detected in groundwater samples from these monitoring sites. The Newberry EGS Demonstration groundwater monitoring program is currently on-going.

  14. Exploring the efficacy of a 5-day course of transcranial direct current stimulation (TDCS) on depression and memory function in patients with well-controlled temporal lobe epilepsy.

    PubMed

    Liu, Anli; Bryant, Andrew; Jefferson, Ashlie; Friedman, Daniel; Minhas, Preet; Barnard, Sarah; Barr, William; Thesen, Thomas; O'Connor, Margaret; Shafi, Mouhsin; Herman, Susan; Devinsky, Orrin; Pascual-Leone, Alvaro; Schachter, Steven

    2016-02-01

    Depression and memory dysfunction significantly impact the quality of life of patients with epilepsy. Current therapies for these cognitive and psychiatric comorbidities are limited. We explored the efficacy and safety of transcranial direct current stimulation (TDCS) for treating depression and memory dysfunction in patients with temporal lobe epilepsy (TLE). Thirty-seven (37) adults with well-controlled TLE were enrolled in a double-blinded, sham-controlled, randomized, parallel-group study of 5 days of fixed-dose (2 mA, 20 min) TDCS. Subjects were randomized to receive either real or sham TDCS, both delivered over the left dorsolateral prefrontal cortex. Patients received neuropsychological testing and a 20-minute scalp EEG at baseline immediately after the TDCS course and at 2- and 4-week follow-up. There was improvement in depression scores immediately after real TDCS, but not sham TDCS, as measured by changes in the Beck Depression Inventory (BDI change: -1.68 vs. 1.27, p<0.05) and NDDI-E (-0.83 vs. 0.9091, p=0.05). There was no difference between the groups at the 2- or 4-week follow-up. There was no effect on delayed or working memory performance. Transcranial direct current stimulation was well-tolerated and did not increase seizure frequency or interictal discharge frequency. Transcranial direct current stimulation induced an increase in delta frequency band power over the frontal region and delta, alpha, and theta band power in the occipital region after real stimulation compared to sham stimulation, although the difference did not reach statistical significance. This study provides evidence for the use of TDCS as a safe and well-tolerated nonpharmacologic approach to improving depressive symptoms in patients with well-controlled TLE. However, there were no changes in memory function immediately following or persisting after a stimulation course. Further studies may determine optimal stimulation parameters for maximal mood benefit. Copyright © 2015. Published by Elsevier Inc.

  15. The role of aromatase inhibitors in ameliorating deleterious effects of ovarian stimulation on outcome of infertility treatment

    PubMed Central

    Mitwally, Mohamed FM; Casper, Robert F; Diamond, Michael P

    2005-01-01

    Clinical utilization of ovulation stimulation to facilitate the ability of a couple to conceive has not only provided a valuable therapeutic approach, but has also yielded extensive information on the physiology of ovarian follicular recruitment, endometrial receptivity and early embryo competency. One of the consequences of the use of fertility enhancing agents for ovarian stimulation has been the creation of a hyperestrogenic state, which may influence each of these parameters. Use of aromatase inhibitors reduces hyperestrogenism inevitably attained during ovarian stimulation. In addition, the adjunct use of aromatase inhibitors during ovarian stimulation reduces amount of gonadotropins required for optimum stimulation. The unique approach of reducing hyperestrogenism, as well as lowering amount of gonadotropins without affecting the number of mature ovarian follicles is an exciting strategy that could result in improvement in the treatment outcome by ameliorating the deleterious effects of the ovarian stimulation on follicular development, endometrial receptivity, as well as oocyte and embryo quality. PMID:16202169

  16. Numerical modeling of injection, stress and permeability enhancement during shear stimulation at the Desert Peak Enhanced Geothermal System

    USGS Publications Warehouse

    Dempsey, David; Kelkar, Sharad; Davatzes, Nick; Hickman, Stephen H.; Moos, Daniel

    2015-01-01

    Creation of an Enhanced Geothermal System relies on stimulation of fracture permeability through self-propping shear failure that creates a complex fracture network with high surface area for efficient heat transfer. In 2010, shear stimulation was carried out in well 27-15 at Desert Peak geothermal field, Nevada, by injecting cold water at pressure less than the minimum principal stress. An order-of-magnitude improvement in well injectivity was recorded. Here, we describe a numerical model that accounts for injection-induced stress changes and permeability enhancement during this stimulation. In a two-part study, we use the coupled thermo-hydrological-mechanical simulator FEHM to: (i) construct a wellbore model for non-steady bottom-hole temperature and pressure conditions during the injection, and (ii) apply these pressures and temperatures as a source term in a numerical model of the stimulation. In this model, a Mohr-Coulomb failure criterion and empirical fracture permeability is developed to describe permeability evolution of the fractured rock. The numerical model is calibrated using laboratory measurements of material properties on representative core samples and wellhead records of injection pressure and mass flow during the shear stimulation. The model captures both the absence of stimulation at low wellhead pressure (WHP ≤1.7 and ≤2.4 MPa) as well as the timing and magnitude of injectivity rise at medium WHP (3.1 MPa). Results indicate that thermoelastic effects near the wellbore and the associated non-local stresses further from the well combine to propagate a failure front away from the injection well. Elevated WHP promotes failure, increases the injection rate, and cools the wellbore; however, as the overpressure drops off with distance, thermal and non-local stresses play an ongoing role in promoting shear failure at increasing distance from the well.

  17. Spatial Risk Analysis of Hydraulic Fracturing near Abandoned and Converted Oil and Gas Wells.

    PubMed

    Brownlow, Joshua W; Yelderman, Joe C; James, Scott C

    2017-03-01

    Interaction between hydraulically generated fractures and existing wells (frac hits) could represent a potential risk to groundwater. In particular, frac hits on abandoned oil and gas wells could lead to upward leakage into overlying aquifers, provided migration pathways are present along the abandoned well. However, potential risk to groundwater is relatively unknown because few studies have investigated the probability of frac hits on abandoned wells. In this study, actual numbers of frac hits were not determined. Rather, the probability for abandoned wells to intersect hypothetical stimulated reservoir sizes of horizontal wells was investigated. Well data were compiled and analyzed for location and reservoir information, and sensitivity analyses were conducted by varying assumed sizes of stimulated reservoirs. This study used public and industry data for the Eagle Ford Shale play in south Texas, with specific attention paid to abandoned oil and gas wells converted into water wells (converted wells). In counties with Eagle Ford Shale activity, well-data analysis identified 55,720 abandoned wells with a median age of 1983, and 2400 converted wells with a median age of 1954. The most aggressive scenario resulted in 823 abandoned wells and 184 converted wells intersecting the largest assumed stimulated reservoir size. Analysis showed abandoned wells have the potential to be intersected by multiple stimulated reservoirs, and risks for intersection would increase if currently permitted horizontal wells in the Eagle Ford Shale are actually completed. Results underscore the need to evaluate historical oil and gas activities in areas with modern unconventional oil and gas activities. © 2016, National Ground Water Association.

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

    PubMed

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

    2003-03-01

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

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

    PubMed Central

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

    2015-01-01

    Deep brain stimulation has become a well-established symptomatic treatment for Parkinson's disease during the last 25 years. Besides improving motor symptoms and long-term motor complications, positive effects on patients’ mobility, activities of daily living, emotional well-being and health-related quality of life have been recognized. Apart from that, numerous clinical trials analyzed effects on non-motor symptoms and side effects of deep brain stimulation. Several technical issues and stimulation paradigms have been and are still being developed to optimize the therapeutic effects, minimize the side effects and facilitate handling. This review summarizes current therapeutic issues, i.e., patient and target selection, surgical procedure and programming paradigms. In addition it focuses on neuropsychological effects and side effects of deep brain stimulation. PMID:26330809

  20. Newberry Volcano EGS Demonstration: Plans and Results

    NASA Astrophysics Data System (ADS)

    Cladouhos, T. T.; Petty, S.; Moore, M.; Nordin, Y.; De Rocher, T.; Callahan, O.; Perry, D.

    2012-12-01

    Engineered or Enhanced Geothermal Systems (EGS) have the potential to expand the availability of clean renewable, baseload energy beyond conventional geothermal areas. An EGS reservoir is created by injecting large volumes of cold water into hot, low-permeability rock to induce seismic slip and enhance the permeability of pre-existing fractures. To date, EGS demonstrations have been limited to a single stimulation per well and sub-economic production rates because a method to isolate the first fracture in a hot well has been lacking. In addition, some recent EGS demonstrations have been negatively impacted by induced seismicity felt by area residents. The Newberry Volcano Enhanced Geothermal System (EGS) Demonstration in central Oregon, funded in part by DOE Grant DE-EE0002777, is now in the field operations phase after two years of planning. The stimulation well, NWG 55-29 drilled in 2008, has very little natural permeability but is very hot, with a bottom hole temperature over 300°C. The Demonstration will test recent technological advances designed to reduce the cost of power generated by EGS and the risk of felt seismicity. First, the stimulation pumps used were designed to run for weeks with little downtime and deliver large volumes of water (1000 gpm, 63 l/s) at relatively low well-head pressure (max. 3000 psi, 20 MPa). This pump specification is based on the rock mechanics-based model of hydroshearing, reduction of effective normal stress and friction on existing fractures, which promotes shear slip and enhances permeability. In contrast, pumps used in hydrofracking, creation of permeability through tensile failure of the rock, operate for shorter periods at much lower volumes and higher pressures. Second, multiple zone stimulation in the open-hole sections of EGS wells would significantly reduce the cost of EGS power production by increasing the productivity of each well. To facilitate multiple zone stimulation, AltaRock Energy has developed a suite of thermo-degradable zonal isolation materials (TZIMs) to temporarily seal off fractures in a geothermal well, allowing for stimulation of secondary and tertiary fracture zones, thus optimizing the injection/production profile of the entire well. TZIMs with ranges of thermal degradation properties have been extensively tested in the lab and two conventional geothermal fields. At Newberry, TZIMs that are stable at 200°C and degrade quickly at 300°C will be used. Third, the project follows a project-specific Induced Seismicity Mitigation Plan (ISMP) to evaluate, monitor for, and mitigate felt induced seismicity. During stimulation, 16 seismic stations, installed within 4 km of the target stimulation zone, monitor microseismicity and growth of the EGS reservoir. Seismicity occurring in undesirable locations or with ground accelerations or magnitudes above agreed thresholds, would result in operational changes to prevent unwanted seismicity, such as the use of TZIMs or lower well head pressures. Results of the Demonstration, shared with the public, geothermal and scientific communities include the real-time microseismicity, injection pressures and flow rates, and final injectivity of the stimulated well.

  1. Concurrent OCT imaging of stimulus evoked retinal neural activation and hemodynamic responses

    NASA Astrophysics Data System (ADS)

    Son, Taeyoon; Wang, Benquan; Lu, Yiming; Chen, Yanjun; Cao, Dingcai; Yao, Xincheng

    2017-02-01

    It is well established that major retinal diseases involve distortions of the retinal neural physiology and blood vascular structures. However, the details of distortions in retinal neurovascular coupling associated with major eye diseases are not well understood. In this study, a multi-modal optical coherence tomography (OCT) imaging system was developed to enable concurrent imaging of retinal neural activity and vascular hemodynamics. Flicker light stimulation was applied to mouse retinas to evoke retinal neural responses and hemodynamic changes. The OCT images were acquired continuously during the pre-stimulation, light-stimulation, and post-stimulation phases. Stimulus-evoked intrinsic optical signals (IOSs) and hemodynamic changes were observed over time in blood-free and blood regions, respectively. Rapid IOSs change occurred almost immediately after stimulation. Both positive and negative signals were observed in adjacent retinal areas. The hemodynamic changes showed time delays after stimulation. The signal magnitudes induced by light stimulation were observed in blood regions and did not show significant changes in blood-free regions. These differences may arise from different mechanisms in blood vessels and neural tissues in response to light stimulation. These characteristics agreed well with our previous observations in mouse retinas. Further development of the multimodal OCT may provide a new imaging method for studying how retinal structures and metabolic and neural functions are affected by age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and other diseases, which promises novel noninvasive biomarkers for early disease detection and reliable treatment evaluations of eye diseases.

  2. Long wavelength stimulated emission up to 9.5 μm from HgCdTe quantum well heterostructures

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Morozov, S. V.; Rumyantsev, V. V., E-mail: rumyantsev@ipmras.ru; Dubinov, A. A.

    2016-02-29

    Stimulated emission from waveguide HgCdTe structures with several quantum wells inside waveguide core is demonstrated at wavelengths up to 9.5 μm. Photoluminescence line narrowing down to kT energy, as well as superlinear rise in its intensity evidence the onset of the stimulated emission, which takes place under optical pumping with intensity as small as ∼0.1 kW/cm{sup 2} at 18 K and 1 kW/cm{sup 2} at 80 K. One can conclude that HgCdTe structures potential for long-wavelength lasers is not exhausted.

  3. Electrical stimulation of the insular region attenuates nicotine-taking and nicotine-seeking behaviors.

    PubMed

    Pushparaj, Abhiram; Hamani, Clement; Yu, Wilson; Shin, Damian S; Kang, Bin; Nobrega, José N; Le Foll, Bernard

    2013-03-01

    Pharmacological inactivation of the granular insular cortex is able to block nicotine-taking and -seeking behaviors in rats. In this study, we explored the potential of modulating activity in the insular region using electrical stimulation. Animals were trained to self-administer nicotine (0.03 mg/kg per infusion) under a fixed ratio-5 (FR-5) schedule of reinforcement followed by a progressive ratio (PR) schedule. Evaluation of the effect of stimulation in the insular region was performed on nicotine self-administration under FR-5 and PR schedules, as well on reinstatement of nicotine-seeking behavior induced by nicotine-associated cues or nicotine-priming injections. The effect of stimulation was also examined in brain slices containing insular neurons. Stimulation significantly attenuated nicotine-taking, under both schedules of reinforcement, as well as nicotine-seeking behavior induced by cues and priming. These effects appear to be specific to nicotine-associated behaviors, as stimulation did not have any effect on food-taking behavior. They appear to be anatomically specific, as stimulation surrounding the insular region had no effect on behavior. Stimulation of brain slices containing the insular region was found to inactivate insular neurons. Our results suggest that deep brain stimulation to modulate insular activity should be further explored.

  4. Desynchronizing electrical and sensory coordinated reset neuromodulation

    PubMed Central

    Popovych, Oleksandr V.; Tass, Peter A.

    2012-01-01

    Coordinated reset (CR) stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS), to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling). Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated) excitatory and inhibitory stimulation. Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronal synchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals) and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers) of deep brain CR neuromodulation may be similar or even identical. Furthermore, our results indicate that an effective desynchronization and anti-kindling can even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders. PMID:22454622

  5. Desynchronizing electrical and sensory coordinated reset neuromodulation.

    PubMed

    Popovych, Oleksandr V; Tass, Peter A

    2012-01-01

    Coordinated reset (CR) stimulation is a desynchronizing stimulation technique based on timely coordinated phase resets of sub-populations of a synchronized neuronal ensemble. It has initially been computationally developed for electrical deep brain stimulation (DBS), to enable an effective desynchronization and unlearning of pathological synchrony and connectivity (anti-kindling). Here we computationally show for ensembles of spiking and bursting model neurons interacting via excitatory and inhibitory adaptive synapses that a phase reset of neuronal populations as well as a desynchronization and an anti-kindling can robustly be achieved by direct electrical stimulation or indirect (synaptically-mediated) excitatory and inhibitory stimulation. Our findings are relevant for DBS as well as for sensory stimulation in neurological disorders characterized by pathological neuronal synchrony. Based on the obtained results, we may expect that the local effects in the vicinity of a depth electrode (realized by direct stimulation of the neurons' somata or stimulation of axon terminals) and the non-local CR effects (realized by stimulation of excitatory or inhibitory efferent fibers) of deep brain CR neuromodulation may be similar or even identical. Furthermore, our results indicate that an effective desynchronization and anti-kindling can even be achieved by non-invasive, sensory CR neuromodulation. We discuss the concept of sensory CR neuromodulation in the context of neurological disorders.

  6. Quantitative aspects of the clinical performance of transverse tripolar spinal cord stimulation.

    PubMed

    Wesselink, W A; Holsheimer, J; King, G W; Torgerson, N A; Boom, H B

    1999-01-01

    A multicenter study was initiated to evaluate the performance of the transverse tripolar system for spinal cord stimulation. Computer modeling had predicted steering of paresthesia with a dual channel stimulator to be the main benefit of the system. The quantitative analysis presented here includes the results of 484 tests in 30 patients. For each test, paresthesia coverage as a function of voltage levels was stored in a computerized database, including a body map which enabled calculation of the degree of paresthesia coverage of separate body areas, as well as the overlap with the painful areas. The results show that with the transverse tripolar system steering of the paresthesia is possible, although optimal steering requires proper placement of the electrode with respect to the spinal cord. Therefore, with this steering ability as well as a larger therapeutic stimulation window as compared to conventional systems, we expect an increase of the long-term efficacy of spinal cord stimulation. Moreover, in view of the stimulation-induced paresthesia patterns, the system allows selective stimulation of the medial dorsal columns.

  7. Comparison of chemical-use between hydraulic fracturing, acidizing, and routine oil and gas development

    DOE PAGES

    Stringfellow, William T.; Camarillo, Mary Kay; Domen, Jeremy K.; ...

    2017-04-19

    The potential hazards and risks associated with well-stimulation in unconventional oil and gas development (hydraulic fracturing, acid fracturing, and matrix acidizing) have been investigated and evaluated and federal and state regulations requiring chemical disclosure for well-stimulation have been implemented as part of an overall risk management strategy for unconventional oil and gas development. Similar evaluations for chemicals used in other routine oil and gas development activities, such as maintenance acidizing, gravel packing, and well drilling, have not been previously conducted, in part due to a lack of reliable information concerning on-field chemical-use. In this study, we compare chemical-use between routinemore » activities and the more closely regulated well-stimulation activities using data collected by the South Coast Air Quality Monitoring District (SCAQMD), which mandates the reporting of both unconventional and routine on-field chemical-use for parts of Southern California. Analysis of this data shows that there is significant overlap in chemical-use between so-called unconventional activities and routine activities conducted for well maintenance, well-completion, or rework. A comparison within the SCAQMD shows a significant overlap between both types and amounts of chemicals used for well-stimulation treatments included under State mandatory-disclosure regulations and routine treatments that are not included under State regulations. A comparison between SCAQMD chemical-use for routine treatments and state-wide chemical-use for hydraulic fracturing also showed close similarity in chemical-use between activities covered under chemical disclosure requirements (e.g. hydraulic fracturing) and many other oil and gas field activities. The results of this study indicate regulations and risk assessments focused exclusively on chemicals used in well-stimulation activities may underestimate potential hazard or risk from overall oil field chemical-use.« less

  8. Comparison of chemical-use between hydraulic fracturing, acidizing, and routine oil and gas development

    PubMed Central

    Camarillo, Mary Kay; Domen, Jeremy K.; Shonkoff, Seth B. C.

    2017-01-01

    The potential hazards and risks associated with well-stimulation in unconventional oil and gas development (hydraulic fracturing, acid fracturing, and matrix acidizing) have been investigated and evaluated and federal and state regulations requiring chemical disclosure for well-stimulation have been implemented as part of an overall risk management strategy for unconventional oil and gas development. Similar evaluations for chemicals used in other routine oil and gas development activities, such as maintenance acidizing, gravel packing, and well drilling, have not been previously conducted, in part due to a lack of reliable information concerning on-field chemical-use. In this study, we compare chemical-use between routine activities and the more closely regulated well-stimulation activities using data collected by the South Coast Air Quality Monitoring District (SCAQMD), which mandates the reporting of both unconventional and routine on-field chemical-use for parts of Southern California. Analysis of this data shows that there is significant overlap in chemical-use between so-called unconventional activities and routine activities conducted for well maintenance, well-completion, or rework. A comparison within the SCAQMD shows a significant overlap between both types and amounts of chemicals used for well-stimulation treatments included under State mandatory-disclosure regulations and routine treatments that are not included under State regulations. A comparison between SCAQMD chemical-use for routine treatments and state-wide chemical-use for hydraulic fracturing also showed close similarity in chemical-use between activities covered under chemical disclosure requirements (e.g. hydraulic fracturing) and many other oil and gas field activities. The results of this study indicate regulations and risk assessments focused exclusively on chemicals used in well-stimulation activities may underestimate potential hazard or risk from overall oil field chemical-use. PMID:28422971

  9. Comparison of chemical-use between hydraulic fracturing, acidizing, and routine oil and gas development.

    PubMed

    Stringfellow, William T; Camarillo, Mary Kay; Domen, Jeremy K; Shonkoff, Seth B C

    2017-01-01

    The potential hazards and risks associated with well-stimulation in unconventional oil and gas development (hydraulic fracturing, acid fracturing, and matrix acidizing) have been investigated and evaluated and federal and state regulations requiring chemical disclosure for well-stimulation have been implemented as part of an overall risk management strategy for unconventional oil and gas development. Similar evaluations for chemicals used in other routine oil and gas development activities, such as maintenance acidizing, gravel packing, and well drilling, have not been previously conducted, in part due to a lack of reliable information concerning on-field chemical-use. In this study, we compare chemical-use between routine activities and the more closely regulated well-stimulation activities using data collected by the South Coast Air Quality Monitoring District (SCAQMD), which mandates the reporting of both unconventional and routine on-field chemical-use for parts of Southern California. Analysis of this data shows that there is significant overlap in chemical-use between so-called unconventional activities and routine activities conducted for well maintenance, well-completion, or rework. A comparison within the SCAQMD shows a significant overlap between both types and amounts of chemicals used for well-stimulation treatments included under State mandatory-disclosure regulations and routine treatments that are not included under State regulations. A comparison between SCAQMD chemical-use for routine treatments and state-wide chemical-use for hydraulic fracturing also showed close similarity in chemical-use between activities covered under chemical disclosure requirements (e.g. hydraulic fracturing) and many other oil and gas field activities. The results of this study indicate regulations and risk assessments focused exclusively on chemicals used in well-stimulation activities may underestimate potential hazard or risk from overall oil field chemical-use.

  10. Comparison of chemical-use between hydraulic fracturing, acidizing, and routine oil and gas development

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stringfellow, William T.; Camarillo, Mary Kay; Domen, Jeremy K.

    The potential hazards and risks associated with well-stimulation in unconventional oil and gas development (hydraulic fracturing, acid fracturing, and matrix acidizing) have been investigated and evaluated and federal and state regulations requiring chemical disclosure for well-stimulation have been implemented as part of an overall risk management strategy for unconventional oil and gas development. Similar evaluations for chemicals used in other routine oil and gas development activities, such as maintenance acidizing, gravel packing, and well drilling, have not been previously conducted, in part due to a lack of reliable information concerning on-field chemical-use. In this study, we compare chemical-use between routinemore » activities and the more closely regulated well-stimulation activities using data collected by the South Coast Air Quality Monitoring District (SCAQMD), which mandates the reporting of both unconventional and routine on-field chemical-use for parts of Southern California. Analysis of this data shows that there is significant overlap in chemical-use between so-called unconventional activities and routine activities conducted for well maintenance, well-completion, or rework. A comparison within the SCAQMD shows a significant overlap between both types and amounts of chemicals used for well-stimulation treatments included under State mandatory-disclosure regulations and routine treatments that are not included under State regulations. A comparison between SCAQMD chemical-use for routine treatments and state-wide chemical-use for hydraulic fracturing also showed close similarity in chemical-use between activities covered under chemical disclosure requirements (e.g. hydraulic fracturing) and many other oil and gas field activities. The results of this study indicate regulations and risk assessments focused exclusively on chemicals used in well-stimulation activities may underestimate potential hazard or risk from overall oil field chemical-use.« less

  11. FIELD TESTING & OPTIMIZATION OF CO2/SAND FRACTURING TECHNOLOGY

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Raymond L. Mazza

    2004-11-30

    These contract efforts involved the demonstration of a unique liquid free stimulation technology which was, at the beginning of these efforts, in 1993 unavailable in the US. The process had been developed, and patented in Canada in 1981, and held promise for stimulating liquid sensitive reservoirs in the US. The technology differs from that conventionally used in that liquid carbon dioxide (CO{sub 2}), instead of water is the base fluid. The CO{sub 2} is pumped as a liquid and then vaporizes at reservoir conditions, and because no other liquids or chemicals are used, a liquid free fracture is created. Themore » process requires a specialized closed system blender to mix the liquid CO{sub 2} with proppant under pressure. These efforts were funded to consist of up to 21 cost-shared stimulation events. Because of the vagaries of CO{sub 2} supplies, service company support and operator interest only 19 stimulation events were performed in Montana, New Mexico, and Texas. Final reports have been prepared for each of the four demonstration groups, and the specifics of those demonstrations are summarized. A summary of the demonstrations of a novel liquid-free stimulation process which was performed in four groups of ''Candidate Wells'' situated in Crockett Co., TX; San Juan Co., NM; Phillips Co., MT; and Blaine Co., MT. The stimulation process which employs CO{sub 2} as the working fluid and the production responses were compared with those from wells treated with conventional stimulation technologies, primarily N{sub 2} foam, excepting those in Blaine Co., MT where the reservoir pressure is too low to clean up spent stimulation liquids. A total of 19 liquid-free CO{sub 2}/sand stimulations were performed in 16 wells and the production improvements were generally uneconomic.« less

  12. Mental wellbeing in people with dementia following Cognitive Stimulation Therapy: Innovative practice.

    PubMed

    Allward, Catherine; Dunn, Rosie; Forshaw, Gemma; Rewston, Chris; Wass, Nicola

    2017-01-01

    The benefits of Cognitive Stimulation Therapy in supporting cognitive functioning for people with dementia are well recognised. It has been proposed that Cognitive Stimulation Therapy may offer additional benefits in terms of a person's sense of general wellbeing. A service evaluation of 60 participants attending Cognitive Stimulation Therapy groups was conducted using the Short Warwick-Edinburgh Mental Well-Being Scale. Although this evaluation did not demonstrate a significant difference between pre- and post-treatment scores (t = -1.75, df = -59, p = -0.085), there was a trend in participants' reported optimism about the future and confidence. Recommendations about future research in relation to mental wellbeing in dementia care are discussed.

  13. Prenatal Cigarette Exposure and Infant Learning Stimulation as Predictors of Cognitive Control in Childhood

    ERIC Educational Resources Information Center

    Mezzacappa, Enrico; Buckner, John C.; Earls, Felton

    2011-01-01

    Prenatal exposures to neurotoxins and postnatal parenting practices have been shown to independently predict variations in the cognitive development and emotional-behavioral well-being of infants and children. We examined the independent contributions of prenatal cigarette exposure and infant learning stimulation, as well as their…

  14. Investigation of a BeO-based optically stimulated luminescence dosemeter.

    PubMed

    Sommer, M; Henniger, J

    2006-01-01

    The optical sensitivity of BeO-based luminophors has been well-known for many years. The optical stimulation of BeO with blue light is most effective. Then the dosemeters emit luminescent light in the ultraviolet-range around 325 nm. Matched on these facts a simple optically stimulated luminescence (OSL) treatment has been developed. Intense blue light-emitting diodes are used for cw-stimulation. A Hamamatsu solar blind photomultiplier detects the OSL-light. Good separation of both spectral ranges by optical filters is very important. The dosemeter has a linear dose response between approximately 20 muGy and >10 Gy. It was suggested, that a modification of stimulation conditions would allow measurements down to 1 muGy. Fading, photon energy dependence and reproducibility of OSL-signal correspond well with requirements to clinical and personal dosemeters. In addition, basic questions of the OSL-process in BeO have been investigated. A relevant point of interest was the dependency of the OSL-signal on stimulation power.

  15. The Northwest Geysers EGS Demonstration Project, California – Part 2: Modeling and interpretation

    DOE PAGES

    Rutqvist, Jonny; Jeanne, Pierre; Dobson, Patrick F.; ...

    2015-09-02

    In this paper, we summarize the results of coupled thermal, hydraulic, and mechanical (THM) modeling in support of the Northwest Geysers EGS Demonstration Project, which aims at enhancing production from a known High Temperature Reservoir (HTR) (280–400 °C) located under the conventional (240 °C) geothermal steam reservoir. The THM modeling was conducted to investigate geomechanical effects of cold-water injection during the stimulation of the EGS, first to predict the extent of the stimulation zone for a given injection schedule, and then to conduct interpretive analyses of the actual stimulation. By using a calibrated THM model based on historic injection and microseismic datamore » at a nearby well, we could reasonably predict the extent of the stimulation zone around the injection well, at least for the first few months of injection. However, observed microseismic evolution and pressure responses over the one-year stimulation-injection revealed more heterogeneous behavior as a result of more complex geology, including a network of shear zones. Therefore, for an interpretive analysis of the one-year stimulation campaign, we included two sets of vertical shear zones within the model; a set of more permeable NW-striking shear zones and a set of less permeable NE-striking shear zones. Our modeling indicates that the microseismic events in this system are related to shear reactivation of pre-existing fractures, triggered by the combined effects of injection-induced cooling around the injection well and rapid (but small) changes in steam pressure as far as a kilometer from the injection well. Overall, the integrated monitoring and modeling of microseismicity, ground surface deformations, reservoir pressure, fluid chemical composition, and seismic tomography depict an EGS system hydraulically bounded by some of the NE-striking low permeability shear zones, with the more permeable NW-striking shear zone providing liquid flow paths for stimulation deep (several kilometers) down into the HTR. The mo deling indicates that a significant mechanical degradation (damage) inferred from seismic tomography, and potential changes in fracture porosity inferred from cross-well pressure responses, are related to shear rupture in the stimulation zone driven by both pressure and cooling effects.« less

  16. The Northwest Geysers EGS Demonstration Project, California – Part 2: Modeling and interpretation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rutqvist, Jonny; Jeanne, Pierre; Dobson, Patrick F.

    In this paper, we summarize the results of coupled thermal, hydraulic, and mechanical (THM) modeling in support of the Northwest Geysers EGS Demonstration Project, which aims at enhancing production from a known High Temperature Reservoir (HTR) (280–400 °C) located under the conventional (240 °C) geothermal steam reservoir. The THM modeling was conducted to investigate geomechanical effects of cold-water injection during the stimulation of the EGS, first to predict the extent of the stimulation zone for a given injection schedule, and then to conduct interpretive analyses of the actual stimulation. By using a calibrated THM model based on historic injection and microseismic datamore » at a nearby well, we could reasonably predict the extent of the stimulation zone around the injection well, at least for the first few months of injection. However, observed microseismic evolution and pressure responses over the one-year stimulation-injection revealed more heterogeneous behavior as a result of more complex geology, including a network of shear zones. Therefore, for an interpretive analysis of the one-year stimulation campaign, we included two sets of vertical shear zones within the model; a set of more permeable NW-striking shear zones and a set of less permeable NE-striking shear zones. Our modeling indicates that the microseismic events in this system are related to shear reactivation of pre-existing fractures, triggered by the combined effects of injection-induced cooling around the injection well and rapid (but small) changes in steam pressure as far as a kilometer from the injection well. Overall, the integrated monitoring and modeling of microseismicity, ground surface deformations, reservoir pressure, fluid chemical composition, and seismic tomography depict an EGS system hydraulically bounded by some of the NE-striking low permeability shear zones, with the more permeable NW-striking shear zone providing liquid flow paths for stimulation deep (several kilometers) down into the HTR. The mo deling indicates that a significant mechanical degradation (damage) inferred from seismic tomography, and potential changes in fracture porosity inferred from cross-well pressure responses, are related to shear rupture in the stimulation zone driven by both pressure and cooling effects.« less

  17. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Warpinski, N.R.; Branagan, P.T.; Sattler, A.R.

    This paper is a case study of the stimulation and testing of tight, lenticular sands in the paludal interval of the Mesaverde group in the Piceance basin at DOE's Multiwell Experiment (MWX) site in Colorado. Topics discussed include geologic data, stress test results, well testing, laboratory core studies, stimulation and stimulation analyses, and postfracture operations.

  18. Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

    NASA Astrophysics Data System (ADS)

    Crook, J. J.; Brouillard, C. B. J.; Irazoqui, P. P.; Lovick, T. A.

    2018-04-01

    Objective. Neuromodulation of autonomic nerve activity to regulate physiological processes is an emerging field. Vagal stimulation has received most attention whereas the potential of modulate visceral function by targeting autonomic nerves within the abdominal cavity remains under-exploited. Surgery to locate intra-abdominal targets is inherently more stressful than for peripheral nerves. Electrode leads risk becoming entrapped by intestines and loss of functionality in the nerve-target organ connection could result from electrode migration or twisting. Since nociceptor afferents are intermingled with similar-sized visceral autonomic fibres, stimulation may induce pain. In anaesthetised rats high frequency stimulation of the pelvic nerve can suppress urinary voiding but it is not known how conscious animals would react to this procedure. Our objective therefore was to determine how rats tolerated chronic implantation of cuff electrodes on the pelvic nerve, whether nerve stimulation would be aversive and whether nerve-bladder functionality would be compromised. Approach. We carried out a preliminary de-risking study to investigate how conscious rats tolerated chronic implantation of electrodes on the pelvic nerve, their responsiveness to intermittent high frequency stimulation and whether functionality of the nerve-bladder connection became compromised. Main results. Implantation of cuff electrodes was well-tolerated. The normal diurnal pattern of urinary voiding was not disrupted. Pelvic nerve stimulation (up to 4 mA, 3 kHz) for 30 min periods evoked mild alerting at stimulus onset but no signs of pain. Stimulation evoked a modest (<0.5 °C) increase in nerve temperature but the functional integrity of the nerve-bladder connection, reflected by contraction of the detrusor muscle in response to 10 Hz nerve stimulation, was not compromised. Significance. Chronic implantation of cuff electrodes on the pelvic nerve was found to be a well-tolerated procedure in rats and high frequency stimulation did not lead to loss of nerve functionality. Pelvic nerve stimulation has development potential for normalizing voiding dysfunction in conscious rats.

  19. Rational modulation of neuronal processing with applied electric fields.

    PubMed

    Bikson, Marom; Radman, Thomas; Datta, Abhishek

    2006-01-01

    Traditional approaches to electrical stimulation, using trains of supra-threshold pulses to trigger action potentials, may be replaced or augmented by using 'rational' sub-threshold stimulation protocols that incorporate knowledge of single neuron geometry, inhomogeneous tissue properties, and nervous system information coding. Sub-threshold stimulation, at intensities (well) below those sufficient to trigger action potentials, may none-the-less exert a profound effect on brain function through modulation of concomitant neuronal activity. For example, small DC fields may coherently polarize a network of neurons and thus modulate the simultaneous processing of afferent synaptic input as well as resulting changes in synaptic plasticity. Through 'activity-dependent plasticity', sub-threshold fields may allow specific targeting of pathological networks and are thus particularly suitable to overcome the poor anatomical focus of noninvasive (transcranial) electrical stimulation. Additional approaches to improve targeting in transcranial stimulation using novel electrode configurations are also introduced.

  20. Integrated Approach to Drilling Project in Unconventional Reservoir Using Reservoir Simulation

    NASA Astrophysics Data System (ADS)

    Stopa, Jerzy; Wiśniowski, Rafał; Wojnarowski, Paweł; Janiga, Damian; Skrzypaszek, Krzysztof

    2018-03-01

    Accumulation and flow mechanisms in unconventional reservoir are different compared to conventional. This requires a special approach of field management with drilling and stimulation treatments as major factor for further production. Integrated approach of unconventional reservoir production optimization assumes coupling drilling project with full scale reservoir simulation for determine best well placement, well length, fracturing treatment design and mid-length distance between wells. Full scale reservoir simulation model emulate a part of polish shale - gas field. The aim of this paper is to establish influence of technical factor for gas production from shale gas field. Due to low reservoir permeability, stimulation treatment should be direct towards maximizing the hydraulic contact. On the basis of production scenarios, 15 stages hydraulic fracturing allows boost gas production over 1.5 times compared to 8 stages. Due to the possible interference of the wells, it is necessary to determine the distance between the horizontal parts of the wells trajectories. In order to determine the distance between the wells allowing to maximize recovery factor of resources in the stimulated zone, a numerical algorithm based on a dynamic model was developed and implemented. Numerical testing and comparative study show that the most favourable arrangement assumes a minimum allowable distance between the wells. This is related to the volume ratio of the drainage zone to the total volume of the stimulated zone.

  1. The Impact of Monaural Beat Stimulation on Anxiety and Cognition.

    PubMed

    Chaieb, Leila; Wilpert, Elke C; Hoppe, Christian; Axmacher, Nikolai; Fell, Juergen

    2017-01-01

    Application of auditory beat stimulation has been speculated to provide a promising new tool with which to alleviate symptoms of anxiety and to enhance cognition. In spite of reportedly similar EEG effects of binaural and monaural beats, data on behavioral effects of monaural beats are still lacking. Therefore, we examined the impact of monaural beat stimulation on anxiety, mood and memory performance. We aimed to target states related to anxiety levels and general well-being, in addition to long-term and working memory processes, using monaural beats within the range of main cortical rhythms. Theta (6 Hz), alpha (10 Hz) and gamma (40 Hz) beat frequencies, as well as a control stimulus were applied to healthy participants for 5 min. After each stimulation period, participants were asked to evaluate their current mood state and to perform cognitive tasks examining long-term and working memory processes, in addition to a vigilance task. Monaural beat stimulation was found to reduce state anxiety. When evaluating responses for the individual beat frequencies, positive effects on state anxiety were observed for all monaural beat conditions compared to control stimulation. Our results indicate a role for monaural beat stimulation in modulating state anxiety and are in line with previous studies reporting anxiety-reducing effects of auditory beat stimulation.

  2. The Impact of Monaural Beat Stimulation on Anxiety and Cognition

    PubMed Central

    Chaieb, Leila; Wilpert, Elke C.; Hoppe, Christian; Axmacher, Nikolai; Fell, Juergen

    2017-01-01

    Application of auditory beat stimulation has been speculated to provide a promising new tool with which to alleviate symptoms of anxiety and to enhance cognition. In spite of reportedly similar EEG effects of binaural and monaural beats, data on behavioral effects of monaural beats are still lacking. Therefore, we examined the impact of monaural beat stimulation on anxiety, mood and memory performance. We aimed to target states related to anxiety levels and general well-being, in addition to long-term and working memory processes, using monaural beats within the range of main cortical rhythms. Theta (6 Hz), alpha (10 Hz) and gamma (40 Hz) beat frequencies, as well as a control stimulus were applied to healthy participants for 5 min. After each stimulation period, participants were asked to evaluate their current mood state and to perform cognitive tasks examining long-term and working memory processes, in addition to a vigilance task. Monaural beat stimulation was found to reduce state anxiety. When evaluating responses for the individual beat frequencies, positive effects on state anxiety were observed for all monaural beat conditions compared to control stimulation. Our results indicate a role for monaural beat stimulation in modulating state anxiety and are in line with previous studies reporting anxiety-reducing effects of auditory beat stimulation. PMID:28555100

  3. Fracture stimulation treatment design optimization: What can the NPV vs X{sub f} plot tell us?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Huffman, C.H.; Harkrider, J.D.; Thompson, R.S.

    1996-12-31

    Fracture stimulation production response coupled with the hydrocarbon sales price determines the value of a fracture stimulation treatment. Many factors can significantly effect the production response of a fracture stimulated well. Some examples include stimulation fluid selection, proppant selection, pumping rates, rock properties, reservoir fluid properties, in-situ stresses, stress variations, on-site execution, post-treatment stimulation fluid recovery, and operating practices. The production response in economic terms portrays the net effect of these variables. This paper presents a case study that demonstrates how post-treatment evaluations expressed in economic terms can be used to assess the performance of stimulations and to guide futuremore » design choices.« less

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

    PubMed

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

    2017-04-01

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

  5. Stretch-stimulated glucose transport in skeletal muscle is regulated by Rac1.

    PubMed

    Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; Richter, Erik A; Jensen, Thomas E

    2015-02-01

    Rac1 regulates stretch-stimulated (i.e. mechanical stress) glucose transport in muscle. Actin depolymerization decreases stretch-induced glucose transport in skeletal muscle. Rac1 is a required part of the mechanical stress-component of the contraction-stimulus to glucose transport in skeletal muscle. An alternative to the canonical insulin signalling pathway for glucose transport is muscle contraction/exercise. Mechanical stress is an integrated part of the muscle contraction/relaxation cycle, and passive stretch stimulates muscle glucose transport. However, the signalling mechanism regulating stretch-stimulated glucose transport is not well understood. We recently reported that the actin cytoskeleton regulating GTPase, Rac1, was activated in mouse muscle in response to stretching. Rac1 is a regulator of contraction- and insulin-stimulated glucose transport, however, its role in stretch-stimulated glucose transport and signalling is unknown. We therefore investigated whether stretch-induced glucose transport in skeletal muscle required Rac1 and the actin cytoskeleton. We used muscle-specific inducible Rac1 knockout mice as well as pharmacological inhibitors of Rac1 and the actin cytoskeleton in isolated soleus and extensor digitorum longus muscles. In addition, the role of Rac1 in contraction-stimulated glucose transport during conditions without mechanical load on the muscles was evaluated in loosely hanging muscles and muscles in which cross-bridge formation was blocked by the myosin ATPase inhibitors BTS and Blebbistatin. Knockout as well as pharmacological inhibition of Rac1 reduced stretch-stimulated glucose transport by 30-50% in soleus and extensor digitorum longus muscle. The actin depolymerizing agent latrunculin B similarly decreased glucose transport in response to stretching by 40-50%. Rac1 inhibition reduced contraction-stimulated glucose transport by 30-40% in tension developing muscle but did not affect contraction-stimulated glucose transport in muscles in which force development was prevented. Our findings suggest that Rac1 and the actin cytoskeleton regulate stretch-stimulated glucose transport and that Rac1 is a required part of the mechanical stress-component of the contraction-stimulus to glucose transport in skeletal muscle. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  6. Stretch-stimulated glucose transport in skeletal muscle is regulated by Rac1

    PubMed Central

    Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; Richter, Erik A; Jensen, Thomas E

    2015-01-01

    An alternative to the canonical insulin signalling pathway for glucose transport is muscle contraction/exercise. Mechanical stress is an integrated part of the muscle contraction/relaxation cycle, and passive stretch stimulates muscle glucose transport. However, the signalling mechanism regulating stretch-stimulated glucose transport is not well understood. We recently reported that the actin cytoskeleton regulating GTPase, Rac1, was activated in mouse muscle in response to stretching. Rac1 is a regulator of contraction- and insulin-stimulated glucose transport, however, its role in stretch-stimulated glucose transport and signalling is unknown. We therefore investigated whether stretch-induced glucose transport in skeletal muscle required Rac1 and the actin cytoskeleton. We used muscle-specific inducible Rac1 knockout mice as well as pharmacological inhibitors of Rac1 and the actin cytoskeleton in isolated soleus and extensor digitorum longus muscles. In addition, the role of Rac1 in contraction-stimulated glucose transport during conditions without mechanical load on the muscles was evaluated in loosely hanging muscles and muscles in which cross-bridge formation was blocked by the myosin ATPase inhibitors BTS and Blebbistatin. Knockout as well as pharmacological inhibition of Rac1 reduced stretch-stimulated glucose transport by 30–50% in soleus and extensor digitorum longus muscle. The actin depolymerizing agent latrunculin B similarly decreased glucose transport in response to stretching by 40–50%. Rac1 inhibition reduced contraction-stimulated glucose transport by 30–40% in tension developing muscle but did not affect contraction-stimulated glucose transport in muscles in which force development was prevented. Our findings suggest that Rac1 and the actin cytoskeleton regulate stretch-stimulated glucose transport and that Rac1 is a required part of the mechanical stress-component of the contraction-stimulus to glucose transport in skeletal muscle. Key points Rac1 regulates stretch-stimulated (i.e. mechanical stress) glucose transport in muscle. Actin depolymerization decreases stretch-induced glucose transport in skeletal muscle. Rac1 is a required part of the mechanical stress-component of the contraction-stimulus to glucose transport in skeletal muscle. PMID:25416624

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

    PubMed Central

    Vidal, Jose; Ghovanloo, Maysam

    2013-01-01

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

  8. An Independent Scientific Assessment of Well Stimulation in California Volume III

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jane C.S. Long; Laura C. Feinstein; Birkholzer, Jens

    This study is issued in three volumes. Volume I, issued in January 2015, describes how well stimulation technologies work, how and where operators deploy these technologies for oil and gas production in California, and where they might enable production in the future. Volume II, issued in July 2015, discusses how well stimulation could affect water, atmosphere, seismic activity, wildlife and vegetation, and human health. Volume II reviews available data, and identifies knowledge gaps and alternative practices that could avoid or mitigate these possible impacts. Volume III, this volume, presents case studies that assess environmental issues and qualitative risks for specificmore » geographic regions. The Summary Report summarizes key findings, conclusions and recommendations of all three volumes.« less

  9. An Independent Scientific Assessment of Well Stimulation in California Volume II

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jane C.S. Long; Laura C. Feinstein; Corinne E. Bachmann

    This study is issued in three volumes. Volume I, issued in January 2015, describes how well stimulation technologies work, how and where operators deploy these technologies for oil and gas production in California, and where they might enable production in the future. Volume II, the present volume, discusses how well stimulation could affect water, atmosphere, seismic activity, wildlife and vegetation, and human health. Volume II reviews available data, and identifies knowledge gaps and alternative practices that could avoid or mitigate these possible impacts. Volume III, also issued in July 2015, presents case studies that assess environmental issues and qualitative risksmore » for specific geographic regions. A final Summary Report summarizes key findings, conclusions and recommendations of all three volumes.« less

  10. Infant Stimulation and the Etiology of Cognitive Processes.

    ERIC Educational Resources Information Center

    Fowler, William

    What data, problems, and concepts are most relevant in determining the role of stimulation in human development? A critical analysis of the relationships between long term stimulation, behavior, and cognitive functioning and development points up biases and gaps in past as well as contemporary approaches. Each of the four sections of this paper…

  11. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Willis-Richards, J.; Watanable, K.; Yamaguchi, T.

    A set of models of HDR systems is presented which attempts to explain the formation and operation of HDR systems using only the in-situ properties of the fractured rock mass, the earth stress field, the engineering intervention applied by way of stimulation and the relative positions and pressures of the well(s). A statistical and rock mechanics description of fractures in low permeability rocks provides the basis for modeling of stimulation, circulation and water loss in HDR systems. The model uses a large number of parameters, chiefly simple directly measurable quantities, describing the rock mass and fracture system. The effect ofmore » stimulation (raised fluid pressure allowing slip) on fracture apertures is calculated, and the volume of rock affected per volume of fluid pumped estimated. The total rock volume affected by stimulation is equated with the rock volume containing the associated AE (microseismicity). The aperture and compliance properties of the stimulated fractures are used to estimate impedance and flow within the reservoir. Fluid loss from the boundary of the stimulated volume is treated using radial leak-off with pressure-dependent permeability.« less

  12. Source mechanism characterization and integrated interpretation of microseismic data monitoring two hydraulic stimulations in pouce coupe field, Alberta

    NASA Astrophysics Data System (ADS)

    Lindholm, Garrison J.

    The study of the Pouce Coupe Field is a joint effort between the Reservoir Characterization Project (RCP) and Talisman Energy Inc. My study focuses on the hydraulic stimulation of two horizontal wells within the Montney Formation located in north-western Alberta. The Montney is an example of a modern-day tight, engineering-driven play in which recent advances in drilling of horizontal wells and hydraulic fracturing have made shale gas exploitation economical. The wells were completed in December 2008 and were part of a science driven project in which a multitude of data were collected including multicomponent seismic, microseismic, and production logs. Since this time, a number of studies have been performed by students at Colorado School of Mines to better understand the effects the completions have had on the reservoir. This thesis utilizes the microseismic data that were recorded during the stimulation of the two horizontal wells in order to understand the origin of the microseismic events themselves. The data are then used to understand and correlate to the well production. To gain insight into the source of the microseismic events, amplitude ratios of recorded seismic modes (P, Sh and Sv) for the microseismic events are studied. By fitting trends of simple end member source mechanisms (strike-slip, dip-slip, and tensile) to groups of amplitude ratio data, the events are found to be of strike-slip nature. By comparing the focal mechanisms to other independent natural fracture determination techniques (shear-wave splitting analysis, FMI log), it is shown that the source of recorded microseismic events is likely to be a portion of the shear slip along existing weak planes (fractures) within a reservoir. The technique described in this work is one that is occasionally but increasingly used but offers the opportunity to draw further information from microseismic data using results that are already part of a typical processing workflow. The microseismic events are then used as a tool to analyze the effectiveness of the hydraulic stimulation and why production varies on a well and stage basis. The study shows that production disparities may be related to communication between horizontal wells, a potential weak zone of sub-seismic scale faults/fractures at the toe of one of the completed horizontal wells, and most importantly the quality of the stimulated rock. The results suggest that the quality of the stimulated reservoir rock is a greater driver of production than the total stimulated volume. By integrating the microseismic with other data (seismic and engineering), this work shows that the key to the understanding of these engineering-driven plays is an integrated solution. The methods shown in this thesis are applicable to many similar plays across North America and the world. The complicated nature of these tight reservoirs underscores the need for effective well planning, placement, and stimulation for economical development of shale resource plays.

  13. Compact, Energy-Efficient High-Frequency Switched Capacitor Neural Stimulator With Active Charge Balancing.

    PubMed

    Hsu, Wen-Yang; Schmid, Alexandre

    2017-08-01

    Safety and energy efficiency are two major concerns for implantable neural stimulators. This paper presents a novel high-frequency, switched capacitor (HFSC) stimulation and active charge balancing scheme, which achieves high energy efficiency and well-controlled stimulation charge in the presence of large electrode impedance variations. Furthermore, the HFSC can be implemented in a compact size without any external component to simultaneously enable multichannel stimulation by deploying multiple stimulators. The theoretical analysis shows significant benefits over the constant-current and voltage-mode stimulation methods. The proposed solution was fabricated using a 0.18 μm high-voltage technology, and occupies only 0.035 mm 2 for a single stimulator. The measurement result shows 50% peak energy efficiency and confirms the effectiveness of active charge balancing to prevent the electrode dissolution.

  14. Nanostructured cavity devices for extracellular stimulation of HL-1 cells

    NASA Astrophysics Data System (ADS)

    Czeschik, Anna; Rinklin, Philipp; Derra, Ulrike; Ullmann, Sabrina; Holik, Peter; Steltenkamp, Siegfried; Offenhäusser, Andreas; Wolfrum, Bernhard

    2015-05-01

    Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network. Electronic supplementary information (ESI) available: Comparison of non-filtered and Savitzky-Golay filtered action potential recordings, electrical signals and corresponding optical signals. See DOI: 10.1039/c5nr01690h

  15. Imbibition well stimulation via neural network design

    DOEpatents

    Weiss, William [Socorro, NM

    2007-08-14

    A method for stimulation of hydrocarbon production via imbibition by utilization of surfactants. The method includes use of fuzzy logic and neural network architecture constructs to determine surfactant use.

  16. Imaging the Spatio-Temporal Dynamics of Supragranular Activity in the Rat Somatosensory Cortex in Response to Stimulation of the Paws

    PubMed Central

    Morales-Botello, M. L.; Aguilar, J.; Foffani, G.

    2012-01-01

    We employed voltage-sensitive dye (VSD) imaging to investigate the spatio-temporal dynamics of the responses of the supragranular somatosensory cortex to stimulation of the four paws in urethane-anesthetized rats. We obtained the following main results. (1) Stimulation of the contralateral forepaw evoked VSD responses with greater amplitude and smaller latency than stimulation of the contralateral hindpaw, and ipsilateral VSD responses had a lower amplitude and greater latency than contralateral responses. (2) While the contralateral stimulation initially activated only one focus, the ipsilateral stimulation initially activated two foci: one focus was typically medial to the focus activated by contralateral stimulation and was stereotaxically localized in the motor cortex; the other focus was typically posterior to the focus activated by contralateral stimulation and was stereotaxically localized in the somatosensory cortex. (3) Forepaw and hindpaw somatosensory stimuli activated large areas of the sensorimotor cortex, well beyond the forepaw and hindpaw somatosensory areas of classical somatotopic maps, and forepaw stimuli activated larger cortical areas with greater activation velocity than hindpaw stimuli. (4) Stimulation of the forepaw and hindpaw evoked different cortical activation dynamics: forepaw responses displayed a clear medial directionality, whereas hindpaw responses were much more uniform in all directions. In conclusion, this work offers a complete spatio-temporal map of the supragranular VSD cortical activation in response to stimulation of the paws, showing important somatotopic differences between contralateral and ipsilateral maps as well as differences in the spatio-temporal activation dynamics in response to forepaw and hindpaw stimuli. PMID:22829873

  17. [Sacral nerve stimulation in fecal incontinence].

    PubMed

    Rasmussen, Ole Ø; Christiansen, John

    2002-08-12

    Sacral nerve stimulation for the treatment of faecal incontinence has gained increasing use in Europe over the last two years. Experience with the first patients treated in Denmark is described here. Fourteen patients with severe faecal incontinence were given sacral nerve stimulation. The first treatment was temporary, and if this was successful they had a device for permanent stimulation implanted. The result of the test stimulation was good in ten of the 14 patients and a permanent system was implanted. After a median of 4.5 months' stimulation, nine of the ten patients continued to respond to respond well. Sacral nerve stimulation in the treatment of faecal incontinence shows promising results. Compared to other more advanced forms of treatment, this method is minimally invasive.

  18. Hydraulic fracturing near domestic groundwater wells.

    PubMed

    Jasechko, Scott; Perrone, Debra

    2017-12-12

    Hydraulic fracturing operations are generating considerable discussion about their potential to contaminate aquifers tapped by domestic groundwater wells. Groundwater wells located closer to hydraulically fractured wells are more likely to be exposed to contaminants derived from on-site spills and well-bore failures, should they occur. Nevertheless, the proximity of hydraulic fracturing operations to domestic groundwater wells is unknown. Here, we analyze the distance between domestic groundwater wells (public and self-supply) constructed between 2000 and 2014 and hydraulically fractured wells stimulated in 2014 in 14 states. We show that 37% of all recorded hydraulically fractured wells stimulated during 2014 exist within 2 km of at least one recently constructed (2000-2014) domestic groundwater well. Furthermore, we identify 11 counties where most ([Formula: see text]50%) recorded domestic groundwater wells exist within 2 km of one or more hydraulically fractured wells stimulated during 2014. Our findings suggest that understanding how frequently hydraulic fracturing operations impact groundwater quality is of widespread importance to drinking water safety in many areas where hydraulic fracturing is common. We also identify 236 counties where most recorded domestic groundwater wells exist within 2 km of one or more recorded oil and gas wells producing during 2014. Our analysis identifies hotspots where both conventional and unconventional oil and gas wells frequently exist near recorded domestic groundwater wells that may be targeted for further water-quality monitoring.

  19. Hydraulic fracturing near domestic groundwater wells

    PubMed Central

    Jasechko, Scott; Perrone, Debra

    2017-01-01

    Hydraulic fracturing operations are generating considerable discussion about their potential to contaminate aquifers tapped by domestic groundwater wells. Groundwater wells located closer to hydraulically fractured wells are more likely to be exposed to contaminants derived from on-site spills and well-bore failures, should they occur. Nevertheless, the proximity of hydraulic fracturing operations to domestic groundwater wells is unknown. Here, we analyze the distance between domestic groundwater wells (public and self-supply) constructed between 2000 and 2014 and hydraulically fractured wells stimulated in 2014 in 14 states. We show that 37% of all recorded hydraulically fractured wells stimulated during 2014 exist within 2 km of at least one recently constructed (2000–2014) domestic groundwater well. Furthermore, we identify 11 counties where most (>50%) recorded domestic groundwater wells exist within 2 km of one or more hydraulically fractured wells stimulated during 2014. Our findings suggest that understanding how frequently hydraulic fracturing operations impact groundwater quality is of widespread importance to drinking water safety in many areas where hydraulic fracturing is common. We also identify 236 counties where most recorded domestic groundwater wells exist within 2 km of one or more recorded oil and gas wells producing during 2014. Our analysis identifies hotspots where both conventional and unconventional oil and gas wells frequently exist near recorded domestic groundwater wells that may be targeted for further water-quality monitoring. PMID:29180405

  20. Chart Audit and Chart Stimulated Recall as Methods of Needs Assessment in Continuing Professional Health Education.

    ERIC Educational Resources Information Center

    Affleck, Louise; Jennett, Penny

    1998-01-01

    Chart audit (assessment of patient medical records) is a cost-effective continuing-education needs-assessment method. Chart stimulated recall, in which physicians' memory of particular cases is stimulated by records, potentially increases content validity and exploration of clinical reasoning as well as the context of clinical decisions. (SK)

  1. 75 FR 65673 - Notice of Information Collection

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-26

    ... purpose of this survey is to assimilate lunar regolith stimulant requirements as well as Apollo sample.... III. Data Title: Lunar Regolith & Stimulant Users' Survey for the In Situ Resource Utilization Web...

  2. 75 FR 53349 - Notice of Information Collection

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-31

    ... purpose of this survey is to assimilate lunar regolith stimulant requirements as well as Apollo sample.... III. Data Title: Lunar Regolith & Stimulant Users' Survey for the In Situ Resource Utilization Web...

  3. Matching native electrical stimulation by graded chemical stimulation in isolated mouse adrenal chromaffin cells.

    PubMed

    Fulop, Tiberiu; Smith, Corey

    2007-11-30

    Adrenal chromaffin cells release multiple transmitters in response to sympathetic stimulation. Modest cell firing, matching sympathetic tone, releases small freely soluble catecholamines. Elevated electrical firing rates matching input under sympathetic stress results in release of catecholamines as well as semi-soluble vaso- and neuro-active peptides packaged within the dense core of the secretory granule. This activity-dependent differential transmitter release has been shown to rely on a mechanistic shift in the mode of exocytosis through the regulated dilation of the secretory fusion pore between granule and cell surface membranes. However, biochemical description of the mechanism regulating fusion pore dilation remains elusive. In the experimental setting, electrical stimulation designed to mimic sympathetic input, is achieved through single-cell voltage-clamp. While precise, this approach is incompatible with biochemical and proteomic analysis, both of which require large sample sizes. We address this limitation in the current study. We describe a bulk chemical stimulation paradigm calibrated to match defined electrical activity. We utilize calcium and single-cell amperometric measurements to match extracellular potassium concentrations to physiological electrical stimulation under sympathetic tone as well as acute stress conditions. This approach provides larger samples of uniformly stimulated cells for determining molecular players in activity-dependent differential transmitter release from adrenal chromaffin cells.

  4. 3D Modeling and Characterization of Hydraulic Fracture Efficiency Integrated with 4D/9C Time-Lapse Seismic Interpretations in the Niobrara Formation, Wattenberg Field, Denver Basin

    NASA Astrophysics Data System (ADS)

    Alfataierge, Ahmed

    Hydrocarbon recovery rates within the Niobrara Shale are estimated as low as 2-8%. These recovery rates are controlled by the ability to effectively hydraulic fracture stimulate the reservoir using multistage horizontal wells. Subsequent to any mechanical issues that affect production from lateral wells, the variability in production performance and reserve recovery along multistage lateral shale wells is controlled by the reservoir heterogeneity and its consequent effect on hydraulic fracture stimulation efficiency. Using identical stimulation designs on a number of wells that are as close as 600ft apart can yield variable production and recovery rates due to inefficiencies in hydraulic fracture stimulation that result from the variability in elastic rock properties and in-situ stress conditions. As a means for examining the effect of the geological heterogeneity on hydraulic fracturing and production within the Niobrara Formation, a 3D geomechanical model is derived using geostatistical methods and volumetric calculations as an input to hydraulic fracture stimulation. The 3D geomechanical model incorporates the faults, lithological facies changes and lateral variation in reservoir properties and elastic rock properties that best represent the static reservoir conditions pre-hydraulic fracturing. Using a 3D numerical reservoir simulator, a hydraulic fracture predictive model is generated and calibrated to field diagnostic measurements (DFIT) and observations (microseismic and 4D/9C multicomponent time-lapse seismic). By incorporating the geological heterogeneity into the 3D hydraulic fracture simulation, a more representative response is generated that demonstrate the variability in hydraulic fracturing efficiency along the lateral wells that will inevitability influence production performance. Based on the 3D hydraulic fracture simulation results, integrated with microseismic observations and 4D/9C time-lapse seismic analysis (post-hydraulic fracturing & post production), the variability in production performance within the Niobrara Shale wells is shown to significantly be affected by the lateral variability in reservoir quality, well and stage positioning relative to the target interval, and the relative completion efficiency. The variation in reservoir properties, faults, rock strength parameters, and in-situ stress conditions are shown to influence and control the hydraulic fracturing geometry and stimulation efficiency resulting in complex and isolated induced fracture geometries to form within the reservoir. This consequently impacts the effective drainage areas, production performance and recovery rates from inefficiently stimulated horizontal wells. The 3D simulation results coupled with the 4D seismic interpretations illustrate that there is still room for improvement to be made in optimizing well spacing and hydraulic fracturing efficiency within the Niobrara Formation. Integrated analysis show that the Niobrara reservoir is not uniformly stimulated. The vertical and lateral variability in rock properties control the hydraulic fracturing efficiency and geometry. Better production is also correlated to higher fracture conductivity. 4D seismic interpretation is also shown to be essential for the validation and calibration hydraulic fracture simulation models. The hydraulic fracture modeling also demonstrations that there is bypassed pay in the Niobrara B chalk resulting from initial Niobrara C chalk stimulation treatments. Forward modeling also shows that low pressure intervals within the Niobrara reservoir influence hydraulic fracturing and infill drilling during field development.

  5. Hydraulic Stimulation of Fracture Permeability in Volcanic and Metasedimentary Rocks at the Desert Peak Geothermal Field, Nevada

    NASA Astrophysics Data System (ADS)

    Hickman, S.; Davatzes, N. C.; Zemach, E.; Stacey, R.; Drakos, P. S.; Lutz, S.; Rose, P. E.; Majer, E.; Robertson-Tait, A.

    2011-12-01

    An integrated study of fluid flow, fracturing, stress and rock mechanical properties is being conducted to develop the geomechanical framework for creating an Enhanced Geothermal System (EGS) through hydraulic stimulation. This stimulation is being carried out in the relatively impermeable well 27-15 located on the margins of the Desert Peak Geothermal Field, in silicified rhyolite tuffs and metamorphosed mudstones at depths of ~0.9 to 1.1 km and ambient temperatures of ~180 to 195° C. Extensive drilling-induced tensile fractures seen in image logs from well 27-15 indicate that the direction of the minimum horizontal principal stress, Shmin, is 114±17°. This orientation is consistent with normal faulting on ESE- and WNW-dipping normal faults also seen in these image logs. A hydraulic fracturing stress test conducted at 931 m indicates that the magnitude of Shmin is 13.8 MPa, which is ~0.61 of the calculated vertical stress, Sv. Coulomb failure calculations using these stresses and friction coefficients measured on core indicate that shear failure should be induced on pre-existing fractures once fluid pressures are increased ~2.5 MPa or more above the ambient formation fluid pressure. The resulting activation of faults well-oriented for shear failure should generate a zone of enhanced permeability propagating to the SSW, in the direction of nearby geothermal injection and production wells, and to the NNE, into an unexploited part of the field. Stimulation of well 27-15 began in August 2010, and is being monitored by flow-rate/pressure recording, a local seismic network, periodic temperature-pressure-flowmeter logging, tracer tests and pressure transient analyses. An initial phase of shear stimulation was carried out over 110 days at low pressures (< Shmin) and low injection rates (< 380 l/min), employing stepwise increases in pressure to induce shear failure along pre-existing natural fractures. This phase increased injectivity by one order of magnitude. Chelating agents and mud acid treatments were then used to dissolve mineral precipitates and open up partially sealed fractures. This chemical stimulation phase only temporarily increased injectivity and worsened the stability of the wellbore. A large-volume hydraulic fracturing operation was subsequently carried out at high pressures (> Shmin) and high injection rates (up to 2800 l/min) over 23 days to promote fluid pressure transfer to greater distances from the borehole, resulting in an additional 4-fold increase in injectivity. Locations of microseismic events induced by these operations plus tracer testing showed growth of the stimulated volume between well 27-15 and active geothermal wells located ~0.5 to 2 km to the SSW, as predicted by the stress model. Future plans for the Desert Peak EGS project involve augmenting the seismic array before executing additional hydraulic fracturing and shear stimulation to further improve the injection performance of well 27-15.

  6. Limited output transcranial electrical stimulation (LOTES-2017): Engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk.

    PubMed

    Bikson, Marom; Paneri, Bhaskar; Mourdoukoutas, Andoni; Esmaeilpour, Zeinab; Badran, Bashar W; Azzam, Robin; Adair, Devin; Datta, Abhishek; Fang, Xiao Hui; Wingeier, Brett; Chao, Daniel; Alonso-Alonso, Miguel; Lee, Kiwon; Knotkova, Helena; Woods, Adam J; Hagedorn, David; Jeffery, Doug; Giordano, James; Tyler, William J

    We present device standards for low-power non-invasive electrical brain stimulation devices classified as limited output transcranial electrical stimulation (tES). Emerging applications of limited output tES to modulate brain function span techniques to stimulate brain or nerve structures, including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial pulsed current stimulation (tPCS), have engendered discussion on how access to technology should be regulated. In regards to legal regulations and manufacturing standards for comparable technologies, a comprehensive framework already exists, including quality systems (QS), risk management, and (inter)national electrotechnical standards (IEC). In Part 1, relevant statutes are described for medical and wellness application. While agencies overseeing medical devices have broad jurisdiction, enforcement typically focuses on those devices with medical claims or posing significant risk. Consumer protections regarding responsible marketing and manufacture apply regardless. In Part 2 of this paper, we classify the electrical output performance of devices cleared by the United States Food and Drug Administration (FDA) including over-the-counter (OTC) and prescription electrostimulation devices, devices available for therapeutic or cosmetic purposes, and devices indicated for stimulation of the body or head. Examples include iontophoresis devices, powered muscle stimulators (PMS), cranial electrotherapy stimulation (CES), and transcutaneous electrical nerve stimulation (TENS) devices. Spanning over 13 FDA product codes, more than 1200 electrical stimulators have been cleared for marketing since 1977. The output characteristics of conventional tDCS, tACS, and tPCS techniques are well below those of most FDA cleared devices, including devices that are available OTC and those intended for stimulation on the head. This engineering analysis demonstrates that with regard to output performance and standing regulation, the availability of tDCS, tACS, or tPCS to the public would not introduce risk, provided such devices are responsibly manufactured and legally marketed. In Part 3, we develop voluntary manufacturer guidance for limited output tES that is aligned with current regulatory standards. Based on established medical engineering and scientific principles, we outline a robust and transparent technical framework for ensuring limited output tES devices are designed to minimize risks, while also supporting access and innovation. Alongside applicable medical and government activities, this voluntary industry standard (LOTES-2017) further serves an important role in supporting informed decisions by the public. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Brain Stimulation in Addiction

    PubMed Central

    Salling, Michael C; Martinez, Diana

    2016-01-01

    Localized stimulation of the human brain to treat neuropsychiatric disorders has been in place for over 20 years. Although these methods have been used to a greater extent for mood and movement disorders, recent work has explored brain stimulation methods as potential treatments for addiction. The rationale behind stimulation therapy in addiction involves reestablishing normal brain function in target regions in an effort to dampen addictive behaviors. In this review, we present the rationale and studies investigating brain stimulation in addiction, including transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation. Overall, these studies indicate that brain stimulation has an acute effect on craving for drugs and alcohol, but few studies have investigated the effect of brain stimulation on actual drug and alcohol use or relapse. Stimulation therapies may achieve their effect through direct or indirect modulation of brain regions involved in addiction, either acutely or through plastic changes in neuronal transmission. Although these mechanisms are not well understood, further identification of the underlying neurobiology of addiction and rigorous evaluation of brain stimulation methods has the potential for unlocking an effective, long-term treatment of addiction. PMID:27240657

  8. Transcranial magnetic stimulation--may be useful as a preoperative screen of motor tract function.

    PubMed

    Galloway, Gloria M; Dias, Brennan R; Brown, Judy L; Henry, Christina M; Brooks, David A; Buggie, Ed W

    2013-08-01

    Transcranial motor stimulation with noninvasive cortical surface stimulation, using a high-intensity magnetic field referred to as transcranial magnetic stimulation generally, is considered a nonpainful technique. In contrast, transcranial electric stimulation of the motor tracts typically cannot be done in unanesthesized patients. Intraoperative monitoring of motor tract function with transcranial electric stimulation is considered a standard practice in many institutions for patients during surgical procedures in which there is potential risk of motor tract impairment so that the risk of paraplegia or paraparesis can be reduced. Because transcranial electric stimulation cannot be typically done in the outpatient setting, transcranial magnetic stimulation may be able to provide a well-tolerated method for evaluation of the corticospinal motor tracts before surgery. One hundred fifty-five patients aged 5 to 20 years were evaluated preoperatively with single-stimulation nonrepetitive transcranial magnetic stimulation for preoperative assessment. The presence of responses to transcranial magnetic stimulation reliably predicted the presence of responses to transcranial electric stimulation intraoperatively. No complications occurred during the testing, and findings were correlated to the clinical history and used in the setup of the surgical monitoring.

  9. Fractures, stress and fluid flow prior to stimulation of well 27-15, Desert Peak, Nevada, EGS project

    USGS Publications Warehouse

    Davatzes, Nicholas C.; Hickman, Stephen H.

    2009-01-01

    A suite of geophysical logs has been acquired for structural, fluid flow and stress analysis of well 27-15 in the Desert Peak Geothermal Field, Nevada, in preparation for stimulation and development of an Enhanced Geothermal System (EGS). Advanced Logic Technologies Borehole Televiewer (BHTV) and Schlumberger Formation MicroScanner (FMS) image logs reveal extensive drilling-induced tensile fractures, showing that the current minimum compressive horizontal stress, Shmin, in the vicinity of well 27-15 is oriented along an azimuth of 114±17°. This orientation is consistent with the dip direction of recently active normal faults mapped at the surface and with extensive sets of fractures and some formation boundaries seen in the BHTV and FMS logs. Temperature and spinner flowmeter surveys reveal several minor flowing fractures that are well oriented for normal slip, although over-all permeability in the well is quite low. These results indicate that well 27-15 is a viable candidate for EGS stimulation and complements research by other investigators including cuttings analysis, a reflection seismic survey, pressure transient and tracer testing, and micro-seismic monitoring.

  10. A comparative study of approaches to compute the field distribution of deep brain stimulation in the Hemiparkinson rat model.

    PubMed

    Bohme, Andrea; van Rienen, Ursula

    2016-08-01

    Computational modeling of the stimulating field distribution during Deep Brain Stimulation provides an opportunity to advance our knowledge of this neurosurgical therapy for Parkinson's disease. There exist several approaches to model the target region for Deep Brain Stimulation in Hemi-parkinson Rats with volume conductor models. We have described and compared the normalized mapping approach as well as the modeling with three-dimensional structures, which include curvilinear coordinates to assure an anatomically realistic conductivity tensor orientation.

  11. Nanostructured cavity devices for extracellular stimulation of HL-1 cells.

    PubMed

    Czeschik, Anna; Rinklin, Philipp; Derra, Ulrike; Ullmann, Sabrina; Holik, Peter; Steltenkamp, Siegfried; Offenhäusser, Andreas; Wolfrum, Bernhard

    2015-01-01

    Microelectrode arrays (MEAs) are state-of-the-art devices for extracellular recording and stimulation on biological tissue. Furthermore, they are a relevant tool for the development of biomedical applications like retina, cochlear and motor prostheses, cardiac pacemakers and drug screening. Hence, research on functional cell-sensor interfaces, as well as the development of new surface structures and modifications for improved electrode characteristics, is a vivid and well established field. However, combining single-cell resolution with sufficient signal coupling remains challenging due to poor cell-electrode sealing. Furthermore, electrodes with diameters below 20 µm often suffer from a high electrical impedance affecting the noise during voltage recordings. In this study, we report on a nanocavity sensor array for voltage-controlled stimulation and extracellular action potential recordings on cellular networks. Nanocavity devices combine the advantages of low-impedance electrodes with small cell-chip interfaces, preserving a high spatial resolution for recording and stimulation. A reservoir between opening aperture and electrode is provided, allowing the cell to access the structure for a tight cell-sensor sealing. We present the well-controlled fabrication process and the effect of cavity formation and electrode patterning on the sensor's impedance. Further, we demonstrate reliable voltage-controlled stimulation using nanostructured cavity devices by capturing the pacemaker of an HL-1 cell network.

  12. 75 FR 39957 - Certificate of Alternative Compliance for the Offshore Supply Vessel/Well Stimulation Vessel BLUE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-13

    ... Compliance for the Offshore Supply Vessel/Well Stimulation Vessel BLUE TARPON AGENCY: Coast Guard, DHS... issued for the offshore supply vessel BLUE TARPON as required by 33 U.S.C. 1605(c) and 33 CFR 81.18... Regulation, Parts 81 and 89, has been issued for the offshore supply vessel BLUE TARPON, O.N. 1226288. The...

  13. Atomoxetine versus Stimulants in the Community Treatment of Children with ADHD: An Electronic Diary Study

    ERIC Educational Resources Information Center

    Whalen, Carol K.; Henker, Barbara; Ishikawa, Sharon S.; Emmerson, Natasha A.; Swindle, Ralph; Johnston, Joseph A.

    2010-01-01

    Objective: To compare the morning and afternoon/evening functioning of children with ADHD treated in the community with either atomoxetine or long-acting stimulants and reported to be doing well. Method: 109 8- to 12-year-olds and their mothers participated in one of three groups: stimulants (STIM, N = 26), atomoxetine (ATMX, N = 25), or…

  14. Electro-acupuncture stimulation acts on the basal ganglia output pathway to ameliorate motor impairment in Parkinsonian model rats.

    PubMed

    Jia, Jun; Li, Bo; Sun, Zuo-Li; Yu, Fen; Wang, Xuan; Wang, Xiao-Min

    2010-04-01

    The role of electro-acupuncture (EA) stimulation on motor symptoms in Parkinson's disease (PD) has not been well studied. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), EA stimulation improved motor impairment in a frequency-dependent manner. Whereas EA stimulation at a low frequency (2 Hz) had no effect, EA stimulation at a high frequency (100 Hz) significantly improved motor coordination. However, neither low nor high EA stimulation could significantly enhance dopamine levels in the striatum. EA stimulation at 100 Hz normalized the MFB lesion-induced increase in midbrain GABA content, but it had no effect on GABA content in the globus pallidus. These results suggest that high-frequency EA stimulation improves motor impairment in MFB-lesioned rats by increasing GABAergic inhibition in the output structure of the basal ganglia.

  15. Infrared neural stimulation in the cochlea

    PubMed Central

    Richter, Claus-Peter; Rajguru, Suhrud; Bendett, Mark

    2014-01-01

    The application of photonics to manipulate and stimulate neurons and to study neural networks has gained momentum over the last decade. Two general methods have been used: the genetic expression of light or temperature sensitive ion channels in the plasma membrane of neurons (Optogenetics and Thermogenetics) and the direct stimulation of neurons using infrared radiation (Infrared Neural Stimulation, INS). Both approaches have their strengths and challenges, which are well understood with a profound understanding of the light tissue interaction(s). This paper compares the opportunities of the methods for the use in cochlear prostheses. Ample data are already available on the stimulation of the cochlea with INS. The data show that the stimulation is selective, feasible at rates that would be sufficient to encode acoustic information and may be beneficial over conventional pulsed electrical stimulation. A third approach, using lasers in stress confinement to generate pressure waves and to stimulate the functional cochlea mechanically will also be discussed. PMID:25075260

  16. Infrared neural stimulation in the cochlea

    NASA Astrophysics Data System (ADS)

    Richter, Claus-Peter; Rajguru, Suhrud; Bendett, Mark

    2013-03-01

    The application of photonics to manipulate and stimulate neurons and to study neural networks has gained momentum over the last decade. Two general methods have been used: the genetic expression of light or temperature sensitive ion channels in the plasma membrane of neurons (Optogenetics and Thermogenetics) and the direct stimulation of neurons using infrared radiation (Infrared Neural Stimulation, INS). Both approaches have their strengths and challenges, which are well understood with a profound understanding of the light tissue interaction(s). This paper compares the opportunities of the methods for the use in cochlear prostheses. Ample data are already available on the stimulation of the cochlea with INS. The data show that the stimulation is selective, feasible at rates that would be sufficient to encode acoustic information and may be beneficial over conventional pulsed electrical stimulation. A third approach, using lasers in stress confinement to generate pressure waves and to stimulate the functional cochlea mechanically will also be discussed.

  17. Nonmedical Use of Prescription Stimulants among College Students: Associations with ADHD and Polydrug Use

    PubMed Central

    Arria, Amelia M.; Caldeira, Kimberly M.; O’Grady, Kevin E.; Vincent, Kathryn B.; Johnson, Erin P.; Wish, Eric D.

    2008-01-01

    Study Objectives This study examines nonmedical use of prescription stimulants (NPS) among 1,253 first-year college students. Comparisons are made between non-users, nonmedical users, and medical users of prescription stimulants for ADHD (ADHD+), some of whom overused their medication. Design Cross-sectional study. Setting Large public university in the mid-Atlantic region. Subjects Twelve hundred fifty three college students. Measurements and Main Results Of 1,208 students who were not using prescription stimulants medically for ADHD (ADHD-), 18.0% (n = 218) engaged in NPS. Among 45 ADHD+ students, 26.7% (n = 12) overused their ADHD medication at least once in their lifetime, and 15.6% (n = 7) nonmedically used someone else’s prescription stimulants at least once in their lifetime. Among nonmedical users, NPS was infrequent and mainly associated with studying, although 15.6% used prescription stimulants to party or to get high. Lifetime NPS was associated with past-year other drug use. Both NPS and overuse of prescribed stimulants for ADHD were independently associated with past-year use of five drugs, holding constant sociodemographic characteristics. NPS was also associated with alcohol and marijuana dependence. Conclusions Physicians should be vigilant for possible overuse and/or diversion of prescription stimulants among ADHD+ patients attending college, as well as the co-occurrence of illicit drug use with NPS. Initiation of comprehensive drug prevention activities that involve parents as well as colleges is encouraged to raise awareness of NPS and its association with illicit drug use. PMID:18225963

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

    PubMed

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

    2016-01-01

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

  19. Auditory subliminal stimulation: a re-examination.

    PubMed

    Urban, M J

    1992-04-01

    Unconscious or subliminal perception has historically been a thorny issue in psychology. It has been the subject of debate and experimentation since the turn of the century. While psychologists now agree that the phenomenon of visual subliminal stimulation is real, disagreement continues over the effects of such stimulation as well as to its existence in other sensory modalities, notably the auditory. The present paper provides an overview of unresolved issues in auditory subliminal stimulation which explains much of the difficulty that has been encountered in experimental work in this area. A context is proposed for considering the effects of auditory subliminal stimulation and an overview of current investigations in this field is provided.

  20. Graded activation of the intrinsic laryngeal muscles for vocal fold posturing

    PubMed Central

    Chhetri, Dinesh K.; Neubauer, Juergen; Berry, David A.

    2010-01-01

    Previous investigations using in vivo models to study the role of intrinsic laryngeal muscles in phonation have used neuromuscular stimulation to study voice parameters. However, these studies used coarse stimulation techniques using limited levels of neuromuscular stimulation. In the current investigation, a technique for fine control of laryngeal posturing was developed using graded stimulation of the laryngeal nerves. Vocal fold strain history to graded stimulation and a methodology for establishing symmetric laryngeal activation is presented. This methodology has immediate applications for the study of laryngeal paralysis and paresis, as well as general questions of neuromuscular control of the larynx. PMID:20369979

  1. Functional MRI Detection of Hemodynamic Response of Repeated Median Nerve Stimulation

    PubMed Central

    Ai, Leo; Oya, Hiroyuki; Howard, Matthew; Xiong, Jinhu

    2012-01-01

    Median nerve stimulation is a commonly used technique in the clinical setting to determine areas of neuronal function in the brain. Neuronal activity of repeated median nerve stimulation is well studied. The cerebral hemodynamic response of the stimulation, on the other hand, is not very clear. In this study, we investigate how cerebral hemodynamics behaves over time using the same repeated median nerve stimulation. Ten subjects received constant repeated electrical stimulation to the right median nerve. Each subject had fMRI scans while receiving said stimulations for seven runs. Our results show that the BOLD signal significantly decreases across each run. Significant BOLD signal decreases can also be seen within runs. These results are consistent with studies that have studied the hemodynamic habituation effect with other forms of stimulation. However, the results do not completely agree with the findings of studies where evoked potentials were examined. Thus, further inquiry of how evoked potentials and cerebral hemodynamics are coupled when using constant stimulations is needed. PMID:23228312

  2. Newberry Volcano EGS Demonstration Stimulation Modeling

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Trenton T. Cladouhos, Matthew Clyne, Maisie Nichols,; Susan Petty, William L. Osborn, Laura Nofziger

    2011-10-23

    As a part of Phase I of the Newberry Volcano EGS Demonstration project, several data sets were collected to characterize the rock volume around the well. Fracture, fault, stress, and seismicity data has been collected by borehole televiewer, LiDAR elevation maps, and microseismic monitoring. Well logs and cuttings from the target well (NWG 55-29) and core from a nearby core hole (USGS N-2) have been analyzed to develop geothermal, geochemical, mineralogical and strength models of the rock matrix, altered zones, and fracture fillings (see Osborn et al., this volume). These characterization data sets provide inputs to models used to planmore » and predict EGS reservoir creation and productivity. One model used is AltaStim, a stochastic fracture and flow software model developed by AltaRock. The software's purpose is to model and visualize EGS stimulation scenarios and provide guidance for final planning. The process of creating an AltaStim model requires synthesis of geologic observations at the well, the modeled stress conditions, and the stimulation plan. Any geomechanical model of an EGS stimulation will require many assumptions and unknowns; thus, the model developed here should not be considered a definitive prediction, but a plausible outcome given reasonable assumptions. AltaStim is a tool for understanding the effect of known constraints, assumptions, and conceptual models on plausible outcomes.« less

  3. Optogenetic stimulation of multiwell MEA plates for neural and cardiac applications

    NASA Astrophysics Data System (ADS)

    Clements, Isaac P.; Millard, Daniel C.; Nicolini, Anthony M.; Preyer, Amanda J.; Grier, Robert; Heckerling, Andrew; Blum, Richard A.; Tyler, Phillip; McSweeney, K. M.; Lu, Yi-Fan; Hall, Diana; Ross, James D.

    2016-03-01

    Microelectrode array (MEA) technology enables advanced drug screening and "disease-in-a-dish" modeling by measuring the electrical activity of cultured networks of neural or cardiac cells. Recent developments in human stem cell technologies, advancements in genetic models, and regulatory initiatives for drug screening have increased the demand for MEA-based assays. In response, Axion Biosystems previously developed a multiwell MEA platform, providing up to 96 MEA culture wells arrayed into a standard microplate format. Multiwell MEA-based assays would be further enhanced by optogenetic stimulation, which enables selective excitation and inhibition of targeted cell types. This capability for selective control over cell culture states would allow finer pacing and probing of cell networks for more reliable and complete characterization of complex network dynamics. Here we describe a system for independent optogenetic stimulation of each well of a 48-well MEA plate. The system enables finely graded control of light delivery during simultaneous recording of network activity in each well. Using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes and rodent primary neuronal cultures, we demonstrate high channel-count light-based excitation and suppression in several proof-of-concept experimental models. Our findings demonstrate advantages of combining multiwell optical stimulation and MEA recording for applications including cardiac safety screening, neural toxicity assessment, and advanced characterization of complex neuronal diseases.

  4. Concepts and methods in neuromodulation and functional electrical stimulation: an introduction.

    PubMed

    Holsheimer, J

    1998-04-01

    This article introduces two clinical fields in which stimulation is applied to the nervous system: neuromodulation and functional electrical stimulation. The concepts underlying these fields and their main clinical applications, as well as the methods and techniques used in each field, are described. Concepts and techniques common in one field that might be beneficial to the other are discussed. 1998 Blackwell Science, Inc.

  5. Criminality Among Rural Stimulant Users in the United States

    PubMed Central

    Leukefeld, Carl; Staton-Tindall, Michele; Duvall, Jamieson; Garrity, Thomas; Stoops, William; Falck, Russel; Wang, Jichuan; Carlson, Robert; Sexton, Rocky; Wright, Patricia; Booth, Brenda

    2009-01-01

    Despite the increase in media attention on “meth cooking” in rural areas of the United States, little is known about rural stimulant use, particularly the criminality associated with stimulant use. Data were collected from community stimulant users in rural Ohio, Arkansas, and Kentucky (N=709). Findings from three logistic regression models indicate that younger stimulant users (x =32.55, SD = 10.35), those with more convictions, and those who used crack frequently were significantly more likely to have been arrested for committing a substance-related crime, a property crime, or another crime in the 6-months before entering the study. Implications include the need for longitudinal studies to further understand rural stimulant use as well as increasing community and corrections-based drug abuse prevention and treatment interventions for stimulant users who live in rural areas. PMID:21686091

  6. Criminality Among Rural Stimulant Users in the United States.

    PubMed

    Oser, Carrie; Leukefeld, Carl; Staton-Tindall, Michele; Duvall, Jamieson; Garrity, Thomas; Stoops, William; Falck, Russel; Wang, Jichuan; Carlson, Robert; Sexton, Rocky; Wright, Patricia; Booth, Brenda

    2011-07-01

    Despite the increase in media attention on "meth cooking" in rural areas of the United States, little is known about rural stimulant use, particularly the criminality associated with stimulant use. Data were collected from community stimulant users in rural Ohio, Arkansas, and Kentucky (N=709). Findings from three logistic regression models indicate that younger stimulant users (x =32.55, SD = 10.35), those with more convictions, and those who used crack frequently were significantly more likely to have been arrested for committing a substance-related crime, a property crime, or another crime in the 6-months before entering the study. Implications include the need for longitudinal studies to further understand rural stimulant use as well as increasing community and corrections-based drug abuse prevention and treatment interventions for stimulant users who live in rural areas.

  7. Surgical treatment of insular tumours with tractography, functional magnetic resonance imaging, transcranial electrical stimulation and direct subcortical stimulation support.

    PubMed

    Majchrzak, Krzysztof; Bobek-Billewicz, Barbara; Tymowski, Michał; Adamczyk, Piotr; Majchrzak, Hneryk; Ladziński, Piotr

    2011-01-01

    Surgical treatment of insular tumours carries significant risks of limb paresis or speech disturbances due to their localization. The development of intraoperative neuromonitoring techniques that involve evoked motor potentials induced via both direct and transcranial cortical electrical stimulation as well as direct subcortical white matter stimulation, intraoperative application of preoperative tractography and functional magnetic resonance imaging (fMRI) in conjunction with neuronavigation resulted in significant reduction of postoperative disabilities that enabled widening of indications for surgical treatment. The aim of this study was to present the authors' own experience with surgical treatment of insular gliomas. Our cohort comprises 30 patients with insular gliomas treated at the Department of Neurosurgery in Sosnowiec. Clinical symptoms included sensorimotor partial seizures in 86.6%; generalized seizures in 23.3%; persistent headaches in 16.6% and hemiparesis in 6.6%. All the patients were operated on with intraoperative neuromonitoring that included transcranial cortical stimulation, direct subcortical white matter stimulation as well as tractography and fMRI concurrently with neuronavigation. The analysis in-cluded postoperative neurological evaluation along with the assessment of the radicalism of resection evaluated based on postoperative MRI. Postoperatively, four patients had permanent hemiparesis (13.3%); importantly, two out of those patients had preoperative deficits (6.6%). Persistent speech disturbances were present in four patients (13.3%). Partial sensorimotor seizures were noted in two patients (6.6%). Seizures in the other patients receded. Intraoperative transcranial electrical stimulation as well as direct subcortical white matter stimulation along with tractography (DTI) and fMRI facilitated gross total resection of insular gliomas in 53.5%, subtotal in 13.3% and partial resection in 33.1%. Implementation of TES, direct subcortical white master stimulation, DTI and fMRI into the management protocol of the surgical treatment of insular tumours resulted in total and subtotal resections in 66% of cases with permanent motor disability in 6.6% of patients. Poor prognosis for independent living after surgery mainly affects patients with WHO grade III or IV.

  8. REAL-TIME TRACER MONITORING OF RESERVOIR STIMULATION PROCEDURES VIA ELECTRONIC WIRELINE AND TELEMETRY DATA TRANSMISSION

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    George L. Scott III

    2005-01-01

    Finalized Phase 2-3 project work has field-proven two separate real-time reservoir processes that were co-developed via funding by the National Energy Technology Laboratory (NETL). Both technologies are presently patented in the United States and select foreign markets; a downhole-commingled reservoir stimulation procedure and a real-time tracer-logged fracturing diagnostic system. Phase 2 and early Phase 3 project work included the research, development and well testing of a U.S. patented gamma tracer fracturing diagnostic system. This stimulation logging process was successfully field-demonstrated; real-time tracer measurement of fracture height while fracturing was accomplished and proven technically possible. However, after the initial well tests,more » there were several licensing issues that developed between service providers that restricted and minimized Realtimezone's (RTZ) ability to field-test the real-time gamma diagnostic system as was originally outlined for this project. Said restrictions were encountered after when one major provider agreed to license their gamma logging tools to another. Both of these companies previously promised contributory support toward Realtimezone's DE-FC26-99FT40129 project work, however, actual support was less than desired when newly-licensed wireline gamma logging tools from one company were converted by the other from electric wireline into slickline, batter-powered ''memory'' tools for post-stimulation logging purposes. Unfortunately, the converted post-fracture measurement memory tools have no applications in experimentally monitoring real-time movement of tracers in the reservoir concurrent with the fracturing treatment. RTZ subsequently worked with other tracer gamma-logging tool companies for basic gamma logging services, but with lessened results due to lack of multiple-isotope detection capability. In addition to real-time logging system development and well testing, final Phase 2 and Phase 3 project work included the development of a real-time reservoir stimulation procedure, which was successfully field-demonstrated and is presently patented in the U.S. and select foreign countries, including Venezuela, Brazil and Canada. Said patents are co-owned by RTZ and the National Energy Technology Lab (NETL). In 2002, Realtimezone and the NETL licensed said patents to Halliburton Energy Services (HES). Additional licensing agreements (LA) are anticipated with other service industry companies in 2005. Final Phase 3 work has led to commercial applications of the real-time reservoir stimulation procedure. Four successfully downhole-mixed well tests were conducted with commercially expected production results. The most recent, fourth field test was a downhole-mixed stimulated well completed in June, 2004, which currently produces 11 BOPD with 90 barrels of water per day. Conducted Phase 2 and Phase 3 field-test work to date has resulted in the fine-tuning of a real-time enhanced stimulation system that will significantly increase future petroleum well recoveries in the United States and foreign petroleum fields, both onshore and offshore, and in vertical and horizontal wells.« less

  9. Endothelial cells of extremely premature infants display impaired immune response after proinflammatory stimulation.

    PubMed

    Wisgrill, Lukas; Muck, Martina; Wessely, Isabelle; Berger, Angelika; Spittler, Andreas; Förster-Waldl, Elisabeth; Sadeghi, Kambis

    2018-01-01

    BackgroundEndothelial cells (ECs) exert immunological functions such as production of proinflammatory cytokines/chemokines as well as facilitation of extravasation of immune cells into infected tissue. Limited data are available on the functionality of ECs from extremely preterm neonates during infection. Accordingly, the aim of our study was to investigate the immune response of premature ECs after proinflammatory stimulation.MethodsCell adhesion receptors' expression and function, nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFκB) signaling, and chemokine production were analyzed in umbilical cord ECs from extremely preterm and term neonates after proinflammatory stimulation.ResultsP-selectin and E-selectin surface expression as well as NFκB signaling were lower after lipopolysaccharide (LPS) stimulation in premature ECs. Preterm ECs exhibited lower, but significant, cell-adhesive functions after LPS stimulation compared with term ECs. CCL2/CXCL8 chemokine secretion was significantly upregulated after proinflammatory stimulation in both groups. CXCL10 production was significantly increased in term but not in preterm ECs upon stimulation with tumor necrosis factor compared with unstimulated ECs.ConclusionExtremely premature ECs showed partly reduced expression levels and function of cell adhesion molecules. Both NFκB signaling and chemokine/cytokine production were reduced in premature ECs. The diminished endothelial proinflammatory immune response might result in impaired infection control of preterm newborns rendering them prone to severe infection.

  10. Deep brain stimulation mechanisms: beyond the concept of local functional inhibition.

    PubMed

    Deniau, Jean-Michel; Degos, Bertrand; Bosch, Clémentine; Maurice, Nicolas

    2010-10-01

    Deep brain electrical stimulation has become a recognized therapy in the treatment of a variety of motor disorders and has potentially promising applications in a wide range of neurological diseases including neuropsychiatry. Behavioural observation that electrical high-frequency stimulation of a given brain area induces an effect similar to a lesion suggested a mechanism of functional inhibition. In vitro and in vivo experiments as well as per operative recordings in patients have revealed a variety of effects involving local changes of neuronal excitability as well as widespread effects throughout the connected network resulting from activation of axons, including antidromic activation. Here we review current data regarding the local and network activity changes induced by high-frequency stimulation of the subthalamic nucleus and discuss this in the context of motor restoration in Parkinson's disease. Stressing the important functional consequences of axonal activation in deep brain stimulation mechanisms, we highlight the importance of developing anatomical knowledge concerning the fibre connections of the putative therapeutic targets. © 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  11. Optimal stimulation as theoretical basis of hyperactivity.

    PubMed

    Zentall, Sydney

    1975-07-01

    Current theory and practice in the clinical and educational management of hyperactive children recommend reduction of environmental stimulation, assuming hyperactive and distractable behaviors to be due to overstimulation. This paper reviews research suggesting that hyperactive behavior may result from a homeostatic mechanism that functions to increase stimulation for a child experienceing insufficient sensory stimulation. It is suggested that the effectiveness of drug and behavior therapies, as well as evidence from the field of sensory deprivation, further support the theory of a homeostatic mechanism that attempts to optimize sensory input.

  12. A clinical repetitive transcranial magnetic stimulation service in Australia: 6 years on.

    PubMed

    Galletly, Cherrie A; Clarke, Patrick; Carnell, Benjamin L; Gill, Shane

    2015-11-01

    There is considerable research evidence for the effectiveness of repetitive transcranial magnetic stimulation in the treatment of depression. However, there is little information about its acceptability and outcomes in clinical settings. This naturalistic study reports on a clinical repetitive transcranial magnetic stimulation service that has been running in Adelaide, South Australia (SA), for 6 years. During this time, 214 complete acute courses were provided to patients with treatment-resistant Major Depressive Disorder. Patients received either sequential bilateral or right unilateral repetitive transcranial magnetic stimulation treatment involving either 18 or 20 sessions given over 6 or 4 weeks respectively. Data included patient demographic details, duration of depression, and medication at the beginning of their repetitive transcranial magnetic stimulation course. The Hamilton Depression Rating Scale was used to assess response to repetitive transcranial magnetic stimulation. Of those undergoing a first-time acute treatment course of repetitive transcranial magnetic stimulation (N = 167), 28% achieved remission, while a further 12% met the criteria for a response to treatment. Most patients (N = 123, 77%) had previously been treated with five or more antidepressant medications, and 77 (47%) had previously received electroconvulsive therapy. Referral rates remained high over the 6 years, indicating acceptance of the treatment by referring psychiatrists. There were no significant adverse events, and the treatment was generally well tolerated. In all, 41 patients (25%) had a second course of repetitive transcranial magnetic stimulation and 6 (4%) patients had a third course; 21 patients subsequently received maintenance repetitive transcranial magnetic stimulation. This naturalistic study showed that repetitive transcranial magnetic stimulation was well accepted by both psychiatrists and patients, and has good efficacy and safety. Furthermore, repetitive transcranial magnetic stimulation can provide a useful treatment alternative as part of outpatient mental health services for people with depression. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  13. Long-wavelength stimulated emission and carrier lifetimes in HgCdTe-based waveguide structures with quantum wells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rumyantsev, V. V., E-mail: rumyantsev@ipm.sci-nnov.ru; Fadeev, M. A.; Morozov, S. V.

    2016-12-15

    The interband photoconductivity and photoluminescence in narrow-gap HgCdTe-based waveguide structures with quantum wells (QWs) (designed for long-wavelength stimulated emission under optical pumping) are investigated. The photoconductivity relaxation times in n-type structures reach several microseconds, due to which stimulated emission at a wavelength of 10.2 μm occurs at a low threshold pump intensity (~100 W/cm{sup 2}) at 20 K. In the p-type structures obtained by annealing (to increase the mercury vacancy concentration), even spontaneous emission from the QWs is not detected because of a dramatic decrease in the carrier lifetime with respect to Shockley–Read–Hall nonradiative recombination.

  14. Reducing interaction in simultaneous paired stimulation with CI.

    PubMed

    Vellinga, Dirk; Bruijn, Saskia; Briaire, Jeroen J; Kalkman, Randy K; Frijns, Johan H M

    2017-01-01

    In this study simultaneous paired stimulation of electrodes in cochlear implants is investigated by psychophysical experiments in 8 post-lingually deaf subjects (and one extra subject who only participated in part of the experiments). Simultaneous and sequential monopolar stimulation modes are used as references and are compared to channel interaction compensation, partial tripolar stimulation and a novel sequential stimulation strategy named phased array compensation. Psychophysical experiments are performed to investigate both the loudness integration during paired stimulation at the main electrodes as well as the interaction with the electrode contact located halfway between the stimulating pair. The study shows that simultaneous monopolar stimulation has more loudness integration on the main electrodes and more interaction in between the electrodes than sequential stimulation. Channel interaction compensation works to reduce the loudness integration at the main electrodes, but does not reduce the interaction in between the electrodes caused by paired stimulation. Partial tripolar stimulation uses much more current to reach the needed loudness, but shows the same interaction in between the electrodes as sequential monopolar stimulation. In phased array compensation we have used the individual impedance matrix of each subject to calculate the current needed on each electrode to exactly match the stimulation voltage along the array to that of sequential stimulation. The results show that the interaction in between the electrodes is the same as monopolar stimulation. The strategy uses less current than partial tripolar stimulation, but more than monopolar stimulation. In conclusion, the paper shows that paired stimulation is possible if the interaction is compensated.

  15. The Northwest Geysers EGS Demonstration Project, California. Pre-stimulation Modeling and Interpretation of the Stimulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rutqvist, Jonny; Dobson, Patrick F.; Garcia, Julio

    The Northwest Geysers Enhanced Geothermal System (EGS) demonstration project aims to create an EGS by directly and systematically injecting cool water at relatively low pressure into a known High Temperature (280–400 °C) Zone (HTZ) located under the conventional (240 °C) geothermal steam reservoir at The Geysers geothermal field in California. Here we report that , the results of coupled thermal, hydraulic, and mechanical (THM) analyses made using a model developed as part of the pre-stimulation phase of the EGS demonstration project is presented. The model simulations were conducted in order to investigate injection strategies and the resulting effects of cold-watermore » injection upon the EGS system; in particular to predict the extent of the stimulation zone for a given injection schedule. The actual injection began on October 6, 2011, and in this paper a comparison of pre-stimulation model predictions with micro-earthquake (MEQ) monitoring data over the first few months of a one-year injection program is presented. The results show that, by using a calibrated THM model based on historic injection and MEQ data at a nearby well, the predicted extent of the stimulation zone (defined as a zone of high MEQ density around the injection well) compares well with observed seismicity. The modeling indicates that the MEQ events are related to shear reactivation of preexisting fractures, which is triggered by the combined effects of injection-induced cooling around the injection well and small changes in steam pressure as far as half a kilometer away from the injection well. Pressure-monitoring data at adjacent wells and satellite-based ground-surface deformation data were also used to validate and further calibrate reservoir-scale hydraulic and mechanical model properties. The pressure signature monitored from the start of the injection was particularly useful for a precise back-calculation of reservoir porosity. Ultimately, the first few months of reservoir pressure and surface deformation data were useful for estimating the reservoir-rock permeability and elastic modulus. Finally, although the extent of the calculated stimulation zone matches the field observations over the first few months of injection, the observed surface deformations and MEQ evolution showed more heterogeneous behavior as a result of more complex geology, including minor faults and fracture zones that are important for consideration in the analysis of energy production and the long-term evolution of the EGS system.« less

  16. The Northwest Geysers EGS Demonstration Project, California. Pre-stimulation Modeling and Interpretation of the Stimulation

    DOE PAGES

    Rutqvist, Jonny; Dobson, Patrick F.; Garcia, Julio; ...

    2013-10-17

    The Northwest Geysers Enhanced Geothermal System (EGS) demonstration project aims to create an EGS by directly and systematically injecting cool water at relatively low pressure into a known High Temperature (280–400 °C) Zone (HTZ) located under the conventional (240 °C) geothermal steam reservoir at The Geysers geothermal field in California. Here we report that , the results of coupled thermal, hydraulic, and mechanical (THM) analyses made using a model developed as part of the pre-stimulation phase of the EGS demonstration project is presented. The model simulations were conducted in order to investigate injection strategies and the resulting effects of cold-watermore » injection upon the EGS system; in particular to predict the extent of the stimulation zone for a given injection schedule. The actual injection began on October 6, 2011, and in this paper a comparison of pre-stimulation model predictions with micro-earthquake (MEQ) monitoring data over the first few months of a one-year injection program is presented. The results show that, by using a calibrated THM model based on historic injection and MEQ data at a nearby well, the predicted extent of the stimulation zone (defined as a zone of high MEQ density around the injection well) compares well with observed seismicity. The modeling indicates that the MEQ events are related to shear reactivation of preexisting fractures, which is triggered by the combined effects of injection-induced cooling around the injection well and small changes in steam pressure as far as half a kilometer away from the injection well. Pressure-monitoring data at adjacent wells and satellite-based ground-surface deformation data were also used to validate and further calibrate reservoir-scale hydraulic and mechanical model properties. The pressure signature monitored from the start of the injection was particularly useful for a precise back-calculation of reservoir porosity. Ultimately, the first few months of reservoir pressure and surface deformation data were useful for estimating the reservoir-rock permeability and elastic modulus. Finally, although the extent of the calculated stimulation zone matches the field observations over the first few months of injection, the observed surface deformations and MEQ evolution showed more heterogeneous behavior as a result of more complex geology, including minor faults and fracture zones that are important for consideration in the analysis of energy production and the long-term evolution of the EGS system.« less

  17. Preparation of acellular myocardial scaffolds with well-preserved cardiomyocyte lacunae, and method for applying mechanical and electrical simulation to tissue construct.

    PubMed

    Wang, Bo; Williams, Lakiesha N; de Jongh Curry, Amy L; Liao, Jun

    2014-01-01

    Cardiac tissue engineering/regeneration using decellularized myocardium has attracted great research attention due to its potential benefit for myocardial infarction (MI) treatment. Here we describe an optimal decellularization protocol to generate 3D porcine myocardial scaffolds with well-preserved cardiomyocyte lacunae and a multi-stimulation bioreactor that is able to provide coordinated mechanical and electrical stimulation for facilitating cardiac construct development.

  18. Sensorimotor Modulation of Mood and Depression: In Search of an Optimal Mode of Stimulation

    PubMed Central

    Canbeyli, Resit

    2013-01-01

    Depression involves a dysfunction in an affective fronto-limbic circuitry including the prefrontal cortices, several limbic structures including the cingulate cortex, the amygdala, and the hippocampus as well as the basal ganglia. A major emphasis of research on the etiology and treatment of mood disorders has been to assess the impact of centrally generated (top-down) processes impacting the affective fronto-limbic circuitry. The present review shows that peripheral (bottom-up) unipolar stimulation via the visual and the auditory modalities as well as by physical exercise modulates mood and depressive symptoms in humans and animals and activates the same central affective neurocircuitry involved in depression. It is proposed that the amygdala serves as a gateway by articulating the mood regulatory sensorimotor stimulation with the central affective circuitry by emotionally labeling and mediating the storage of such emotional events in long-term memory. Since both amelioration and aggravation of mood is shown to be possible by unipolar stimulation, the review suggests that a psychophysical assessment of mood modulation by multimodal stimulation may uncover mood ameliorative synergisms and serve as adjunctive treatment for depression. Thus, the integrative review not only emphasizes the relevance of investigating the optimal levels of mood regulatory sensorimotor stimulation, but also provides a conceptual springboard for related future research. PMID:23908624

  19. Neurologic Complications of Psychomotor Stimulant Abuse.

    PubMed

    Sanchez-Ramos, Juan

    2015-01-01

    Psychomotor stimulants are drugs that act on the central nervous system (CNS) to increase alertness, elevate mood, and produce a sense of well-being. These drugs also decrease appetite and the need for sleep. Stimulants can enhance stamina and improve performance in tasks that have been impaired by fatigue or boredom. Approved therapeutic applications of stimulants include attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. These agents also possess potent reinforcing properties that can result in excessive self-administration and abuse. Chronic use is associated with adverse effects including psychosis, seizures, and cerebrovascular accidents, though these complications usually occur in individuals with preexisting risk factors. This chapter reviews the adverse neurologic consequences of chronic psychomotor stimulant use and abuse, with a focus on two prototypical stimulants methamphetamine and cocaine. © 2015 Elsevier Inc. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2018-04-01

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

  1. Optogenetic stimulation of myelination (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Yang, In Hong; Lee, Hae Ung; Thakor, Nitish V.

    2016-03-01

    Myelination is governed by axon-glia interaction which is modulated by neural activity. Currently, the effects of subcellular activation of neurons which induce neural activity upon myelination are not well understood. To identify if subcellular neuronal stimulation can enhance myelination, we developed a novel system for focal stimulation of neural activity with optogenetic in a compartmentalized microfluidic platform. In our systems, stimulation for neurons in restricted subcellular parts, such as cell bodies and axons promoted oligodendrocyte differentiation and the myelination of axons the just as much as whole cell activation of neurons did. The number of premature O4 positive oligodendrocytes was reduced and the numbers of mature and myelin basic protein-positive oligodendrocytes was increased both by subcellular optogenetic stimulation.

  2. A technical guide to tDCS, and related non-invasive brain stimulation tools

    PubMed Central

    Woods, AJ; Antal, A; Bikson, M; Boggio, PS; Brunoni, AR; Celnik, P; Cohen, LG; Fregni, F; Herrmann, CS; Kappenman, ES; Knotkova, H; Liebetanz, D; Miniussi, C; Miranda, PC; Paulus, W; Priori, A; Reato, D; Stagg, C; Wenderoth, N; Nitsche, MA

    2015-01-01

    Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain. PMID:26652115

  3. [Response of peripheral blood mononuclear leukocyte to nickel stimulation in patients with systemic and contact allergy to nickel].

    PubMed

    Czarnobilska, Ewa; Thor, Piotr; Kaszuba-Zwoinska, Jolanta; Słodowska-Hajduk, Zofia; Stobiecki, Marcin; Dyga, Wojciech; Wsołek, Katarzyna; Obtułowicz, Krystyna

    2006-01-01

    Nickel is knows as the most common cause of allergic contact dermatitis, as well as diffuse eczema, allergic rhinitis and bronchial asthma. The mechanism of contact allergy to nickel is well known. In spite of numerous investigations, the mechanism of systemic allergy to nickel is still not clear. 22 patients with positive patch tests to nickel were analyzed. On basis of clinical symptoms the patients were divided into two groups: 1. with contact allergy dermatitis to nickel--8 patients 2. with systemic allergy to nickel (allergic rhinitis and/or diffuse eczema--14 patients. The control group included non-atopic patients with negative patch test to nickel--6 patients. 10 ml of blood were taken from each patient and peripheral mononuclear blood cells (PMBC) were isolated. In PBMC culture, NiSO4 and PHA were stimulated. The control group was non-stimulated cells. The supernatants were collected after 3 and 6 days of culture and the levels of cytokines IL-5, 4 and IFNgamma were measured (ELISA). The concentration of IFNgamma in supernatants from stimulated as well as non-stimulated cells from patients with contact allergy to nickel was higher in comparison to the control group. The concentration of IL-5 in this group was low. There was an increase in the production of IFNgamma and IL-5 after NiSO4 stimulation in patients with systemic allergy to nickel. The higher concentration of IFNgamma in the same groups of patients investigated was in supernatants from the third day of PBMC culture were compared to the sixth day. After 3 and 6 days of culture, the concentration of IL-4 (ELISA) was below detection level in all supernatants analyzed. IFNgamma plays an essential role in the mechanism of developing of contact allergy to nickel; and IFNgamma as well as IL-5 play a role in the mechanism of developing systemic allergy to nickel. The third day of PBMC culture is more reliable for IFNgamma estimation.

  4. Use of Vagus Nerve Stimulator on Children With Primary Generalized Epilepsy.

    PubMed

    Welch, William P; Sitwat, Bilal; Sogawa, Yoshimi

    2018-06-01

    To describe the response to vagus nerve stimulator (VNS) in otherwise neurotypical children with medically intractable primary generalized epilepsy. Retrospective chart review of patients who underwent vagus nerve stimulator surgery between January 2011 and December 2015. Eleven patients were identified. Median follow-up duration was 2.5 years (1.2-8.4 years). Prior to vagus nerve stimulator surgery, all patients had at least 1 seizure per week, and 7/11 (64%) had daily seizures. At 1-year follow-up after vagus nerve stimulator, 7/11 (64%) reported improved seizure frequency and 6/11 (55%) reported fewer than 1 seizure per month. Three patients (27%) reported complications related to vagus nerve stimulator surgery, and no patients required device removal. In children with medically intractable primary generalized epilepsy, vagus nerve stimulator is well tolerated and appears to lead to improvement in seizure frequency. Improvement was not attributable to epilepsy classification, age at vagus nerve stimulator implantation, output current, duty cycle, or follow-up duration.

  5. Fluid mechanics in dentinal microtubules provides mechanistic insights into the difference between hot and cold dental pain.

    PubMed

    Lin, Min; Luo, Zheng Yuan; Bai, Bo Feng; Xu, Feng; Lu, Tian Jian

    2011-03-23

    Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not "equally sensitive" to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices.

  6. Fluid Mechanics in Dentinal Microtubules Provides Mechanistic Insights into the Difference between Hot and Cold Dental Pain

    PubMed Central

    Lin, Min; Luo, Zheng Yuan; Bai, Bo Feng; Xu, Feng; Lu, Tian Jian

    2011-01-01

    Dental thermal pain is a significant health problem in daily life and dentistry. There is a long-standing question regarding the phenomenon that cold stimulation evokes sharper and more shooting pain sensations than hot stimulation. This phenomenon, however, outlives the well-known hydrodynamic theory used to explain dental thermal pain mechanism. Here, we present a mathematical model based on the hypothesis that hot or cold stimulation-induced different directions of dentinal fluid flow and the corresponding odontoblast movements in dentinal microtubules contribute to different dental pain responses. We coupled a computational fluid dynamics model, describing the fluid mechanics in dentinal microtubules, with a modified Hodgkin-Huxley model, describing the discharge behavior of intradental neuron. The simulated results agreed well with existing experimental measurements. We thence demonstrated theoretically that intradental mechano-sensitive nociceptors are not “equally sensitive” to inward (into the pulp) and outward (away from the pulp) fluid flows, providing mechanistic insights into the difference between hot and cold dental pain. The model developed here could enable better diagnosis in endodontics which requires an understanding of pulpal histology, neurology and physiology, as well as their dynamic response to the thermal stimulation used in dental practices. PMID:21448459

  7. Fundamentals of Transcranial Electric and Magnetic Stimulation Dose: Definition, Selection, and Reporting Practices

    PubMed Central

    Peterchev, Angel V.; Wagner, Timothy A.; Miranda, Pedro C.; Nitsche, Michael A.; Paulus, Walter; Lisanby, Sarah H.; Pascual-Leone, Alvaro; Bikson, Marom

    2011-01-01

    The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported. The biological effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biological effects of EM stimulation. We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated. This paper provides fundamental definition and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol. PMID:22305345

  8. Fundamentals of transcranial electric and magnetic stimulation dose: definition, selection, and reporting practices.

    PubMed

    Peterchev, Angel V; Wagner, Timothy A; Miranda, Pedro C; Nitsche, Michael A; Paulus, Walter; Lisanby, Sarah H; Pascual-Leone, Alvaro; Bikson, Marom

    2012-10-01

    The growing use of transcranial electric and magnetic (EM) brain stimulation in basic research and in clinical applications necessitates a clear understanding of what constitutes the dose of EM stimulation and how it should be reported. This paper provides fundamental definitions and principles for reporting of dose that encompass any transcranial EM brain stimulation protocol. The biologic effects of EM stimulation are mediated through an electromagnetic field injected (via electric stimulation) or induced (via magnetic stimulation) in the body. Therefore, transcranial EM stimulation dose ought to be defined by all parameters of the stimulation device that affect the electromagnetic field generated in the body, including the stimulation electrode or coil configuration parameters: shape, size, position, and electrical properties, as well as the electrode or coil current (or voltage) waveform parameters: pulse shape, amplitude, width, polarity, and repetition frequency; duration of and interval between bursts or trains of pulses; total number of pulses; and interval between stimulation sessions and total number of sessions. Knowledge of the electromagnetic field generated in the body may not be sufficient but is necessary to understand the biologic effects of EM stimulation. We believe that reporting of EM stimulation dose should be guided by the principle of reproducibility: sufficient information about the stimulation parameters should be provided so that the dose can be replicated. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. State of the Art: Novel Applications for Cortical Stimulation.

    PubMed

    De Ridder, Dirk; Perera, Sanjaya; Vanneste, Sven

    2017-04-01

    Electrical stimulation via implanted electrodes that overlie the cortex of the brain is an upcoming neurosurgical technique that was hindered for a long time by insufficient knowledge of how the brain functions in a dynamic, physiological, and pathological way, as well as by technological limitations of the implantable stimulation devices. This paper provides an overview of cortex stimulation via implantable devices and introduces future possibilities to improve cortex stimulation. Cortex stimulation was initially used preoperatively as a technique to localize functions in the brain and only later evolved into a treatment technique. It was first used for pain, but more recently a multitude of pathologies are being targeted by cortex stimulation. These disorders are being treated by stimulating different cortical areas of the brain. Risks and complications are essentially similar to those related to deep brain stimulation and predominantly include haemorrhage, seizures, infection, and hardware failures. For cortex stimulation to fully mature, further technological development is required to predict its outcomes and improve stimulation designs. This includes the development of network science-based functional connectivity approaches, genetic analyses, development of navigated high definition transcranial alternating current stimulation, and development of pseudorandom stimulation designs for preventing habituation. In conclusion, cortex stimulation is a nascent but very promising approach to treating a variety of diseases, but requires further technological development for predicting outcomes, such as network science based functional connectivity approaches, genetic analyses, development of navigated transcranial electrical stimulation, and development of pseudorandom stimulation designs for preventing habituation. © 2017 International Neuromodulation Society.

  10. From Target Selection to Post-Stimulation Analysis: Example of an Unconventional Faulted Reservoir

    NASA Astrophysics Data System (ADS)

    LeCalvez, J. H.; Williams, M.; Xu, W.; Stokes, J.; Moros, H.; Maxwell, S. C.; Conners, S.

    2011-12-01

    As the global balance of supply and demand forces the hydrocarbon industry toward unconventional resources, technology- and economics-driven shale oil and gas production is gaining momentum throughout many basins worldwide. Production from such unconventional plays is facilitated by massive hydraulic fracturing treatments aimed at increasing permeability and reactivating natural fractures. Large-scale faulting and fracturing partly control stress distribution, hence stimulation-derived hydraulically-induced fracture systems development. Therefore, careful integrated approaches to target selection, treatment staging, and stimulation methods need to be used to economically maximize ultimate hydrocarbon recovery. We present a case study of a multistage, multilateral stimulation project in the Fort Worth Basin, Texas. Wells had to be drilled within city limits in a commercially developing building area. Well locations and trajectories were determined in and around large-scale faults using 3D surface seismic with throws varying from seven to thirty meters. As a result, three horizontal wells were drilled in the Lower Barnett Shale section, 150 m apart with the central well landed about 25 m shallower than the outside laterals. Surface seismic indicates that the surface locations are on top of a major fault complex with the lateral sections drilling away from the major fault system and through a smaller fault. Modeling of the borehole-based microseismic monitoring options led to the selection of an optimum set of configurations given the operational restrictions faced: monitoring would mainly take place using a horizontal array to be tractored downhole and moved according to the well and stage to be monitored. Wells were completed using a perf-and-plug approach allowing for each stimulation stage to obtain a precise orientation of the various three-component accelerometers of the monitoring array as well as the calibration of the velocity model used to process the microseismic data acquired. Real-time microseismic monitoring allowed (i) to avoid the water-bearing formation below the zone of interest, (ii) to bypass the faulted zone, and (iii) to modify as needed the perforation and stimulation plans. Completion led to an initial gas production of over 3 MMCF/day each. Early decline rates confirm successful completion in avoiding the faulted areas. Initial observations of the slickwater fracturing stimulation treatments for these three wells using an integrated approach involving mechanical modelling calibrated using microseismic data indicate that (i) a long bi-wing-like fracture system initiated prior to being followed by a complex fracture network; thus, explaining the fact that some events are mapped relatively far away from the injection site, (ii) proppant generally settled down in the near wellbore area during the fracture network development due to rapid decrease of fluid flow velocity away from the injection side. Initial b-value results seem to indicate that the target reservoir is naturally fractured and that the influence of a large fault system in the vicinity of the treated zone could be asserted.

  11. High frequency switched-mode stimulation can evoke post synaptic responses in cerebellar principal neurons

    PubMed Central

    van Dongen, Marijn N.; Hoebeek, Freek E.; Koekkoek, S. K. E.; De Zeeuw, Chris I.; Serdijn, Wouter A.

    2015-01-01

    This paper investigates the efficacy of high frequency switched-mode neural stimulation. Instead of using a constant stimulation amplitude, the stimulus is switched on and off repeatedly with a high frequency (up to 100 kHz) duty cycled signal. By means of tissue modeling that includes the dynamic properties of both the tissue material as well as the axon membrane, it is first shown that switched-mode stimulation depolarizes the cell membrane in a similar way as classical constant amplitude stimulation. These findings are subsequently verified using in vitro experiments in which the response of a Purkinje cell is measured due to a stimulation signal in the molecular layer of the cerebellum of a mouse. For this purpose a stimulator circuit is developed that is able to produce a monophasic high frequency switched-mode stimulation signal. The results confirm the modeling by showing that switched-mode stimulation is able to induce similar responses in the Purkinje cell as classical stimulation using a constant current source. This conclusion opens up possibilities for novel stimulation designs that can improve the performance of the stimulator circuitry. Care has to be taken to avoid losses in the system due to the higher operating frequency. PMID:25798105

  12. In vitro stimulation with a strongly pulsed electromagnetic field on rat basophilic leukemia cells

    NASA Astrophysics Data System (ADS)

    Choi, J. W.; Shin, S. C.; Kim, S.; Chung, E. R.; Bang, J. H.; Cho, G. I.; Choi, S. D.; Park, Y. S.; Jang, T. S.; Yoo, Y. M.; Lee, S. S.; Hwang, D. G.

    2010-05-01

    In this study, the effects of pulsed electromagnetic field stimulation with a strong magnetic field on rat basophilic leukemia (RBL-2H3) cells were investigated to confirm the efficacy of the magnetic stimulator for biomedical applications. The maximum intensity of the magnetic field generated from the stimulation coil was 0.203 T, and the transition time was 126 μs. The oscillation time and frequency of the pulsed field were almost 0.1 ms and 8 kHz, respectively. The cell count as well as the mRNA expression and DNA sequence of the cytokine genes, such as the tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4), of the stimulated RBL-2H3 cells were analyzed with a hemocytometer and via reverse transcriptase polymerase chain reaction to determine the physiological response under a strong pulse field. After 12 h stimulation, cell death was observed at an increasing scale with the increase in the stimulation time. On the other hand, the cells that were stimulated for 10 min almost doubled as the interval time between the stimulations was extended.

  13. Effect of anatomical variability in brain on transcranial magnetic stimulation treatment

    NASA Astrophysics Data System (ADS)

    Syeda, F.; Magsood, H.; Lee, E. G.; El-Gendy, A. A.; Jiles, D. C.; Hadimani, R. L.

    2017-05-01

    Transcranial Magnetic Stimulation is a non-invasive clinical therapy used to treat depression and migraine, and shows further promise as treatment for Parkinson's disease, Alzheimer's disease, and other neurological disorders. However, it is yet unclear as to how anatomical differences may affect stimulation from this treatment. We use finite element analysis to model and analyze the results of Transcranial Magnetic Stimulation in various head models. A number of heterogeneous head models have been developed using MRI data of real patients, including healthy individuals as well as patients of Parkinson's disease. Simulations of Transcranial Magnetic Stimulation performed on 22 anatomically different models highlight the differences in induced stimulation. A standard Figure of 8 coil is used with frequency 2.5 kHz, placed 5 mm above the head. We compare cortical stimulation, volume of brain tissue stimulated, specificity, and maximum E-field induced in the brain for models ranging from ages 20 to 60. Results show that stimulation varies drastically between patients of the same age and health status depending upon brain-scalp distance, which is not necessarily a linear progression with age.

  14. Effect of Parkinson's Disease in Transcranial Magnetic Stimulation Treatment

    NASA Astrophysics Data System (ADS)

    Syeda, Farheen; Magsood, Hamzah; Lee, Erik; El-Gendy, Ahmed; Jiles, David; Hadimani, Ravi

    Transcranial Magnetic Stimulation is a non-invasive clinical therapy used to treat depression and migraine, and shows further promise as treatment for Parkinson's disease, Alzheimer's disease, and other neurological disorders. However, it is yet unclear as to how anatomical differences may affect stimulation from this treatment. We use finite element analysis to model and analyze the results of Transcranial Magnetic Stimulation in various head models. A number of heterogeneous head models have been developed using MRI data of real patients, including healthy individuals as well as patients of Parkinson's disease. Simulations of Transcranial Magnetic Stimulation performed on 22 anatomically different models highlight the differences in induced stimulation. A standard Figure of 8 coil is used with frequency 2.5 kHz, placed 5 mm above the head. We compare cortical stimulation, volume of brain tissue stimulated, specificity, and maximum E-field induced in the brain for models ranging from ages 20 to 60. Results show that stimulation varies drastically between patients of the same age and health status depending upon brain-scalp distance, which is not necessarily a linear progression with age.

  15. Psychostimulants and Cognition: A Continuum of Behavioral and Cognitive Activation

    PubMed Central

    Wood, Suzanne; Sage, Jennifer R.; Shuman, Tristan

    2014-01-01

    Psychostimulants such as cocaine have been used as performance enhancers throughout recorded history. Although psychostimulants are commonly prescribed to improve attention and cognition, a great deal of literature has described their ability to induce cognitive deficits, as well as addiction. How can a single drug class be known to produce both cognitive enhancement and impairment? Properties of the particular stimulant drug itself and individual differences between users have both been suggested to dictate the outcome of stimulant use. A more parsimonious alternative, which we endorse, is that dose is the critical determining factor in cognitive effects of stimulant drugs. Herein, we review several popular stimulants (cocaine, amphetamine, methylphenidate, modafinil, and caffeine), outlining their history of use, mechanism of action, and use and abuse today. One common graphic depiction of the cognitive effects of psychostimulants is an inverted U–shaped dose-effect curve. Moderate arousal is beneficial to cognition, whereas too much activation leads to cognitive impairment. In parallel to this schematic, we propose a continuum of psychostimulant activation that covers the transition from one drug effect to another as stimulant intake is increased. Low doses of stimulants effect increased arousal, attention, and cognitive enhancement; moderate doses can lead to feelings of euphoria and power, as well as addiction and cognitive impairment; and very high doses lead to psychosis and circulatory collapse. This continuum helps account for the seemingly disparate effects of stimulant drugs, with the same drug being associated with cognitive enhancement and impairment. PMID:24344115

  16. Multisensory Stimulation to Improve Low- and Higher-Level Sensory Deficits after Stroke: A Systematic Review.

    PubMed

    Tinga, Angelica Maria; Visser-Meily, Johanna Maria Augusta; van der Smagt, Maarten Jeroen; Van der Stigchel, Stefan; van Ee, Raymond; Nijboer, Tanja Cornelia Wilhelmina

    2016-03-01

    The aim of this systematic review was to integrate and assess evidence for the effectiveness of multisensory stimulation (i.e., stimulating at least two of the following sensory systems: visual, auditory, and somatosensory) as a possible rehabilitation method after stroke. Evidence was considered with a focus on low-level, perceptual (visual, auditory and somatosensory deficits), as well as higher-level, cognitive, sensory deficits. We referred to the electronic databases Scopus and PubMed to search for articles that were published before May 2015. Studies were included which evaluated the effects of multisensory stimulation on patients with low- or higher-level sensory deficits caused by stroke. Twenty-one studies were included in this review and the quality of these studies was assessed (based on eight elements: randomization, inclusion of control patient group, blinding of participants, blinding of researchers, follow-up, group size, reporting effect sizes, and reporting time post-stroke). Twenty of the twenty-one included studies demonstrate beneficial effects on low- and/or higher-level sensory deficits after stroke. Notwithstanding these beneficial effects, the quality of the studies is insufficient for valid conclusion that multisensory stimulation can be successfully applied as an effective intervention. A valuable and necessary next step would be to set up well-designed randomized controlled trials to examine the effectiveness of multisensory stimulation as an intervention for low- and/or higher-level sensory deficits after stroke. Finally, we consider the potential mechanisms of multisensory stimulation for rehabilitation to guide this future research.

  17. Hydraulic stimulation or low water injection in fractured reservoir of the geothermal well GRT-1 at Rittershoffen (France)?

    NASA Astrophysics Data System (ADS)

    Vidal, J.; Genter, A.; Schmittbuhl, J.; Baujard, C.

    2016-12-01

    In the Upper Rhine Graben, several deep geothermal projects, such as at Soultz-sous-Forêts (France) or Basel (Switzerland), were based on the Enhanced Geothermal System technology. The principle underlying this technology consists of increasing the low initial natural hydraulic performance of pre-existing natural fractures in the geothermal granitic reservoir via hydraulic and/or chemical stimulations. Hydraulic stimulation consists of injection of a large amount of water at a high flow rate to promote hydroshearing of pre-existing fractures. At Soultz-sous-Forêts and Basel, the maximum wellhead pressures were 16 MPa and 30 MPa respectively which induced larger magnitude seismic events of 2.9 and 3.4 respectively. Those specific induced seismicity events were felt by local population. At Rittershoffen (France), the geothermal well GRT-1 was drilled in 2012 down to a depth of 2.6 km and penetrates fractured sandstones and granite. The reservoir temperature reaches more than 160°C but the production flowrate was too low for an industrial project economically viable. Thus, the well was subjected to Thermal, Chemical and Hydraulic stimulations, which improved the injectivity index five-fold. During the hydraulic operation, a moderate volume of water was injected from the wellhead with a low pressure of 3 MPa. Approximately 300 microseismic events were detected during the hydraulic stimulations. Due to the low wellhead pressure during injection, no events were felt by nearby residents. The goal of the study was to assess the impact of the stimulation by comparing pre- and post-stimulation acoustic image logs. This comparison revealed minor modifications of almost all the natural fractures. However, not all of these fractures are associated with permeability enhancement. The most important permeability enhancement was observed on the originally permeable fault zone affecting the top of the granitic basement. In the Upper Rhine Graben, several deep geothermal projects, such as at Soultz-sous-Forêts (France) or Basel (Switzerland), were based on the Enhanced Geothermal System technology. The principle underlying this technology consists of increasing the low initial natural hydraulic performance of pre-existing natural fractures in the geothermal granitic reservoir via hydraulic and/or chemical stimulations. Hydraulic stimulation consists of injection of a large amount of water at a high flow rate to promote hydroshearing of pre-existing fractures. At Soultz-sous-Forêts and Basel, the maximum wellhead pressures were 16 MPa and 30 MPa respectively which induced larger magnitude seismic events of 2.9 and 3.4 respectively. Those specific induced seismicity events were felt by local population. At Rittershoffen (France), the geothermal well GRT-1 was drilled in 2012 down to a depth of 2.6 km and penetrates fractured sandstones and granite. The reservoir temperature reaches more than 160°C but the production flowrate was too low for an industrial project economically viable. Thus, the well was subjected to Thermal, Chemical and Hydraulic stimulations, which improved the injectivity index five-fold. During the hydraulic operation, a moderate volume of water was injected from the wellhead with a low pressure of 3 MPa. Approximately 300 microseismic events were detected during the hydraulic stimulations. Due to the low wellhead pressure during injection, no events were felt by nearby residents. The goal of the study was to assess the impact of the stimulation by comparing pre- and post-stimulation acoustic image logs. This comparison revealed minor modifications of almost all the natural fractures. However, not all of these fractures are associated with permeability enhancement. The most important permeability enhancement was observed on the originally permeable fault zone affecting the top of the granitic basement.

  18. Design and Application of a Circuit for Measuring Frequency and Duty Cycle of Stimulated Bioelectrical Signal

    NASA Astrophysics Data System (ADS)

    Tang, Li-Ming; Chang, Ben-Kang; Liu, Tie-Bing; Wu, Min; Ling, Gang

    2002-12-01

    To design a new type of circuit for measuring frequency & duty cycle of stimulated bioelectrical signal for the project of 'the map of neuron-threshold in human brain and its clinical application'. This circuit was designed according to the character of stimulated bioelectrical signals. It was tested and improved and then used in the neuron -threshold stimulator. The circuit was found to be very accurate for measuring frequency and the error for measuring duty cycle was below 0.2%. This circuit is well-designed, simple, easy to use, and can be applied in many systems.

  19. Note: Automated optical focusing on encapsulated devices for scanning light stimulation systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bitzer, L. A.; Benson, N., E-mail: niels.benson@uni-due.de; Schmechel, R.

    Recently, a scanning light stimulation system with an automated, adaptive focus correction during the measurement was introduced. Here, its application on encapsulated devices is discussed. This includes the changes an encapsulating optical medium introduces to the focusing process as well as to the subsequent light stimulation measurement. Further, the focusing method is modified to compensate for the influence of refraction and to maintain a minimum beam diameter on the sample surface.

  20. Superantigens and their association with dermatological inflammatory diseases: facts and hypotheses.

    PubMed

    Jappe, U

    2000-01-01

    Superantigens have been suggested to play an important role in the pathogenesis of several inflammatory skin diseases as well as systemic diseases such as atopic dermatitis, psoriasis, vasculitis, T-cell lymphoma and autoimmune diseases. Infections often precede the onset and relapse of these diseases, and antibiotic treatment with or without additional glucocorticosteroids and immunoglobulins is occasionally successful. Superantigens are microbial proteins that are able to stimulate up to 20% of the naive T-cell population in a non-specific way. They are produced by gram-positive and -negative bacteria as well as by viruses, parasites and yeasts. The importance of the pathogenic role of superantigens is determined by the potency to induce inflammation by extensive cytokine release after T-cell stimulation and/or T-cell-mediated cytotoxicity and, thereby, tissue damage. Furthermore, superantigens may be able to induce autoimmune processes by stimulation of autoreactive T-cells as well as autoantibody production by stimulation of B-cells. Among the diseases associated with superantigens, atopic dermatitis, guttate and chronic plaque psoriasis, as well as Kawasaki disease, are by far the best-characterized. Nevertheless, conflicting results have been obtained and formal proof of a pathogenic role of superantigens in these diseases is still lacking. The aim of this review is to summarize the data on superantigens in terms of their distribution in microorganisms, their interactions with the adaptive immune system and their contribution to skin pathology.

  1. Triiodothyronine stimulates VEGF expression and secretion via steroids and HIF-1α in murine Leydig cells.

    PubMed

    Dhole, Bodhana; Gupta, Surabhi; Venugopal, Senthil Kumar; Kumar, Anand

    2018-06-01

    Leydig cells are the principal steroidogenic cells of the testis. Leydig cells also secrete a number of growth factors including vascular endothelial growth factor (VEGF) which has been shown to regulate both testicular steroidogenesis and spermatogenesis. The thyroid hormone, T 3, is known to stimulate steroidogenesis in Leydig cells. T 3 has also been shown to stimulate VEGF production in a variety of cell lines. However, studies regarding the effect of T 3 on VEGF synthesis and secretion by the Leydig cells were lacking. Therefore, we investigated the effect of T 3 on VEGF synthesis and secretion in a mouse Leydig tumour cell line, MLTC-1. The effect of T 3 was compared with that of LH/cAMP and hypoxia, two known stimulators of Leydig cell functions. The cells were treated with T 3 , 8-Br-cAMP (a cAMP analogue), or CoCl 2 (a hypoxia mimetic) and VEGF secreted in the cell supernatant was measured using ELISA. The mRNA levels of VEGF were measured by quantitative RT-PCR. In the MLTC-1 cells, T 3 , 8-Br-cAMP, and CoCl 2 stimulated VEGF mRNA levels and the protein secretion. T 3 also increased steroid secretion as well as HIF-1α protein levels, two well-established upstream regulators of VEGF. Inhibitors of steroidogenesis as well as HIF-1α resulted in inhibition of T 3 -stimulated VEGF secretion by the MLTC-1 cells. This suggested a mediatory role of steroids and HIF-1α protein in T 3 -stimulated VEGF secretion by MLTC-1 cells. The mediation by steroids and HIF-1α were independent of each other. 8-Br-cAMP: 8-bromo - 3', 5' cyclic adenosine monophosphate; CoCl 2 : cobalt chloride; HIF-1α: hypoxia inducible factor -1α; LH: luteinizing hormone; T 3 : 3, 5, 3'-L-triiodothyronine; VEGF: vascular endothelial growth factor.

  2. Immediate effect of laryngeal surface electrical stimulation on swallowing performance.

    PubMed

    Takahashi, Keizo; Hori, Kazuhiro; Hayashi, Hirokazu; Fujiu-Kurachi, Masako; Ono, Takahiro; Tsujimura, Takanori; Magara, Jin; Inoue, Makoto

    2018-01-01

    Surface electrical stimulation of the laryngeal region is used to improve swallowing in dysphagic patients. However, little is known about how electrical stimulation affects tongue movements and related functions. We investigated the effect of electrical stimulation on tongue pressure and hyoid movement, as well as suprahyoid and infrahyoid muscle activity, in 18 healthy young participants. Electrical stimulation (0.2-ms duration, 80 Hz, 80% of each participant's maximal tolerance) of the laryngeal region was applied. Each subject swallowed 5 ml of barium sulfate liquid 36 times at 10-s intervals. During the middle 2 min, electrical stimulation was delivered. Tongue pressure, electromyographic activity of the suprahyoid and infrahyoid muscles, and videofluorographic images were simultaneously recorded. Tongue pressure during stimulation was significantly lower than before or after stimulation and was significantly greater after stimulation than at baseline. Suprahyoid activity after stimulation was larger than at baseline, while infrahyoid muscle activity did not change. During stimulation, the position of the hyoid at rest was descended, the highest hyoid position was significantly inferior, and the vertical movement was greater than before or after stimulation. After stimulation, the positions of the hyoid at rest and at the maximum elevation were more superior than before stimulation. The deviation of the highest positions of the hyoid before and after stimulation corresponded to the differences in tongue pressures at those times. These results suggest that surface electrical stimulation applied to the laryngeal region during swallowing may facilitate subsequent hyoid movement and tongue pressure generation after stimulation. NEW & NOTEWORTHY Surface electrical stimulation applied to the laryngeal region during swallowing may facilitate subsequent hyoid movement and tongue pressure generation after stimulation. Tongue muscles may contribute to overshot recovery more than hyoid muscles.

  3. Coupling BCI and cortical stimulation for brain-state-dependent stimulation: methods for spectral estimation in the presence of stimulation after-effects

    PubMed Central

    Walter, Armin; Murguialday, Ander R.; Rosenstiel, Wolfgang; Birbaumer, Niels; Bogdan, Martin

    2012-01-01

    Brain-state-dependent stimulation (BSDS) combines brain-computer interfaces (BCIs) and cortical stimulation into one paradigm that allows the online decoding for example of movement intention from brain signals while simultaneously applying stimulation. If the BCI decoding is performed by spectral features, stimulation after-effects such as artefacts and evoked activity present a challenge for a successful implementation of BSDS because they can impair the detection of targeted brain states. Therefore, efficient and robust methods are needed to minimize the influence of the stimulation-induced effects on spectral estimation without violating the real-time constraints of the BCI. In this work, we compared four methods for spectral estimation with autoregressive (AR) models in the presence of pulsed cortical stimulation. Using combined EEG-TMS (electroencephalography-transcranial magnetic stimulation) as well as combined electrocorticography (ECoG) and epidural electrical stimulation, three patients performed a motor task using a sensorimotor-rhythm BCI. Three stimulation paradigms were varied between sessions: (1) no stimulation, (2) single stimulation pulses applied independently (open-loop), or (3) coupled to the BCI output (closed-loop) such that stimulation was given only while an intention to move was detected using neural data. We found that removing the stimulation after-effects by linear interpolation can introduce a bias in the estimation of the spectral power of the sensorimotor rhythm, leading to an overestimation of decoding performance in the closed-loop setting. We propose the use of the Burg algorithm for segmented data to deal with stimulation after-effects. This work shows that the combination of BCIs controlled with spectral features and cortical stimulation in a closed-loop fashion is possible when the influence of stimulation after-effects on spectral estimation is minimized. PMID:23162436

  4. Brain-controlled muscle stimulation for the restoration of motor function

    PubMed Central

    Ethier, Christian; Miller, Lee E

    2014-01-01

    Loss of the ability to move, as a consequence of spinal cord injury or neuromuscular disorder, has devastating consequences for the paralyzed individual, and great economic consequences for society. Functional Electrical Stimulation (FES) offers one means to restore some mobility to these individuals, improving not only their autonomy, but potentially their general health and well-being as well. FES uses electrical stimulation to cause the paralyzed muscles to contract. Existing clinical systems require the stimulation to be preprogrammed, with the patient typically using residual voluntary movement of another body part to trigger and control the patterned stimulation. The rapid development of neural interfacing in the past decade offers the promise of dramatically improved control for these patients, potentially allowing continuous control of FES through signals recorded from motor cortex, as the patient attempts to control the paralyzed body part. While application of these ‘Brain Machine Interfaces’ (BMIs) has undergone dramatic development for control of computer cursors and even robotic limbs, their use as an interface for FES has been much more limited. In this review, we consider both FES and BMI technologies and discuss the prospect for combining the two to provide important new options for paralyzed individuals. PMID:25447224

  5. Cognitive enhancement as a pharmacotherapy target for stimulant addiction.

    PubMed

    Sofuoglu, Mehmet

    2010-01-01

    No medications have been proven to be effective for cocaine and methamphetamine addiction. Attenuation of drug reward has been the main strategy for medications development, but this approach has not led to effective treatments. Thus, there is a need to identify novel treatment targets in addition to the brain reward system. To propose a novel treatment strategy for stimulant addiction that will focus on medications enhancing cognitive function and attenuating drug reward. Pre-clinical and clinical literature on potential use of cognitive enhancers for stimulant addiction pharmacotherapy was reviewed. Cocaine and methamphetamine users show significant cognitive impairments, especially in attention, working memory and response inhibition functions. The cognitive impairments seem to be predictive of poor treatment retention and outcome. Medications targeting acetylcholine and norepinephrine are particularly well suited for enhancing cognitive function in stimulant users. Many cholinergic and noradrenergic medications are on the market and have a good safety profile and low abuse potential. These include galantamine, donepezil and rivastigmine (cholinesterase inhibitors), varenicline (partial nicotine agonist), guanfacine (alpha(2)-adrenergic agonist) and atomoxetine (norepinephrine transporter inhibitor). Future clinical studies designed optimally to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these cognitive enhancers for stimulant addiction.

  6. Motor unit recruitment during neuromuscular electrical stimulation: a critical appraisal.

    PubMed

    Bickel, C Scott; Gregory, Chris M; Dean, Jesse C

    2011-10-01

    Neuromuscular electrical stimulation (NMES) is commonly used in clinical settings to activate skeletal muscle in an effort to mimic voluntary contractions and enhance the rehabilitation of human skeletal muscles. It is also used as a tool in research to assess muscle performance and/or neuromuscular activation levels. However, there are fundamental differences between voluntary- and artificial-activation of motor units that need to be appreciated before NMES protocol design can be most effective. The unique effects of NMES have been attributed to several mechanisms, most notably, a reversal of the voluntary recruitment pattern that is known to occur during voluntary muscle contractions. This review outlines the assertion that electrical stimulation recruits motor units in a nonselective, spatially fixed, and temporally synchronous pattern. Additionally, it synthesizes the evidence that supports the contention that this recruitment pattern contributes to increased muscle fatigue when compared with voluntary actions and provides some commentary on the parameters of electrical stimulation as well as emerging technologies being developed to facilitate NMES implementation. A greater understanding of how electrical stimulation recruits motor units, as well as the benefits and limitations of its use, is highly relevant when using this tool for testing and training in rehabilitation, exercise, and/or research.

  7. A technical guide to tDCS, and related non-invasive brain stimulation tools.

    PubMed

    Woods, A J; Antal, A; Bikson, M; Boggio, P S; Brunoni, A R; Celnik, P; Cohen, L G; Fregni, F; Herrmann, C S; Kappenman, E S; Knotkova, H; Liebetanz, D; Miniussi, C; Miranda, P C; Paulus, W; Priori, A; Reato, D; Stagg, C; Wenderoth, N; Nitsche, M A

    2016-02-01

    Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain. Copyright © 2015 International Federation of Clinical Neurophysiology. All rights reserved.

  8. Reservoir response to thermal and high-pressure well stimulation efforts at Raft River, Idaho

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Plummer, Mitchell; Bradford, Jacob; Moore, Joseph

    An injection stimulation test begun at the Raft River geothermal reservoir in June, 2013 has produced a wealth of data describing well and reservoir response via high-resolution temperature logging and distributed temperature sensing, seismic monitoring, periodic borehole televiewer logging, periodic stepped flow rate tests and tracer injections before and after stimulation efforts. One of the primary measures of response to the stimulation is the relationship between fluid pressure and flow rate, short-term during forced flow rate changes and the long-term change in injectivity. In this paper we examine that hydraulic response using standard pumping test analysis methods, largely because pressuremore » response to the stimulation was not detected, or measurable, in other wells. Analysis of stepped rate flow tests supports the inference from other data that a large fracture, with a radial extent of one to several meters, intersects the well in the target reservoir, suggests that the flow regime is radial to a distance of only several meters and demonstrates that the pressure build-up cone reaches an effective constant head at that distance. The well’s longer term hydraulic response demonstrated continually increasing injectivity but at a dramatically faster rate later from ~2 years out and continuing to the present. The net change in injectivity is significantly greater than observed in other longterm injectivity monitoring studies, with an approximately 150–fold increase occurring over ~2.5 years. While gradually increasing injectivity is a likely consequence of slow migration of a cooling front, and consequent dilation of fractures, the steady, ongoing, rate of increase is contrary to what would be expected in a radial or linear flow regime, where the cooling front would slow with time. As a result, occasional step-like changes in injectivity, immediately following high-flow rate tests suggest that hydro shearing during high-pressure testing altered the near-well permeability structure.« less

  9. Common neural structures activated by epidural and transcutaneous lumbar spinal cord stimulation: Elicitation of posterior root-muscle reflexes

    PubMed Central

    Freundl, Brigitta; Binder, Heinrich; Minassian, Karen

    2018-01-01

    Epidural electrical stimulation of the lumbar spinal cord is currently regaining momentum as a neuromodulation intervention in spinal cord injury (SCI) to modify dysregulated sensorimotor functions and augment residual motor capacity. There is ample evidence that it engages spinal circuits through the electrical stimulation of large-to-medium diameter afferent fibers within lumbar and upper sacral posterior roots. Recent pilot studies suggested that the surface electrode-based method of transcutaneous spinal cord stimulation (SCS) may produce similar neuromodulatory effects as caused by epidural SCS. Neurophysiological and computer modeling studies proposed that this noninvasive technique stimulates posterior-root fibers as well, likely activating similar input structures to the spinal cord as epidural stimulation. Here, we add a yet missing piece of evidence substantiating this assumption. We conducted in-depth analyses and direct comparisons of the electromyographic (EMG) characteristics of short-latency responses in multiple leg muscles to both stimulation techniques derived from ten individuals with SCI each. Post-activation depression of responses evoked by paired pulses applied either epidurally or transcutaneously confirmed the reflex nature of the responses. The muscle responses to both techniques had the same latencies, EMG peak-to-peak amplitudes, and waveforms, except for smaller responses with shorter onset latencies in the triceps surae muscle group and shorter offsets of the responses in the biceps femoris muscle during epidural stimulation. Responses obtained in three subjects tested with both methods at different time points had near-identical waveforms per muscle group as well as same onset latencies. The present results strongly corroborate the activation of common neural input structures to the lumbar spinal cord—predominantly primary afferent fibers within multiple posterior roots—by both techniques and add to unraveling the basic mechanisms underlying electrical SCS. PMID:29381748

  10. Cortical presynaptic control of dorsal horn C-afferents in the rat.

    PubMed

    Moreno-López, Yunuen; Pérez-Sánchez, Jimena; Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

    2013-01-01

    Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C-fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C-fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C-fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C-fibers by means of GABAergic inhibitory interneurons.

  11. Cortical Presynaptic Control of Dorsal Horn C–Afferents in the Rat

    PubMed Central

    Martínez-Lorenzana, Guadalupe; Condés-Lara, Miguel; Rojas-Piloni, Gerardo

    2013-01-01

    Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C–fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C–fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C–fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C–fibers by means of GABAergic inhibitory interneurons. PMID:23935924

  12. Perifornical orexinergic neurons modulate REM sleep by influencing locus coeruleus neurons in rats.

    PubMed

    Choudhary, R C; Khanday, M A; Mitra, A; Mallick, B N

    2014-10-24

    Activation of the orexin (OX)-ergic neurons in the perifornical (PeF) area has been reported to induce waking and reduce rapid eye movement sleep (REMS). The activities of OX-ergic neurons are maximum during active waking and they progressively reduce during non-REMS (NREMS) and REMS. Apparently, the locus coeruleus (LC) neurons also behave in a comparable manner as that of the OX-ergic neurons particularly in relation to waking and REMS. Further, as PeF OX-ergic neurons send dense projections to LC, we argued that the former could drive the LC neurons to modulate waking and REMS. Studies in freely moving normally behaving animals where simultaneously neuro-chemo-anatomo-physio-behavioral information could be deciphered would significantly strengthen our understanding on the regulation of REMS. Therefore, in this study in freely behaving chronically prepared rats we stimulated the PeF neurons without or with simultaneous blocking of specific subtypes of OX-ergic receptors in the LC while electrophysiological recording characterizing sleep-waking was continued. Single dose of glutamate stimulation as well as sustained mild electrical stimulation of PeF (both bilateral) significantly increased waking and reduced REMS as compared to baseline. Simultaneous application of OX-receptor1 (OX1R) antagonist bilaterally into the LC prevented PeF stimulation-induced REMS suppression. Also, the effect of electrical stimulation of the PeF was long lasting as compared to that of the glutamate stimulation. Further, sustained electrical stimulation significantly decreased both REMS duration as well as REMS frequency, while glutamate stimulation decreased REMS duration only. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Changes in the frequency of swallowing during electrical stimulation of superior laryngeal nerve in rats.

    PubMed

    Tsuji, Kojun; Tsujimura, Takanori; Magara, Jin; Sakai, Shogo; Nakamura, Yuki; Inoue, Makoto

    2015-02-01

    The aim of the present study was to investigate the adaptation of the swallowing reflex in terms of reduced swallowing reflex initiation following continuous superior laryngeal nerve stimulation. Forty-four male Sprague Dawley rats were anesthetized with urethane. To identify swallowing, electromyographic activity of the left mylohyoid and thyrohyoid muscles was recorded. To evoke the swallowing response, the superior laryngeal nerve (SLN), recurrent laryngeal nerve, or cortical swallowing area was electrically stimulated. Repetitive swallowing evoked by continuous SLN stimulation was gradually reduced, and this reduction was dependent on the resting time duration between stimulations. Prior SLN stimulation also suppressed subsequent swallowing initiation. The reduction in evoked swallows induced by recurrent laryngeal nerve or cortical swallowing area stimulation was less than that following superior laryngeal nerve stimulation. Decerebration had no effect on the reduction in evoked swallows. Prior subthreshold stimulation reduced subsequent initiation of swallowing, suggesting that there was no relationship between swallowing movement evoked by prior stimulation and the subsequent reduction in swallowing initiation. Overall, these data suggest that reduced sensory afferent nerve firing and/or trans-synaptic responses, as well as part of the brainstem central pattern generator, are involved in adaptation of the swallowing reflex following continuous stimulation of swallow-inducing peripheral nerves and cortical areas. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. High-Frequency Transcutaneous Peripheral Nerve Stimulation Induces a Higher Increase of Heat Pain Threshold in the Cutaneous Area of the Stimulated Nerve When Confronted to the Neighbouring Areas

    PubMed Central

    Buonocore, M.; Camuzzini, N.; Cecini, M.; Dalla Toffola, E.

    2013-01-01

    Background. TENS (transcutaneous electrical nerve stimulation) is probably the most diffused physical therapy used for antalgic purposes. Although it continues to be used by trial and error, correct targeting of paresthesias evoked by the electrical stimulation on the painful area is diffusely considered very important for pain relief. Aim. To investigate if TENS antalgic effect is higher in the cutaneous area of the stimulated nerve when confronted to neighbouring areas. Methods. 10 volunteers (4 males, 6 females) underwent three different sessions: in two, heat pain thresholds (HPTs) were measured on the dorsal hand skin before, during and after electrical stimulation (100 Hz, 0.1 msec) of superficial radial nerve; in the third session HPTs, were measured without any stimulation. Results. Radial nerve stimulation induced an increase of HPT significantly higher in its cutaneous territory when confronted to the neighbouring ulnar nerve territory, and antalgic effect persisted beyond the stimulation time. Conclusions. The location of TENS electrodes is crucial for obtaining the strongest pain relief, and peripheral nerve trunk stimulation is advised whenever possible. Moreover, the present study indicates that continuous stimulation could be unnecessary, suggesting a strategy for avoiding the well-known tolerance-like effect of prolonged TENS application. PMID:24027756

  15. Electrical stimulation vs. pulsed and continuous-wave optical stimulation of the rat prostate cavernous nerves, in vivo

    NASA Astrophysics Data System (ADS)

    Perkins, William C.; Lagoda, Gwen A.; Burnett, Arthur; Fried, Nathaniel M.

    2015-07-01

    Identification and preservation of the cavernous nerves (CNs) during prostate cancer surgery is critical for post-operative sexual function. Electrical nerve stimulation (ENS) mapping has previously been tested as an intraoperative tool for CN identification, but was found to be unreliable. ENS is limited by the need for electrode-tissue contact, poor spatial precision from electrical current spreading, and stimulation artifacts interfering with detection. Alternatively, optical nerve stimulation (ONS) provides noncontact stimulation, improved spatial selectivity, and elimination of stimulation artifacts. This study compares ENS to pulsed/CW ONS to explore the ONS mechanism. A total of eighty stimulations were performed in 5 rats, in vivo. ENS (4 V, 5 ms, 10 Hz) was compared to ONS using a pulsed diode laser nerve stimulator (1873 nm, 5 ms, 10 Hz) or CW diode laser nerve stimulator (1455 nm). Intracavernous pressure (ICP) response and nerve compound action potentials (nCAPs) were measured. All three stimulation modes (ENS, ONS-CW, ONS-P) produced comparable ICP magnitudes. However, ENS demonstrated more rapid ICP response times and well defined nCAPs compared to unmeasurable nCAPs for ONS. Further experiments measuring single action potentials during ENS and ONS are warranted to further understand differences in the ENS and ONS mechanisms.

  16. Evaluation of production tests in oil wells stimulated by massive acid fracturing offshore Qatar

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McDonald, S.W.

    This paper presents the evaluation of pressure-buildup data from production tests in wells that have been stimulated by massive acid fracturing. Fracture type curves are used in combination with conventional semilog analysis techniques. Fracture characteristics are calculated from a match of the early-time pressure data with the type curves, and reservoir characteristics are calculated from a conventional semilog plot of late-time data. Unexpectedly high formation permeabilities are evaluated, and fracture half-lengths are much shorter than design values.

  17. Stimulated emission from HgCdTe quantum well heterostructures at wavelengths up to 19.5 μm

    NASA Astrophysics Data System (ADS)

    Morozov, S. V.; Rumyantsev, V. V.; Fadeev, M. A.; Zholudev, M. S.; Kudryavtsev, K. E.; Antonov, A. V.; Kadykov, A. M.; Dubinov, A. A.; Mikhailov, N. N.; Dvoretsky, S. A.; Gavrilenko, V. I.

    2017-11-01

    We report on stimulated emission at wavelengths up to 19.5 μm from HgTe/HgCdTe quantum well heterostructures with wide-gap HgCdTe dielectric waveguide, grown by molecular beam epitaxy on GaAs(013) substrates. The mitigation of Auger processes in structures under study is exemplified, and the promising routes towards the 20-50 μm wavelength range, where HgCdTe lasers may be competitive to the prominent emitters, are discussed.

  18. Electrical Stimulation of Afferent Pathways for the Suppression of Pathological Tremor

    PubMed Central

    Dideriksen, Jakob L.; Laine, Christopher M.; Dosen, Strahinja; Muceli, Silvia; Rocon, Eduardo; Pons, José L.; Benito-Leon, Julian; Farina, Dario

    2017-01-01

    Pathological tremors are involuntary oscillatory movements which cannot be fully attenuated using conventional treatments. For this reason, several studies have investigated the use of neuromuscular electrical stimulation for tremor suppression. In a recent study, however, we found that electrical stimulation below the motor threshold also suppressed tremor, indicating involvement of afferent pathways. In this study, we further explored this possibility by systematically investigating how tremor suppression by afferent stimulation depends on the stimulation settings. In this way, we aimed at identifying the optimal stimulation strategy, as well as to elucidate the underlying physiological mechanisms of tremor suppression. Stimulation strategies varying the stimulation intensity and pulse timing were tested in nine tremor patients using either intramuscular or surface stimulation. Significant tremor suppression was observed in six patients (tremor suppression > 75% was observed in three patients) and the average optimal suppression level observed across all subjects was 52%. The efficiency for each stimulation setting, however, varied substantially across patients and it was not possible to identify a single set of stimulation parameters that yielded positive results in all patients. For example, tremor suppression was achieved both with stimulation delivered in an out-of-phase pattern with respect to the tremor, and with random timing of the stimulation. Overall, these results indicate that low-current stimulation of afferent fibers is a promising approach for tremor suppression, but that further research is required to identify how the effect can be maximized in the individual patient. PMID:28420958

  19. Nonmedical use of prescription stimulants among college students: associations with attention-deficit-hyperactivity disorder and polydrug use.

    PubMed

    Arria, Amelia M; Caldeira, Kimberly M; O'Grady, Kevin E; Vincent, Kathryn B; Johnson, Erin P; Wish, Eric D

    2008-02-01

    To define, among a sample of college students, the nature and extent of nonmedical use of prescription stimulants (NPS), including both overuse and use of someone else's drug, for attention-deficit-hyperactivity disorder (ADHD); to characterize NPS among individuals not medically using a prescription stimulant for ADHD; and to determine whether NPS and overuse of a medically prescribed stimulant for ADHD were independently associated with an increased risk of other illicit drug use and dependence on alcohol and marijuana. Cross-sectional analysis of personal interview data. Large public university in the mid-Atlantic region. Participants. A cohort of 1253 first-year college students aged 17-20 years. All students completed a 2-hour personal interview to ascertain medical use and overuse of prescription stimulants, NPS, nonmedical use of other prescription drugs and illicit drug use, and dependence on alcohol and marijuana. Comparisons were made among nonusers, nonmedical users, and medical users of prescription stimulants for ADHD (ADHD+), some of whom overused their drug. Of 1208 students who were not using prescription stimulants medically for ADHD (ADHD-), 218 (18.0%) engaged in NPS. Of 45 ADHD+ students, 12 (26.7%) overused their ADHD drug at least once in their lifetime, and seven (15.6%) nonmedically used someone else's prescription stimulants at least once in their lifetime. Among 225 nonmedical users, NPS was infrequent and mainly associated with studying, although 35 (15.6%) used prescription stimulants to party or to get high. Lifetime NPS was associated with past-year other drug use. Both NPS and overuse of prescribed stimulants for ADHD were independently associated with past-year use of five drugs, holding constant sociodemographic characteristics; NPS was also associated with alcohol and marijuana dependence. Physicians should be vigilant for possible overuse and/or diversion of prescription stimulants for ADHD among college students who are medical users of these drugs, as well as the occurrence of illicit drug use with NPS. Initiation of comprehensive drug prevention activities that involve parents as well as college personnel is encouraged to raise awareness of NPS and its association with illicit drug use.

  20. Minimal enteral nutrition to improve adaptation after intestinal resection in piglets and infants

    USDA-ARS?s Scientific Manuscript database

    Minimal enteral nutrition (MEN) may induce a diet-dependent stimulation of gut adaptation following intestinal resection. Bovine colostrum is rich in growth factors, and we hypothesized that MEN with colostrum would stimulate intestinal adaptation, compared with formula, and would be well tolerated ...

  1. Analysis of the Thermal and Hydraulic Stimulation Program at Raft River, Idaho

    NASA Astrophysics Data System (ADS)

    Bradford, Jacob; McLennan, John; Moore, Joseph; Podgorney, Robert; Plummer, Mitchell; Nash, Greg

    2017-05-01

    The Raft River geothermal field, located in southern Idaho, roughly 100 miles northwest of Salt Lake City, is the site of a Department of Energy Enhanced Geothermal System project designed to develop new techniques for enhancing the permeability of geothermal wells. RRG-9 ST1, the target stimulation well, was drilled to a measured depth of 5962 ft. and cased to 5551 ft. The open-hole section of the well penetrates Precambrian quartzite and quartz monzonite. The well encountered a temperature of 282 °F at its base. Thermal and hydraulic stimulation was initiated in June 2013. Several injection strategies have been employed. These strategies have included the continuous injection of water at temperatures ranging from 53 to 115 °F at wellhead pressures of approximately 275 psi and three short-term hydraulic stimulations at pressures up to approximately 1150 psi. Flow rates, wellhead and line pressures and fluid temperatures are measured continuously. These data are being utilized to assess the effectiveness of the stimulation program. As of August 2014, nearly 90 million gallons have been injected. A modified Hall plot has been used to characterize the relationships between the bottom-hole flowing pressure and the cumulative injection fluid volume. The data indicate that the skin factor is decreased, and/or the permeability around the wellbore has increased since the stimulation program was initiated. The injectivity index also indicates a positive improvement with values ranging from 0.15 gal/min psi in July 2013 to 1.73 gal/min psi in February 2015. Absolute flow rates have increased from approximately 20 to 475 gpm by February 2 2015. Geologic, downhole temperature and seismic data suggest the injected fluid enters a fracture zone at 5650 ft and then travels upward to a permeable horizon at the contact between the Precambrian rocks and the overlying Tertiary sedimentary and volcanic deposits. The reservoir simulation program FALCON developed at the Idaho National Laboratory is being used to simulate and visualize the effects of the injection. The simulation model uses a discrete fracture network generated for RRG-9 using acoustic borehole imaging and analysis of microseismic activity. By adjusting the permeability of the fractures, a pressure history match for the first part of the stimulation program was obtained. The results of this model indicate that hydraulic fracturing is the dominant mechanism for permeability improvement for this part of the stimulation program.

  2. Restoration of gait by functional electrical stimulation in paraplegic patients: a modified programme of treatment.

    PubMed

    Malezic, M; Hesse, S

    1995-03-01

    Restoration of standing and of gait by functional electrical stimulation in clinically complete paraplegic patients was modified in the course of treatment and in the stimulation parameters. By substituting an initial cyclic muscle strengthening with an active stimulated standing, four patients with T3-11 lesions started walking with electrical stimulation in 10-17 days. They walked without ankle-foot orthoses. With a satisfactory stride length of 0.75-0.97 m, their gait velocity ranged from very slow to that of a leisurely healthy gait. Already established stimulation of the quadriceps muscles for standing and of the peroneal nerves for lower limb flexion during the swing phase of gait was applied. Diminished limb flexion after several weeks was restored by an increase of the stimulation frequency of the peroneal nerve from 20 to 60 Hz. EMG and kinesiological measurements displayed an improved direct response of the ankle as well as of the reflex mediated hip, knee and ankle flexion response. At the same time stimulation frequency was reduced to 16 Hz for the quadriceps muscles in order to reduce fatigue.

  3. Luteinizing hormone-stimulated pituitary adenylate cyclase-activating polypeptide system and its role in progesterone production in human luteinized granulosa cells.

    PubMed

    Park, Hyun-Jeong; Choi, Bum-Chae; Song, Sang-Jin; Lee, Dong-Sik; Roh, Jaesook; Chun, Sang-Young

    2010-01-01

    The present study examined the gonadotropin regulation of pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP type I receptor (PAC(1)-R) expression, and its role in progesterone production in the human luteinized granulosa cells. The stimulation of both PACAP and PAC(1)-R mRNA levels by LH was detected using a competitive reverse transcription-polymerase chain reaction (RT-PCR). PACAP transcript was stimulated by LH reaching maximum levels at 12 hours in a dose dependent manner. LH treatment also stimulated PAC(1)-R mRNA levels within 24 hours. Addition of PACAP-38 (10(-7) M) as well as LH significantly stimulated progesterone production during 48 hours culture. Furthermore, co-treatment with PACAP antagonist partially inhibited LH-stimulated progesterone production. Treatment with vasoactive intestinal peptide, however, did not affect progesterone production. Taken together, the present study demonstrates that LH causes a transient stimulation of PACAP and PAC(1)-R expression and that PACAP stimulates progesterone production in the human luteinized granulosa cells, suggesting a possible role of PACAP as a local ovarian regulator in luteinization.

  4. Prescribing Some Criminological Theory: An Examination of the Illicit Use of Prescription Stimulants Among College Students.

    PubMed

    Maahs, Jeffrey R; Weidner, Robert R; Smith, Ryan

    2016-02-01

    Recent evidence indicates that the illicit use of prescription stimulants such as Adderall and Ritalin is common across college campuses and in professions (e.g., trucking) where staying awake and focused is valued. Existing research has established use patterns and explored respondents' reasons for using these stimulants. Less is known, however, about whether or how well mainstream criminological theory explains this type of illegal activity. This article reports results from a survey (N = 484) of college students from a Midwestern university, examining whether measures of strain, self-control, and social learning predict the illicit use of prescription stimulants. Measures from social learning and social control theories were significant predictors of illicit use of prescription stimulants, whereas the measure of academic strain was not; the strongest predictor of illicit use of prescription stimulants was general deviance. Implications of these findings are discussed. © The Author(s) 2014.

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

    PubMed

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

    2016-01-01

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

  6. Thalamic modulation of aggression.

    PubMed

    Andy, O J; Giurintano, L; Giurintano, S; McDonald, T

    1975-01-01

    This experiment extends Pavlov's method of contrasts for 8 components of aggression were quantitatively evaluated in 11 freely moving adult cats. Aggression was elicited from the perifornix septohypothalamic areas by a series of progressively increasing and decreasing stimulation parameters. Three levels of thalamic stimulation (low, medium, and high) were combined with the perifornix stimulations. High level thalamic stimulation tended to facilitate the aggressive response elicited by low level perifornix stimulation. Thalamic lesions attenuated the aggression response, especially those elicited during high level perifornix stimulation. It was suggested that within the hypothalamic induced aggression circuitry the center median nucleus modulates the excitatory state of the system. The discussion concerns anatomic and physiologic pathways through which the center median nucleus may modulate the sensory, motor, and affective-autonomic subsystems into a well integrated aggressive state. These experimental findings are supported by the clinically established treatment of aggression by stereotaxic lesions placed in the center median nucleus.

  7. An analysis of stimulation treatments of the Randolph Sand in the Semitropic field, Kern County, California

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mitchell, M.D.; Chamberlain, C.R.

    1983-03-01

    The Semitropic field is located approximately ten miles west of Wasco in the San Joaquin Valley of California. The original productive zones in the field were the Mya and the Mulinia gas sands occuring at depths of 2,200' to 4,400'. In the last six years, the Randolph Oil Sand at 7,800' has been actively developed and is now the major productive interval. Recently, several of the Randolph wells have been stimulated with hydraulic fracturing treatments. A majority of these wells have shown productive increases of varying degrees depending upon field location, job volume and proppant size. This paper discusses themore » geologic production history of the Randolph Zone, completion techniques, reservoir characteristics and stimulation design and treatments.« less

  8. A High-Voltage Bipolar Transconductance Amplifier for Electrotactile Stimulation

    PubMed Central

    Schaning, Matthew A.; Kaczmarek, Kurt A.

    2008-01-01

    This article describes a high-performance transconductance amplifier specifically designed for electrotactile (electrocutaneous) stimulation. It enables voltages up to ±600 V to be produced at the output which will allow the psychophysiological performance associated with stimulation of the fingertip using various stimulation waveforms to be studied more thoroughly. The design has a transconductance of up to 20 mA/V, an 8.8-MΩ output resistance, and can provide output currents up to ±20 mA. A complete schematic diagram is presented along with a discussion of theory of operation and safety issues as well as performance and derating plots from the implemented design. PMID:18838369

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

    PubMed

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

    2017-09-01

    Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8-54 months). The sample included four females and three males, with a mean age of 46 years (range, 37-59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15-38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Deep brain stimulation was an effective treatment for obsessive-compulsive disorder in these highly selected patients. The extent of the response to deep brain stimulation varied between patients, as well as during the course of treatment for each patient. The results of this series are comparable with the literature, as well as having similar efficacy to ablative psychosurgery techniques such as capsulotomy and cingulotomy. Deep brain stimulation provides advantages over lesional psychosurgery but is more expensive and requires significant multidisciplinary input at all stages, pre- and post-operatively, ideally within a specialised tertiary clinical and/or academic centre. Ongoing research is required to better understand the neurobiological basis for obsessive-compulsive disorder and how this can be manipulated with deep brain stimulation to further improve the efficacy of this emerging treatment.

  10. Timing of pulsed electromagnetic field stimulation does not affect the promotion of bone cell development.

    PubMed

    Hannay, Gwynne; Leavesley, David; Pearcy, Mark

    2005-12-01

    Pulsed electromagnetic field (PEMF) devices have been used clinically to promote the healing of surgically resistant fractures in vivo. However, there is a sparsity of data on how the timing of an applied PEMF effects the osteogenic cells that would be present within the fracture gap. The purpose of this study was to examine the response of osteoblast-like cells to a PEMF stimulus, mimicking that of a clinically available device, using four protocols for the timing of the stimulus. The PEMF signal consisted of a 5 ms pulse burst (containing 20 pulses) repeated at 15 Hz. Cultures of a human osteosarcoma cell line, SaOS-2, were exposed to the four timing protocols, each conducted over 3 days. Protocol one stimulated the cells for 8 h each day, protocol two stimulated the cells for 24 h on the first day, protocol three stimulated the cells for 24 h on the second day, and protocol four stimulated the cells for 24 h on the third day. Cells were seeded with either 25,000 or 50,000 cells/well (24-well cell culture plates). All assays showed reduced proliferation and increased differentiation (alkaline phosphatase activity) in the PEMF stimulated cultures compared with the control cultures, except for protocol four alkaline phosphatase measurements. No clear trend was observed between the four protocols; however this may be due to cell density. The results indicated that an osteoblast-like cell line is responsive to a 15 Hz PEMF stimulus, which will stimulate the cell line to into an increasing state of maturity. Bioelectromagnetics (c) 2005 Wiley-Liss, Inc

  11. Sensory stimulation for persons with dementia: a review of the literature.

    PubMed

    Strøm, Benedicte S; Ytrehus, Siri; Grov, Ellen-Karine

    2016-07-01

    To provide an overview of available sensory stimulation interventions, and their effect on persons with dementia and to present theoretical and methodological characteristics of the studies included. Different sensory stimulation interventions are used for persons with dementia to increase alertness, reduce agitation and improve quality of life. However, the effect of these interventions is not clear, neither are their characteristics. A systematic search and review of the literature with description of the content and an evaluation of theoretical and methodological approaches. Systematic searches in CINAHL, PubMed (Medline), The Cochrane library and PsycINFO. Studies included have been subject to quality assessment by means of Critical Appraisal Skills Programme. Fifty-five studies were included and thirty of these documented significant effect. The effect of the sensory stimulation interventions mainly reported on negative behaviours, except from five studies assessing quality of life and well-being. The majority of the studies had methodological limitations. The different sensory stimulation interventions were organised into eight categories: music, light therapy, acupressure/reflexology, massage/aromatherapy and doll therapy/pet therapy/toy therapy, the Sonas programme and Snoezelen. More studies are needed to clarify appropriate substantial background for the specific interventions. However, most of the studies based their interventions on a theoretical foundation. Furthermore, more research is needed to measure the effect of sensory stimulation on communication as well as quality of life. In addition, studies are to focus on whether the effect depends on the stage of dementia. Nurses are to be aware of sensory stimulation as a possible intervention to improve persons' quality of life. © 2016 John Wiley & Sons Ltd.

  12. A functional magnetic resonance imaging study of human brain in pain-related areas induced by electrical stimulation with different intensities.

    PubMed

    Yuan, Wang; Ming, Zhang; Rana, Netra; Hai, Liu; Chen-wang, Jin; Shao-hui, Ma

    2010-01-01

    Pain-related studies have mainly been performed through traditional methods, which lack the rigorous analysis of anatomical locations. Functional magnetic resonance imaging (fMRI) is a noninvasive method detecting neural activity, and has the ability to precisely locate related activations in vivo. Moreover, few studies have used painful stimulation of changed intensity to investigate relevant functioning nuclei in the human brain. This study mainly focused on the pain-related activations induced by electrical stimulation with different intensities using fMRI. Furthermore, the electrophysiological characteristics of different pain-susceptible-neurons were analyzed to construct the pain modulatory network, which was corresponding to painful stimulus of changed intensity. Twelve volunteers underwent functional scanning receiving different electrical stimulation. The data were collected and analyzed to generate the corresponding functional activation maps and response time curves related to pain. The common activations were mainly located in several specific regions, including the secondary somatosensory cortex (SII), insula, anterior cingulate cortex (ACC), thalamus, and other cerebral regions. Moreover, innocuous electrical stimulation primarily activated the lateral portions of SII and thalamus, as well as the posterior insula, anterior ACC, whereas noxious electrical stimulation primarily activated the medial portions of SII and thalamus, as well as the anterior insula, the posterior ACC, with larger extensions and greater intensities. Several specified cerebral regions displayed different response patterns during electrical stimulation by means of fMRI, which implied that the corresponding pain-susceptible-neurons might process specific aspects of pain. Elucidation of functions on pain-related regions will help to understand the delicate pain modulation of human brain.

  13. Spatially divergent cardiac responses to nicotinic stimulation of ganglionated plexus neurons in the canine heart.

    PubMed

    Cardinal, René; Pagé, Pierre; Vermeulen, Michel; Ardell, Jeffrey L; Armour, J Andrew

    2009-01-28

    Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50-95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22-75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.

  14. Cisplatin-induced gastric dysrhythmia and emesis in dogs and possible role of gastric electrical stimulation.

    PubMed

    Yu, Xiaoyun; Yang, Jie; Hou, Xiaohua; Zhang, Kan; Qian, Wei; Chen, J D Z

    2009-05-01

    The aim of this study was to investigate the effect of cisplatin on gastric myoelectrical activity and the role of gastric electrical stimulation in the treatment of cisplatin-induced emesis in dogs. Seven dogs implanted with electrodes on the gastric serosa were used in a two-session study. Cisplatin was infused in both the control session and the gastric electrical stimulation session, and gastric electrical stimulation was applied in the gastric electrical stimulation session. Gastric slow waves and emesis, as well as behaviors suggestive of nausea, were recorded during each session. The results were as follows: (1) cisplatin induced vomiting and other symptoms and induced gastric dysrhythmia. The percentage of normal slow waves decreased significantly during the 2.5 h before vomiting (P=0.01) and the period of vomiting (P<0.001). (2) Gastric electrical stimulation reduced emesis and the symptoms score. The total score in the control session was higher than that in the gastric electrical stimulation session (P=0.02). However, gastric electrical stimulation had no effects on gastric dysrhythmia. It is concluded that cisplatin induces emesis and gastric dysrhythmia. Gastric electrical stimulation may play a role in relieving chemotherapy-induced emetic responses and deserves further investigation.

  15. Stimulation at Desert Peak -modeling with the coupled THM code FEHM

    DOE Data Explorer

    kelkar, sharad

    2013-04-30

    Numerical modeling of the 2011 shear stimulation at the Desert Peak well 27-15. This submission contains the FEHM executable code for a 64-bit PC Windows-7 machine, and the input and output files for the results presented in the included paper from ARMA-213 meeting.

  16. Effect of Chlorotriazine Pesticides on Gonadotrophin Releasing Hormone in the Neuronal GT1-7 Cell Line and Hypothalamic Explants

    EPA Science Inventory

    Gonadotrophin releasing hormone (GnRH) stimulates the release of pituitary luteinizing hormone (LH) and follicle stimulating hormone. These pituitary hormones are necessary for normal reproductive function in both males and females. It is well recognized that disruption of nor...

  17. Affect of deep brain stimulation on limb paresis after stroke.

    PubMed

    Phillips, N I; Bhakta, B B

    2000-07-15

    A deep brain stimulator was implanted in the periventricular grey matter of the third ventricle for pain after stroke in a man aged 48 years. As well as a beneficial analgesic effect, the patient reported improved function in the contralateral paretic arm, which was confirmed on formal testing.

  18. Stimulate Students' Interest by Genetics Exordium Teaching

    ERIC Educational Resources Information Center

    Li, Yan

    2009-01-01

    Genetics is the important specialized course of bioscience and whether exordium is taught wonderfully or not plays the important and pivotal role. Well teaching exordium class may stimulate students, deep interest and intense desire for knowledge in this class. This text, according to teaching experience and taste, puts forward several teaching…

  19. [Use of stimulation techniques in pain treatment].

    PubMed

    Rosted, Palle; Andersen, Claus

    2006-05-15

    Stimulation techniques (SB) include manipulation, acupuncture, acupressure, physiotherapy, transcutaneous electrical nerve stimulation, reflexotherapy, laser treatment and epidural stimulation technique. The purpose of this paper is to investigate the scientific evidence for these techniques. The Cochrane Library and Medline were searched for all techniques from 2000 to date. Only randomised controlled studies written in English were included. Search words were used, such as; acupuncture and neck pain, shoulder pain, etc. In total 587 papers were identified for the following diseases; headache, neck pain, shoulder pain, elbow pain, low back pain and knee pain. 415 papers were excluded, and the remaining 172 papers, a total of 20,431 patients, are the basis for this study. The effect of acupuncture and epidural stimulation technique is scientifically well-supported. For the remaining techniques, the scientific evidence is dubious.

  20. Stimulated Rayleigh-Bragg scattering in two-photon absorbing media

    NASA Astrophysics Data System (ADS)

    He, Guang S.; Lu, Changgui; Zheng, Qingdong; Prasad, Paras N.; Zerom, Petros; Boyd, Robert W.; Samoc, Marek

    2005-06-01

    The origin and mechanism of backward stimulated Rayleigh scattering in two-photon absorbing media are studied theoretically and experimentally. This type of stimulated scattering has the unusual features of no frequency shift and low pump threshold requirement compared to all other known stimulated scattering effects. This frequency-unshifted stimulated Rayleigh scattering effect can be well explained by a two-photon-excitation-enhanced Bragg grating reflection model. The reflection of the forward pump beam from this stationary Bragg grating may substantially enhance the backward Rayleigh scattering beam, providing a positive feedback mechanism without causing any frequency shift. A two-counterpropagating-beam-formed grating experiment in a two-photon absorbing dye solution is conducted. The measured dynamic behavior of Bragg grating formation and reflectivity properties are basically consistent with the predictions from the proposed model.

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

    PubMed

    Talsma, Lotte J; Kroese, Henryk A; Slagter, Heleen A

    2017-04-01

    Transcranial direct current stimulation (tDCS) is a promising tool for neurocognitive enhancement. Several studies have shown that just a single session of tDCS over the left dorsolateral pFC (lDLPFC) can improve the core cognitive function of working memory (WM) in healthy adults. Yet, recent studies combining multiple sessions of anodal tDCS over lDLPFC with verbal WM training did not observe additional benefits of tDCS in subsequent stimulation sessions nor transfer of benefits to novel WM tasks posttraining. Using an enhanced stimulation protocol as well as a design that included a baseline measure each day, the current study aimed to further investigate the effects of multiple sessions of tDCS on WM. Specifically, we investigated the effects of three subsequent days of stimulation with anodal (20 min, 1 mA) versus sham tDCS (1 min, 1 mA) over lDLPFC (with a right supraorbital reference) paired with a challenging verbal WM task. WM performance was measured with a verbal WM updating task (the letter n-back) in the stimulation sessions and several WM transfer tasks (different letter set n-back, spatial n-back, operation span) before and 2 days after stimulation. Anodal tDCS over lDLPFC enhanced WM performance in the first stimulation session, an effect that remained visible 24 hr later. However, no further gains of anodal tDCS were observed in the second and third stimulation sessions, nor did benefits transfer to other WM tasks at the group level. Yet, interestingly, post hoc individual difference analyses revealed that in the anodal stimulation group the extent of change in WM performance on the first day of stimulation predicted pre to post changes on both the verbal and the spatial transfer task. Notably, this relationship was not observed in the sham group. Performance of two individuals worsened during anodal stimulation and on the transfer tasks. Together, these findings suggest that repeated anodal tDCS over lDLPFC combined with a challenging WM task may be an effective method to enhance domain-independent WM functioning in some individuals, but not others, or can even impair WM. They thus call for a thorough investigation into individual differences in tDCS respondence as well as further research into the design of multisession tDCS protocols that may be optimal for boosting cognition across a wide range of individuals.

  2. The subsurface impact of hydraulic fracturing in shales- Perspectives from the well and reservoir

    NASA Astrophysics Data System (ADS)

    ter Heege, Jan; Coles, Rhys

    2017-04-01

    It has been identified that the main risks of subsurface shale gas operations in the U.S.A. and Canada are associated with (1) drilling and well integrity, (2) hydraulic fracturing, and (3) induced seismicity. Although it is unlikely that hydraulic fracturing operations result in direct pathways of enhanced migration between stimulated fracture disturbed rock volume and shallow aquifers, operations may jeopardize well integrity or induce seismicity. From the well perspective, it is often assumed that fluid injection leads to the initiation of tensile (mode I) fractures at different perforation intervals along the horizontal sections of shale gas wells if pore pressure exceeds the minimum principal stress. From the reservoir perspective, rise in pore pressure resulting from fluid injection may lead to initiation of tensile fractures, reactivation of shear (mode II) fractures if the criterion for failure in shear is exceeded, or combinations of different fracturing modes. In this study, we compare tensile fracturing simulations using conventional well-based models with shear fracturing simulations using a fractured shale model with characteristic fault populations. In the fractured shale model, stimulated permeability is described by an analytical model that incorporates populations of reactivated faults and that combines 3D permeability tensors for layered shale matrix, damage zone and fault core. Well-based models applied to wells crosscutting the Posidonia Shale Formation are compared to generic fractured shale models, and fractured shale models are compared to micro-seismic data from the Marcellus Shale. Focus is on comparing the spatial distribution of permeability, stimulated reservoir volume and seismicity, and on differences in fracture initiation pressure and fracture orientation for tensile and shear fracturing end-members. It is shown that incorporation of fault populations (for example resulting from analysis of 3D seismics or outcrops) in hydraulic fracturing models provides better constraints on well pressures, stimulated fracture disturbed volume and induced seismicity. Thereby, it helps assessing the subsurface impact of hydraulic fracturing in shales and mitigating risks associated with loss of loss of well integrity, loss of fracture containment, and induced seismicity.

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

    PubMed

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

    2015-01-01

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

  4. Ultrafiltered pig leukocyte extract (IMUNOR) decreases nitric oxide formation and hematopoiesis-stimulating cytokine production in lipopolysaccharide-stimulated RAW 264.7 macrophages.

    PubMed

    Hofer, Michal; Vacek, Antonín; Lojek, Antonín; Holá, Jirina; Streitová, Denisa

    2007-10-01

    A low-molecular-weight (<12 kDa) ultrafiltered pig leukocyte extract, IMUNOR, was tested in experiments in vitro on non-stimulated and lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages in order to assess modulation of nitric oxide (NO) production (measured indirectly as the concentration of nitrites), hematopoiesis-stimulating activity of the supernatant of the macrophage cells (ascertained by counting cell colonies growing from progenitor cells for granulocytes and macrophages (GM-CFC) in vitro), and the release of hematopoiesis-stimulating cytokines. No hematopoiesis-stimulating activity and cytokine or NO production were found in the supernatant of non-stimulated macrophages. It was found that IMUNOR does not influence this status. Supernatant of LPS-stimulated macrophages was characterized by hematopoiesis-stimulating activity, as well as by the presence of nitrites, interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF). A key role in the hematopoiesis-stimulating activity of the supernatant of LPS-stimulated macrophages could be ascribed to G-CSF since the formation of the colonies could be abrogated nearly completely by monoclonal antibodies against G-CSF. IMUNOR was found to suppress all the mentioned manifestations of the LPS-activated macrophages. When considering these results together with those from our previous in vivo study revealing stimulatory effects of IMUNOR on radiation-suppressed hematopoiesis, a hypothesis may be formulated which postulates a homeostatic role of IMUNOR, consisting in stimulation of impaired immune and hematopoietic systems but also in cutting back the production of proinflammatory mediators in cases of overstimulation which threats with undesirable consequences.

  5. Recreational stimulants, herbal, and spice cannabis: The core psychobiological processes that underlie their damaging effects.

    PubMed

    Parrott, Andrew C; Hayley, Amie C; Downey, Luke A

    2017-05-01

    Recreational drugs are taken for their positive mood effects, yet their regular usage damages well-being. The psychobiological mechanisms underlying these damaging effects will be debated. The empirical literature on recreational cannabinoids and stimulant drugs is reviewed. A theoretical explanation for how they cause similar types of damage is outlined. All psychoactive drugs cause moods and psychological states to fluctuate. The acute mood gains underlie their recreational usage, while the mood deficits on withdrawal explain their addictiveness. Cyclical mood changes are found with every central nervous system stimulant and also occur with cannabis. These mood state changes provide a surface index for more profound psychobiological fluctuations. Homeostatic balance is altered, with repetitive disturbances of the hypothalamic-pituitary-adrenal axis, and disrupted cortisol-neurohormonal secretions. Hence, these drugs cause increased stress, disturbed sleep, neurocognitive impairments, altered brain activity, and psychiatric vulnerability. Equivalent deficits occur with novel psychoactive stimulants such as mephedrone and artificial "spice" cannabinoids. These psychobiological fluctuations underlie drug dependency and make cessation difficult. Psychobiological stability and homeostatic balance are optimally restored by quitting psychoactive drugs. Recreational stimulants such as cocaine or MDMA (3.4-methylenedioxymethamphetamine) and sedative drugs such as cannabis damage human homeostasis and well-being through similar core psychobiological mechanisms. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Therapeutic orthosis and electrical stimulation for upper extremity hemiplegia after stroke: a review of effectiveness based on evidence.

    PubMed

    Aoyagi, Yoichiro; Tsubahara, Akio

    2004-01-01

    Upper extremity hemiplegia after stroke is common and disabling. Apart from conventional physical and occupational therapy, a number of additional approaches that use devices such as orthoses, prostheses, electrical stimulation, and robots have been introduced. The purpose of this review was to assess the clinical efficacy of such devices used for the affected upper extremities of acute, subacute, and chronic stroke patients. Assessments of their effectiveness and recommendations were based on the weight of published scientific evidence. The amount of evidence with respect to hand splints and shoulder slings is limited. Further study with a well-designed randomized controlled trial (RCT) is required to investigate accurately their short- and long-term efficacy. A number of studies suggested that the use of electrical stimulation for reducing shoulder subluxation or improving the function of wrist and finger extensors is effective during or shortly after the daily treatment period. The robotic approach to hemiplegic upper extremities appears to be a novel therapeutic strategy that may help improve hand and arm function. However, the longer term effectiveness after discontinuation as well as the motor recovery mechanism of electrical stimulation or robotic devices remains unclear. More research is needed to determine the evidence-based effectiveness of electrical stimulation or other devices for stroke survivors.

  7. Neuromodulation: Selected approaches and challenges

    PubMed Central

    Parpura, Vladimir; Silva, Gabriel A.; Tass, Peter A.; Bennet, Kevin E.; Meyyappan, Meyya; Koehne, Jessica; Lee, Kendall H.; Andrews, Russell J.

    2012-01-01

    The brain operates through complex interactions in the flow of information and signal processing within neural networks. The “wiring” of such networks, being neuronal or glial, can physically and/or functionally go rogue in various pathological states. Neuromodulation, as a multidisciplinary venture, attempts to correct such faulty nets. In this review, selected approaches and challenges in neuromoduation are discussed. The use of water-dispersible carbon nanotubes have proven effective in modulation of neurite outgrowth in culture as well as in aiding regeneration after spinal cord injury in vivo. Studying neural circuits using computational biology and analytical engineering approaches brings to light geometrical mapping of dynamics within neural networks, much needed information for stimulation interventions in medical practice. Indeed, sophisticated desynchronization approaches used for brain stimulation have been successful in coaxing “misfiring” neuronal circuits to resume productive firing patterns in various human disorders. Devices have been developed for the real time measurement of various neurotransmitters as well as electrical activity in the human brain during electrical deep brain stimulation. Such devices can establish the dynamics of electrochemical changes in the brain during stimulation. With increasing application of nanomaterials in devices for electrical and chemical recording and stimulating in the brain, the era of cellular, and even intracellular, precision neuromodulation will soon be upon us. PMID:23190025

  8. Cow's milk and linear growth in industrialized and developing countries.

    PubMed

    Hoppe, Camilla; Mølgaard, Christian; Michaelsen, Kim F

    2006-01-01

    The strongest evidence that cow's milk stimulates linear growth comes from observational and intervention studies in developing countries that show considerable effects. Additionally, many observational studies from well-nourished populations also show an association between milk intake and growth. These results suggest that milk has a growth-stimulating effect even in situations where the nutrient intake is adequate. This effect is supported by studies that show milk intake stimulates circulating insulin-like growth factor (IGF)-I, which suggests that at least part of the growth-stimulating effects of milk occur through the stimulation of IGFs. Given that the biological purpose of milk is to support the newborn during a period of high growth velocity, such an effect seems plausible. Adding cow's milk to the diet of stunted children is likely to improve linear growth and thereby reduce morbidity. In well-nourished children, the long-term consequences of an increased consumption of cow's milk, which may lead to higher levels of IGF-I in circulation or an increase in the velocity of linear growth, are likely to be both positive and negative. Based on emerging data that suggest both growth and diet during early life program the IGF axis, the association between milk intake and later health is likely to be complex.

  9. Selective pelvic autonomic nerve stimulation with simultaneous intraoperative monitoring of internal anal sphincter and bladder innervation.

    PubMed

    Kneist, W; Kauff, D W; Koch, K P; Schmidtmann, I; Heimann, A; Hoffmann, K P; Lang, H

    2011-01-01

    Pelvic autonomic nerve preservation avoids postoperative functional disturbances. The aim of this feasibility study was to develop a neuromonitoring system with simultaneous intraoperative verification of internal anal sphincter (IAS) activity and intravesical pressure. 14 pigs underwent low anterior rectal resection. During intermittent bipolar electric stimulation of the inferior hypogastric plexus (IHP) and the pelvic splanchnic nerves (PSN), electromyographic signals of the IAS and manometry of the urinary bladder were observed simultaneously. Stimulation of IHP and PSN as well as simultaneous intraoperative monitoring could be realized with an adapted neuromonitoring device. Neurostimulation resulted in either bladder or IAS activation or concerted activation of both. Intravesical pressure increase as well as amplitude increase of the IAS neuromonitoring signal did not differ significantly between stimulation of IHP and PSN [6.0 cm H(2)O (interquartile range [IQR] 3.5-9.0) vs. 6.0 cm H(2)O (IQR 3.0-10.0) and 12.1 μV (IQR 3.0-36.7) vs. 40.1 μV (IQR 9.0-64.3)] (p > 0.05). Pelvic autonomic nerve stimulation with simultaneous intraoperative monitoring of IAS and bladder innervation is feasible. The method may enable neuromonitoring with increasing selectivity for pelvic autonomic nerve preservation. Copyright © 2011 S. Karger AG, Basel.

  10. Predictors of Stimulant Abuse Treatment Outcomes in Severely Mentally Ill Outpatients

    PubMed Central

    Angelo, Frank N.; McDonell, Michael G.; Lewin, Michael R.; Srebnik, Debra; Lowe, Jessica; Roll, John; Ries, Richard

    2012-01-01

    Background Severe mental illness is often exclusionary criteria for studies examining factors that influence addiction treatment outcome. Therefore, little is known about predictors of treatment response of individuals receiving psychosocial treatments for addictions who suffer from co-occurring severe mental illness. Methods The impact of demographic, substance abuse severity, psychiatric severity, and service utilization variables on in-treatment performance (i.e., longest duration of abstinence) in a 12-week contingency management (CM) intervention for stimulant abuse in 96 severely mentally ill adults was investigated. A 4-step linear regression was used to identify independent predictors of in-treatment abstinence. Results This model accounted for 37.4% of variance in the longest duration of abstinence outcome. Lower levels of stimulant use (i.e., stimulant-negative urine test) and psychiatric severity (i.e., lower levels of psychiatric distress), as well as higher rates of outpatient treatment utilization at study entry were independently associated with longer duration of drug abstinence. Conclusion These data suggest that individuals with low levels of stimulant use and psychiatric severity, as well as those actively engaged in services are most likely to succeed in a typical CM intervention. For others, modifications to CM interventions, such as increasing the value of reinforcement or adding CM to evidence based psychiatric interventions may improve treatment outcomes. PMID:23273776

  11. An infrared optical pacing system for high-throughput screening of cardiac electrophysiology in human cardiomyocytes (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    McPheeters, Matt T.; Wang, Yves T.; Laurita, Kenneth R.; Jenkins, Michael W.

    2017-02-01

    Cardiomyocytes derived from human induced pluripotent stem cells (hiPS-HCM) have the potential to provide individualized therapies for patients and to test drug candidates for cardiac toxicity. In order for hiPS-CM to be useful for such applications, there is a need for high-throughput technology to rapidly assess cardiac electrophysiology parameters. Here, we designed and tested a fully contactless optical mapping (OM) and optical pacing (OP) system capable of imaging and point stimulation of hiPS-CM in small wells. OM allowed us to characterize cardiac electrophysiological parameters (conduction velocity, action potential duration, etc.) using voltage-sensitive dyes with high temporal and spatial resolution over the entire well. To improve OM signal-to-noise ratio, we tested a new voltage-sensitive dye (Fluovolt) for accuracy and phototoxicity. Stimulation is essential because most electrophysiological parameters are rate dependent; however, traditional methods utilizing electrical stimulation is difficult in small wells. To overcome this limitation, we utilized OP (λ = 1464 nm) to precisely control heart rate with spatial precision without the addition of exogenous agents. We optimized OP parameters (e.g., well size, pulse width, spot size) to achieve robust pacing and minimize the threshold radiant exposure. Finally, we tested system sensitivity using Flecainide, a drug with well described action on multiple electrophysiological properties.

  12. Repetitive transcranial magnetic stimulation as an alternative therapy for dysphagia after stroke: a systematic review and meta-analysis.

    PubMed

    Liao, Xiang; Xing, Guoqiang; Guo, Zhiwei; Jin, Yu; Tang, Qing; He, Bin; McClure, Morgan A; Liu, Hua; Chen, Huaping; Mu, Qiwen

    2017-03-01

    A meta-analysis and systematic review was conducted to investigate the potential effects of repetitive transcranial magnetic stimulation on dysphagia in patients with stroke, including different parameters of frequency and stimulation site. PubMed, Embase, MEDLINE databases and the Cochrane Library, were searched for randomized controlled studies of repetitive transcranial magnetic stimulation treatment of dysphagia published before March 2016. Six clinical randomized controlled studies of a total of 163 stroke patients were included in this meta-analysis. A significant effect size of 1.24 was found for dysphagic outcome (mean effect size, 1.24; 95% confidence interval (CI), 0.67-1.81). A subgroup analysis based on frequency showed that the clinical scores were significantly improved in dysphagic patients with low frequency repetitive transcranial magnetic stimulation treatment ( P < 0.05) as well as high frequency repetitive transcranial magnetic stimulation treatment ( P < 0.05). A stimulation site stratified subgroup analysis implied significant changes in stroke patients with dysphagia for the unaffected hemisphere ( P < 0.05) and the bilateral hemisphere stimulation ( P < 0.05), but not for the affected hemisphere ( P > 0.05). The analysis of the follow-up data shows that patients in the repetitive transcranial magnetic stimulation groups still maintained the therapeutic benefit of repetitive transcranial magnetic stimulation four weeks after the last session of repetitive transcranial magnetic stimulation therapy ( P < 0.05). This meta-analysis indicates that repetitive transcranial magnetic stimulation has a positive effect on dysphagia after stroke. Compared with low-frequency repetitive transcranial magnetic stimulation, high-frequency repetitive transcranial magnetic stimulation may be more beneficial to the patients. This meta-analysis also supports that repetitive transcranial magnetic stimulation on an unaffected - or bilateral - hemisphere has a significant therapeutic effect on dysphagia.

  13. Binaural Hearing Ability With Bilateral Bone Conduction Stimulation in Subjects With Normal Hearing: Implications for Bone Conduction Hearing Aids.

    PubMed

    Zeitooni, Mehrnaz; Mäki-Torkko, Elina; Stenfelt, Stefan

    The purpose of this study is to evaluate binaural hearing ability in adults with normal hearing when bone conduction (BC) stimulation is bilaterally applied at the bone conduction hearing aid (BCHA) implant position as well as at the audiometric position on the mastoid. The results with BC stimulation are compared with bilateral air conduction (AC) stimulation through earphones. Binaural hearing ability is investigated with tests of spatial release from masking and binaural intelligibility level difference using sentence material, binaural masking level difference with tonal chirp stimulation, and precedence effect using noise stimulus. In all tests, results with bilateral BC stimulation at the BCHA position illustrate an ability to extract binaural cues similar to BC stimulation at the mastoid position. The binaural benefit is overall greater with AC stimulation than BC stimulation at both positions. The binaural benefit for BC stimulation at the mastoid and BCHA position is approximately half in terms of decibels compared with AC stimulation in the speech based tests (spatial release from masking and binaural intelligibility level difference). For binaural masking level difference, the binaural benefit for the two BC positions with chirp signal phase inversion is approximately twice the benefit with inverted phase of the noise. The precedence effect results with BC stimulation at the mastoid and BCHA position are similar for low frequency noise stimulation but differ with high-frequency noise stimulation. The results confirm that binaural hearing processing with bilateral BC stimulation at the mastoid position is also present at the BCHA implant position. This indicates the ability for binaural hearing in patients with good cochlear function when using bilateral BCHAs.

  14. Lack of body positional effects on paresthesias when stimulating the dorsal root ganglion (DRG) in the treatment of chronic pain.

    PubMed

    Kramer, Jeffery; Liem, Liong; Russo, Marc; Smet, Iris; Van Buyten, Jean-Pierre; Huygen, Frank

    2015-01-01

    One prominent side effect from neurostimulation techniques, and in particular spinal cord stimulation (SCS), is the change in intensity of stimulation when moving from an upright (vertical) to a recumbent or supine (horizontal) position and vice versa. It is well understood that the effects of gravity combined with highly conductive cerebrospinal fluid provide the mechanism by which changes in body position can alter the intensity of stimulation-induced paresthesias. While these effects are well established for leads that are placed within the more medial aspects of the spinal canal, little is known about these potential effects in leads placed in the lateral epidural space and in particular within the neural foramina near the dorsal root ganglion (DRG). We prospectively validated a newly developed paresthesia intensity rating scale and compared perceived paresthesia intensities when subjects assumed upright vs. supine bodily positions during neuromodulation of the DRG. On average, the correlation coefficient between stimulation intensity (pulse amplitude) and perceived paresthesia intensity was 0.83, demonstrating a strong linear relationship. No significant differences in paresthesia intensities were reported within subjects when moving from an upright (4.5 ± 0.14) to supine position 4.5 (± 0.12) (p > 0.05). This effect persisted through 12 months following implant. Neuromodulation of the DRG produces paresthesias that remain consistent across body positions, suggesting that this paradigm may be less susceptible to positional effects than dorsal column stimulation. © 2014 International Neuromodulation Society.

  15. Transcranial electrical stimulation over visual cortex evokes phosphenes with a retinal origin.

    PubMed

    Kar, Kohitij; Krekelberg, Bart

    2012-10-01

    Transcranial electrical stimulation (tES) is a promising therapeutic tool for a range of neurological diseases. Understanding how the small currents used in tES spread across the scalp and penetrate the brain will be important for the rational design of tES therapies. Alternating currents applied transcranially above visual cortex induce the perception of flashes of light (phosphenes). This makes the visual system a useful model to study tES. One hypothesis is that tES generates phosphenes by direct stimulation of the cortex underneath the transcranial electrode. Here, we provide evidence for the alternative hypothesis that phosphenes are generated in the retina by current spread from the occipital electrode. Building on the existing literature, we first confirm that phosphenes are induced at lower currents when electrodes are placed farther away from visual cortex and closer to the eye. Second, we explain the temporal frequency tuning of phosphenes based on the well-known response properties of primate retinal ganglion cells. Third, we show that there is no difference in the time it takes to evoke phosphenes in the retina or by stimulation above visual cortex. Together, these findings suggest that phosphenes induced by tES over visual cortex originate in the retina. From this, we infer that tES currents spread well beyond the area of stimulation and are unlikely to lead to focal neural activation. Novel stimulation protocols that optimize current distributions are needed to overcome these limitations of tES.

  16. FORT UNION DEEP

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lyle A. Johnson Jr.

    2002-09-01

    Coalbed methane (CBM) is currently the hottest area of energy development in the Rocky Mountain area. The Powder River Basin (PRB) is the largest CBM area in Wyoming and has attracted the majority of the attention because of its high permeability and relatively shallow depth. Other Wyoming coal regions are also being targeted for development, but most of these areas have lower permeability and deeper coal seams. This project consists of the development of a CBM stimulation system for deep coal resources and involves three work areas: (1) Well Placement, (2) Well Stimulation, and (3) Production Monitoring and Evaluation. Themore » focus of this project is the Washakie Basin. Timberline Energy, Inc., the cosponsor, has a project area in southern Carbon County, Wyoming, and northern Moffat County, Colorado. The target coal is found near the top of the lower Fort Union formation. The well for this project, Evans No.1, was drilled to a depth of 2,700 ft. Three coal seams were encountered with sandstone and some interbedded shale between seams. Well logs indicated that the coal seams and the sandstone contained gas. For the testing, the upper seam at 2,000 ft was selected. The well, drilled and completed for this project, produced very little water and only occasional burps of methane. To enhance the well, a mild severity fracture was conducted to fracture the coal seam and not the adjacent sandstone. Fracturing data indicated a fracture half-length of 34 ft, a coal permeability of 0.2226 md, and permeability of 15.3 md. Following fracturing, the gas production rate stabilized at 10 Mscf/day within water production of 18 bpd. The Western Research Institute (WRI) CBM model was used to design a 14-day stimulation cycle followed by a 30-day production period. A maximum injection pressure of 1,200 psig to remain well below the fracture pressure was selected. Model predictions were 20 Mscf/day of air injection for 14 days, a one-day shut-in, then flowback. The predicted flowback was a four-fold increase over the prestimulation rate with production essentially returning to prestimulation rates after 30 days. The physical stimulation was conducted over a 14-day period. Problems with the stimulation injection resulted in a coal bed fire that was quickly quenched when production was resumed. The poststimulation, stabilized production was three to four times the prestimulation rate. The methane content was approximately 45% after one day and increased to 65% at the end of 30 days. The gas production rate was still two and one-half times the prestimulation rate at the end of the 30-day test period. The field results were a good match to the numerical simulator predictions. The physical stimulation did increase the production, but did not produce a commercial rate.« less

  17. FORT UNION DEEP

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lyle A. Johnson Jr.

    2002-03-01

    Coalbed methane (CBM) is currently the hottest area of energy development in the Rocky Mountain area. The Powder River Basin (PRB) is the largest CBM area in Wyoming and has attracted the majority of the attention because of its high permeability and relatively shallow depth. Other Wyoming coal regions are also being targeted for development, but most of these areas have lower permeability and deeper coal seams. This project consists of the development of a CBM stimulation system for deep coal resources and involves three work areas: (1) Well Placement, (2) Well Stimulation, and (3) Production Monitoring and Evaluation. Themore » focus of this project is the Washakie Basin. Timberline Energy, Inc., the cosponsor, has a project area in southern Carbon County, Wyoming, and northern Moffat County, Colorado. The target coal is found near the top of the lower Fort Union formation. The well for this project, Evans No.1, was drilled to a depth of 2,700 ft. Three coal seams were encountered with sandstone and some interbedded shale between seams. Well logs indicated that the coal seams and the sandstone contained gas. For the testing, the upper seam at 2,000 ft was selected. The well, drilled and completed for this project, produced very little water and only occasional burps of methane. To enhance the well, a mild severity fracture was conducted to fracture the coal seam and not the adjacent sandstone. Fracturing data indicated a fracture half-length of 34 ft, a coal permeability of 0.2226 md, and permeability of 15.3 md. Following fracturing, the gas production rate stabilized at 10 Mscf/day within water production of 18 bpd. The Western Research Institute (WRI) CBM model was used to design a 14-day stimulation cycle followed by a 30-day production period. A maximum injection pressure of 1,200 psig to remain well below the fracture pressure was selected. Model predictions were 20 Mscf/day of air injection for 14 days, a one-day shut-in, then flowback. The predicted flowback was a four-fold increase over the prestimulation rate with production essentially returning to prestimulation rates after 30 days. The physical stimulation was conducted over a 14-day period. Problems with the stimulation injection resulted in a coal bed fire that was quickly quenched when production was resumed. The poststimulation, stabilized production was three to four times the prestimulation rate. The methane content was approximately 45% after one day and increased to 65% at the end of 30 days. The gas production rate was still two and one-half times the prestimulation rate at the end of the 30-day test period. The field results were a good match to the numerical simulator predictions. The physical stimulation did increase the production, but did not produce a commercial rate.« less

  18. [Design of an embedded stroke rehabilitation apparatus system based on Linux computer engineering].

    PubMed

    Zhuang, Pengfei; Tian, XueLong; Zhu, Lin

    2014-04-01

    A realizaton project of electrical stimulator aimed at motor dysfunction of stroke is proposed in this paper. Based on neurophysiological biofeedback, this system, using an ARM9 S3C2440 as the core processor, integrates collection and display of surface electromyography (sEMG) signal, as well as neuromuscular electrical stimulation (NMES) into one system. By embedding Linux system, the project is able to use Qt/Embedded as a graphical interface design tool to accomplish the design of stroke rehabilitation apparatus. Experiments showed that this system worked well.

  19. Microbial diversity and methanogenic activity of Antrim Shale formation waters from recently fractured wells

    PubMed Central

    Wuchter, Cornelia; Banning, Erin; Mincer, Tracy J.; Drenzek, Nicholas J.; Coolen, Marco J. L.

    2013-01-01

    The Antrim Shale in the Michigan Basin is one of the most productive shale gas formations in the U.S., but optimal resource recovery strategies must rely on a thorough understanding of the complex biogeochemical, microbial, and physical interdependencies in this and similar systems. We used Illumina MiSeq 16S rDNA sequencing to analyze the diversity and relative abundance of prokaryotic communities present in Antrim shale formation water of three closely spaced recently fractured gas-producing wells. In addition, the well waters were incubated with a suite of fermentative and methanogenic substrates in an effort to stimulate microbial methane generation. The three wells exhibited substantial differences in their community structure that may arise from their different drilling and fracturing histories. Bacterial sequences greatly outnumbered those of archaea and shared highest similarity to previously described cultures of mesophiles and moderate halophiles within the Firmicutes, Bacteroidetes, and δ- and ε-Proteobacteria. The majority of archaeal sequences shared highest sequence similarity to uncultured euryarchaeotal environmental clones. Some sequences closely related to cultured methylotrophic and hydrogenotrophic methanogens were also present in the initial well water. Incubation with methanol and trimethylamine stimulated methylotrophic methanogens and resulted in the largest increase in methane production in the formation waters, while fermentation triggered by the addition of yeast extract and formate indirectly stimulated hydrogenotrophic methanogens. The addition of sterile powdered shale as a complex natural substrate stimulated the rate of methane production without affecting total methane yields. Depletion of methane indicative of anaerobic methane oxidation (AMO) was observed over the course of incubation with some substrates. This process could constitute a substantial loss of methane in the shale formation. PMID:24367357

  20. R&D Funding Sources and University Technology Transfer: What Is Stimulating Universities to Be More Entrepreneurial?

    ERIC Educational Resources Information Center

    Powers, Joshua B.

    2004-01-01

    In recent years, universities have become increasingly entrepreneurial as evidenced by their rapid escalation into technology transfer, the process by which university-developed technologies are commercialized. Stimulated in part by a favorable policy environment for patenting and licensing as well as increased competition for limited resources,…

  1. Medial Auditory Thalamic Stimulation as a Conditioned Stimulus for Eyeblink Conditioning in Rats

    ERIC Educational Resources Information Center

    Campolattaro, Matthew M.; Halverson, Hunter E.; Freeman, John H.

    2007-01-01

    The neural pathways that convey conditioned stimulus (CS) information to the cerebellum during eyeblink conditioning have not been fully delineated. It is well established that pontine mossy fiber inputs to the cerebellum convey CS-related stimulation for different sensory modalities (e.g., auditory, visual, tactile). Less is known about the…

  2. Coupled THM Modeling of Hydroshearing Stimulation in Tight Fractured Volcanic Rock

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rinaldi, A. P.; Rutqvist, J.; Sonnenthal, E. L.

    Here, we use the TOUGH-FLAC simulator for coupled thermo–hydro-mechanical modeling of well stimulation for an Enhanced Geothermal System (EGS) project. We also analyze the potential for injection-induced fracturing and reactivation of natural fractures in a porous medium with associated permeability enhancement. Our analysis aims to understand how far the EGS reservoir may grow and how the hydroshearing process relates to system conditions. We analyze the enhanced reservoir, or hydrosheared zone, by studying the extent of the failure zone using an elasto-plastic model, and accounting for permeability changes as a function of the induced stresses. For both fully saturated and unsaturatedmore » medium cases, the results demonstrate how EGS reservoir growth depends on the initial fluid phase, and how the reservoir extent changes as a function of two critical parameters: (1) the coefficient of friction, and (2) the permeability-enhancement factor. Furthermore, while well stimulation is driven by pressure exceeding the hydroshearing threshold, the modeling also demonstrates how injection-induced cooling further extends the effects of stimulation.« less

  3. Coupled THM Modeling of Hydroshearing Stimulation in Tight Fractured Volcanic Rock

    DOE PAGES

    Rinaldi, A. P.; Rutqvist, J.; Sonnenthal, E. L.; ...

    2014-03-18

    Here, we use the TOUGH-FLAC simulator for coupled thermo–hydro-mechanical modeling of well stimulation for an Enhanced Geothermal System (EGS) project. We also analyze the potential for injection-induced fracturing and reactivation of natural fractures in a porous medium with associated permeability enhancement. Our analysis aims to understand how far the EGS reservoir may grow and how the hydroshearing process relates to system conditions. We analyze the enhanced reservoir, or hydrosheared zone, by studying the extent of the failure zone using an elasto-plastic model, and accounting for permeability changes as a function of the induced stresses. For both fully saturated and unsaturatedmore » medium cases, the results demonstrate how EGS reservoir growth depends on the initial fluid phase, and how the reservoir extent changes as a function of two critical parameters: (1) the coefficient of friction, and (2) the permeability-enhancement factor. Furthermore, while well stimulation is driven by pressure exceeding the hydroshearing threshold, the modeling also demonstrates how injection-induced cooling further extends the effects of stimulation.« less

  4. Impact of an indigenous microbial enhanced oil recovery field trial on microbial community structure in a high pour-point oil reservoir.

    PubMed

    Zhang, Fan; She, Yue-Hui; Li, Hua-Min; Zhang, Xiao-Tao; Shu, Fu-Chang; Wang, Zheng-Liang; Yu, Long-Jiang; Hou, Du-Jie

    2012-08-01

    Based on preliminary investigation of microbial populations in a high pour-point oil reservoir, an indigenous microbial enhanced oil recovery (MEOR) field trial was carried out. The purpose of the study is to reveal the impact of the indigenous MEOR process on microbial community structure in the oil reservoir using 16Sr DNA clone library technique. The detailed monitoring results showed significant response of microbial communities during the field trial and large discrepancies of stimulated microorganisms in the laboratory and in the natural oil reservoir. More specifically, after nutrients injection, the original dominant populations of Petrobacter and Alishewanella in the production wells almost disappeared. The expected desirable population of Pseudomonas aeruginosa, determined by enrichment experiments in laboratory, was stimulated successfully in two wells of the five monitored wells. Unexpectedly, another potential population of Pseudomonas pseudoalcaligenes which were not detected in the enrichment culture in laboratory was stimulated in the other three monitored production wells. In this study, monitoring of microbial community displayed a comprehensive alteration of microbial populations during the field trial to remedy the deficiency of culture-dependent monitoring methods. The results would help to develop and apply more MEOR processes.

  5. Deep brain stimulation of the internal pallidum in multiple system atrophy.

    PubMed

    Santens, Patrick; Patrick, Santens; Vonck, Kristl; Kristl, Vonck; De Letter, Miet; Miet, De Letter; Van Driessche, Katya; Katya, Van Driessche; Sieben, Anne; Anne, Sieben; De Reuck, Jacques; Jacques, De Reuck; Van Roost, Dirk; Dirk, Van Roost; Boon, Paul; Paul, Boon

    2006-04-01

    We describe the outcome of deep brain stimulation of the internal pallidum in a 57-year old patient with multiple system atrophy. Although the prominent dystonic features of this patient were markedly attenuated post-operatively, the outcome was to be considered unfavourable. There was a severe increase in akinesia resulting in overall decrease of mobility in limbs as well as in the face. As a result, the patient was anarthric and displayed dysphagia. A laterality effect of stimulation on oro-facial movements was demonstrated. The patient died 7 months post-operatively. This report adds to the growing consensus that multiple system atrophy patients are unsuitable candidates for deep brain stimulation.

  6. Food deprivation increases the low-dose locomotor stimulant response to ethanol in Drosophila melanogaster.

    PubMed

    Kliethermes, Christopher L

    2013-10-01

    Acute and chronic states of food deprivation result in increased sensitivity to a variety of natural reinforcers as well as to drugs of abuse. Food deprived animals show increased locomotor activity during periods of food deprivation, as well as increased locomotor stimulant responses to drugs of abuse, including cocaine, amphetamine, morphine, and ethanol, implying that drugs of abuse act in part on neural systems that underlie responses towards food. To determine whether this effect extends to an invertebrate, highly genetically tractable animal, the locomotor stimulant effects of low dose ethanol were assessed under a variety of feeding conditions in the fruit fly, Drosophila melanogaster. Food deprivation resulted in strain specific increases in ethanol-stimulated locomotor activity in most strains tested, although elevated baseline activity confounded interpretation in some strains. Experiments conducted with Canton S flies found that the effects of food deprivation on the locomotor stimulant response to ethanol increased with the duration of deprivation, and could be blocked by refeeding the flies with standard food or sucrose, but not yeast, immediately prior to the ethanol exposure. Life-span extending dietary depletion procedures or previous periods of food deprivation did not affect the response to ethanol, indicating that only animals in an acutely food deprived state are more sensitive to the stimulant effects of ethanol. These results suggest that increased sensitivity to the stimulant effects of some drugs of abuse might reflect an evolutionarily conserved neural mechanism that underlies behavioral responses to natural reinforcers and drugs of abuse. The identification of this mechanism, and the genes that underlie its development and function, will constitute a novel approach towards the study of alcohol abuse and dependence. © 2013.

  7. In situ and Enriched Microbial Community Composition and Function Associated with Coal Bed Methane from Powder River Basin Coals

    NASA Astrophysics Data System (ADS)

    Barnhart, Elliott; Davis, Katherine; Varonka, Matthew; Orem, William; Fields, Matthew

    2016-04-01

    Coal bed methane (CBM) is a relatively clean source of energy but current CBM production techniques have not sustained long-term production or produced enough methane to remain economically practical with lower natural gas prices. Enhancement of the in situ microbial community that actively generates CBM with the addition of specific nutrients could potentially sustain development. CBM production more than doubled from native microbial populations from Powder River Basin (PRB) coal beds, when yeast extract and several individual components of yeast extract (proteins and amino acids) were added to laboratory microcosms. Microbial populations capable of hydrogenotrophic (hydrogen production/utilization) methanogenesis were detected in situ and under non-stimulated conditions. Stimulation with yeast extract caused a shift in the community to microorganisms capable of acetoclastic (acetate production/utilization) methanogenesis. Previous isotope analysis from CBM production wells indicated a similar microbial community shift as observed in stimulation experiments: hydrogenotrophic methanogenesis was found throughout the PRB, but acetoclastic methanogenesis dominated major recharge areas. In conjunction, a high proportion of cyanobacterial and algal SSU rRNA gene sequences were detected in a CBM well within a major recharge area, suggesting that these phototrophic organisms naturally stimulate methane production. In laboratory studies, adding phototrophic (algal) biomass stimulated CBM production by PRB microorganisms similarly to yeast extract (~40μg methane increase per gram of coal). Analysis of the British thermal unit (BTU) content of coal from long-term incubations indicated >99.5% of BTU content remained after CBM stimulation with either algae or yeast extract. Biomimicry of in situ algal CBM stimulation could lead to technologies that utilize coupled biological systems (photosynthesis and methane production) that sustainably enhance CBM production and generate algal biofuels while also sequestering carbon dioxide (CO2).

  8. Optoacoustic effect is responsible for laser-induced cochlear responses

    NASA Astrophysics Data System (ADS)

    Kallweit, N.; Baumhoff, P.; Krueger, A.; Tinne, N.; Kral, A.; Ripken, T.; Maier, H.

    2016-06-01

    Optical stimulation of the cochlea with laser light has been suggested as an alternative to conventional treatment of sensorineural hearing loss with cochlear implants. The underlying mechanisms are controversially discussed: The stimulation can either be based on a direct excitation of neurons, or it is a result of an optoacoustic pressure wave acting on the basilar membrane. Animal studies comparing the intra-cochlear optical stimulation of hearing and deafened guinea pigs have indicated that the stimulation requires intact hair cells. Therefore, optoacoustic stimulation seems to be the underlying mechanism. The present study investigates optoacoustic characteristics using pulsed laser stimulation for in vivo experiments on hearing guinea pigs and pressure measurements in water. As a result, in vivo as well as pressure measurements showed corresponding signal shapes. The amplitude of the signal for both measurements depended on the absorption coefficient and on the maximum of the first time-derivative of laser pulse power (velocity of heat deposition). In conclusion, the pressure measurements directly demonstrated that laser light generates acoustic waves, with amplitudes suitable for stimulating the (partially) intact cochlea. These findings corroborate optoacoustic as the basic mechanism of optical intra-cochlear stimulation.

  9. Construction and application of a bovine immune-endocrine cDNA microarray.

    PubMed

    Tao, Wenjing; Mallard, Bonnie; Karrow, Niel; Bridle, Byram

    2004-09-01

    A variety of commercial DNA arrays specific for humans and rodents are widely available; however, microarrays containing well-characterized genes to study pathway-specific gene expression are not as accessible for domestic animals, such as cattle, sheep and pigs. Therefore, a small-scale application-targeted bovine immune-endocrine cDNA array was developed to evaluate genetic pathways involved in the immune-endocrine axis of cattle during periods of altered homeostasis provoked by physiological or environmental stressors, such as infection, vaccination or disease. For this purpose, 167 cDNA sequences corresponding to immune, endocrine and inflammatory response genes were collected and categorized. Positive controls included 5 housekeeping genes (glyceraldehydes-3-phosphate dehydrogenase, hypoxanthine phosphoribosyltransferase, ribosomal protein L19, beta-actin, beta2-microglobulin) and bovine genomic DNA. Negative controls were a bacterial gene (Rhodococcus equi 17-kDa virulence-associated protein) and a partial sequence of the plasmid pACYC177. In addition, RNA extracted from un-stimulated, as well as superantigen (Staphylococcus aureus enterotoxin-A, S. aureus Cowan Pansorbin Cells) and mitogen-stimulated (LPS, ConA) bovine blood leukocytes was mixed, reverse transcribed and PCR amplified using gene-specific primers. The endocrine-associated genes were amplified from cDNA derived from un-stimulated bovine hypothalamus, pituitary, adrenal and thyroid gland tissues. The array was constructed in 4 repeating grids of 180 duplicated spots by coupling the PCR amplified 213-630 bp gene fragments onto poly-l-lysine coated glass slides. The bovine immune-endocrine arrays were standardized and preliminary gene expression profiles generated using Cy3 and Cy5 labelled cDNA from un-stimulated and ConA (5 microg/ml) stimulated PBMC of 4 healthy Holstein cows (2-4 replicate arrays/cow) in a time course study. Mononuclear cell-derived cytokine and chemokine (IL-2, IL-1alpha, TNFalpha, IFN-gamma, TGFbeta-1, MCP-1, MCP-2 and MIP-3alpha) mRNA exhibited a repeatable and consistently low expression in un-stimulated cells and at least a two-fold increased expression following 6 and 24 h ConA stimulation as compared to 0 h un-stimulated controls. In contrast, expression of antigen presenting molecules, MHC-DR, MHC-DQ and MHC-DY, were consistently at least two-fold lower following 6 and 24 h ConA stimulation. The only endocrine gene with differential expression following ConA stimulation was prolactin. Additionally, due to the high level of genetic homology between ovine, swine and bovine genes, RNA similarly acquired from sheep and pigs was evaluated and similar gene expression patterns were noted. These data demonstrate that this application-targeted array containing a set of well characterized genes can be used to determine the relative gene expression corresponding to immune-endocrine responses of cattle and related species, sheep and pigs.

  10. 1H-Magnetic resonance spectroscopy study of stimulant medication effect on brain metabolites in French Canadian children with attention deficit hyperactivity disorder

    PubMed Central

    Benamor, Leila

    2014-01-01

    Background Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in school aged children. Functional abnormalities have been reported in brain imaging studies in ADHD populations. Psychostimulants are considered as the first line treatment for ADHD. However, little is known of the effect of stimulants on brain metabolites in ADHD patients. Objectives To compare the brain metabolite concentrations in children with ADHD and on stimulants with those of drug naïve children with ADHD, versus typically developed children, in a homogenous genetic sample of French Canadians. Methods Children with ADHD on stimulants (n=57) and drug naïve children with ADHD (n=45) were recruited, as well as typically developed children (n=38). The presence or absence of ADHD diagnosis (Diagnostic and Statistical Manual of Mental Disorders IV criteria) was based on clinical evaluation and The Diagnostic Interview Schedule for Children IV. All children (n=140) underwent a proton magnetic resonance spectroscopy session to measure the ratio of N-acetyl-aspartate, choline, glutamate, and glutamate–glutamine to creatine, respectively, in the left and right prefrontal and striatal regions of the brain, as well as in the left cerebellum. Results When compared with drug naïve children with ADHD, children with ADHD on stimulants and children typically developed were found to have higher choline ratios in the left prefrontal region (P=0.04) and lower N-acetyl-aspartate ratios in the left striatum region (P=0.01), as well as lower glutamate–glutamine ratios in the left cerebellum (P=0.05). In these three regions, there was no difference between children with ADHD on stimulants and typically developed children. Conclusion Therapeutic psychostimulant effects in children with ADHD may be mediated by normalization of brain metabolite levels, particularly in the left fronto-striato-cerebellar regions. PMID:24476627

  11. Two-photon absorption induced stimulated Rayleigh-Bragg scattering

    NASA Astrophysics Data System (ADS)

    He, Guang S.; Prasad, Paras N.

    2005-01-01

    A frequency-unshifted and backward stimulated scattering can be efficiently generated in one-photon-absorption free but two-photon absorbing materials. Using a number of novel two-photon absorbing dye solutions as the scattering media and nanosecond pulsed laser as the pump beams, a highly directional backward stimulated scattering at the exact pump wavelength can be readily observed once the pump intensity is higher than a certain threshold level. The spectral and spatial structures as well as the temporal behavior and optical phase-conjugation property of this new type of backward stimulated scattering have been experimentally studied. This stimulated scattering phenomenon can be explained by using a model of two-photon-excitation enhanced standing-wave Bragg grating initially formed by the strong forward pump beam and much weaker backward Rayleigh scattering beam; the partial reflection of the pump beam from this grating provides an positive feedback to the initial backward Rayleigh scattering beam without suffering linear attenuation influence. Comparing to other known stimulated (Raman, Brillouin, Rayleigh-wing, and Kerr) scattering effects, the stimulated Rayleigh-Bragg scattering exhibits the advantages of no frequency-shift, low pump threshold, and low spectral linewidth requirement.

  12. Electrophysiologic studies of neronal activities under ischemia condition.

    PubMed

    Huang, Shun-Ho; Wang, Ping-Hsien; Chen, Jia-Jin Jason

    2008-01-01

    Substrate with integrated microelectrode arrays (MEAs) provides an alternative electrophysiological method. With MEAS, one can measure the impedance and elicit electrical stimulation from multiple sites of MEAs to determine the electrophysiological conditions of cells. The aims of this research were to construct an impedance and action potential measurement system for neurons cultured on MEAs for observing the electrophysiological signal transmission in neuronal network during glucose and oxygen deprivation (OGD). An extracellular stimulator producing the biphasic micro-current pulse for neuron stimulation was built in this study. From the time-course recording of impedance, OGD condition effectively induced damage in neurons in vitro. It is known that the results of cell stimulation are affected by electrode impedance, so does the result of neuron cells covered on the electrode can measure the sealing resistance. For extracellular stimulation study, cortical neuronal activity was recorded and the suitable stimulation window was determined. However, the stimulation results were affected by electrode impedance as well as sealing impedance resulting from neuron cells covering the electrode. Further development of surface modification for cultured neuron network should provide a better way for in vitro impedance and electrophysiological measurements.

  13. The Fast and Transient Transcriptional Network of Gravity and Mechanical Stimulation in the Arabidopsis Root Apex1[w

    PubMed Central

    Kimbrough, Jeffery M.; Salinas-Mondragon, Raul; Boss, Wendy F.; Brown, Christopher S.; Sederoff, Heike Winter

    2004-01-01

    Plant root growth is affected by both gravity and mechanical stimulation (Massa GD, Gilroy S [2003] Plant J 33: 435–445). A coordinated response to both stimuli requires specific and common elements. To delineate the transcriptional response mechanisms, we carried out whole-genome microarray analysis of Arabidopsis root apices after gravity stimulation (reorientation) and mechanical stimulation and monitored transcript levels of 22,744 genes in a time course during the first hour after either stimulus. Rapid, transient changes in the relative abundance of specific transcripts occurred in response to gravity or mechanical stimulation, and these transcript level changes reveal clusters of coordinated events. Transcriptional regulation occurs in the root apices within less than 2 min after either stimulus. We identified genes responding specifically to each stimulus as well as transcripts regulated in both signal transduction pathways. Several unknown genes were specifically induced only during gravitropic stimulation (gravity induced genes). We also analyzed the network of transcriptional regulation during the early stages of gravitropism and mechanical stimulation. PMID:15347791

  14. Labial and vaginal blood volume responses to visual and tactile stimuli.

    PubMed

    Henson, D E; Rubin, H B; Henson, C

    1982-02-01

    Five women volunteers participated in two experimental sessions designed to evaluate the response patterns of two objective psychophysiological measure of women's sexual arousal to different methods (and intensities) of sexual stimulation (i.e., an erotic film and manual self-stimulation). A vaginal photoplethysmograph was used to measure vaginal blood volume response and a labial thermistor-clip was used to measure temperature changes of one of the minor labia. Both measures usually covaried in a highly significant manner during both types of stimulation, with the largest responses typically being evoked by the physical stimulation. The response patterns for the two measures were also similar following both methods of stimulation if the woman did not experience orgasm; both measures decreased to some extent after the stimulation ended but usually remained well above the prestimulatory baseline. Orgasm, however, affected the two genital measures differently. The vaginal blood volume measure decreased dramatically during the reported orgasm, possibly because of vaginal contractions, and then increased to at least the preorgasmic level that occurred during the stimulation. The labial measure did not change during the reported orgasm but decreased relatively rapidly soon after.

  15. tDCS Stimulation of the dlPFC Selectively Moderates the Detrimental Impact of Emotion on Analytical Reasoning.

    PubMed

    Trémolière, Bastien; Maheux-Caron, Véronique; Lepage, Jean-François; Blanchette, Isabelle

    2018-01-01

    There is evidence of a detrimental effect of emotion on reasoning. Recent studies suggest that this relationship is mediated by working memory, a function closely associated with the dorsolateral prefrontal cortex (dlPFC). Relying on transcranial direct current stimulation (tDCS), the present research explores the possibility that anodal stimulation of the dlPFC has the potential to prevent the effect of emotion on analytical reasoning. Thirty-four participants took part in a lab experiment and were tested twice: one session using offline anodal stimulation (with a 2 mA current stimulation applied to the left dlPFC for 20 min), one session using a control (sham) stimulation. In each session, participants solved syllogistic reasoning problems featuring neutral and emotionally negative contents. Results showed that anodal stimulation diminished the deleterious effect of emotion on syllogistic reasoning, but only for a subclass of problems: problems where the conclusion was logically valid. We discuss our results in the light of the reasoning literature as well as the apparent variability of tDCS effects.

  16. Non-Invasive Electrical Brain Stimulation Montages for Modulation of Human Motor Function.

    PubMed

    Curado, Marco; Fritsch, Brita; Reis, Janine

    2016-02-04

    Non-invasive electrical brain stimulation (NEBS) is used to modulate brain function and behavior, both for research and clinical purposes. In particular, NEBS can be applied transcranially either as direct current stimulation (tDCS) or alternating current stimulation (tACS). These stimulation types exert time-, dose- and in the case of tDCS polarity-specific effects on motor function and skill learning in healthy subjects. Lately, tDCS has been used to augment the therapy of motor disabilities in patients with stroke or movement disorders. This article provides a step-by-step protocol for targeting the primary motor cortex with tDCS and transcranial random noise stimulation (tRNS), a specific form of tACS using an electrical current applied randomly within a pre-defined frequency range. The setup of two different stimulation montages is explained. In both montages the emitting electrode (the anode for tDCS) is placed on the primary motor cortex of interest. For unilateral motor cortex stimulation the receiving electrode is placed on the contralateral forehead while for bilateral motor cortex stimulation the receiving electrode is placed on the opposite primary motor cortex. The advantages and disadvantages of each montage for the modulation of cortical excitability and motor function including learning are discussed, as well as safety, tolerability and blinding aspects.

  17. Comparison of side effects of pentagastrin test and calcium stimulation test in patients with increased basal calcitonin concentration: the gender-specific differences.

    PubMed

    Ubl, Philipp; Gincu, Tatiana; Keilani, Mohammad; Ponhold, Lothar; Crevenna, Richard; Niederle, Bruno; Hacker, Marcus; Li, Shuren

    2014-08-01

    The aim of this study was to compare the side effects of the pentagastrin test and the calcium stimulation test in patients with increased basal calcitonin concentration, especially the gender-specific differences of side effects. A total of 256 patients (123 females and 133 males, mean age of 56 ± 27 years, range 21-83 years) had both pentagastrin and calcium stimulation tests. All patients filled in a questionnaire regarding the side effects within 30 min after completion of the stimulation tests. The differences of side effects between female and male patients as well as between the pentagastrin stimulation test and the calcium stimulation test were evaluated. Warmth feeling was the most frequent occurring side effect in all patients who had both pentagastrin and calcium stimulation tests, followed by nausea, altered gustatory sensation, and dizziness. The incidences of urgency to micturate (p < 0.05) and dizziness (p < 0.05) were significantly increased in the female patients as compared to male patients by calcium stimulation test. Significant higher incidences of urgency to micturate (p < 0.05) and warmth feeling (p < 0.05) were found by calcium stimulation test as compared with those by pentagastrin test in female patients. The incidences of nausea (p < 0.05) and abdominal cramping (p < 0.05) in male patients were significantly higher by pentagastrin stimulation test than by calcium stimulation test. There is a significant gender-specific difference in side effects induced by calcium stimulation test. Female patients have fewer side effects by pentagastrin test than by calcium stimulation test. Male patients may tolerate the calcium stimulation test better than the pentagastrin test.

  18. The Codacs™ Direct Acoustic Cochlear Implant Actuator: Exploring Alternative Stimulation Sites and Their Stimulation Efficiency

    PubMed Central

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

    2015-01-01

    This work assesses the efficiency of the Codacs system actuator (Cochlear Ltd., Sydney Australia) in different inner ear stimulation modalities. Originally the actuator was intended for direct perilymph stimulation after stapedotomy using a piston prosthesis. A possible alternative application is the stimulation of middle ear structures or the round window (RW). Here the perilymph stimulation with a K-piston through a stapes footplate (SFP) fenestration (N = 10) as well as stimulation of the stapes head (SH) with a Bell prosthesis (N = 9), SFP stimulation with an Omega/Aerial prosthesis (N = 8) and reverse RW stimulation (N = 10) were performed in cadaveric human temporal bones (TBs). Codacs actuator output is expressed as equivalent sound pressure level (eq. SPL) using RW and SFP displacement responses, measured by Laser Doppler velocimetry as reference. The axial actuator coupling force in stimulation of stapes and RW was adjusted to ~ 5 mN. The Bell prosthesis and Omega/Aerial prosthesis stimulation generated similar mean eq. SPLs (Bell: 127.5–141.8 eq. dB SPL; Omega/Aerial: 123.6–143.9 eq. dB SPL), being significantly more efficient than K-piston perilymph stimulation (108.6–131.6 eq. dB SPL) and RW stimulation (108.3–128.2 eq. dB SPL). Our results demonstrate that SH, SFP and RW are adequate alternative stimulation sites for the Codacs actuator using coupling prostheses and an axial coupling force of ~ 5 mN. Based on the eq. SPLs, all investigated methods were adequate for in vivo hearing aid applications, provided that experimental conditions including constant coupling force will be implemented. PMID:25785860

  19. Contributions to muscle force and EMG by combined neural excitation and electrical stimulation

    NASA Astrophysics Data System (ADS)

    Crago, Patrick E.; Makowski, Nathaniel S.; Cole, Natalie M.

    2014-10-01

    Objective. Stimulation of muscle for research or clinical interventions is often superimposed on ongoing physiological activity without a quantitative understanding of the impact of the stimulation on the net muscle activity and the physiological response. Experimental studies show that total force during stimulation is less than the sum of the isolated voluntary and stimulated forces, but the occlusion mechanism is not understood. Approach. We develop a model of efferent motor activity elicited by superimposing stimulation during a physiologically activated contraction. The model combines action potential interactions due to collision block, source resetting, and refractory periods with previously published models of physiological motor unit recruitment, rate modulation, force production, and EMG generation in human first dorsal interosseous muscle to investigate the mechanisms and effectiveness of stimulation on the net muscle force and EMG. Main results. Stimulation during a physiological contraction demonstrates partial occlusion of force and the neural component of the EMG, due to action potential interactions in motor units activated by both sources. Depending on neural and stimulation firing rates as well as on force-frequency properties, individual motor unit forces can be greater, smaller, or unchanged by the stimulation. In contrast, voluntary motor unit EMG potentials in simultaneously stimulated motor units show progressive occlusion with increasing stimulus rate. The simulations predict that occlusion would be decreased by a reverse stimulation recruitment order. Significance. The results are consistent with and provide a mechanistic interpretation of previously published experimental evidence of force occlusion. The models also predict two effects that have not been reported previously—voluntary EMG occlusion and the advantages of a proximal stimulation site. This study provides a basis for the rational design of both future experiments and clinical neuroprosthetic interventions involving either motor or sensory stimulation.

  20. Contributions to muscle force and EMG by combined neural excitation and electrical stimulation

    PubMed Central

    Crago, Patrick E; Makowski, Nathaniel S; Cole, Natalie M

    2014-01-01

    Objective Stimulation of muscle for research or clinical interventions is often superimposed on ongoing physiological activity, without a quantitative understanding of the impact of the stimulation on the net muscle activity and the physiological response. Experimental studies show that total force during stimulation is less than the sum of the isolated voluntary and stimulated forces, but the occlusion mechanism is not understood. Approach We develop a model of efferent motor activity elicited by superimposing stimulation during a physiologically activated contraction. The model combines action potential interactions due to collision block, source resetting, and refractory periods with previously published models of physiological motor unit recruitment, rate modulation, force production, and EMG generation in human first dorsal interosseous muscle to investigate the mechanisms and effectiveness of stimulation on the net muscle force and EMG. Main Results Stimulation during a physiological contraction demonstrates partial occlusion of force and the neural component of the EMG, due to action potential interactions in motor units activated by both sources. Depending on neural and stimulation firing rates as well as on force-frequency properties, individual motor unit forces can be greater, smaller, or unchanged by the stimulation. In contrast, voluntary motor unit EMG potentials in simultaneously stimulated motor units show progressive occlusion with increasing stimulus rate. The simulations predict that occlusion would be decreased by a reverse stimulation recruitment order. Significance The results are consistent with and provide a mechanistic interpretation of previously published experimental evidence of force occlusion. The models also predict two effects that have not been reported previously - voluntary EMG occlusion and the advantages of a proximal stimulation site. This study provides a basis for the rational design of both future experiments and clinical neuroprosthetic interventions involving either motor or sensory stimulation. PMID:25242203

  1. Stimulant-Responsive and Stimulant-Refractory Aggressive Behavior Among Children with ADHD

    PubMed Central

    Blader, Joseph C.; Pliszka, Steven R.; Jensen, Peter S.; Schooler, Nina R.; Kafantaris, Vivian

    2010-01-01

    OBJECTIVES The objective of this study was to examine factors that are associated with aggression that is responsive versus refractory to individualized optimization of stimulant monotherapy among children with attention-deficit/hyperactivity disorder (ADHD). METHODS Children who were aged 6 to 13 years and had ADHD, either oppositional defiant disorder or conduct disorder, significant aggressive behavior, and a history of insufficient response to stimulants completed an open stimulant monotherapy optimization protocol. Stimulant titration with weekly assessments of behavior and tolerability identified an optimal regimen for each child. Families also received behavioral therapy. Parents completed the Retrospective-Modified Overt Aggression Scale (R-MOAS) at each visit. Children were classified as having stimulant-refractory aggression on the basis of R-MOAS ratings and clinician judgment. Differences that pertained to treatment, demographic, and psychopathology between groups with stimulant monotherapy–responsive and –refractory aggression were evaluated. RESULTS Aggression among 32 (49.3%) of 65 children was reduced sufficiently after stimulant dosage adjustment and behavioral therapy to preclude adjunctive medication. Those who responded to stimulant monotherapy were more likely to benefit from the protocol’s methylphenidate preparation (once-daily, triphasic release), showed a trend for lower average dosages, and received fewer behavioral therapy sessions than did children with stimulant-refractory aggression. Boys, especially those with higher ratings of baseline aggression and of depressive and manic symptoms, more often exhibited stimulant-refractory aggression. CONCLUSIONS Among children whose aggressive behavior develops in the context of ADHD and of oppositional defiant disorder or conduct disorder, and who had insufficient response to previous stimulant treatment in routine clinical care, systematic, well-monitored titration of stimulant monotherapy often culminates in reduced aggression that averts the need for additional agents. PMID:20837589

  2. Chemical stimulation of adherent cells by localized application of acetylcholine from a microfluidic system.

    PubMed

    Zibek, Susanne; Hagmeyer, Britta; Stett, Alfred; Stelzle, Martin

    2010-01-01

    Chemical stimulation of cells is inherently cell type selective in contrast to electro-stimulation. The availability of a system for localized application of minute amounts of chemical stimulants could be useful for dose related response studies to test new compounds. It could also bring forward the development of a novel type of neuroprostheses. In an experimental setup microdroplets of an acetylcholine solution were ejected from a fluidic microsystem and applied to the bottom of a nanoporous membrane. The solution traveled through the pores to the top of the membrane on which TE671 cells were cultivated. Calcium imaging was used to visualize cellular response with temporal and spatial resolution. Experimental demonstration of chemical stimulation for both threshold gated stimulation as well as accumulated dose-response was achieved by either employing acetylcholine as chemical stimulant or applying calcein uptake, respectively. Numerical modeling and simulation of transport mechanisms involved were employed to gain a theoretical understanding of the influence of pore size, concentration of stimulant and droplet volume on the spatial-temporal distribution of stimulant and on the cellular response. Diffusion, pressure driven flow and evaporation effects were taken into account. Fast stimulation kinetic is achieved with pores of 0.82 μm diameter, whereas sustained substance delivery is obtained with nanoporous membranes. In all cases threshold concentrations ranging from 0.01 to 0.015 μM acetylcholine independent of pore size were determined.

  3. The enteric nervous system modulates mammalian duodenal mucosal bicarbonate secretion.

    PubMed

    Hogan, D L; Yao, B; Steinbach, J H; Isenberg, J I

    1993-08-01

    Interaction of the enteric nerves in regulating mammalian duodenal mucosal bicarbonate secretion is not well understood. The purpose of the present experiments was to evaluate the role of the enteric nervous system on bicarbonate secretion from rabbit duodenal mucosa in vitro. Proximal duodenum from male New Zealand White rabbits was stripped of seromuscular layers, mounted in Ussing chambers, and studied under short-circuited conditions. Effects of electrical field stimulation, vasoactive intestinal polypeptide (VIP), carbachol, prostaglandin E2 (PGE2), dibutyryl-cyclic adenosine monophosphate (db-cAMP), and the neurotoxin tetrodotoxin (TTX) and muscarinic blockade by atropine were studied. Electrical field stimulation significantly (P < 0.01) stimulated bicarbonate secretion, short-circuit current (Isc), and electrical potential difference (PD) that was sensitive to both TTX and atropine. VIP-stimulated bicarbonate secretion was significantly inhibited by TTX (-73%), yet Isc and PD remained unchanged. Atropine decreased VIP-induced bicarbonate secretion (-69%) and Isc (-43%). Carbachol-stimulated bicarbonate secretion, Isc, and PD were abolished by atropine, whereas TTX was without affect. Neither TTX nor atropine had a significant effect on PGE2 or db-cAMP-stimulated bicarbonate secretion. These results suggest that (1) enteric nerve stimulation activates an acetylcholine receptor that in turn stimulates duodenal epithelial bicarbonate secretion; (2) VIP stimulates bicarbonate secretion, in large part, via the enteric nervous system; and (3) PGE2 and cAMP stimulate bicarbonate secretion independent of the enteric nervous system.

  4. Non-pharmacological biological treatment approaches to difficult-to-treat depression.

    PubMed

    Fitzgerald, Paul B

    2013-09-16

    There has been substantial recent interest in novel brain stimulation treatments for difficult-to-treat depression. Electroconvulsive therapy (ECT) is a well established, effective treatment for severe depression. ECT's problematic side-effect profile and questions regarding optimal administration methods continue to be investigated. Magnetic seizure therapy, although very early in development, shows promise, with potentially similar efficacy to ECT but fewer side effects. Vagus nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) are clinically available in some countries. Limited research suggests VNS has potentially long-lasting antidepressant effects in a small group of patients. Considerable research supports the efficacy of rTMS. Both techniques require further study of optimal treatment parameters. Transcranial direct current stimulation may provide a low-cost antidepressant option if its efficacy is substantiated in larger samples. Deep brain stimulation is likely to remain reserved for patients with the most severe and difficult-to-treat depression, requiring further exploration of administration methods and its role in depression therapy. New and innovative forms of brain stimulation, including low-intensity ultrasound, low-field magnetic stimulation and epidural stimulation of the cortical surface, are in early stages of exploration and are yet to move into the clinical domain. Ongoing work is required to define which brain stimulation treatments are likely to be most useful, and in which patient groups. Clinical service development of brain stimulation treatments will likely be inconsistent and variable.

  5. Transient finite element modeling of functional electrical stimulation.

    PubMed

    Filipovic, Nenad D; Peulic, Aleksandar S; Zdravkovic, Nebojsa D; Grbovic-Markovic, Vesna M; Jurisic-Skevin, Aleksandra J

    2011-03-01

    Transcutaneous functional electrical stimulation is commonly used for strengthening muscle. However, transient effects during stimulation are not yet well explored. The effect of an amplitude change of the stimulation can be described by static model, but there is no differency for different pulse duration. The aim of this study is to present the finite element (FE) model of a transient electrical stimulation on the forearm. Discrete FE equations were derived by using a standard Galerkin procedure. Different tissue conductive and dielectric properties are fitted using least square method and trial and error analysis from experimental measurement. This study showed that FE modeling of electrical stimulation can give the spatial-temporal distribution of applied current in the forearm. Three different cases were modeled with the same geometry but with different input of the current pulse, in order to fit the tissue properties by using transient FE analysis. All three cases were compared with experimental measurements of intramuscular voltage on one volunteer.

  6. Theoretical performance and clinical evaluation of transverse tripolar spinal cord stimulation.

    PubMed

    Struijk, J J; Holsheimer, J; Spincemaille, G H; Gielen, F L; Hoekema, R

    1998-09-01

    A new type of spinal cord stimulation electrode, providing contact combinations with a transverse orientation, is presented. Electrodes were implanted in the cervical area (C4-C5) of two chronic pain patients and the stimulation results were subsequently simulated with a computer model consisting of a volume conductor model and active nerve fiber models. For various contact combinations a good match was obtained between the modeling results and the measurement data with respect to load resistance (less than 20% difference), perception thresholds (16% difference), asymmetry of paresthesia (significant correlation) and paresthesia distributions (weak correlation). The transversally oriented combinations provided the possibility to select either a preferential dorsal column stimulation, a preferential dorsal root stimulation or a mixed stimulation. The (a)symmetry of paresthesia could largely be affected in a predictable way by the selection of contact combinations as well. The transverse tripolar combination was shown to give a higher selectivity of paresthesia than monopolar and longitudinal dipolar combinations, at the cost of an increased current (more than twice).

  7. Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

    NASA Astrophysics Data System (ADS)

    Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

    1998-12-01

    Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

  8. Light-Stimulated Synaptic Devices Utilizing Interfacial Effect of Organic Field-Effect Transistors.

    PubMed

    Dai, Shilei; Wu, Xiaohan; Liu, Dapeng; Chu, Yingli; Wang, Kai; Yang, Ben; Huang, Jia

    2018-06-14

    Synaptic transistors stimulated by light waves or photons may offer advantages to the devices, such as wide bandwidth, ultrafast signal transmission, and robustness. However, previously reported light-stimulated synaptic devices generally require special photoelectric properties from the semiconductors and sophisticated device's architectures. In this work, a simple and effective strategy for fabricating light-stimulated synaptic transistors is provided by utilizing interface charge trapping effect of organic field-effect transistors (OFETs). Significantly, our devices exhibited highly synapselike behaviors, such as excitatory postsynaptic current (EPSC) and pair-pulse facilitation (PPF), and presented memory and learning ability. The EPSC decay, PPF curves, and forgetting behavior can be well expressed by mathematical equations for synaptic devices, indicating that interfacial charge trapping effect of OFETs can be utilized as a reliable strategy to realize organic light-stimulated synapses. Therefore, this work provides a simple and effective strategy for fabricating light-stimulated synaptic transistors with both memory and learning ability, which enlightens a new direction for developing neuromorphic devices.

  9. NADPH oxidase activation contributes to native low-density lipoprotein-induced proliferation of human aortic smooth muscle cells.

    PubMed

    Park, Il Hwan; Hwang, Hye Mi; Jeon, Byeong Hwa; Kwon, Hyung-Joo; Hoe, Kwang Lae; Kim, Young Myeong; Ryoo, Sungwoo

    2015-06-12

    Elevated plasma concentration of native low-density lipoprotein (nLDL) is associated with vascular smooth muscle cell (VSMC) activation and cardiovascular disease. We investigated the mechanisms of superoxide generation and its contribution to pathophysiological cell proliferation in response to nLDL stimulation. Lucigenin-induced chemiluminescence was used to measure nLDL-induced superoxide production in human aortic smooth muscle cells (hAoSMCs). Superoxide production was increased by nicotinamide adenine dinucleotide phosphate (NADPH) and decreased by NADPH oxidase inhibitors in nLDL-stimulated hAoSMC and hAoSMC homogenates, as well as in prepared membrane fractions. Extracellular signal-regulated kinase 1/2 (Erk1/2), protein kinase C-θ (PKCθ) and protein kinase C-β (PKCβ) were phosphorylated and maximally activated within 3 min of nLDL stimulation. Phosphorylated Erk1/2 mitogen-activated protein kinase, PKCθ and PKCβ stimulated interactions between p47phox and p22phox; these interactions were prevented by MEK and PKC inhibitors (PD98059 and calphostin C, respectively). These inhibitors decreased nLDL-dependent superoxide production and blocked translocation of p47phox to the membrane, as shown by epifluorescence imaging and cellular fractionation experiments. Proliferation assays showed that a small interfering RNA against p47phox, as well as superoxide scavenger and NADPH oxidase inhibitors, blocked nLDL-induced hAoSMC proliferation. The nLDL stimulation in deendothelialized aortic rings from C57BL/6J mice increased dihydroethidine fluorescence and induced p47phox translocation that was blocked by PD98059 or calphostin C. Isolated aortic SMCs from p47phox(-/-) mice (mAoSMCs) did not respond to nLDL stimulation. Furthermore, NADPH oxidase 1 (Nox1) was responsible for superoxide generation and cell proliferation in nLDL-stimulated hAoSMCs. These data demonstrated that NADPH oxidase activation contributed to cell proliferation in nLDL-stimulated hAoSMCs.

  10. Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

    PubMed Central

    Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

    2016-01-01

    Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal modelling revealed a correlation between therapeutic effectiveness and attenuated within-region inhibitory connectivity in cerebellum. Finally, specific subregions of sensorimotor cortex were identified in which deep brain stimulation-evoked activation correlated with the presence of unwanted paraesthesias. These results suggest that thalamic deep brain stimulation in tremor likely exerts its effects through modulation of both olivocerebellar and thalamocortical circuits. In addition, our findings indicate that deep brain stimulation-evoked functional activation maps obtained intraoperatively may contain predictive information pertaining to the therapeutic and adverse effects induced by deep brain stimulation. PMID:27329768

  11. Interactive Book Reading in Early Education: A Tool to Stimulate Print Knowledge as Well as Oral Language

    ERIC Educational Resources Information Center

    Mol, Suzanne E.; Bus, Adriana G.; de Jong, Maria T.

    2009-01-01

    This meta-analysis examines to what extent interactive storybook reading stimulates two pillars of learning to read: vocabulary and print knowledge. The authors quantitatively reviewed 31 (quasi) experiments (n = 2,049 children) in which educators were trained to encourage children to be actively involved before, during, and after joint book…

  12. Stress inversion using borehole images and geometry evolution of the fractures in the Rittershoffen EGS project (Alsace, France).

    NASA Astrophysics Data System (ADS)

    Azzola, Jérôme; Valley, Benoît; Schmittbuhl, Jean; Genter, Albert; Hehn, Régis

    2017-04-01

    In the Upper Rhine Graben, several deep geothermal projects based on the Enhanced Geothermal System (EGS) exploit local geothermal reservoirs. The principle underlying this technology consists of increasing the hydraulic performances of the reservoir by stimulating natural fractures using different methods, in order to extract hot water with commercially flow rates. In this domain, the knowledge of the in-situ stress state is of central importance to predict the response of the rock mass to stimulations. Here we characterized the stress tensor from Ultrasonic Borehole Imager (UBI) in the open hole section of the EGS doublet located in Rittershoffen, France (in the Upper Rhine Graben). Interestingly extensive logging programs were leaded at different key moments of the development of the injection well using hydraulic, thermal and chemical stimulation (Baujard et al., 2017)1. The time lapse UBI dataset consists of images of the injection well before, shortly and lastly after the stimulation. The geometry of the induced fractures in compression (breakouts) picked on the UBI images are used to determine the orientation of the in-situ stress tensor. The magnitude of the principal stresses is deduced from the drilling data. The magnitude of the maximum horizontal principal stress is evaluated using an inversion method with three failure criteria (Mohr-Coulomb, Mogi-Coulomb and modified Hoek-Brown criterion) and under the assumption of a vertical or a deviated well. Moreover, the characteristic of the dataset enables the analysis of the evolution of the borehole fracturing, as the deepening or widening of the induced fractures. The correlation of the UBI image allows firstly to determine the tool trajectory and to adapt the post and pre-stimulation images. It secondly leads to the estimation of a complete displacement field which characterizes the deformation induced by the stimulations. Even if the variable image quality deeply conditions the comparison, the considered dataset enabled a consistent evaluation of the in-situ stress field taking place in the underground of the EGS plant, as showed by the comparison to results obtained in the vicinity. Moreover, the study of the evolution of fracturing shows the influence of the stimulation process on the fractures geometry. 1(Baujard, C., Genter, A., Dalmais, E., Maurer, V., Hehn, R., Rosillette, R., Vidal, J., Schmittbuhl, J., 2017). Hydrothermal Characterization of wells GRT-1 and GRT-2 in Rittershoffen, France: Implications on the understanding of natural flow systems in the Rhine Graben, Geothermics, 65, 255-268.

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

    PubMed

    Meiron, Oded; Lavidor, Michal

    2013-05-01

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

  14. Application of Reservoir Flow Simulation Integrated with Geomechanics in Unconventional Tight Play

    NASA Astrophysics Data System (ADS)

    Lin, Menglu; Chen, Shengnan; Mbia, Ernest; Chen, Zhangxing

    2018-01-01

    Multistage hydraulic fracturing techniques, combined with horizontal drilling, have enabled commercial production from the vast reserves of unconventional tight formations. During hydraulic fracturing, fracturing fluid and proppants are pumped into the reservoir matrix to create the hydraulic fractures. Understanding the propagation mechanism of hydraulic fractures is essential to estimate their properties, such as half-length. In addition, natural fractures are often present in tight formations, which might be activated during the fracturing process and contribute to the post-stimulation well production rates. In this study, reservoir simulation is integrated with rock geomechanics to predict the well post-stimulation productivities. Firstly, a reservoir geological model is built based on the field data collected from the Montney formation in the Western Canadian Sedimentary Basin. The hydraulic fracturing process is then simulated through an integrated approach of fracturing fluid injection, rock geomechanics, and tensile failure criteria. In such a process, the reservoir pore pressure increases with a continuous injection of the fracturing fluid and proppants, decreasing the effective stress exerted on the rock matrix accordingly as the overburden pressure remains constant. Once the effective stress drops to a threshold value, tensile failure of the reservoir rock occurs, creating hydraulic fractures in the formation. The early production history of the stimulated well is history-matched to validate the predicted fracture geometries (e.g., half-length) generated from the fracturing simulation process. The effects of the natural fracture properties and well bottom-hole pressures on well productivity are also studied. It has been found that nearly 40% of hydraulic fractures propagate in the beginning stage (the pad step) of the fracturing schedule. In addition, well post-stimulation productivity will increase significantly if the natural fractures are propped or partially propped by the proppants. This paper provides insights on fracture propagation and can be a reference for fracturing treatments in unconventional tight reservoirs.

  15. Characteristics and management of flowback/produced water from hydraulically fractured wells in California - findings from the California SB 4 assessment

    NASA Astrophysics Data System (ADS)

    Varadharajan, C.; Cooley, H.; Heberger, M. G.; Stringfellow, W. T.; Domen, J. K.; Sandelin, W.; Camarillo, M. K.; Jordan, P. D.; Reagan, M. T.; Donnelly, K.; Birkholzer, J. T.; Long, J. C. S.

    2015-12-01

    As part of a recent assessment of well stimulation in California, we analyzed the hazards and potential impacts of hydraulic fracturing (the primary form of well stimulation in California) on water resources, which included an analysis of the quantity and quality of flowback/produced water generated, current management and disposal practices, associated potential release mechanisms and transport pathways that can lead to contaminants being released into the environment, and practices to mitigate or avoid impacts from produced water on water resources. The wastewater returned after stimulation includes "recovered fluids" (flowback fluids collected into tanks following stimulation, but before the start of production) and "produced water" (water extracted with oil and gas during production). In contrast to hydraulic fracturing in regions with primarily gas production, the quantities of recovered fluids from hydraulically fractured wells in California are small in comparison to the fluids injected (typically <5%), and large quantities of produced water are generated. Our analysis indicates some fraction of returning fracturing fluids is likely present in produced water from wells that have been hydraulically fractured. Chemical measurements of recovered fluids show that some samples can contain high levels of some contaminants, including total carbohydrates (indicating the presence of guar, a component of fracturing fluid), total dissolved solids (TDS), trace elements and naturally occurring radioactive material (NORM). Data on produced water chemistry are more limited. In California, produced water is typically managed via pipelines and disposed or reused in many ways. A majority of produced water from hydraulically fractured wells in California is disposed in percolation pits, many of which may lie in areas with good groundwater quality. Some of the remaining produced water is injected into Class II wells; although a few of the wells are under review or have been shut down since they were injecting into aquifers. Other methods of management of produced water include reuse for irrigation and discharge into sewer systems. Each of these disposal and reuse methods presents its own unique set of concerns that need to be considered together, in designing a produced water management plan.

  16. Postural stability is altered by the stimulation of pain but not warm receptors in humans.

    PubMed

    Blouin, Jean-Sébastien; Corbeil, Philippe; Teasdale, Normand

    2003-10-17

    It is now recognized that large diameter myelinated afferents provide the primary source of lower limb proprioceptive information for maintaining an upright standing position. Small diameter afferents transmitting noxious stimuli, however, can also influence motor behaviors. Despite the possible influence of pain on motor behaviors, the effects of pain on the postural control system have not been well documented. Two cutaneous heat stimulations (experiment 1: non-noxious 40 degrees C; experiment 2: noxious 45 degrees C) were applied bilaterally on the calves of the subject with two thermal grills to stimulate A delta and C warm receptors and nociceptors in order to examine their effects on postural stability. The non-noxious stimulation induced a gentle sensation of warmth and the noxious stimulation induced a perception of heat pain (visual analogue scores of 0 and 46 mm, respectively). For both experiments, ten healthy young adults were tested with and without heat stimulations of the lower limbs while standing upright on a force platform with eyes open, eyes closed and eyes closed with tendon co-vibration of tibialis anterior and triceps surae muscles. The center of pressure displacements were analyzed to examine how both stimulations affected the regulation of quiet standing and if the effects were exacerbated when vision was removed or ankle proprioception perturbed. The stimulation of the warm receptors (40 degrees C) did not induce any postural deterioration. With pain (45 degrees C), subjects showed a significant increase in standard deviation, range and mean velocity of postural oscillations as well as standard deviation of the center of pressure velocity. The effects of heat pain were exacerbated when subjects had both their eyes closed and ankle tendons vibrated (increased standard deviation of the center of pressure velocity and mean velocity of the center of pressure). A non-noxious stimulation (40 degrees C) of the small diameter afferents is not a sufficiently intense sensory stimulation to alter the control of posture. A painful stimulation (45 degrees C) of the skin thermoreceptors, however, yielded a deterioration of the postural control system. The observed deteriorating effects of the combined stimulation of nociceptors and Ia afferents (when ankle tendons were vibrated) could result from the convergence of these afferents at the spinal level. This could certainly lead to the hypothesis that individuals suffering from lower limb pain present alterations of the postural control mechanisms; especially populations already at risk of falling (for example, frail elderly) or populations suffering from concomitant lower limb pain and sensory deficits (for example, diabetic polyneuropathy).

  17. Tunneling modulation of a quantum-well transistor laser

    NASA Astrophysics Data System (ADS)

    Feng, M.; Qiu, J.; Wang, C. Y.; Holonyak, N.

    2016-11-01

    Different than the Bardeen and Brattain transistor (1947) with the current gain depending on the ratio of the base carrier spontaneous recombination lifetime to the emitter-collector transit time, the Feng and Holonyak transistor laser current gain depends upon the base electron-hole (e-h) stimulated recombination, the base dielectric relaxation transport, and the collector stimulated tunneling. For the n-p-n transistor laser tunneling operation, the electron-hole pairs are generated at the collector junction under the influence of intra-cavity photon-assisted tunneling, with electrons drifting to the collector and holes drifting to the base. The excess charge in the base lowers the emitter junction energy barrier, allowing emitter electron injection into the base and satisfying charge neutrality via base dielectric relaxation transport (˜femtoseconds). The excess electrons near the collector junction undergo stimulated recombination at the base quantum-well or transport to the collector, thus supporting tunneling current amplification and optical modulation of the transistor laser.

  18. Effect of the magnetic field on coexisting stimulated Raman and Brillouin backscattering of an extraordinary mode

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vyas, Ashish, E-mail: ashishvyas.optics@gmail.com; Singh, Ram Kishor, E-mail: ram007kishor@gmail.com; Sharma, R. P., E-mail: rpsharma@ces.iitd.ernet.in

    2016-01-15

    This paper presents a model to study the interplay between the stimulated Raman scattering (SRS) and stimulated Brillouin scattering (SBS) in the presence of background magnetic field. This formalism is applicable to laser produced plasma as well as to heating mechanism in toroidal system by an extraordinary electromagnetic wave. In the former case, the magnetic field is self-generated, while in the latter case (toroidal plasmas) magnetic field is applied externally. The behavior of one scattering process is explicitly dependent on the coexisting scattering process as well as on the magnetic field. Explicit expressions for the back-reflectivity of scattered beams (SRSmore » and SBS) are presented. It has been demonstrated that due to the magnetic field and coexistence of the scattering processes (SRS and SBS) the back-reflectivity gets modified significantly. Results are also compared with the three wave interaction case (isolated SRS or SBS case)« less

  19. Stimulant Paste Preparation and Bark Streak Tapping Technique for Pine Oleoresin Extraction.

    PubMed

    Füller, Thanise Nogueira; de Lima, Júlio César; de Costa, Fernanda; Rodrigues-Corrêa, Kelly C S; Fett-Neto, Arthur G

    2016-01-01

    Tapping technique comprises the extraction of pine oleoresin, a non-wood forest product consisting of a complex mixture of mono, sesqui, and diterpenes biosynthesized and exuded as a defense response to wounding. Oleoresin is used to produce gum rosin, turpentine, and their multiple derivatives. Oleoresin yield and quality are objects of interest in pine tree biotechnology, both in terms of environmental and genetic control. Monitoring these parameters in individual trees grown in the field provides a means to examine the control of terpene production in resin canals, as well as the identification of genetic-based differences in resinosis. A typical method of tapping involves the removal of bark and application of a chemical stimulant on the wounded area. Here we describe the methods for preparing the resin-stimulant paste with different adjuvants, as well as the bark streaking process in adult pine trees.

  20. Characteristics of the work environment related to older employees' willingness to continue working: intrinsic motivation as a mediator.

    PubMed

    van den Berg, Peter T

    2011-08-01

    The relationships between older employees' willingness to continue working and characteristics of the work environment for older workers were investigated, as well as a possible mediation by intrinsic motivation. 103 employees ages 50 to 65 years, from various sectors of the Dutch labor market, completed questionnaires that measured willingness to continue working, intrinsic motivation, organizational stimulation, work variety, work challenge, and job autonomy. Hierarchical regression analyses showed organizational stimulation, as well as the various job characteristics, were positively related to employees' willingness to continue working. Moreover, intrinsic motivation fully mediated the relationship of work variety with willingness to continue working and partially mediated the relationships of organizational stimulation, work challenge, and job autonomy with willingness to continue working. It was concluded that organizations can encourage older workers to work until age 65 and beyond by shifting their focus from extrinsic to intrinsic rewards.

  1. Exploring the Relationship between Stimulant Use and Gambling in College Students

    PubMed Central

    Geisner, Irene Markman; Huh, David; Cronce, Jessica M.; Lostutter, Ty W.; Kilmer, Jason; Larimer, Mary E.

    2016-01-01

    Both gambling and stimulant use are common and can lead to problems on college campuses with consequences that impact the financial, emotional, academic and physical well-being of students. Yet few studies have been conducted to understand the co-occurrence of these conditions and the increased risk factors if any that may exist for gambling and related problems. The present study is among the first to document the co-occurrence of these behaviors in both a random sample of students (N = 4640), and then to explore to what extent stimulant use impacts subsequent gambling and related problems 12 months later in an at-risk sample (N = 199). Results revealed a three-fold higher rate of recent problem gambling for those who used stimulants vs. those who had not (11% vs 4%). For those already gambling, stimulant use predicted an increased frequency in gambling 12 months later. Implications for prevention and screening are discussed. PMID:26691633

  2. Granulocyte colony-stimulating factor receptor signaling in severe congenital neutropenia, chronic neutrophilic leukemia, and related malignancies.

    PubMed

    Dwivedi, Pankaj; Greis, Kenneth D

    2017-02-01

    Granulocyte colony-stimulating factor is a hematopoietic cytokine that stimulates neutrophil production and hematopoietic stem cell mobilization by initiating the dimerization of homodimeric granulocyte colony-stimulating factor receptor. Different mutations of CSF3R have been linked to a unique spectrum of myeloid disorders and related malignancies. Myeloid disorders caused by the CSF3R mutations include severe congenital neutropenia, chronic neutrophilic leukemia, and atypical chronic myeloid leukemia. In this review, we provide an analysis of granulocyte colony-stimulating factor receptor, various mutations, and their roles in the severe congenital neutropenia, chronic neutrophilic leukemia, and malignant transformation, as well as the clinical implications and some perspective on approaches that could expand our knowledge with respect to the normal signaling mechanisms and those associated with mutations in the receptor. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  3. The action of sennosides and related compounds on human colon and rectum 1

    PubMed Central

    Hardcastle, J. D.; Wilkins, J. L.

    1970-01-01

    The direct action of intraluminal senna and related compounds on the human colon and rectum has been investigated. Motility was recorded by balloon kymography with recording units inserted into well established transverse colostomies or into the rectum. The motility of the colon was not changed by intraluminal senna glycosides but the introduction of senna previously incubated with faeces or Esch. coli stimulated the colon to peristalt. The peristalsis was similar to that stimulated by rheinanthrone, an oxanthrone produced by chemical hydrolysis and reduction of senna. Both activated senna and rheinanthrone appeared to act in the colon by contact stimulation. No peristaltic response was stimulated in the rectum, either with activated senna or with rheinanthrone. PMID:4929273

  4. Attention Modulates Visual-Tactile Interaction in Spatial Pattern Matching

    PubMed Central

    Göschl, Florian; Engel, Andreas K.; Friese, Uwe

    2014-01-01

    Factors influencing crossmodal interactions are manifold and operate in a stimulus-driven, bottom-up fashion, as well as via top-down control. Here, we evaluate the interplay of stimulus congruence and attention in a visual-tactile task. To this end, we used a matching paradigm requiring the identification of spatial patterns that were concurrently presented visually on a computer screen and haptically to the fingertips by means of a Braille stimulator. Stimulation in our paradigm was always bimodal with only the allocation of attention being manipulated between conditions. In separate blocks of the experiment, participants were instructed to (a) focus on a single modality to detect a specific target pattern, (b) pay attention to both modalities to detect a specific target pattern, or (c) to explicitly evaluate if the patterns in both modalities were congruent or not. For visual as well as tactile targets, congruent stimulus pairs led to quicker and more accurate detection compared to incongruent stimulation. This congruence facilitation effect was more prominent under divided attention. Incongruent stimulation led to behavioral decrements under divided attention as compared to selectively attending a single sensory channel. Additionally, when participants were asked to evaluate congruence explicitly, congruent stimulation was associated with better performance than incongruent stimulation. Our results extend previous findings from audiovisual studies, showing that stimulus congruence also resulted in behavioral improvements in visuotactile pattern matching. The interplay of stimulus processing and attentional control seems to be organized in a highly flexible fashion, with the integration of signals depending on both bottom-up and top-down factors, rather than occurring in an ‘all-or-nothing’ manner. PMID:25203102

  5. Low-frequency electric muscle stimulation combined with physical therapy after total hip arthroplasty for hip osteoarthritis in elderly patients: a randomized controlled trial.

    PubMed

    Gremeaux, Vincent; Renault, Julien; Pardon, Laurent; Deley, Gaelle; Lepers, Romuald; Casillas, Jean-Marie

    2008-12-01

    To assess the effects of low-frequency electric muscle stimulation associated with usual physiotherapy on functional outcome after total hip arthroplasty (THA) for hip osteoarthritis (OA) in elderly subjects. Randomized controlled trial; pre- and posttreatment measurements. Hospital rehabilitation department. Subjects (N=29) referred to the rehabilitation department after THA for hip OA. The intervention group (n=16; 78+/-8 y) received simultaneous low-frequency electric muscle stimulation of bilateral quadriceps and calf muscles (highest tolerated intensity, 1h session, 5 d/wk, for 5 weeks) associated with conventional physical therapy including resistance training. The control group (n=13; 76+/-10 y) received conventional physical therapy alone (25 sessions). Maximal isometric strength of knee extensors, FIM instrument, before and after; a six-minute walk test and a 200 m fast walk test, after; length of stay (LOS). Low-frequency electric muscle stimulation was well tolerated. It resulted in a greater improvement in strength of knee extensors on the operated side (77% vs 23%; P<.01), leading to a better balance of muscle strength between the operated and nonoperated limb. The low-frequency electric muscle stimulation group also showed a greater improvement in FIM scores, though improvements in the walk tests were similar for the 2 groups, as was LOS. Low-frequency electric muscle stimulation is a safe, well-tolerated therapy after THA for hip OA. It improves knee extensor strength, which is one of the factors leading to greater functional independence after THA.

  6. A pilot study of the tolerability and effects of high-definition transcranial direct current stimulation (HD-tDCS) on pain perception.

    PubMed

    Borckardt, Jeffrey J; Bikson, Marom; Frohman, Heather; Reeves, Scott T; Datta, Abhishek; Bansal, Varun; Madan, Alok; Barth, Kelly; George, Mark S

    2012-02-01

    Several brain stimulation technologies are beginning to evidence promise as pain treatments. However, traditional versions of 1 specific technique, transcranial direct current stimulation (tDCS), stimulate broad regions of cortex with poor spatial precision. A new tDCS design, called high definition tDCS (HD-tDCS), allows for focal delivery of the charge to discrete regions of the cortex. We sought to preliminarily test the safety and tolerability of the HD-tDCS technique as well as to evaluate whether HD-tDCS over the motor cortex would decrease pain and sensory experience. Twenty-four healthy adult volunteers underwent quantitative sensory testing before and after 20 minutes of real (n = 13) or sham (n = 11) 2 mA HD-tDCS over the motor cortex. No adverse events occurred and no side effects were reported. Real HD-tDCS was associated with significantly decreased heat and cold sensory thresholds, decreased thermal wind-up pain, and a marginal analgesic effect for cold pain thresholds. No significant effects were observed for mechanical pain thresholds or heat pain thresholds. HD-tDCS appears well tolerated, and produced changes in underlying cortex that are associated with changes in pain perception. Future studies are warranted to investigate HD-tDCS in other applications, and to examine further its potential to affect pain perception. This article presents preliminary tolerability and efficacy data for a new focal brain stimulation technique called high definition transcranial direct current stimulation. This technique may have applications in the management of pain. Copyright © 2012. Published by Elsevier Inc.

  7. Translational Neuromodulation: Approximating Human Transcranial Magnetic Stimulation Protocols In Rats

    PubMed Central

    Vahabzadeh-Hagh, Andrew M.; Muller, Paul A.; Gersner, Roman; Zangen, Abraham; Rotenberg, Alexander

    2015-01-01

    Objective Transcranial magnetic stimulation (TMS) is a well-established clinical protocol with numerous potential therapeutic and diagnostic applications. Yet, much work remains in the elucidation of TMS mechanisms, optimization of protocols, and in development of novel therapeutic applications. As with many technologies, the key to these issues lies in the proper experimentation and translation of TMS methods to animal models, among which rat models have proven popular. A significant increase in the number of rat TMS publications has necessitated analysis of their relevance to human work. We therefore review the essential principles necessary for the approximation of human TMS protocols in rats as well as specific methods that addressed these issues in published studies. Materials and Methods We performed an English language literature search combined with our own experience and data. We address issues that we see as important in the translation of human TMS methods to rat models and provide a summary of key accomplishments in these areas. Results An extensive literature review illustrated the growth of rodent TMS studies in recent years. Current advances in the translation of single, paired-pulse, and repetitive stimulation paradigms to rodent models are presented. The importance of TMS in the generation of data for preclinical trials is also highlighted. Conclusions Rat TMS has several limitations when considering parallels between animal and human stimulation. However, it has proven to be a useful tool in the field of translational brain stimulation and will likely continue to aid in the design and implementation of stimulation protocols for therapeutic and diagnostic applications. PMID:22780329

  8. Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes

    PubMed Central

    Heimann, Emilia; Nyman, Margareta; Degerman, Eva

    2014-01-01

    Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have “anti-obesity properties” by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes. PMID:26167409

  9. Propionic acid and butyric acid inhibit lipolysis and de novo lipogenesis and increase insulin-stimulated glucose uptake in primary rat adipocytes.

    PubMed

    Heimann, Emilia; Nyman, Margareta; Degerman, Eva

    2015-01-01

    Fermentation of dietary fibers by colonic microbiota generates short-chain fatty acids (SCFAs), e.g., propionic acid and butyric acid, which have been described to have "anti-obesity properties" by ameliorating fasting glycaemia, body weight and insulin tolerance in animal models. In the present study, we therefore investigate if propionic acid and butyric acid have effects on lipolysis, de novo lipogenesis and glucose uptake in primary rat adipocytes. We show that both propionic acid and butyric acid inhibit isoproterenol- and adenosine deaminase-stimulated lipolysis as well as isoproterenol-stimulated lipolysis in the presence of a phosphodiesterase (PDE3) inhibitor. In addition, we show that propionic acid and butyric acid inhibit basal and insulin-stimulated de novo lipogenesis, which is associated with increased phosphorylation and thus inhibition of acetyl CoA carboxylase, a rate-limiting enzyme in fatty acid synthesis. Furthermore, we show that propionic acid and butyric acid increase insulin-stimulated glucose uptake. To conclude, our study shows that SCFAs have effects on fat storage and mobilization as well as glucose uptake in rat primary adipocytes. Thus, the SCFAs might contribute to healthier adipocytes and subsequently also to improved energy metabolism with for example less circulating free fatty acids, which is beneficial in the context of obesity and type 2 diabetes.

  10. Elevated [CO2] mitigates the effect of surface drought by stimulating root growth to access sub-soil water.

    PubMed

    Uddin, Shihab; Löw, Markus; Parvin, Shahnaj; Fitzgerald, Glenn J; Tausz-Posch, Sabine; Armstrong, Roger; O'Leary, Garry; Tausz, Michael

    2018-01-01

    Through stimulation of root growth, increasing atmospheric CO2 concentration ([CO2]) may facilitate access of crops to sub-soil water, which could potentially prolong physiological activity in dryland environments, particularly because crops are more water use efficient under elevated [CO2] (e[CO2]). This study investigated the effect of drought in shallow soil versus sub-soil on agronomic and physiological responses of wheat to e[CO2] in a glasshouse experiment. Wheat (Triticum aestivum L. cv. Yitpi) was grown in split-columns with the top (0-30 cm) and bottom (31-60 cm; 'sub-soil') soil layer hydraulically separated by a wax-coated, root-penetrable layer under ambient [CO2] (a[CO2], ∼400 μmol mol-1) or e[CO2] (∼700 μmol mol-1) [CO2]. Drought was imposed from stem-elongation in either the top or bottom soil layer or both by withholding 33% of the irrigation, resulting in four water treatments (WW, WD, DW, DD; D = drought, W = well-watered, letters denote water treatment in top and bottom soil layer, respectively). Leaf gas exchange was measured weekly from stem-elongation until anthesis. Above-and belowground biomass, grain yield and yield components were evaluated at three developmental stages (stem-elongation, anthesis and maturity). Compared with a[CO2], net assimilation rate was higher and stomatal conductance was lower under e[CO2], resulting in greater intrinsic water use efficiency. Elevated [CO2] stimulated both above- and belowground biomass as well as grain yield, however, this stimulation was greater under well-watered (WW) than drought (DD) throughout the whole soil profile. Imposition of drought in either or both soil layers decreased aboveground biomass and grain yield under both [CO2] compared to the well-watered treatment. However, the greatest 'CO2 fertilisation effect' was observed when drought was imposed in the top soil layer only (DW), and this was associated with e[CO2]-stimulation of root growth especially in the well-watered bottom layer. We suggest that stimulation of belowground biomass under e[CO2] will allow better access to sub-soil water during grain filling period, when additional water is converted into additional yield with high efficiency in Mediterranean-type dryland agro-ecosystems. If sufficient water is available in the sub-soil, e[CO2] may help mitigating the effect of drying surface soil.

  11. Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization.

    PubMed

    Manos, Thanos; Zeitler, Magteld; Tass, Peter A

    2018-01-01

    In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long-term desynchronization at comparably short stimulation duration and low integral stimulation duration. Currently, clinical proof of concept is available for deep brain CR stimulation for Parkinson's therapy and acoustic CR stimulation for tinnitus therapy. Promising first in human data is available for vibrotactile CR stimulation for Parkinson's treatment. For the clinical development of these treatments it is mandatory to perform dose-finding studies to reveal optimal stimulation parameters and dosage regimens. Our findings can straightforwardly be tested in human dose-finding studies.

  12. Short-Term Dosage Regimen for Stimulation-Induced Long-Lasting Desynchronization

    PubMed Central

    Manos, Thanos; Zeitler, Magteld; Tass, Peter A.

    2018-01-01

    In this paper, we computationally generate hypotheses for dose-finding studies in the context of desynchronizing neuromodulation techniques. Abnormally strong neuronal synchronization is a hallmark of several brain disorders. Coordinated Reset (CR) stimulation is a spatio-temporally patterned stimulation technique that specifically aims at disrupting abnormal neuronal synchrony. In networks with spike-timing-dependent plasticity CR stimulation may ultimately cause an anti-kindling, i.e., an unlearning of abnormal synaptic connectivity and neuronal synchrony. This long-lasting desynchronization was theoretically predicted and verified in several pre-clinical and clinical studies. We have shown that CR stimulation with rapidly varying sequences (RVS) robustly induces an anti-kindling at low intensities e.g., if the CR stimulation frequency (i.e., stimulus pattern repetition rate) is in the range of the frequency of the neuronal oscillation. In contrast, CR stimulation with slowly varying sequences (SVS) turned out to induce an anti-kindling more strongly, but less robustly with respect to variations of the CR stimulation frequency. Motivated by clinical constraints and inspired by the spacing principle of learning theory, in this computational study we propose a short-term dosage regimen that enables a robust anti-kindling effect of both RVS and SVS CR stimulation, also for those parameter values where RVS and SVS CR stimulation previously turned out to be ineffective. Intriguingly, for the vast majority of parameter values tested, spaced multishot CR stimulation with demand-controlled variation of stimulation frequency and intensity caused a robust and pronounced anti-kindling. In contrast, spaced CR stimulation with fixed stimulation parameters as well as singleshot CR stimulation of equal integral duration failed to improve the stimulation outcome. In the model network under consideration, our short-term dosage regimen enables to robustly induce long-term desynchronization at comparably short stimulation duration and low integral stimulation duration. Currently, clinical proof of concept is available for deep brain CR stimulation for Parkinson's therapy and acoustic CR stimulation for tinnitus therapy. Promising first in human data is available for vibrotactile CR stimulation for Parkinson's treatment. For the clinical development of these treatments it is mandatory to perform dose-finding studies to reveal optimal stimulation parameters and dosage regimens. Our findings can straightforwardly be tested in human dose-finding studies. PMID:29706900

  13. Are Prescription Stimulants “Smart Pills”?

    PubMed Central

    Smith, M. Elizabeth; Farah, Martha J.

    2013-01-01

    Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience literatures in search of answers to these questions. Epidemiological issues addressed include the prevalence of nonmedical stimulant use, user demographics, methods by which users obtain prescription stimulants, and motivations for use. Cognitive neuroscience issues addressed include the effects of prescription stimulants on learning and executive function, as well as the task and individual variables associated with these effects. Little is known about the prevalence of prescription stimulant use for cognitive enhancement outside of student populations. Among college students, estimates of use vary widely but, taken together, suggest that the practice is commonplace. The cognitive effects of stimulants on normal healthy people cannot yet be characterized definitively, despite the volume of research that has been carried out on these issues. Published evidence suggests that declarative memory can be improved by stimulants, with some evidence consistent with enhanced consolidation of memories. Effects on the executive functions of working memory and cognitive control are less reliable but have been found for at least some individuals on some tasks. In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research. PMID:21859174

  14. Neural and Hemodynamic Responses Elicited by Forelimb- and Photo-stimulation in Channelrhodopsin-2 Mice: Insights into the Hemodynamic Point Spread Function

    PubMed Central

    Vazquez, Alberto L.; Fukuda, Mitsuhiro; Crowley, Justin C.; Kim, Seong-Gi

    2014-01-01

    Hemodynamic responses are commonly used to map brain activity; however, their spatial limits have remained unclear because of the lack of a well-defined and malleable spatial stimulus. To examine the properties of neural activity and hemodynamic responses, multiunit activity, local field potential, cerebral blood volume (CBV)-sensitive optical imaging, and laser Doppler flowmetry were measured from the somatosensory cortex of transgenic mice expressing Channelrhodopsin-2 in cortex Layer 5 pyramidal neurons. The magnitude and extent of neural and hemodynamic responses were modulated using different photo-stimulation parameters and compared with those induced by somatosensory stimulation. Photo-stimulation-evoked spiking activity across cortical layers was similar to forelimb stimulation, although their activity originated in different layers. Hemodynamic responses induced by forelimb- and photo-stimulation were similar in magnitude and shape, although the former were slightly larger in amplitude and wider in extent. Altogether, the neurovascular relationship differed between these 2 stimulation pathways, but photo-stimulation-evoked changes in neural and hemodynamic activities were linearly correlated. Hemodynamic point spread functions were estimated from the photo-stimulation data and its full-width at half-maximum ranged between 103 and 175 µm. Therefore, submillimeter functional structures separated by a few hundred micrometers may be resolved using hemodynamic methods, such as optical imaging and functional magnetic resonance imaging. PMID:23761666

  15. Effects of different electrical brain stimulation protocols on subcomponents of motor skill learning.

    PubMed

    Prichard, George; Weiller, Cornelius; Fritsch, Brita; Reis, Janine

    2014-01-01

    Noninvasive electrical brain stimulation (NEBS) with transcranial direct current (tDCS) or random noise stimulation (tRNS) applied to the primary motor cortex (M1) can augment motor learning. We tested whether different types of stimulation alter particular aspects of learning a tracing task over three consecutive days, namely skill acquisition (online/within session effects) or consolidation (offline/between session effects). Motor training on a tracing task over three consecutive days was combined with different types and montages of stimulation (tDCS, tRNS). Unilateral M1 stimulation using tRNS as well as unilateral and bilateral M1 tDCS all enhanced motor skill learning compared to sham stimulation. In all groups, this appeared to be driven by online effects without an additional offline effect. Unilateral tDCS resulted in large skill gains immediately following the onset of stimulation, while tRNS exerted more gradual effects. Control stimulation of the right temporal lobe did not enhance skill learning relative to sham. The mechanisms of action of tDCS and tRNS are likely different. Hence, the time course of skill improvement within sessions could point to specific and temporally distinct interactions with the physiological process of motor skill learning. Exploring the parameters of NEBS on different tasks and in patients with brain injury will allow us to maximize the benefits of NEBS for neurorehabilitation. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Electrical stimulation of rhesus monkey nucleus reticularis gigantocellularis. I. Characteristics of evoked head movements.

    PubMed

    Quessy, Stephan; Freedman, Edward G

    2004-06-01

    The nucleus reticularis gigantocellularis (NRG) receives monosynaptic input from the superior colliculus (SC) and projects directly to neck motor neuron pools. Neurons in NRG are well situated to play a critical role in transforming SC signals into head movement commands. A previous study of movements evoked by NRG stimulation in the primate reported a variety of ipsilateral and contralateral head movements with horizontal, vertical and torsional components. In addition to head movements, it was reported that NRG stimulation could evoke movements of the pinnae, face, upper torso, and co-contraction of neck muscles. In this report, the role of the rhesus monkey NRG in head movement control was investigated using electrical stimulation of the rostral portion of the NRG. The goal was to characterize head movements evoked by NRG stimulation, describe the effects of altering stimulation parameters, and assess the relative movements of the eyes and head. Results indicate that electrical stimulation in the rostral portion of the NRG of the primate can consistently evoke ipsilateral head rotations in the horizontal plane. Head movement amplitude and peak velocity depend upon stimulation parameters (primarily frequency and duration of stimulation trains). During stimulation-induced head movements the eyes counter-rotate (presumably a result of the vestibulo-ocular reflex: VOR). At 46 stimulation sites from two subjects the average gain of this counter-rotation was -0.38 (+/-0.18). After the end of the stimulation train the head generally continued to move. During this epoch, after electrical stimulation ceased, VOR gain remained at this reduced level. In addition, VOR gain was similarly low when electrical stimulation was carried out during active fixation of a visual target. These data extend existing descriptions of head movements evoked by electrical stimulation of the NRG, and add to the understanding of the role of this structure in producing head movements.

  17. High frequency repetitive sensory stimulation improves temporal discrimination in healthy subjects.

    PubMed

    Erro, Roberto; Rocchi, Lorenzo; Antelmi, Elena; Palladino, Raffaele; Tinazzi, Michele; Rothwell, John; Bhatia, Kailash P

    2016-01-01

    High frequency electrical stimulation of an area of skin on a finger improves two-point spatial discrimination in the stimulated area, likely depending on plastic changes in the somatosensory cortex. However, it is unknown whether improvement also applies to temporal discrimination. Twelve young and ten elderly volunteers underwent the stimulation protocol onto the palmar skin of the right index finger. Somatosensory temporal discrimination threshold (STDT) was evaluated before and immediately after stimulation as well as 2.5h and 24h later. There was a significant reduction in somatosensory temporal threshold only on the stimulated finger. The effect was reversible, with STDT returning to the baseline values within 24h, and was smaller in the elderly than in the young participants. High frequency stimulation of the skin focally improves temporal discrimination in the area of stimulation. Given previous suggestions that the perceptual effects rely on plastic changes in the somatosensory cortex, our results are consistent with the idea that the timing of sensory stimuli is, at least partially, encoded in the primary somatosensory cortex. Such a protocol could potentially be used as a therapeutic intervention to ameliorate physiological decline in the elderly or in other disorders of sensorimotor integration. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat.

    PubMed

    Wu, Hemmings; Ghekiere, Hartwin; Beeckmans, Dorien; Tambuyzer, Tim; van Kuyck, Kris; Aerts, Jean-Marie; Nuttin, Bart

    2015-04-21

    Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation.

  19. Can the human lumbar posterior columns be stimulated by transcutaneous spinal cord stimulation? A modeling study

    PubMed Central

    Danner, Simon M.; Hofstoetter, Ursula S.; Ladenbauer, Josef; Rattay, Frank; Minassian, Karen

    2014-01-01

    Stimulation of different spinal cord segments in humans is a widely developed clinical practice for modification of pain, altered sensation and movement. The human lumbar cord has become a target for modification of motor control by epidural and more recently by transcutaneous spinal cord stimulation. Posterior columns of the lumbar spinal cord represent a vertical system of axons and when activated can add other inputs to the motor control of the spinal cord than stimulated posterior roots. We used a detailed three-dimensional volume conductor model of the torso and the McIntyre-Richard-Grill axon model to calculate the thresholds of axons within the posterior columns in response to transcutaneous lumbar spinal cord stimulation. Superficially located large diameter posterior column fibers with multiple collaterals have a threshold of 45.4 V, three times higher than posterior root fibers (14.1 V). With the stimulation strength needed to activate posterior column axons, posterior root fibers of large and small diameters as well as anterior root fibers are co-activated. The reported results inform on these threshold differences, when stimulation is applied to the posterior structures of the lumbar cord at intensities above the threshold of large-diameter posterior root fibers. PMID:21401670

  20. A Tactile Stimulator for Studying Passive Shape Perception

    PubMed Central

    Lane, John W.; Fitzgerald, Paul J.; Yau, Jeffrey M.; Pembeci, Izzet; Hsiao, Steven S.

    2009-01-01

    We describe a computer-controlled tactile stimulator for use in human psychophysical and monkey neurophysiological studies of 3-D shape perception. The stimulator is constructed primarily of commercially available parts, as well as a few custom-built pieces for which we will supply diagrams upon request. There are two components to the stimulator: a tactile component and a hand positioner component. The tactile component consists of multiple stimulating units that move about in a Cartesian plane above the restrained hand. Each stimulating unit contains a servo-controlled linear motor with an attached small rotary stepper motor, allowing arbitrary stimulus shapes to contact the skin through vibration, static indentation, or scanning. The hand positioner component modifies the conformation of the restrained hand through a set of mechanical linkages under motorized control. The present design controls the amount of spread between digits two and three, the spread between digits four and three, and the degree to which digit three is flexed or extended, thereby simulating different conformations of the hand in contact with objects. This design is easily modified to suit the needs of the experimenter. Because the two components of the stimulator are independently controlled, the stimulator allows for parametric study of the mechanoreceptive and proprioceptive contributions to 3-D tactile shape perception. PMID:19800916

  1. Electrical management of neurogenic lower urinary tract disorders.

    PubMed

    Joussain, C; Denys, P

    2015-09-01

    Management of lower urinary tract dysfunction (LUTD) in neurological diseases remains a priority because it leads to many complications such as incontinence, renal failure and decreased quality of life. A pharmacological approach remains the first-line treatment for patients with neurogenic LUTD, but electrical stimulation is a well-validated and recommended second-line treatment. However, clinicians must be aware of the indications, advantages and side effects of the therapy. This report provides an update on the 2 main electrical stimulation therapies for neurogenic LUTD - inducing direct bladder contraction with the Brindley procedure and modulating LUT physiology (sacral neuromodulation, tibial posterior nerve stimulation or pudendal nerve stimulation). We also describe the indications of these therapies for neurogenic LUTD, following international guidelines, as illustrated by their efficacy in patients with neurologic disorders. Electrical stimulation could be proposed for neurogenic LUTD as second-line treatment after failure of oral pharmacologic approaches. Nevertheless, further investigations are needed for a better understanding of the mechanisms of action of these techniques and to confirm their efficacy. Other electrical investigations, such as deep-brain stimulation and repetitive transcranial magnetic stimulation, or improved sacral anterior root stimulation, which could be associated with non-invasive and highly specific deafferentation of posterior roots, may open new fields in the management of neurogenic LUTD. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. Reflections on Addiction in Students Using Stimulants for Neuroenhancement: A Preliminary Interview Study.

    PubMed

    Hildt, Elisabeth; Lieb, Klaus; Bagusat, Christiana; Franke, Andreas G

    2015-01-01

    The use of stimulants for the purpose of pharmacological neuroenhancement (NE) among students is a subject of increasing public awareness. The risk of addiction development by stimulant use for NE is still unanswered. Therefore, face-to-face interviews were carried out among 18 university students experienced in the nonmedical use of methylphenidate and amphetamines for NE assessing aspects of addiction. Interviews were tape-recorded, verbatim-transcribed, and analyzed using a qualitative approach. The interviews showed that participants--the majority had current or lifetime diagnoses of misuse or addiction to alcohol or cannabis-reported an awareness of the risk of addiction development associated with stimulant use and reported various effects which may increase their likelihood of future stimulant use, for example, euphoric effects, increase of self-confidence, and motivation. They also cited measures to counteract the development of addiction as well as measures taken to normalize again after stimulant use. Students were convinced of having control over their stimulant use and of not becoming addicted to stimulants used for NE. We can conclude that behavior and beliefs of the students in our sample appear to be risky in terms of addiction development. However, long-term empirical research is needed to estimate the true risk of addiction.

  3. Conceptualization and validation of an open-source closed-loop deep brain stimulation system in rat

    PubMed Central

    Wu, Hemmings; Ghekiere, Hartwin; Beeckmans, Dorien; Tambuyzer, Tim; van Kuyck, Kris; Aerts, Jean-Marie; Nuttin, Bart

    2015-01-01

    Conventional deep brain stimulation (DBS) applies constant electrical stimulation to specific brain regions to treat neurological disorders. Closed-loop DBS with real-time feedback is gaining attention in recent years, after proved more effective than conventional DBS in terms of pathological symptom control clinically. Here we demonstrate the conceptualization and validation of a closed-loop DBS system using open-source hardware. We used hippocampal theta oscillations as system input, and electrical stimulation in the mesencephalic reticular formation (mRt) as controller output. It is well documented that hippocampal theta oscillations are highly related to locomotion, while electrical stimulation in the mRt induces freezing. We used an Arduino open-source microcontroller between input and output sources. This allowed us to use hippocampal local field potentials (LFPs) to steer electrical stimulation in the mRt. Our results showed that closed-loop DBS significantly suppressed locomotion compared to no stimulation, and required on average only 56% of the stimulation used in open-loop DBS to reach similar effects. The main advantages of open-source hardware include wide selection and availability, high customizability, and affordability. Our open-source closed-loop DBS system is effective, and warrants further research using open-source hardware for closed-loop neuromodulation. PMID:25897892

  4. Real time imaging of peripheral nerve vasculature using optical coherence angiography

    NASA Astrophysics Data System (ADS)

    Vasudevan, Srikanth; Kumsa, Doe; Takmakov, Pavel; Welle, Cristin G.; Hammer, Daniel X.

    2016-03-01

    The peripheral nervous system (PNS) carries bidirectional information between the central nervous system and distal organs. PNS stimulation has been widely used in medical devices for therapeutic indications, such as bladder control and seizure cessation. Investigational uses of PNS stimulation include providing sensory feedback for improved control of prosthetic limbs. While nerve safety has been well documented for stimulation parameters used in marketed devices, novel PNS stimulation devices may require alternative stimulation paradigms to achieve maximum therapeutic benefit. Improved testing paradigms to assess the safety of stimulation will expedite the development process for novel PNS stimulation devices. The objective of this research is to assess peripheral nerve vascular changes in real-time with optical coherence angiography (OCA). A 1300-nm OCA system was used to image vasculature changes in the rat sciatic nerve in the region around a surface contacting single electrode. Nerves and vasculature were imaged without stimulation for 180 minutes to quantify resting blood vessel diameter. Walking track analysis was used to assess motor function before and 6 days following experiments. There was no significant change in vessel diameter between baseline and other time points in all animals. Motor function tests indicated the experiments did not impair functionality. We also evaluated the capabilities to image the nerve during electrical stimulation in a pilot study. Combining OCA with established nerve assessment methods can be used to study the effects of electrical stimulation safety on neural and vascular tissue in the periphery.

  5. Construction and immunological characterization of CD40L or GM-CSF incorporated Hantaan virus like particle

    PubMed Central

    Zhang, Xiaoxiao; Truax, Agnieszka D.; Ma, Ruixue; Liu, Ziyu; Lei, Yingfeng; Zhang, Liang; Ye, Wei; Zhang, Fanglin; Xu, Zhikai; Shang, Lei; Liu, Rongrong; Wang, Fang; Wu, Xingan

    2016-01-01

    Infection of Hantaan virus (HTNV) usually causes hemorrhagic fever with renal syndrome (HFRS). China has the worst epidemic incidence of HFRS as well as high fatality. Inactivated whole virus has been used for HFRS vaccination, however there are still problems such as safety concerns. CD40 ligand (CD40L) and granulocyte macrophage colony-stimulating factor (GM-CSF) are well-known immune stimulating molecules that can enhance antigen presenting, lymphocytes activation and maturation, incorporation of CD40L and GM-CSF to the surface of virus like particles (VLPs) can greatly improve the vaccination effect. We constructed eukaryotic vectors expressing HTNV M segment and S segment, as well as vectors expressing HTNV M segment with CD40L or GM-CSF, our results showed successful production of CD40L or GM-CSF incorporated HTNV VLPs. In vitro stimulation with CD40L or GM-CSF anchored HTNV VLP showed enhanced activation of macrophages and DCs. CD40L/GM-CSF incorporated VLP can induce higher level of HTNV specific antibody and neutralizing antibody in mice. Immunized mice splenocytes showed higher ability of secreting IFN-γ and IL-2, as well as enhancing CTL activity. These results suggest CD40L/GM-CSF incorporated VLP can serve as prospective vaccine candidate. PMID:27542281

  6. THE AVAILABILITY AND PORTRAYAL OF STIMULANTS OVER THE INTERNET

    PubMed Central

    Schepis, Ty S.; Marlowe, Douglas B.; Forman, Robert F.

    2008-01-01

    Purpose To quantify the online availability and portrayal of amphetamine-class prescription stimulants with a focus on those medications commonly prescribed to and abused by adolescents. Methods The Google™ search engine was used in searches to assess the frequency of websites offering to sell controlled stimulants (retail sites) or websites that directly linked to retail sites (portal sites). Also, separate searches evaluated the portrayal of controlled prescription stimulants by the initial 20 websites returned by Google™. Retail and portal website frequency was collected for each search. For searches measuring the portrayal of stimulants, webpages were categorized as pro-abuse, anti-abuse, neutral or other, based on set criteria. Results Sites offering to sell stimulants without a prescription were found for nearly all search terms. Across all searches, the Schedule III stimulants indicated for the treatment of obesity returned more sites offering to sell stimulants without a prescription than Schedule II stimulants indicated for the treatment of ADHD. Internet site portrayal of each stimulant varied. However, sites that contained “methamphetamine” often included anti-abuse information. Discussion The apparent availability of stimulants over the Internet without a prescription indicates the potential for a significant public health problem. The extent to which teens are obtaining these drugs via the Internet remains unclear, but clinicians must be aware of the potential for abuse, concomitant prescription use issues, illicit sources, and diversion of these highly addictive medications. Education of consumers and physicians as well as further governmental interventions is needed to limit the potential scope of this problem. PMID:18407040

  7. How Well Has NCLB Worked? How Do We Get the Revisions We Want?

    ERIC Educational Resources Information Center

    Lewis, Anne C.

    2007-01-01

    In this article, the author presents a description of Phi Delta Kappa International's 2006 Summit on Public Education. The 2006 Summit opened with a stimulating panel discussion on the hottest topic in education--the No Child Left Behind Act. The Summit's emphasis on NCLB had a clear purpose--to stimulate their members to become involved in the…

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

    PubMed Central

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

    2016-01-01

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

  9. A Lack of Clinical Effect of High-frequency rTMS to Dorsolateral Prefrontal Cortex on Bulimic Symptoms: A Randomised, Double-blind Trial.

    PubMed

    Gay, Aurelia; Jaussent, Isabelle; Sigaud, Torrance; Billard, Stephane; Attal, Jerome; Seneque, Maude; Galusca, Bogdan; Van Den Eynde, Frederique; Massoubre, Catherine; Courtet, Philippe; Guillaume, Sebastien

    2016-11-01

    Studies suggest that stimulation of the left dorsolateral prefrontal cortex (DLPFC) reduces food craving in bulimic patients, but evidence supporting repetitive transcranial magnetic stimulation (rTMS) as a therapeutic tool is lacking. We investigated the safety and therapeutic efficacy of an adjunct high-frequency rTMS programme targeting the left DLPFC. Forty-seven women with bulimia nervosa were randomised to a real or sham stimulation group. The real group underwent 10 rTMS sessions, each consisting of 20 trains of 5 seconds with 55-second intervals between trains, at a frequency of 10 Hz. The main outcome was the number of binge episodes in the 15 days following the end of stimulation. Overall, no significant improvement in bingeing and purging symptoms was noted after the programme. rTMS was well tolerated. This suggests that 10 sessions of high-frequency rTMS to the left DLPFC provide no greater benefit than placebo. Future studies should consider methodological issues as well as alternative targets. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

  10. Activation of human B cells by phosphorothioate oligodeoxynucleotides.

    PubMed Central

    Liang, H; Nishioka, Y; Reich, C F; Pisetsky, D S; Lipsky, P E

    1996-01-01

    To investigate the potential of DNA to elicit immune responses in man, we examined the capacity of a variety of oligodeoxynucleotides (ODNs) to stimulate highly purified T cell-depleted human peripheral blood B cells. Among 47 ODNs of various sequences tested, 12 phosphorothioate oligodeoxynucleotides (sODNs) induced marked B cell proliferation and Ig production. IL-2 augmented both proliferation and production of IgM, IgG, and IgA, as well as IgM anti-DNA antibodies, but was not necessary for B cell stimulation. Similarly, T cells enhanced stimulation, but were not necessary for B cell activation. After stimulation with the active sODNs, more than 95% of B cells expressed CD25 and CD86. In addition, B cells stimulated with sODNs expressed all six of the major immunoglobulin VH gene families. These results indicate that the human B cell response to sODN is polyclonal. Active sODN coupled to Sepharose beads stimulated B cells as effectively as the free sODN, suggesting that stimulation resulted from engagement of surface receptors. These data indicate that sODNs can directly induce polyclonal activation of human B cells in a T cell-independent manner by engaging as yet unknown B cell surface receptors. PMID:8787674

  11. Investigation of Stimulation-Response Relationships for Complex Fracture Systems in Enhanced Geothermal Reservoirs

    DOE Data Explorer

    Fu, Pengcheng; Johnson, Scott M.; Carrigan, Charles R.

    2011-01-01

    Hydraulic fracturing is currently the primary method for stimulating low-permeability geothermal reservoirs and creating Enhanced (or Engineered) Geothermal Systems (EGS) with improved permeability and heat production efficiency. Complex natural fracture systems usually exist in the formations to be stimulated and it is therefore critical to understand the interactions between existing fractures and newly created fractures before optimal stimulation strategies can be developed. Our study aims to improve the understanding of EGS stimulation-response relationships by developing and applying computer-based models that can effectively reflect the key mechanisms governing interactions between complex existing fracture networks and newly created hydraulic fractures. In this paper, we first briefly describe the key modules of our methodology, namely a geomechanics solver, a discrete fracture flow solver, a rock joint response model, an adaptive remeshing module, and most importantly their effective coupling. After verifying the numerical model against classical closed-form solutions, we investigate responses of reservoirs with different preexisting natural fractures to a variety of stimulation strategies. The factors investigated include: the in situ stress states (orientation of the principal stresses and the degree of stress anisotropy), pumping pressure, and stimulation sequences of multiple wells.

  12. A feasible repetitive transcranial magnetic stimulation clinical protocol in migraine prevention.

    PubMed

    Zardouz, Shawn; Shi, Lei; Leung, Albert

    2016-01-01

    This case series was conducted to determine the clinical feasibility of a repetitive transcranial magnetic stimulation protocol for the prevention of migraine (with and without aura). Five patients with migraines underwent five repetitive transcranial magnetic stimulation sessions separated in 1- to 2-week intervals for a period of 2 months at a single tertiary medical center. Repetitive transcranial magnetic stimulation was applied to the left motor cortex with 2000 pulses (20 trains with 1s inter-train interval) delivered per session, at a frequency of 10 Hz and 80% resting motor threshold. Pre- and post-treatment numerical rating pain scales were collected, and percent reductions in intensity, frequency, and duration were generated. An average decrease in 37.8%, 32.1%, and 31.2% were noted in the intensity, frequency, and duration of migraines post-repetitive transcranial magnetic stimulation, respectively. A mean decrease in 1.9±1.0 (numerical rating pain scale ± standard deviation; range: 0.4-2.8) in headache intensity scores was noted after the repetitive transcranial magnetic stimulation sessions. The tested repetitive transcranial magnetic stimulation protocol is a well-tolerated, safe, and effective method for migraine prevention.

  13. A Wearable Multi-Site System for NMES-Based Hand Function Restoration.

    PubMed

    Crema, Andrea; Malesevic, Nebojsa; Furfaro, Ivan; Raschella, Flavio; Pedrocchi, Alessandra; Micera, Silvestro

    2018-02-01

    Reaching and grasping impairments significantly affect the quality of life for people who have experienced a stroke or spinal cord injury. The long-term well-being of patients varies greatly according to the restorable residual capabilities. Electrical stimulation could be a promising solution to restore motor functions in these conditions, but its use is not clinically widespread. Here, we introduce the HandNMES, an electrode array (EA) for neuromuscular electrical stimulation (NMES) aimed at grasp training and assistance. The device was designed to deliver electrical stimulation to extrinsic and intrinsic hand muscles. Six independent EAs, positioned on the user forearm and hand, deliver NMES pulses originating from an external stimulator equipped with demultiplexers for interfacing with a large number of electrodes. The garment was designed to be adaptable to user needs and anthropometric characteristics; size, shape, and contact materials can be customized, and stimulation characteristics such as intensity of stimulation and virtual electrode location, and size can be adjusted. We performed extensive tests with nine healthy subjects showing the efficacy of the HandNMES in terms of stimulation performance and personalization. Because encouraging results were achieved, in the coming months, the HandNMES device will be tested in pilot clinical trials.

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

    PubMed

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

    2014-08-01

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

  15. Unilateral pedunculopontine stimulation improves falls in Parkinson's disease.

    PubMed

    Moro, Elena; Hamani, Clement; Poon, Yu-Yan; Al-Khairallah, Thamar; Dostrovsky, Jonathan O; Hutchison, William D; Lozano, Andres M

    2010-01-01

    Postural instability and falls are a major source of disability in patients with advanced Parkinson's disease. These problems are currently not well addressed by either pharmacotherapy nor by subthalamic nucleus deep-brain stimulation surgery. The neuroanatomical substrates of posture and gait are poorly understood but a number of important observations suggest a major role for the pedunculopontine nucleus and adjacent areas in the brainstem. We conducted a double-blinded evaluation of unilateral pedunculopontine nucleus deep-brain stimulation in a pilot study in six advanced Parkinson's disease patients with significant gait and postural abnormalities. There was no significant difference in the double-blinded on versus off stimulation Unified Parkinson's Disease Rating Scale motor scores after 3 or 12 months of continuous stimulation and no improvements in the Unified Parkinson's Disease Rating Scale part III scores compared to baseline. In contrast, patients reported a significant reduction in falls in the on and off medication states both at 3 and 12 months after pedunculopontine nucleus deep-brain stimulation as captured in the Unified Parkinson's Disease Rating Scale part II scores. Our results suggest that pedunculopontine nucleus deep-brain stimulation may be effective in preventing falls in patients with advanced Parkinson's disease but that further evaluation of this procedure is required.

  16. A preparation for studying electrical stimulation of the retina in vivo in rat

    NASA Astrophysics Data System (ADS)

    Baig-Silva, M. S.; Hathcock, C. D.; Hetling, J. R.

    2005-03-01

    A remaining challenge to the development of electronic prostheses for vision is improving the effectiveness of retinal stimulation. Electrode design and stimulus parameters need to be optimized such that the neural output from the retina conveys information to the mind's eye that aids the patient in interpreting his or her environment. This optimization will require a detailed understanding of the response of the retina to electrical stimulation. The identity and response characteristics of the cellular targets of stimulation need to be defined and evaluated. Described here is an in vivo preparation for studying electrical stimulation of the retina in rat at the cellular level. The use of rat makes available a number of well-described models of retinal disease that motivate prosthesis development. Artificial stimulation can be investigated by adapting techniques traditionally employed to study the response of the retina to photic stimuli, such as recording at the cornea, single-cell recording, and pharmacological dissection of the response. Pilot studies include amplitude-intensity response data for subretinal and transretinal stimulation paradigms recorded in wild-type rats and a transgenic rat model of autosomal dominant retinitis pigmentosa. The ability to record single-unit ganglion cell activity in vivo is also demonstrated.

  17. Therapeutic Approaches in the Stimulation of the Coronary Collateral Circulation

    PubMed Central

    Degen, Achim; Millenaar, Dominic; Schirmer, Stephan H.

    2014-01-01

    Arteriogenesis as a way to restore blood flow after arterial occlusion has been under investigation for the treatment of coronary artery disease (CAD) for decades. Therapeutic approaches so far have included delivery of cytokines and growth factors as well as mechanical stimulation such as external counterpulsation. As knowledge on the mechanisms of arteriogenesis expanded, new therapeutic approaches have emerged. This review summarizes recent attempts to stimulate the growth of the coronary vasculature and discusses their potential in clinical application. This article also delivers an overview of current studies and trials on coronary arteriogenesis. PMID:23721076

  18. [Biomechanical air-vibration stimulation in the medical rehabilitation of patients with chronic venous insufficiency of the lower extremities].

    PubMed

    Zhukov, B N; Katorkin, S E

    1993-01-01

    Biomechanical pneumo-vibration stimulation of lower extremities was used in 146 patients with different forms and stages of chronic venous insufficiency of lower extremities during conservative treatment in preoperative preparation and the following early rehabilitation, in 106 patients with consequences of the trauma and diseases of the spinal cord as well as in 35 healthy people. The biomechanical pneumo-vibration stimulation is thought by the authors to be a promising noninvasive conservative method of medical rehabilitation. It can be recommended for clinical use with due regard for contraindications.

  19. Nitric oxide donors, sodium nitroprusside and S-nitroso-N-acetylpencillamine, stimulate myoblast proliferation in vitro

    NASA Technical Reports Server (NTRS)

    Ulibarri, J. A.; Mozdziak, P. E.; Schultz, E.; Cook, C.; Best, T. M.

    1999-01-01

    Nitric oxide (NO) is an inter- and intracellular messenger involved in a variety of physiologic and pathophysiologic conditions. The effect of two NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) and their effect on myoblast proliferation was examined. Both donors stimulated an increase in myoblast cell number over a range (1-10 microM) of donor concentrations. However, 50 microM SNAP inhibited myoblast proliferation. Cell numbers from cultures treated with degraded 10 microM SNAP were equivalent to the control. Therefore, it appears NO can stimulate as well as inhibit myoblast proliferation.

  20. Magnetic field therapy: a review.

    PubMed

    Markov, Marko S

    2007-01-01

    There is increasing interest in using permanent magnets for therapeutic purposes encouraged by basic science publications and clinical reports. Magnetotherapy provides a non invasive, safe, and easy method to directly treat the site of injury, the source of pain and inflammation, and other types of disease. The physiological bases for the use of magnetic fields for tissue repair as well as physical principles of dosimetry and application of various magnetic fields are subjects of this review. Analysis of the magnetic and electromagnetic stimulation is followed by a discussion of the advantage of magnetic field stimulation compared with electric current and electric field stimulation.

  1. Magnetic-Stimulation-Related Physiological Artifacts in Hemodynamic Near-Infrared Spectroscopy Signals

    PubMed Central

    Näsi, Tiina; Mäki, Hanna; Kotilahti, Kalle; Nissilä, Ilkka; Haapalahti, Petri; Ilmoniemi, Risto J.

    2011-01-01

    Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65–0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity. PMID:21887362

  2. Magnetic-stimulation-related physiological artifacts in hemodynamic near-infrared spectroscopy signals.

    PubMed

    Näsi, Tiina; Mäki, Hanna; Kotilahti, Kalle; Nissilä, Ilkka; Haapalahti, Petri; Ilmoniemi, Risto J

    2011-01-01

    Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65-0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity.

  3. Linkage Analyses of Stimulant Dependence, Craving and Heavy Use in American Indians

    PubMed Central

    Ehlers, Cindy L.; Gizer, Ian R.; Gilder, David A.; Wilhelmsen, Kirk C.

    2011-01-01

    Amphetamine-type substances are the second most widely used illicit drugs in the United States. There is evidence to suggest that stimulant use (cocaine and methamphetamine) has a heritable component, yet the areas of the genome underlying these use disorders are yet to be identified. This study’s aims were to map loci linked to stimulant dependence, heavy use, and craving in an American Indian community at high risk for substance dependence. DSM diagnosis of stimulant dependence, as well as indices of stimulant “craving” and “heavy use”, were obtained using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 micro-satellite polymorphisms in 381 members of multiplex families using SOLAR. Stimulant dependence, stimulant “craving” and “heavy stimulant use”, were all found to be heritable. Analyses of multipoint variance component LOD scores, failed to yield evidence of linkage for stimulant dependence. For the stimulant “craving” phenotype, linkage analysis revealed a locus that had a LOD score of 3.02 on chromosome 15q25.3-26.1 near the nicotinic receptor gene cluster. A LOD score of 2.05 was found at this same site for “heavy stimulant use”. Additional loci with LOD scores above 2.00 were found for stimulant “craving” on chromosomes 12p13.33-13.32 and 18q22.3. These results corroborate the importance of “craving” as an important phenotype that is associated with regions on chromosome 12, 15 and 18, that have been highlighted in prior segregation studies in this and other populations for substance dependence-related phenotypes. PMID:21812097

  4. Analysis of the results of hydraulic-fracture stimulation of two crystalline bedrock boreholes, Grand Portage, Minnesota

    USGS Publications Warehouse

    Paillet, Dr. Fredrick L.; Olson, James D.

    1994-01-01

    Hydraulic fracture-stimulation procedures typical of those provided by contractors in the water-well industry were applied to two boreholes in basaltic and gabbroic rocks near Grand Portage, Minnesota.These boreholes were considered incapable of supplying adequate ground water for even a single household although geophysical logs showed both boreholes were intersected by many apparently permeable fractures. Tests made before and after stimulation indicated that the two boreholes would produce about 0.05 and 0.25 gallon per minute before stimulation, and about 1.5 and 1.2 gallons per minute after stimulation. These increases would be enough to obtain adequate domestic water supplies from the two boreholes but would not furnish enough water for more than a single household from either borehole. Profiles of high-resolution flow made during pumping after stimulation indicated that the stimulation enhanced previously small inflows or stimulated new inflow from seven fractures or fracture zones in one borehole and from six fractures or fracture zones in the other.Geophysical logs obtained after stimulation showed no specific changes in these 13 fractures that could be related to stimulation other than the increases in flow indicated by the flowmeter logs. The results indicate that the stimulation has increased inflow to the two boreholes by improving the connectivity of favorably orientated fractures with larger scale flow zones in the surrounding rocks. Three of four possible diagnostics related to measured pressure and flow during the stimulation treatments were weakly correlated with the increases in production associated with each treatment interval. These correlations are not statistically significant on the basis of the limited sample of 16 treatment intervals in two boreholes, but the results indicate that significant correlations might be established from a much larger data set.

  5. The Importance of Field Demonstration Sites: The View from the Unconventional Resource Region of the Appalachian Basin

    NASA Astrophysics Data System (ADS)

    Carr, T.

    2017-12-01

    The Appalachian basin with the Marcellus and Utica shale units is one of the most active unconventional resource plays in North America. Unconventional resource plays are critical and rapidly-growing areas of energy, where research lags behind exploration and production activity. There remains a poor overall understanding of physical, chemical and biological factors that control shale gas production efficiency and possible environmental impacts associated with shale gas development. We have developed an approach that works with local industrial partners and communities and across research organizations. The Marcellus Shale Energy and Environment Laboratory (MSEEL) consists of a multidisciplinary and multi-institutional team undertaking integrated geoscience, engineering and environmental studies in cooperation with the Department of Energy. This approach is being expanded to other sites and to the international arena. MSEEL consists of four horizontal production wells, which are instrumented, a cored and logged vertical pilot bore-hole, and a microseismic observation well. MSEEL has integrated geophysical observations (microseismic and surface), fiber-optic monitoring for distributed acoustic (DAS) and temperature sensing (DTS), well logs, core data and production logging and continued monitoring, to characterize subsurface rock properties, and the propagation pattern of induced fractures in the stimulated reservoir volume. Significant geologic heterogeneity along the lateral affects fracture stimulation efficiency - both completion efficiency (clusters that receive effective stimulation), and production efficiency (clusters effectively contributing to production). MSEEL works to develop new knowledge of subsurface geology and engineering, and surface environmental impact to identify best practices that can optimize hydraulic fracture stimulation to increase flow rates, estimated ultimate recovery in order to reduce the number of wells and environmental impact.

  6. Effect of simultaneously induced environmental stimuli on electrical signalling and gas exchange in maize plants.

    PubMed

    Vuralhan-Eckert, Jasmin; Lautner, Silke; Fromm, Jörg

    2018-04-01

    Electrical signalling in response to environmental stimuli is a well-known phenomenon in higher plants. For example, in maize, different stimuli, such as wounding or re-irrigation after drought, incite characteristic electrical signals which have quite particular effects on gas exchange. What is less well understood is how plants (specifically maize) respond when two different environmental stimuli are applied simultaneously. To explore this, a three-stage experiment was designed. In the first stage, drought conditions were simulated by decreasing the soil water content to 30-40 % of field capacity. In these conditions, and in contrast to well-watered plants, the maize exhibited only 60-70% of the original level of stomatal conductance and 50-60 % of the original photosynthesis rate. In the second stage of the experiment the plants were re-irrigated and heat stimulated separately. Re-irrigation led to specific electrical signals followed by a gradual increase of gas exchange. In contrast, after heat stimulation of a leaf an electrical signal was evoked that reduced the net CO 2 -uptake rate as well as stomatal conductance. In the third stage, to elucidate how plants process simultaneous re-irrigation and heat stimulation, the drought-stressed maize plants were re-watered and heat-stimulated at the same time. Results showed a two phase response. In the first phase there was a rapid decrease in both the CO 2 uptake rate and the stomatal conductance, while in the second phase each of these parameters increased gradually. Thus, the results strongly support the view that the responses from both stimuli were combined, indicating that maize plants can process simultaneously applied stimuli. Copyright © 2018 Elsevier GmbH. All rights reserved.

  7. Enhanced microbial coalbed methane generation: A review of research, commercial activity, and remaining challenges

    USGS Publications Warehouse

    Ritter, Daniel J.; Vinson, David S.; Barnhart, Elliott P.; Akob, Denise M.; Fields, Matthew W.; Cunningham, Al B.; Orem, William H.; McIntosh, Jennifer C.

    2015-01-01

    Coalbed methane (CBM) makes up a significant portion of the world’s natural gas resources. The discovery that approximately 20% of natural gas is microbial in origin has led to interest in microbially enhanced CBM (MECoM), which involves stimulating microorganisms to produce additional CBM from existing production wells. This paper reviews current laboratory and field research on understanding processes and reservoir conditions which are essential for microbial CBM generation, the progress of efforts to stimulate microbial methane generation in coal beds, and key remaining knowledge gaps. Research has been primarily focused on identifying microbial communities present in areas of CBM generation and attempting to determine their function, in-situ reservoir conditions that are most favorable for microbial CBM generation, and geochemical indicators of metabolic pathways of methanogenesis (i.e., acetoclastic or hydrogenotrophic methanogenesis). Meanwhile, researchers at universities, government agencies, and companies have focused on four primary MECoM strategies: 1) microbial stimulation (i.e., addition of nutrients to stimulate native microbes); 2) microbial augmentation (i.e., addition of microbes not native to or abundant in the reservoir of interest); 3) physically increasing microbial access to coal and distribution of amendments; and 4) chemically increasing the bioavailability of coal organics. Most companies interested in MECoM have pursued microbial stimulation: Luca Technologies, Inc., successfully completed a pilot scale field test of their stimulation strategy, while two others, Ciris Energy and Next Fuel, Inc., have undertaken smaller scale field tests. Several key knowledge gaps remain that need to be addressed before MECoM strategies can be implemented commercially. Little is known about the bacterial community responsible for coal biodegradation and how these microorganisms may be stimulated to enhance microbial methanogenesis. In addition, research is needed to understand what fraction of coal is available for biodegradation, and methods need to be developed to determine the extent of in-situ coal biodegradation by MECoM processes for monitoring changes to coal quality. Questions also remain about how well field-scale pilot tests will scale to commercial production, how often amendments will need to be added to maintain new methane generation, and how well MECoM strategies transfer between coal basins with different formation water geochemistries and coal ranks. Addressing these knowledge gaps will be key in determining the feasibility and commercial viability of MECoM technology.

  8. Comparison of Thermo-Elastic and Poro-Elastic Effects during Shear Stimulation of Desert Peak EGS Well 27-15 Using a Coupled Thermal-Hydrological-Mechanical Simulator

    NASA Astrophysics Data System (ADS)

    Kelkar, S.; Dempsey, D.; Hickman, S. H.; Davatzes, N. C.; Moos, D.; Zemach, E.

    2013-12-01

    High-temperature rock formations at moderate depths with low permeability are candidates for Enhanced Geothermal Systems (EGS) projects. Hydraulic stimulation can be employed in such systems to create flow paths with low hydraulic impedance while maintaining significant heat transfer area to avoid premature cooling of the formation and the creation of short-circuit flow paths. Here we present results from a coupled thermal-hydrological-mechanical numerical model of a successful EGS stimulation in well 27-15 at the Desert Peak Geothermal Field, Nevada. This stimulation was carried out over two different depth intervals and multiple injection pressures, beginning in September 2010. The subject of this study is the initial shear stimulation phase, which was carried out at depths of 0.9 to 1.1 km over a period of about 100 days. The reservoir temperature at these depths is ~182 to 195° C. This treatment consisted of injection of 20 to 30° C water at wellhead pressures (WHP) of 1.5, 2.2, 3.1 and 3.7 MPa followed by periods of shut-in. To avoid hydraulic fracturing, these pressure steps were intentionally selected to stay below the minimum principal stress measured in the well. The injectivity did not change at WHP steps of 1.5 and 2.2 MPa, but improved significantly during injection at 3.1 MPa, from about 0.1 to 1.5 kg s-1 MPa-1. This improvement was attributed to self-propping shear failure of pre-existing natural fractures. The model incorporates physical processes thought to be important during this low-pressure shear stimulation phase. The relatively long periods of injection of water that was significantly cooler than the ambient formation temperature required incorporating in the model both thermo-mechanical and poroelastic effects, which were coupled to fluid flow via Mohr-Coulomb failure and shear-induced increases in fracture permeability. This model resulted in a good match to the wellhead injection data recorded during the stimulation. This numerical model was also used to separate the thermo-mechanical and poroelastic effects, compare their spatial and temporal evolution and carry out sensitivity analyses. To varying degrees, model results depended on variations in permeability anisotropy, elastic and thermal rock properties, Mohr-Coulomb parameters of static and dynamic friction and cohesion, shear-dilatation parameters, injection pressure and length of the injection zone. The thermoelastic and poroelastic effects are realized over different time scales, and their magnitudes are governed by different material properties; in general, model results show greater sensitivity to variations in the coefficient of thermal expansion than in the Biot poroelastic factor. Both thermal and poroelastic contributions to stressing of fractures significantly impact the onset as well as the magnitude of shear-induced permeability gains realized during this low-pressure stimulation.

  9. Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Silva, P.; Stoff, J.S.; Solomon, R.J.

    1987-01-01

    Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallelmore » with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters.« less

  10. Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions

    PubMed Central

    Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

    2017-01-01

    Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping. PMID:28700619

  11. Utilizing sensory prediction errors for movement intention decoding: A new methodology

    PubMed Central

    Nakamura, Keigo; Ando, Hideyuki

    2018-01-01

    We propose a new methodology for decoding movement intentions of humans. This methodology is motivated by the well-documented ability of the brain to predict sensory outcomes of self-generated and imagined actions using so-called forward models. We propose to subliminally stimulate the sensory modality corresponding to a user’s intended movement, and decode a user’s movement intention from his electroencephalography (EEG), by decoding for prediction errors—whether the sensory prediction corresponding to a user’s intended movement matches the subliminal sensory stimulation we induce. We tested our proposal in a binary wheelchair turning task in which users thought of turning their wheelchair either left or right. We stimulated their vestibular system subliminally, toward either the left or the right direction, using a galvanic vestibular stimulator and show that the decoding for prediction errors from the EEG can radically improve movement intention decoding performance. We observed an 87.2% median single-trial decoding accuracy across tested participants, with zero user training, within 96 ms of the stimulation, and with no additional cognitive load on the users because the stimulation was subliminal. PMID:29750195

  12. cAMP dependent and independent regulation of thyroglobulin synthesis by two clones of the OVNIS 6H thyroid cell line.

    PubMed

    Aouani, A; Hovsépian, S; Fayet, G

    1987-07-01

    The hormonal regulation of thyroglobulin synthesis has been studied using two independent clones of the OVNIS 6H cell line. Insulin, hydrocortisone and TSH were able to stimulate thyroglobulin synthesis, whereas transferrin, somatostatin and glycyl-histidyl-lysine were without effect. Insulin stimulated thyroglobulin synthesis without affecting cAMP production. Hydrocortisone, when combined with insulin was a stimulator too; this stimulation was not accompanied by an increase in cAMP. TSH alone was unable to stimulate either cAMP or thyroglobulin synthesis. The stimulatory effect of TSH on thyroglobulin synthesis took place only when combined with insulin or insulin plus hydrocortisone, and was mediated by cAMP. Consequently, insulin and hydrocortisone stimulated thyroglobulin synthesis by cAMP-independent mechanisms, whereas TSH acted via the cAMP system. Forskolin mimicked TSH effects on cAMP and thyroglobulin synthesis. Calf serum inhibited cAMP and thyroglobulin production. Optimal cAMP and thyroglobulin synthesis as well as TSH responsiveness were obtained in serum-free medium supplemented with 5 micrograms/ml insulin, 100 nM hydrocortisone and 1 mU/ml TSH.

  13. Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

    PubMed

    Gonen, Tal; Gazit, Tomer; Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

    2017-01-01

    Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

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

    PubMed

    Heth, Inbahl; Lavidor, Michal

    2015-04-01

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

  15. Specific CA3 neurons decode neural information of dentate granule cells evoked by paired-pulse stimulation in co-cultured networks.

    PubMed

    Poli, Daniele; DeMarse, Thomas B; Wheeler, Bruce C; Brewer, Gregory J

    2017-07-01

    CA3 and dentate gyrus (DG) neurons are cultured in two-chamber devices on multi-electrode arrays (MEAs) and connected via micro-tunnels. In order to evoke time-locked activity, paired-pulse stimulation is applied to 22 different sites and repeated 25 times in each well in 5 MEA co-cultures and results compared to CA3-CA3 and DG-DG networks homologous controls. In these hippocampal sub-regions, we focus on the mechanisms underpinning a network's ability to decode the identity of site specific stimulation from analysis of evoked network responses using a support vector machine classifier. Our results indicate that a pool of CA3 neurons is able to reliably decode the identity of DG stimulation site information.

  16. Transcranial direct current stimulation improves seizure control in patients with Rasmussen encephalitis.

    PubMed

    Tekturk, Pinar; Erdogan, Ezgi Tuna; Kurt, Adnan; Kocagoncu, Ece; Kucuk, Zeynep; Kinay, Demet; Yapici, Zuhal; Aksu, Serkan; Baykan, Betul; Karamursel, Sacit

    2016-03-01

    Rasmussen encephalitis is associated with severe seizures that are unresponsive to antiepileptic drugs, as well as immunosuppressants. Transcranial direct current stimulation (t-DCS) is a non-invasive and safe method tried mostly for focal epilepsies with different aetiologies. To date, there is only one published study with two case reports describing the effect of t-DCS in Rasmussen encephalitis. Our aim was to investigate the effect of t-DCS on seizures in Rasmussen encephalitis and to clarify its safety. Five patients (mean age: 19; three females), diagnosed with Rasmussen encephalitis were included in this study. Patients received first cathodal, then anodal (2 mA for 30 minutes on three consecutive days for non-sham stimulations), and finally sham stimulation with two-month intervals, respectively. Three patients received classic (DC) cathodal t-DCS whereas two patients received cathodal stimulation with amplitude modulation at 12 Hz. Afterwards, all patients received anodal stimulation with amplitude modulation at 12 Hz. In the last part of the trial, sham stimulation (a 60-second stimulation with gradually decreasing amplitude to zero in the last 15 seconds) was applied to three patients. Maximum current density was 571 mA/m2 using 70 mm x 50 mm wet sponge electrodes with 2-mA maximum, current controlled stimulator, and maximum charge density was 1028 C/m2 for a 30-minute stimulation period. After cathodal stimulation, all but one patient had a greater than 50% decrease in seizure frequency. Two patients who received modulated cathodal t-DCS had better results. The longest positive effect lasted for one month. A second trial with modulated anodal stimulation and a third with sham stimulation were not effective. No adverse effect was reported with all types of stimulations. Both classic and modulated cathodal t-DCS may be suitable alternative methods for improving seizure outcome in Rasmussen encephalitis patients.

  17. Novel Mechanistic Link between Focal Adhesion Remodeling and Glucose-stimulated Insulin Secretion*

    PubMed Central

    Rondas, Dieter; Tomas, Alejandra; Soto-Ribeiro, Martinho; Wehrle-Haller, Bernhard; Halban, Philippe A.

    2012-01-01

    Actin cytoskeleton remodeling is well known to be positively involved in glucose-stimulated pancreatic β cell insulin secretion. We have observed glucose-stimulated focal adhesion remodeling at the β cell surface and have shown this to be crucial for glucose-stimulated insulin secretion. However, the mechanistic link between such remodeling and the insulin secretory machinery remained unknown and was the major aim of this study. MIN6B1 cells, a previously validated model of primary β cell function, were used for all experiments. Total internal reflection fluorescence microscopy revealed the glucose-responsive co-localization of focal adhesion kinase (FAK) and paxillin with integrin β1 at the basal cell surface after short term stimulation. In addition, blockade of the interaction between β1 integrins and the extracellular matrix with an anti-β1 integrin antibody (Ha2/5) inhibited short term glucose-induced phosphorylation of FAK (Tyr-397), paxillin (Tyr-118), and ERK1/2 (Thr-202/Tyr-204). Pharmacological inhibition of FAK activity blocked glucose-induced actin cytoskeleton remodeling and glucose-induced disruption of the F-actin/SNAP-25 association at the plasma membrane as well as the distribution of insulin granules to regions in close proximity to the plasma membrane. Furthermore, FAK inhibition also completely blocked short term glucose-induced activation of the Akt/AS160 signaling pathway. In conclusion, these results indicate 1) that glucose-induced activation of FAK, paxillin, and ERK1/2 is mediated by β1 integrin intracellular signaling, 2) a mechanism whereby FAK mediates glucose-induced actin cytoskeleton remodeling, hence allowing docking and fusion of insulin granules to the plasma membrane, and 3) a possible functional role for the Akt/AS160 signaling pathway in the FAK-mediated regulation of glucose-stimulated insulin secretion. PMID:22139838

  18. The added value of auditory cortex transcranial random noise stimulation (tRNS) after bifrontal transcranial direct current stimulation (tDCS) for tinnitus.

    PubMed

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

    2017-01-01

    Tinnitus is the perception of a sound in the absence of a corresponding external sound source. Research has suggested that functional abnormalities in tinnitus patients involve auditory as well as non-auditory brain areas. Transcranial electrical stimulation (tES), such as transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex and transcranial random noise stimulation (tRNS) to the auditory cortex, has demonstrated modulation of brain activity to transiently suppress tinnitus symptoms. Targeting two core regions of the tinnitus network by tES might establish a promising strategy to enhance treatment effects. This proof-of-concept study aims to investigate the effect of a multisite tES treatment protocol on tinnitus intensity and distress. A total of 40 tinnitus patients were enrolled in this study and received either bifrontal tDCS or the multisite treatment of bifrontal tDCS before bilateral auditory cortex tRNS. Both groups were treated on eight sessions (two times a week for 4 weeks). Our results show that a multisite treatment protocol resulted in more pronounced effects when compared with the bifrontal tDCS protocol or the waiting list group, suggesting an added value of auditory cortex tRNS to the bifrontal tDCS protocol for tinnitus patients. These findings support the involvement of the auditory as well as non-auditory brain areas in the pathophysiology of tinnitus and demonstrate the idea of the efficacy of network stimulation in the treatment of neurological disorders. This multisite tES treatment protocol proved to be save and feasible for clinical routine in tinnitus patients.

  19. Randomized controlled trial of home-based 4-week tDCS in chronic minimally conscious state.

    PubMed

    Martens, Géraldine; Lejeune, Nicolas; O'Brien, Anthony Terrence; Fregni, Felipe; Martial, Charlotte; Wannez, Sarah; Laureys, Steven; Thibaut, Aurore

    2018-05-02

    Patients with chronic disorders of consciousness face a significant lack of treatment options. We aimed at investigating the feasibility and the behavioral effects of home-based transcranial direct current stimulation (tDCS), applied by relatives or caregivers, in chronic patients in minimally conscious state (MCS). Each participant received, in a randomized order, 20 sessions of active and 20 sessions of sham tDCS applied over the prefrontal cortex for 4 weeks; separated by 8 weeks of washout. Level of consciousness was assessed using the Coma Recovery Scale-Revised before the first stimulation (baseline), at the end of the 20 tDCS sessions (direct effects) and 8 weeks after the end of each stimulation period (long-term effects). Reported adverse events and data relative to the adherence (i.e., amount of sessions effectively received) were collected as well. Twenty-seven patients completed the study and 22 patients received at least 80% of the stimulation sessions. All patients tolerated tDCS well, no severe adverse events were noticed after real stimulation and the overall adherence (i.e., total duration of stimulation) was good. A moderate effect size (0.47 and 0.53, for modified intention to treat and per protocol analysis, respectively) was observed at the end of the 4 weeks of tDCS in favor of the active treatment. We demonstrated that home-based tDCS can be used adequately outside a research facility or hospital by patients' relatives or caregivers. In addition, 4 weeks of tDCS moderately improved the recovery of signs of consciousness in chronic MCS patients. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Regulation of proliferation of rat cartilage and bone by sex steroid hormones.

    PubMed

    Sömjen, D; Weisman, Y; Mor, Z; Harell, A; Kaye, A M

    1991-01-01

    We have demonstrated previously that 17 beta-estradiol (E2) stimulates proliferation of skeletal tissues, both in vivo and in vitro, as measured by increased DNA synthesis and creatine kinase (CK) specific activity. The effect of E2 on bone is sex specific. E2 is active only in females and androgens only in males. By contrast, in cartilage of both sexes, dihydrotestosterone (DHT) as well as E2 stimulates CK specific activity and DNA synthesis. In bone, we find that sex steroids stimulate skeletal cell proliferation in gonadectomized as well as in immature rats. Ovariectomized (OVX) rats, between 1 and 4 weeks after surgery, show stimulation of CK by E2. The basal activity and response of CK changes with the varying endogenous levels of E2 in cycling rats, in which the highest basal activity is at proestrus and estrus and the highest response is in diestrus. In rats of all ages tested, both the basal and stimulated specific activity of CK is higher in diaphysis and epiphysis than in the uterus, or in the adipose tissue adjacent to the uterus, which has a response similar to that of the uterus itself. The effect of E2 in vivo, and in chrondroblasts and osteoblasts in vitro, is inhibited by high levels of the antiestrogen tamoxifen which, by itself, in similar high concentrations, shows stimulatory effects. In addition to the sex steroids, skeletal cells are also stimulated by secosteroid and peptide calciotrophic hormones. The interactions of the sex steroids with these hormones modulate the response of cartilage and bone cells to both sex steroids and the other calciotrophic hormones. These results provide the first steps towards understanding the regulation of bone cell proliferation and growth by the concerted action of a variety of hormones and growth factors.

  1. Rapid changes in substance P signaling and neutral endopeptidase induced by skin-scratching stimulation in mice.

    PubMed

    Yamaoka, Junichi; Kawana, Seiji

    2007-11-01

    Skin-scratching is a commonly seen behavior in patients with pruritus which sometimes exacerbates original lesions. Substance P (SP) signaling may play a predominant role in the pathophysiology induced by skin-scratching, however, it has not been well-elucidated. To clarify changes in SP, its receptor NK-1R and a degradating enzyme neutral endopeptidase (NEP) induced by skin-scratching stimulation in mice. After skin-scratching stimulation was given to mice, changes in SP signaling were investigated as follows. Mast cell degranulation was examined with toluidine blue staining. SP-immunoreactive nerve fibers and the expressions of NK-1R and NEP were examined with immunofluorescence. Protein contents of SP and the enzymatic activity of NEP were examined with an ELISA and a colorimetric assay, respectively. After skin-scratching stimulation, mast cells significantly degranulated within several minutes. SP-immunoreactive nerve fibers disappeared immediately from sensory nerve fibers, indicating the quick secretion and the depletion of SP. Both protein contents of SP and NEP activity in skin decreased dramatically soon after skin-scratching stimulation and thereafter they returned to the basal level within a week. The expression of NK-1R was significantly upregulated in epidermal basal keratinocytes after several days, in which NEP and NK-1R were well-coexpressed. Blocking NK-1R by an NK-1R antagonist suppressed scratching-induced decreases in SP-immunoreactive nerve fibers and in NEP activity. The present study clarified changing patterns of factors involved in SP signaling and NEP induced by skin-scratching stimulation. These findings provide basic and useful information to understand the pathophysiology of scratching-associated pruritic skin diseases.

  2. Conditioned medium of dental pulp cells stimulated by Chinese propolis show neuroprotection and neurite extension in vitro.

    PubMed

    Kudo, Daichi; Inden, Masatoshi; Sekine, Shin-Ichiro; Tamaoki, Naritaka; Iida, Kazuki; Naito, Eiji; Watanabe, Kazuhiro; Kamishina, Hiroaki; Shibata, Toshiyuki; Hozumi, Isao

    2015-03-04

    The purpose of this study was to clarify the effect of Chinese propolis on the expression level of neurotrophic factors in dental pulp cells (DPCs). We also investigated that the effects of the conditioned medium (CM) of DPCs stimulated by the propolis against oxidative and endoplasmic reticulum (ER) stresses in human neuroblastoma SH-SY5Y cells, and on neurite extensions in rat adrenal pheochromocytoma PC12 cells. To investigate the effect of the propolis on the levels of neurotrophic factors in DPCs, we performed a qRT-PCR experiment. As results, NGF, but not BDNF and NT-3, in DPCs was significantly elevated by the propolis in a concentration-dependent manner. H2O2-induced cell death was significantly inhibited by the treatment with the CM of DPCs. In addition, the treatment with the propolis-stimulated CM of DPCs had a more protective effect than that with the CM of DPCs. We also examine the effect of the propolis-stimulated CM of DPCs against a tunicamycin-induced ER stress. The treatment with the propolis-stimulated CM as well as the CM of DPCs significantly inhibited tunicamycin-induced cell death. Moreover, the treatment with the propolis-stimulated CM of DPCs significantly induced neurite outgrowth from PC12 cells than that with the CM of DPCs. These results suggest that the CM of DPCs as well as DPCs will be an efficient source of new treatments for neurodegenerative diseases and that the propolis promote the advantage of the CM of DPCs via producing neurotrophic factors. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Neurostimulation for the treatment of axial back pain: a review of mechanisms, techniques, outcomes, and future advances.

    PubMed

    Deer, Timothy; Pope, Jason; Hayek, Salim; Narouze, Samer; Patil, Parag; Foreman, Robert; Sharan, Ashwini; Levy, Robert

    2014-10-01

    The use of spinal cord stimulation (SCS) is well established in the treatment of neuropathic pain. This procedure has been approved in the United States for neuropathic pain of the trunk and limbs from various conditions. International use is variable based on governmental policy. Most studies showing efficacy have focused on pain primarily in the limbs for such conditions as complex regional pain syndrome (CRPS), sciatica, radiculitis, ischemic limb pain, and peripheral neuropathy. Data on success in neuropathic pain of the trunk and particularly of the axial back are limited. New understanding about the targets of neuromodulation and their treatment with novel neurostimulation approaches has led to a new dawn of enthusiasm for spinal cord stimulation for axial low back pain. The authors review mechanisms, current and future targets, techniques, and their outcomes for treating axial back pain with neurostimulation. The paper discusses many newer methods and targets that may substantially improve results for the treatment of this patient group. The continuing evolution of technology and new data may well change these recommendations over time and regular updates of this manuscript will be critical moving forward. Improved technology and a better understanding of the goals of stimulation have led to a new ability to stimulate the axial low back and increase the effectiveness of these therapies to reduce pain. New paddle lead constructs, percutaneous paddle lead introduction, and other new technologies have led to an increased number of potential candidates for spinal cord stimulation. Optimizing the application of neurostimulation for chronic axial back pain will depend upon answering questions relating to patient selection, implantation technique, and stimulation parameters. © 2014 International Neuromodulation Society.

  4. Role of G protein-coupled estrogen receptor-1, matrix metalloproteinases 2 and 9, and heparin binding epidermal growth factor-like growth factor in estradiol-17β-stimulated bovine satellite cell proliferation.

    PubMed

    Kamanga-Sollo, E; Thornton, K J; White, M E; Dayton, W R

    2014-10-01

    In feedlot steers, estradiol-17β (E2) and combined E2 and trenbolone acetate (a testosterone analog) implants enhance rate and efficiency of muscle growth; and, consequently, these compounds are widely used as growth promoters. Although the positive effects of E2 on rate and efficiency of bovine muscle growth are well established, the mechanisms involved in these effects are not well understood. Combined E2 and trenbolone acetate implants result in significantly increased muscle satellite cell number in feedlot steers. Additionally, E2 treatment stimulates proliferation of cultured bovine satellite cells (BSC). Studies in nonmuscle cells have shown that binding of E2 to G protein-coupled estrogen receptor (GPER)-1 results in activation of matrix metalloproteinases 2 and 9 (MMP2/9) resulting in proteolytic release of heparin binding epidermal growth factor-like growth factor (hbEGF) from the cell surface. Released hbEGF binds to and activates the epidermal growth factor receptor resulting in increased proliferation. To assess if GPER-1, MMP2/9, and/or hbEGF are involved in the mechanism of E2-stimulated BSC proliferation, we have examined the effects of G36 (a specific inhibitor of GPER-1), CRM197 (a specific inhibitor of hbEGF), and MMP-2/MMP-9 Inhibitor II (an inhibitor of MMP2/9 activity) on E2-stimulated BSC proliferation. Inhibition of GPER-1, MMP2/9, or hbEGF suppresses E2-stimulated BSC proliferation (P < 0.001) suggesting that all these are required in order for E2 to stimulate BSC proliferation. These results strongly suggest that E2 may stimulate BSC proliferation by binding to GPER-1 resulting in MMP2/9-catalyzed release of cell membrane-bound hbEGF and subsequent activation of epidermal growth factor receptor by binding of released hbEGF. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Computer-assisted three-dimensional reconstructions of ( sup 14 C)-2-deoxy-D-glucose metabolism in cat lumbosacral spinal cord following cutaneous stimulation of the hindfoot

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Crockett, D.P.; Smith, W.K.; Proshansky, E.

    1989-10-08

    We report on computer-assisted three-dimensional reconstruction of spinal cord activity associated with stimulation of the plantar cushion (PC) as revealed by (14C)-2-deoxy-D-glucose (2-DG) serial autoradiographs. Moderate PC stimulation in cats elicits a reflex phasic plantar flexion of the toes. Four cats were chronically spinalized at about T6 under barbiturate anesthesia. Four to 11 days later, the cats were injected (i.v.) with 2-DG (100 microCi/kg) and the PC was electrically stimulated with needle electrodes at 2-5 times threshold for eliciting a reflex. Following stimulation, the spinal cord was processed for autoradiography. Subsequently, autoradiographs, representing approximately 8-18 mm from spinal segments L6-S1,more » were digitized for computer analysis and 3-D reconstruction. Several strategies of analysis were employed: (1) Three-dimensional volume images were color-coded to represent different levels of functional activity. (2) On the reconstructed volumes, virtual sections were made in the horizontal, sagittal, and transverse planes to view regions of 2-DG activity. (3) In addition, we were able to sample different regions within the grey and white matter semi-quantitatively (i.e., pixel intensity) from section to section to reveal differences between ipsi- and contralateral activity, as well as possible variation between sections. These analyses revealed 2-DG activity associated with moderate PC stimulation, not only in the ipsilateral dorsal horn as we had previously demonstrated, but also in both the ipsilateral and contralateral ventral horns, as well as in the intermediate grey matter. The use of novel computer analysis techniques--combined with an unanesthetized preparation--enabled us to demonstrate that the increased metabolic activity in the lumbosacral spinal cord associated with PC stimulation was much more extensive than had heretofore been observed.« less

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

    NASA Astrophysics Data System (ADS)

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

    2018-02-01

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

  7. Educational Games Based on Distributed and Tangible User Interfaces to Stimulate Cognitive Abilities in Children with ADHD

    ERIC Educational Resources Information Center

    de la Guía, Elena; Lozano, María D.; Penichet, Víctor M. R.

    2015-01-01

    Children with attention deficit hyperactivity disorder (ADHD) experience behavioural and learning problems at home and at school, as well as a lack of self-control in their lives. We can take advantage of the evolution of new technologies to develop applications with the aim of enhancing and stimulating the learning process of children with ADHD.…

  8. Methods of Coping with Stress: A Taxonomy

    DTIC Science & Technology

    1992-03-01

    hypnosis (Feuerstein, Labbe, & Kuczmierczyk, 1986)), as well as more recent additions such as acupuncture (Hanson, 1989). Where, with a minimum of...phone index. REFERENCE: Hanson, 1989 #: 33 NAME: LEFT-BRAIN STIMULATION DEFINITION: Stimulating intellect and memory , e. g., in learning to play an...progressive muscle relaxation and hypnosis , leading to the control of the level of arousal in the body, binging on a restful, peaceful state. REFERENCE

  9. Mobilization of colloidal particles by low-frequency dynamic stress stimulation.

    PubMed

    Beckham, Richard E; Abdel-Fattah, Amr I; Roberts, Peter M; Ibrahim, Reem; Tarimala, Sowmitri

    2010-01-05

    Naturally occurring seismic events and artificially generated low-frequency (1 to 500 Hz) elastic waves have been observed to alter the production rates of oil and water wells, sometimes increasing and sometimes decreasing production, and to influence the turbidity of surface and well water. The decreases in production are of particular concern, especially when artificially generated elastic waves are applied as a method for enhanced oil recovery. The exact conditions that result in a decrease in production remain unknown. Although the underlying environment is certainly complex, the observed increase in water well turbidity after natural seismic events suggests the existence of a mechanism that can affect both the subsurface flow paths and the mobilization of in situ colloidal particles. This article explores the macroscopic and microscopic effects of low-frequency dynamic stress stimulations on the release of colloidal particles from an analog core representing an infinitesimal section along the propagation paths of an elastic wave. Experiments on a column packed with 1 mm borosilicate beads and loaded with polystyrene microparticles demonstrate that axial mechanical stress oscillations enhance the mobilization of captured microparticles. Increasing the amplitude of the oscillations increases the number of microparticles released and can also result in cyclical spikes in effluent microparticle concentration during stimulation. Under a prolonged period of stimulation, the cyclical effluent spikes coincided with fluctuations in the column pressure data and continued at a diminished level after stimulation. This behavior can be attributed to rearrangements of the beads in the column, resulting in possible changes in the void space and/or tortuosity of the packing. Optical microscopy observations of the beads during low-frequency oscillations reveal that individual beads rotate, thereby rubbing against each other and scraping away portions of the adsorbed microparticles. These results support the theory that mechanical interactions between porous matrix grains are important mechanisms in flow path alteration and the mobilization of naturally occurring colloidal particles during elastic wave stimulation. These results also point to both continuous and discrete en masse releases of colloidal particles, perhaps because of circulation cells within the packing material.

  10. The short- and long-term benefit in chronic low back pain through adjuvant electrical versus manual auricular acupuncture.

    PubMed

    Sator-Katzenschlager, Sabine M; Scharbert, Gisela; Kozek-Langenecker, Sibylle A; Szeles, Jozef C; Finster, Gabriele; Schiesser, Andreas W; Heinze, Georg; Kress, Hans Georg

    2004-05-01

    Acupuncture is an established adjuvant analgesic modality for the treatment of chronic pain. Electrical stimulation of acupuncture points is considered to increase acupuncture analgesia. In this prospective, randomized, double-blind, controlled study we tested the hypothesis that auricular electroacupuncture (EA) relieves pain more effectively than conventional manual auricular acupuncture (CO) in chronic low back pain patients with insufficient pain relief (visual analogue scale [VAS] > or = 5) treated with standardized analgesic therapy. Disposable acupuncture needles were inserted in the auricular acupuncture points 29, 40, and 55 of the dominant side and connected to a newly developed battery-powered miniaturized stimulator worn behind the ear. Patients were randomized into group EA (n = 31) with continuous low-frequency auricular EA (1 Hz biphasic constant current of 2 mA) and group CO (n = 30) without electrical stimulation (sham-electroacupuncture). Treatment was performed once weekly for 6 wk, and in each group needles were withdrawn 48 h after insertion. During the study period and a 3-mo follow-up, patients were asked to complete the McGill questionnaire. Psychological well being, activity level, quality of sleep, and pain intensity were assessed by means of VAS; moreover, analgesic drug consumption was documented. Pain relief was significantly better in group EA during the study and the follow-up period as compared with group CO. Similarly, psychological well-being, activity, and sleep were significantly improved in group EA versus group CO, the consumption of analgesic rescue medication was less, and more patients returned to full-time employment. Neuropathic pain in particular improved in patients treated with EA. There were no adverse side effects. These results are the first to demonstrate that continuous EA stimulation of auricular acupuncture points improves the treatment of chronic low back pain in an outpatient population. Continuous electrical stimulation of auricular acupuncture points using the new point stimulation device P-stim significantly decreases pain intensity and improves psychological well-being, activity, and sleep in chronic low back pain patients.

  11. Monitoring artificially stimulated fluid movement in the Cretaceous Dakota aquifer, western Kansas

    USGS Publications Warehouse

    Macfarlane, P.A.; Forster, A.; Merriam, D.F.; Schrotter, J.; Healey, J.M.

    2002-01-01

    Aquifer properties can be evaluated by monitoring artificially stimulated fluid movements between wells, if the fluid is heated. Changes in the temperature profile recorded in observation wells indicate the flow path of the heated fluid, which in effect acts as a tracer. A fluid-flow experiment in the Cretaceous Dakota Formation at the Hodgeman County site, west-central Kansas, demonstrated the advantage of using the distributed optical-fiber temperature sensing method for monitoring transient temperature conditions in his hydrological application. The fluid flow in the aquifer was increased by producing water from a pumping well and injecting heated water in an injection well 13 m (43 ft) distant from the pumping well. The time-temperature series data obtained and compared with results from previous pumping tests point to interwell heterogeneity of the aquifer and to a zone in the sandstone aquifer of high hydraulic conductivity. However, the experiment would have allowed further clarification of aquifer heterogeneity and thermal properties if at least one observation well had been present between the injection and production wells.

  12. GAS INJECTION/WELL STIMULATION PROJECT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    John K. Godwin

    2005-12-01

    Driver Production proposes to conduct a gas repressurization/well stimulation project on a six well, 80-acre portion of the Dutcher Sand of the East Edna Field, Okmulgee County, Oklahoma. The site has been location of previous successful flue gas injection demonstration but due to changing economic and sales conditions, finds new opportunities to use associated natural gas that is currently being vented to the atmosphere to repressurize the reservoir to produce additional oil. The established infrastructure and known geological conditions should allow quick startup and much lower operating costs than flue gas. Lessons learned from the previous project, the lessons learnedmore » form cyclical oil prices and from other operators in the area will be applied. Technology transfer of the lessons learned from both projects could be applied by other small independent operators.« less

  13. The neural basis of sex differences in sexual behavior: A quantitative meta-analysis

    PubMed Central

    Poeppl, Timm B.; Langguth, Berthold; Rupprecht, Rainer; Safron, Adam; Bzdok, Danilo; Laird, Angela R.; Eickhoff, Simon B.

    2016-01-01

    Sexuality as to its etymology presupposes the duality of sexes. Using quantitative neuroimaging meta-analyses, we demonstrate robust sex differences in the neural processing of sexual stimuli in thalamus, hypothalamus, and basal ganglia. In a narrative review, we show how these relate to the well-established sex differences on the behavioral level. More specifically, we describe the neural bases of known poor agreement between self-reported and genital measures of female sexual arousal, of previously proposed male proneness to affective sexual conditioning, as well as hints of unconscious activation of bonding mechanisms during sexual stimulation in women. In summary, our meta-analytic review demonstrates that neurofunctional sex differences during sexual stimulation can account for well-established sex differences in sexual behavior. PMID:27742561

  14. The neural basis of sex differences in sexual behavior: A quantitative meta-analysis.

    PubMed

    Poeppl, Timm B; Langguth, Berthold; Rupprecht, Rainer; Safron, Adam; Bzdok, Danilo; Laird, Angela R; Eickhoff, Simon B

    2016-10-01

    Sexuality as to its etymology presupposes the duality of sexes. Using quantitative neuroimaging meta-analyses, we demonstrate robust sex differences in the neural processing of sexual stimuli in thalamus, hypothalamus, and basal ganglia. In a narrative review, we show how these relate to the well-established sex differences on the behavioral level. More specifically, we describe the neural bases of known poor agreement between self-reported and genital measures of female sexual arousal, of previously proposed male proneness to affective sexual conditioning, as well as hints of unconscious activation of bonding mechanisms during sexual stimulation in women. In summary, our meta-analytic review demonstrates that neurofunctional sex differences during sexual stimulation can account for well-established sex differences in sexual behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. SCHOOL HEALTH SERVICE IN NEW YORK STATE.

    PubMed

    Howe, W A

    1921-10-01

    That normal wisdom is the result of normal health, physical and mental, is the basic principle of the program of health education in the schools of New York State as here outlined. The aim of course is the formation and development by children of automatic good-health habits, as well as the stimulation of normal play. The program provides for giving school credit for health improvement as well as for mental progress. Emphasis is laid upon the need of adequately trained teachers of physical education; the education of the community to assume its own responsibility for efficient administration; and the stimulation of executives and legislators to grant necessary appropriations.

  16. SCHOOL HEALTH SERVICE IN NEW YORK STATE

    PubMed Central

    Howe, William A.

    1921-01-01

    That normal wisdom is the result of normal health, physical and mental, is the basic principle of the program of health education in the schools of New York State as here outlined. The aim of course is the formation and development by children of automatic good-health habits, as well as the stimulation of normal play. The program provides for giving school credit for health improvement as well as for mental progress. Emphasis is laid upon the need of adequately trained teachers of physical education; the education of the community to assume its own responsibility for efficient administration; and the stimulation of executives and legislators to grant necessary appropriations. PMID:18010569

  17. Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

    PubMed

    Sliutz, G; Speiser, P; Schultz, A M; Spona, J; Zeillinger, R

    1993-05-01

    In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.

  18. Hydraulic fracture treatment design and postfracture analysis: Maxus Exploration Company, Ellis Ranch Field, Ochiltree County, Texas. Carl Ellis E/3 Cleveland Sand. Topical report, October 1992

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    A discussion of a hydraulic fracture treatment and post-fracture tests on a tight gas sands well is presented. The treatment design was based on the results of an analysis of the stimulation of another well in the same field and a minifracture analysis of the Carl Ellis E-3. The quality and consistency of the interpretation and evaluation of the Carl Ellis E-3 and H.T. Glasgow No. 2 suggest that a consistent reservoir model has been developed that allows for further improvement of the stimulation technique in the Cleveland Formation.

  19. Stimulating the cerebellum affects visuomotor adaptation but not intermanual transfer of learning.

    PubMed

    Block, Hannah; Celnik, Pablo

    2013-12-01

    When systematic movement errors occur, the brain responds with a systematic change in motor behavior. This type of adaptive motor learning can transfer intermanually; adaptation of movements of the right hand in response to training with a perturbed visual signal (visuomotor adaptation) may carry over to the left hand. While visuomotor adaptation has been studied extensively, it is unclear whether the cerebellum, a structure involved in adaptation, is important for intermanual transfer as well. We addressed this question with three experiments in which subjects reached with their right hands as a 30° visuomotor rotation was introduced. Subjects received anodal or sham transcranial direct current stimulation on the trained (experiment 1) or untrained (experiment 2) hemisphere of the cerebellum, or, for comparison, motor cortex (M1). After the training period, subjects reached with their left hand, without visual feedback, to assess intermanual transfer of learning aftereffects. Stimulation of the right cerebellum caused faster adaptation, but none of the stimulation sites affected transfer. To ascertain whether cerebellar stimulation would increase transfer if subjects learned faster as well as a larger amount, in experiment 3 anodal and sham cerebellar groups experienced a shortened training block such that the anodal group learned more than sham. Despite the difference in adaptation magnitude, transfer was similar across these groups, although smaller than in experiment 1. Our results suggest that intermanual transfer of visuomotor learning does not depend on cerebellar activity and that the number of movements performed at plateau is an important predictor of transfer.

  20. Methods of automated absence seizure detection, interference by stimulation, and possibilities for prediction in genetic absence models.

    PubMed

    van Luijtelaar, Gilles; Lüttjohann, Annika; Makarov, Vladimir V; Maksimenko, Vladimir A; Koronovskii, Alexei A; Hramov, Alexander E

    2016-02-15

    Genetic rat models for childhood absence epilepsy have become instrumental in developing theories on the origin of absence epilepsy, the evaluation of new and experimental treatments, as well as in developing new methods for automatic seizure detection, prediction, and/or interference of seizures. Various methods for automated off and on-line analyses of ECoG in rodent models are reviewed, as well as data on how to interfere with the spike-wave discharges by different types of invasive and non-invasive electrical, magnetic, and optical brain stimulation. Also a new method for seizure prediction is proposed. Many selective and specific methods for off- and on-line spike-wave discharge detection seem excellent, with possibilities to overcome the issue of individual differences. Moreover, electrical deep brain stimulation is rather effective in interrupting ongoing spike-wave discharges with low stimulation intensity. A network based method is proposed for absence seizures prediction with a high sensitivity but a low selectivity. Solutions that prevent false alarms, integrated in a closed loop brain stimulation system open the ways for experimental seizure control. The presence of preictal cursor activity detected with state of the art time frequency and network analyses shows that spike-wave discharges are not caused by sudden and abrupt transitions but that there are detectable dynamic events. Their changes in time-space-frequency characteristics might yield new options for seizure prediction and seizure control. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Rapid fast to slow fiber transformation in response to chronic stimulation of immobilized muscles of the rabbit.

    PubMed

    Cotter, M; Phillips, P

    1986-09-01

    Limb immobilization causes muscle atrophy particularly of slow oxidative fibers which also suffer the greatest decrement in neural activation. In this study a fast muscle, tibialis anterior, was chronically stimulated using an activity pattern characteristic of nerve fibers to slow muscles to see whether or not this could prevent immobilization induced slow fiber atrophy. Four groups of rabbits were used: unoperated controls, stimulated (10 Hz, 8 h/day), immobilized (neutral position), and a stimulated plus immobilized group. The experimental period was 28 to 30 days or 44 to 50 days. Immobilization caused significant decrease in slow oxidative fiber area which was completely prevented by stimulation. In animals tested for the longer period there was 56% hypertrophy. In addition, the combination of stimulation and immobilization caused a two-fold increase in the number of slow oxidative fibers and greatly increased the proportion of intermediate fibers. Stimulation without immobilization had no effect. Slow fibers in stimulated immobilized muscles had a bimodal area distribution; the number of large fibers (mean area 7059 micron2) was the same as the number of slow oxidative fibers in contralateral muscles, suggesting that they were the preexisting slow fibers, and a small fiber population (mean area 3143 micron2) represented newly converted fast fibers. We conclude that slow muscle units benefit from restoration of activity by chronic stimulation. In addition, the combination of stimulation and immobilization accelerates fast to slow fiber conversion. We suggest that isometric conditions as well as enhanced glucocorticoid effects could account for these findings.

  2. Are prescription stimulants "smart pills"? The epidemiology and cognitive neuroscience of prescription stimulant use by normal healthy individuals.

    PubMed

    Smith, M Elizabeth; Farah, Martha J

    2011-09-01

    Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience literatures in search of answers to these questions. Epidemiological issues addressed include the prevalence of nonmedical stimulant use, user demographics, methods by which users obtain prescription stimulants, and motivations for use. Cognitive neuroscience issues addressed include the effects of prescription stimulants on learning and executive function, as well as the task and individual variables associated with these effects. Little is known about the prevalence of prescription stimulant use for cognitive enhancement outside of student populations. Among college students, estimates of use vary widely but, taken together, suggest that the practice is commonplace. The cognitive effects of stimulants on normal healthy people cannot yet be characterized definitively, despite the volume of research that has been carried out on these issues. Published evidence suggests that declarative memory can be improved by stimulants, with some evidence consistent with enhanced consolidation of memories. Effects on the executive functions of working memory and cognitive control are less reliable but have been found for at least some individuals on some tasks. In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  3. Method to Reduce Muscle Fatigue During Transcutaneous Neuromuscular Electrical Stimulation in Major Knee and Ankle Muscle Groups.

    PubMed

    Sayenko, Dimitry G; Nguyen, Robert; Hirabayashi, Tomoyo; Popovic, Milos R; Masani, Kei

    2015-09-01

    A critical limitation with transcutaneous neuromuscular electrical stimulation as a rehabilitative approach is the rapid onset of muscle fatigue during repeated contractions. We have developed a method called spatially distributed sequential stimulation (SDSS) to reduce muscle fatigue by distributing the center of electrical field over a wide area within a single stimulation site, using an array of surface electrodes. To extend the previous findings and to prove feasibility of the method by exploring the fatigue-reducing ability of SDSS for lower limb muscle groups in the able-bodied population, as well as in individuals with spinal cord injury (SCI). SDSS was delivered through 4 active electrodes applied to the knee extensors and flexors, plantarflexors, and dorsiflexors, sending a stimulation pulse to each electrode one after another with 90° phase shift between successive electrodes. Isometric ankle torque was measured during fatiguing stimulations using SDSS and conventional single active electrode stimulation lasting 2 minutes. We demonstrated greater fatigue-reducing ability of SDSS compared with the conventional protocol, as revealed by larger values of fatigue index and/or torque peak mean in all muscles except knee flexors of able-bodied individuals, and in all muscles tested in individuals with SCI. Our study has revealed improvements in fatigue tolerance during transcutaneous neuromuscular electrical stimulation using SDSS, a stimulation strategy that alternates activation of subcompartments of muscles. The SDSS protocol can provide greater stimulation times with less decrement in mechanical output compared with the conventional protocol. © The Author(s) 2014.

  4. Neuromodulation for the Treatment of Lower Urinary Tract Symptoms.

    PubMed

    Yamanishi, Tomonori; Kaga, Kanya; Fuse, Miki; Shibata, Chiharu; Uchiyama, Tomoyuki

    2015-09-01

    Neuromodulation therapy incorporates electrical stimulation to target specific nerves that control lower urinary tract symptoms (LUTS). The objectives of this article are to review the mechanism of action, the type of neuromodulation, and the efficacy of neuromodulation mainly according to the results of randomized controlled trials. Neuromodulation includes pelvic floor electrical stimulation (ES) using vaginal, anal and surface electrodes, interferential therapy (IF), magnetic stimulation (MS), percutaneous tibial nerve stimulation, and sacral nerve stimulation (SNS). The former four stimulations are used for external periodic (short-term) stimulation, and SNS are used for internal, chronic (long-term) stimulation. All of these therapies have been reported to be effective for overactive bladder or urgency urinary incontinence. Pelvic floor ES, IF, and MS have also been reported to be effective for stress urinary incontinence. The mechanism of neuromodulation for overactive bladder has been reported to be the reflex inhibition of detrusor contraction by the activation of afferent fibers by three actions, i.e., the activation of hypogastric nerve, the direct inhibition of the pelvic nerve within the sacral cord and the supraspinal inhibition of the detrusor reflex. The mechanism of neuromodulation for stress incontinence is contraction of the pelvic floor muscles through an effect on the muscle fibers as well as through the stimulation of pudendal nerves. Overall, cure and improvement rates of these therapies for urinary incontinence are 30-50, and 60-90% respectively. MS has been considered to be a technique for stimulating nervous system noninvasively. SNS is indicated for patients with refractory overactive bladder and urinary retention. © 2015 Wiley Publishing Asia Pty Ltd.

  5. CD28 co-stimulation restores T cell responsiveness in NOD mice by overcoming deficiencies in Rac-1/p38 mitogen-activated protein kinase signaling and IL-2 and IL-4 gene transcription.

    PubMed

    Zhang, J; Salojin, K V; Delovitch, T L

    2001-03-01

    Previously, we reported that T cell hyporesponsiveness induced by TCR ligation is causal to autoimmune diabetes in NOD mice. Neonatal CD28 co-stimulation reverses T cell hyporesponsiveness and protects NOD mice from diabetes by an IL-4-mediated mechanism, indicating that a deficiency in TCR signaling may be overcome by CD28/B7-2 co-stimulation in NOD T cells. To investigate which co-stimulation-induced signaling events mediate this protection, we analyzed the activity of Ras, Rac-1, mitogen-activated protein kinases (MAPK) and several transcription factors in TCR-activated NOD T cells in the presence or absence of CD28 co-stimulation. We show that CD28 co-stimulation restores normal TCR-induced activation of Rac-1 and p38 MAPK in NOD T cells. Deficiencies in TCR-induced nuclear expression of activating protein (AP)-1 binding proteins as well as activation of AP-1 and NF-AT in the IL-2 and IL-4 P1 promoters are also corrected by CD28 co-stimulation. Thus, CD28 co-stimulation reverses NOD T cell hyporesponsiveness by restoring TCR signaling leading to the activation of AP-1 and NF-AT during IL-2 and IL-4 gene transcription. Our findings provide additional evidence that CD28 co-stimulation amplifies signals delivered by the TCR and further explain the mechanism by which CD28 co-stimulation may protect against autoimmune diabetes.

  6. Bidirectional Modulation of Recognition Memory

    PubMed Central

    Ho, Jonathan W.; Poeta, Devon L.; Jacobson, Tara K.; Zolnik, Timothy A.; Neske, Garrett T.; Connors, Barry W.

    2015-01-01

    Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects. For example, animals and humans with perirhinal damage are unable to distinguish familiar from novel objects in recognition memory tasks. In the normal brain, perirhinal neurons respond to novelty and familiarity by increasing or decreasing firing rates. Recent work also implicates oscillatory activity in the low-beta and low-gamma frequency bands in sensory detection, perception, and recognition. Using optogenetic methods in a spontaneous object exploration (SOR) task, we altered recognition memory performance in rats. In the SOR task, normal rats preferentially explore novel images over familiar ones. We modulated exploratory behavior in this task by optically stimulating channelrhodopsin-expressing perirhinal neurons at various frequencies while rats looked at novel or familiar 2D images. Stimulation at 30–40 Hz during looking caused rats to treat a familiar image as if it were novel by increasing time looking at the image. Stimulation at 30–40 Hz was not effective in increasing exploration of novel images. Stimulation at 10–15 Hz caused animals to treat a novel image as familiar by decreasing time looking at the image, but did not affect looking times for images that were already familiar. We conclude that optical stimulation of PER at different frequencies can alter visual recognition memory bidirectionally. SIGNIFICANCE STATEMENT Recognition of novelty and familiarity are important for learning, memory, and decision making. Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects, but how novelty and familiarity are encoded and transmitted in the brain is not known. Perirhinal neurons respond to novelty and familiarity by changing firing rates, but recent work suggests that brain oscillations may also be important for recognition. In this study, we showed that stimulation of the PER could increase or decrease exploration of novel and familiar images depending on the frequency of stimulation. Our findings suggest that optical stimulation of PER at specific frequencies can predictably alter recognition memory. PMID:26424881

  7. On the efficiency of FES cycling: a framework and systematic review.

    PubMed

    Hunt, K J; Fang, J; Saengsuwan, J; Grob, M; Laubacher, M

    2012-01-01

    Research and development in the art of cycling using functional electrical stimulation (FES) of the paralysed leg muscles has been going on for around thirty years. A range of physiological benefits has been observed in clinical studies but an outstanding problem with FES-cycling is that efficiency and power output are very low. The present work had the following aims: (i) to provide a tutorial introduction to a novel framework and methods of estimation of metabolic efficiency using example data sets, and to propose benchmark measures for evaluating FES-cycling performance; (ii) to systematically review the literature pertaining specifically to the metabolic efficiency of FES-cycling, to analyse the observations and possible explanations for the low efficiency, and to pose hypotheses for future studies which aim to improve performance. We recommend the following as benchmark measures for assessment of the performance of FES-cycling: (i) total work efficiency, delta efficiency and stimulation cost; (ii) we recommend, further, that these benchmark measures be complemented by mechanical measures of maximum power output, sustainable steady-state power output and endurance. Performance assessments should be carried out at a well-defined operating point, i.e. under conditions of well controlled work rate and cadence, because these variables have a strong effect on energy expenditure. Future work should focus on the two main factors which affect FES-cycling performance, namely: (i) unfavourable biomechanics, i.e. crude recruitment of muscle groups, non-optimal timing of muscle activation, and lack of synergistic and antagonistic joint control; (ii) non-physiological recruitment of muscle fibres, i.e. mixed recruitment of fibres of different type and deterministic constant-frequency stimulation. We hypothesise that the following areas may bring better FES-cycling performance: (i) study of alternative stimulation strategies for muscle activation including irregular stimulation patterns (e.g. doublets, triplets, stochastic patterns) and variable frequency stimulation trains, where it appears that increasing frequency over time may be profitable; (ii) study of better timing parameters for the stimulated muscle groups, and addition of more muscle groups: this path may be approached using EMG studies and constrained numerical optimisation employing dynamic models; (iii) development of optimal stimulation protocols for muscle reconditioning and FES-cycle training.

  8. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

    PubMed Central

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  9. The Social Context of "Do-It-Yourself" Brain Stimulation: Neurohackers, Biohackers, and Lifehackers.

    PubMed

    Wexler, Anna

    2017-01-01

    The "do-it-yourself" (DIY) brain stimulation movement began in earnest in late 2011, when lay individuals began building stimulation devices and applying low levels of electricity to their heads for self-improvement purposes. To date, scholarship on the home use of brain stimulation has focused on characterizing the practices of users via quantitative and qualitative studies, and on analyzing related ethical and regulatory issues. In this perspective piece, however, I take the opposite approach: rather than viewing the home use of brain stimulation on its own, I argue that it must be understood within the context of other DIY and citizen science movements. Seen in this light, the home use of brain stimulation is only a small part of the "neurohacking" movement, which is comprised of individuals attempting to optimize their brains to achieve enhanced performance. Neurohacking itself is an offshoot of the "life hacking" (or "quantified self") movement, in which individuals self-track minute aspects of their daily lives in order to enhance productivity or performance. Additionally, the home or DIY use of brain stimulation is in many ways parallel to the DIY Biology (or "biohacking") movement, which seeks to democratize tools of scientific experimentation. Here, I describe the place of the home use of brain stimulation with regard to neurohackers, lifehackers, and biohackers, and suggest that a policy approach for the home use of brain stimulation should have an appreciation both of individual motivations as well as the broader social context of the movement itself.

  10. Signal and response properties indicate an optoacoustic effect underlying the intra-cochlear laser-optical stimulation

    NASA Astrophysics Data System (ADS)

    Kallweit, Nicole; Baumhoff, Peter; Krueger, Alexander; Tinne, Nadine; Heisterkamp, Alexander; Kral, Andrej; Maier, Hannes; Ripken, Tammo

    2016-02-01

    Optical cochlea stimulation is under investigation as a potential alternative to conventional electric cochlea implants in treatment of sensorineural hearing loss. If direct optical stimulation of spiral ganglion neurons (SGNs) would be feasible, a smaller stimulation volume and, therefore, an improved frequency resolution could be achieved. However, it is unclear whether the mechanism of optical stimulation is based on direct neuronal stimulation or on optoacoustics. Animal studies on hearing vs. deafened guinea pigs already identified the optoacoustic effect as potential mechanism for intra-cochlear optical stimulation. In order to characterize the optoacoustic stimulus more thoroughly the acoustic signal along the beam path of a pulsed laser in water was quantified and compared to the neuronal response properties of hearing guinea pigs stimulated with the same laser parameters. Two pulsed laser systems were used for analyzing the influence of variable pulse duration, pulse energy, pulse peak power and absorption coefficient. Preliminary results of the experiments in water and in vivo suggesta similar dependency of response signals on the applied laser parameters: Both datasets show an onset and offset signal at the beginning and the end of the laser pulse. Further, the resulting signal amplitude depends on the pulse peak power as well as the temporal development of the applied laser pulse. The data indicates the maximum of the first derivative of power as the decisive factor. In conclusion our findings strengthen the hypothesis of optoacoustics as the underlying mechanism for optical stimulation of the cochlea.

  11. Changing Brain Networks Through Non-invasive Neuromodulation

    PubMed Central

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

    2018-01-01

    Background/Objective: Non-invasive neuromodulation techniques, such as repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), have increasingly been investigated for their potential as treatments for neurological and psychiatric disorders. Despite widespread dissemination of these techniques, the underlying therapeutic mechanisms and the ideal stimulation site for a given disorder remain unknown. Increasing evidence support the possibility of non-invasive neuromodulation affecting a brain network rather than just the local stimulation target. In this article, we present evidence in a clinical setting to support the idea that non-invasive neuromodulation changes brain networks. Method: This article addresses the idea that non-invasive neuromodulation modulates brain networks, rather than just the local stimulation target, using neuromodulation studies in tinnitus and major depression as examples. We present studies that support this hypothesis from different perspectives. Main Results/Conclusion: Studies stimulating the same brain region, such as the dorsolateral prefrontal cortex (DLPFC), have shown to be effective for several disorders and studies using different stimulation sites for the same disorder have shown similar results. These findings, as well as results from studies investigating brain network connectivity on both macro and micro levels, suggest that non-invasive neuromodulation affects a brain network rather than just the local stimulation site targeted. We propose that non-invasive neuromodulation should be approached from a network perspective and emphasize the therapeutic potential of this approach through the modulation of targeted brain networks. PMID:29706876

  12. Computational modeling of epidural cortical stimulation

    NASA Astrophysics Data System (ADS)

    Wongsarnpigoon, Amorn; Grill, Warren M.

    2008-12-01

    Epidural cortical stimulation (ECS) is a developing therapy to treat neurological disorders. However, it is not clear how the cortical anatomy or the polarity and position of the electrode affects current flow and neural activation in the cortex. We developed a 3D computational model simulating ECS over the precentral gyrus. With the electrode placed directly above the gyrus, about half of the stimulus current flowed through the crown of the gyrus while current density was low along the banks deep in the sulci. Beneath the electrode, neurons oriented perpendicular to the cortical surface were depolarized by anodic stimulation, and neurons oriented parallel to the boundary were depolarized by cathodic stimulation. Activation was localized to the crown of the gyrus, and neurons on the banks deep in the sulci were not polarized. During regulated voltage stimulation, the magnitude of the activating function was inversely proportional to the thickness of the CSF and dura. During regulated current stimulation, the activating function was not sensitive to the thickness of the dura but was slightly more sensitive than during regulated voltage stimulation to the thickness of the CSF. Varying the width of the gyrus and the position of the electrode altered the distribution of the activating function due to changes in the orientation of the neurons beneath the electrode. Bipolar stimulation, although often used in clinical practice, reduced spatial selectivity as well as selectivity for neuron orientation.

  13. Music acupuncture stimulation method.

    PubMed

    Brătilă, F; Moldovan, C

    2007-01-01

    Harmonic Medicine is the model using the theory that the body rhythms synchronize to an outer rhythm applied for therapeutic purpose, can restores the energy balance in acupuncture channels and organs and the condition of well-being. The purpose of this scientific work was to demonstrate the role played by harmonic sounds in the stimulation of the Lung (LU) Meridian (Shoutaiyin Feijing) and of the Kidney (KI) Meridian (Zushaoyin Shenjing). It was used an original method that included: measurement and electronic sound stimulation of the Meridian Entry Point, measurement of Meridian Exit Point, computer data processing, bio feed-back adjustment of the music stimulation parameters. After data processing, it was found that the sound stimulation of the Lung Meridian Frequency is optimal between 122 Hz and 128 Hz, with an average of 124 Hz (87% of the subjects) and for Kidney Meridian from 118 Hz to 121 Hz, with an average of 120 Hz (67% of the subjects). The acupuncture stimulation was more intense for female subjects (> 7%) than for the male ones. We preliminarily consider that an informational resonance phenomenon can be developed between the acupuncture music stimulation frequency and the cellular dipole frequency, being a really "resonant frequency signature" of an acupoint. The harmonic generation and the electronic excitation or low-excitation status of an acupuncture point may be considered as a resonance mechanism. By this kind of acupunctural stimulation, a symphony may act and play a healer role.

  14. Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach.

    PubMed

    Karamintziou, Sofia D; Custódio, Ana Luísa; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stéphan; Stathis, Pantelis G; Tagaris, George A; Sakas, Damianos E; Polychronaki, Georgia E; Tsirogiannis, George L; David, Olivier; Nikita, Konstantina S

    2017-01-01

    Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson's disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications.

  15. Subthalamic nucleus stimulation influences expression and suppression of impulsive behaviour in Parkinson’s disease

    PubMed Central

    Ridderinkhof, K. Richard; Elias, William J.; Frysinger, Robert C.; Bashore, Theodore R.; Downs, Kara E.; van Wouwe, Nelleke C.; van den Wildenberg, Wery P. M.

    2010-01-01

    Past studies show beneficial as well as detrimental effects of subthalamic nucleus deep-brain stimulation on impulsive behaviour. We address this paradox by investigating individuals with Parkinson’s disease treated with subthalamic nucleus stimulation (n = 17) and healthy controls without Parkinson’s disease (n = 17) on performance in a Simon task. In this reaction time task, conflict between premature response impulses and goal-directed action selection is manipulated. We applied distributional analytic methods to separate the strength of the initial response impulse from the proficiency of inhibitory control engaged subsequently to suppress the impulse. Patients with Parkinson’s disease were tested when stimulation was either turned on or off. Mean conflict interference effects did not differ between controls and patients, or within patients when stimulation was on versus off. In contrast, distributional analyses revealed two dissociable effects of subthalamic nucleus stimulation. Fast response errors indicated that stimulation increased impulsive, premature responding in high conflict situations. Later in the reaction process, however, stimulation improved the proficiency with which inhibitory control was engaged to suppress these impulses selectively, thereby facilitating selection of the correct action. This temporal dissociation supports a conceptual framework for resolving past paradoxical findings and further highlights that dynamic aspects of impulse and inhibitory control underlying goal-directed behaviour rely in part on neural circuitry inclusive of the subthalamic nucleus. PMID:20861152

  16. Should luteal phase support be introduced in ovarian stimulation/IUI programmes? An evidence-based review.

    PubMed

    Cohlen, B J

    2009-01-01

    World-wide, intrauterine insemination (IUI) is still one of the most applied techniques to enhance the probability of conception in couples with longstanding subfertility. The outcome of this treatment option depends on many confounding factors. One of the confounding factors receiving little attention is the quality of the luteal phase. From IVF studies, it is known that ovarian stimulation causes luteal phase deficiency. Based on the best available evidence, this short review summarizes the indications for mild ovarian stimulation combined with IUI and the optimal stimulation programme. While it has been established that stimulated IVF/intracytoplasmic sperm injection cycles have deficient luteal phases, the question remains whether the quality of the luteal phase when only two or three corpora lutea are present (as is the case in stimulated IUI cycles) is impaired as well. There are too few large non-IVF trials studying luteal phase quality to answer this question. Recently a randomized trial has been published that investigated luteal phase support in an IUI programme. This study is discussed in detail. It is recommended to apply luteal phase support in stimulated IUI cycles only when proven costeffective. Further trials are mandatory to investigate both endometrial and hormonal profile changes in the luteal phase after mild ovarian stimulation, and the cost-effectiveness of luteal support in IUI programmes.

  17. Changing Brain Networks Through Non-invasive Neuromodulation.

    PubMed

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

    2018-01-01

    Background/Objective : Non-invasive neuromodulation techniques, such as repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), have increasingly been investigated for their potential as treatments for neurological and psychiatric disorders. Despite widespread dissemination of these techniques, the underlying therapeutic mechanisms and the ideal stimulation site for a given disorder remain unknown. Increasing evidence support the possibility of non-invasive neuromodulation affecting a brain network rather than just the local stimulation target. In this article, we present evidence in a clinical setting to support the idea that non-invasive neuromodulation changes brain networks. Method : This article addresses the idea that non-invasive neuromodulation modulates brain networks, rather than just the local stimulation target, using neuromodulation studies in tinnitus and major depression as examples. We present studies that support this hypothesis from different perspectives. Main Results/Conclusion : Studies stimulating the same brain region, such as the dorsolateral prefrontal cortex (DLPFC), have shown to be effective for several disorders and studies using different stimulation sites for the same disorder have shown similar results. These findings, as well as results from studies investigating brain network connectivity on both macro and micro levels, suggest that non-invasive neuromodulation affects a brain network rather than just the local stimulation site targeted. We propose that non-invasive neuromodulation should be approached from a network perspective and emphasize the therapeutic potential of this approach through the modulation of targeted brain networks.

  18. Technique of electrical stimulation of the vestibular analyzer under clinical conditions

    NASA Technical Reports Server (NTRS)

    Khechinashvili, S. N.; Zargaryan, B. M.; Karakozov, K. G.

    1980-01-01

    Vestibular reactions appear under the action of direct current (dc) on the labyrinth of man and animals. A decrease of the stimulation effect of dc on the extralabyrinthine nervous formations in the suggested method is achieved by the use of electric pulses with steep front and back parts, as well as by previous anesthetization of the skin in the electrode application area by means of novocain solution electrophoresis. For this purpose a pulse producer giving trapezoid pulses with smoothly changing fronts and duration was constructed. With the help of an interrupter it is possible to stop the current increase instantly, and stimulation is performed at the level of the pulse 'plateau'. To induce vestibular reactions under monopolar stimulation, it is necessary to apply the current twice as high as that with bipolar electrode position. The use of short pulses with steep front and back parts for electrode stimulation of the vestibular analyzer is considered to be inexpedient.

  19. A dense array stimulator to generate arbitrary spatio-temporal tactile stimuli

    PubMed Central

    Killebrew, Justin H.; Bensmaïa, Sliman J.; Dammann, John F.; Denchev, Peter; Hsiao, Steven S.; Craig, James C.

    2007-01-01

    The generation and presentation of tactile stimuli presents a unique challenge. Unlike vision and audition, in which standard equipment such as monitors and audio systems can be used for most experiments, tactile stimuli and/or stimulators often have to be tailor-made for a given study. Here, we present a novel tactile stimulator designed to present arbitrary spatio-temporal stimuli to the skin. The stimulator consists of 400 pins, arrayed over a 1 cm2 area, each under independent computer control. The dense array allows for an unprecedented number of stimuli to be presented within an experimental session (e.g., up to 1200 stimuli per minute) and for stimuli to be generated adaptively. The stimulator can be used in a variety of modes and can deliver indented and scanned patterns as well as stimuli defined by mathematical spatio-temporal functions (e.g., drifting sinusoids). We describe the hardware and software of the system, and discuss previous and prospective applications. PMID:17134760

  20. Understanding the effects of stimulant medications on cognition in individuals with attention-deficit hyperactivity disorder: a decade of progress.

    PubMed

    Swanson, James; Baler, Ruben D; Volkow, Nora D

    2011-01-01

    The use of stimulant drugs for the treatment of children with attention-deficit hyperactivity disorder (ADHD) is one of the most widespread pharmacological interventions in child psychiatry and behavioral pediatrics. This treatment is well grounded on controlled studies showing efficacy of low oral doses of methylphenidate and amphetamine in reducing the behavioral symptoms of the disorder as reported by parents and teachers, both for the cognitive (inattention and impulsivity) and non-cognitive (hyperactivity) domains. Our main aim is to review the objectively measured cognitive effects that accompany the subjectively assessed clinical responses to stimulant medications. Recently, methods from the cognitive neurosciences have been used to provide information about brain processes that underlie the cognitive deficits of ADHD and the cognitive effects of stimulant medications. We will review some key findings from the recent literature, and then offer interpretations of the progress that has been made over the past decade in understanding the cognitive effects of stimulant medication on individuals with ADHD.

  1. Severe avoidant/restrictive food intake disorder and coexisting stimulant treated attention deficit hyperactivity disorder.

    PubMed

    Pennell, Alexandra; Couturier, Jennifer; Grant, Christina; Johnson, Natasha

    2016-11-01

    There is a growing body of literature describing the development, clinical course, and treatment of avoidant/restrictive food intake disorder (ARFID), a diagnostic category introduced in the DSM-5. However, information surrounding complex cases of ARFID involving coexisting medical and/or psychiatric disorders remains scarce. Here we report on two cases of young patients diagnosed concurrently with ARFID and attention deficit hyperactivity disorder (ADHD) who both experienced significant growth restriction following initiation of stimulant medication. The appetite suppressant effect of stimulants exacerbated longstanding avoidant and restrictive eating behaviors resulting in growth restriction and admission to an inpatient eating disorders unit. The implications of ARFID exacerbated by stimulant-treated ADHD are explored, as well as the treatment delivered. These cases suggest that further research is needed to explore management options to counteract the appetite suppression effects of stimulants, while simultaneously addressing attention deficit symptoms and oppositional behavior. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1036-1039). © 2016 Wiley Periodicals, Inc.

  2. The effect of stimulus frequency on the analgesic response to percutaneous electrical nerve stimulation in patients with chronic low back pain.

    PubMed

    Ghoname, E S; Craig, W F; White, P F; Ahmed, H E; Hamza, M A; Gajraj, N M; Vakharia, A S; Noe, C E

    1999-04-01

    Low back pain (LBP) is one of the most common medical problems in our society. Increasingly, patients are turning to nonpharmacologic analgesic therapies such as percutaneous electrical nerve stimulation (PENS). We designed this sham-controlled study to compare the effect of three different frequencies of electrical stimulation on the analgesic response to PENS therapy. Sixty-eight consenting patients with LBP secondary to degenerative lumbar disc disease were treated with PENS therapy at 4 Hz, alternating 15 Hz and 30 Hz (15/30 Hz), and 100 Hz, as well as sham-PENS (0 Hz), according to a randomized, cross-over study design. Each treatment was administered for a period of 30 min three times per week for 2 wk. The pre- and posttreatment assessments included the health status survey short form and visual analog scales for pain, physical activity, and quality of sleep. After receiving all four treatments, patients completed a global assessment questionnaire. The sham-PENS treatments failed to produce changes in the degree of pain, physical activity, sleep quality, or daily intake of oral analgesic medications. In contrast, 4-Hz, 15/30-Hz, and 100-Hz stimulation all produced significant decreases in the severity of pain, increases in physical activity, improvements in the quality of sleep, and decreases in oral analgesic requirements (P < 0.01). Of the three frequencies, 15/30 Hz was the most effective in decreasing pain, increasing physical activity, and improving the quality of sleep (P < 0.05). In the global assessment, 40% of the patients reported that 15/30 Hz was the most desirable therapy, and it was also more effective in improving the patient's sense of well-being. We conclude that the frequency of electrical stimulation is an important determinant of the analgesic response to PENS therapy. Alternating stimulation at 15-Hz and 30-Hz frequencies was more effective than either 4 Hz or 100 Hz in improving outcome measures in patients with LBP. The frequency of electrical stimulation seems to be an important determinant of the analgesic efficacy of percutaneous electrical nerve stimulation. Mixed low- and high-frequency stimulation was more effective than either low or high frequencies alone in the treatment of patients with low back pain.

  3. Neuromuscular electrical stimulation prior to presleep protein feeding stimulates the use of protein-derived amino acids for overnight muscle protein synthesis.

    PubMed

    Dirks, Marlou L; Groen, Bart B L; Franssen, Rinske; van Kranenburg, Janneau; van Loon, Luc J C

    2017-01-01

    Short periods of muscle disuse result in substantial skeletal muscle atrophy. Recently, we showed that both neuromuscular electrical stimulation (NMES) as well as presleep dietary protein ingestion represent effective strategies to stimulate muscle protein synthesis rates. In this study, we test our hypothesis that NMES can augment the use of presleep protein-derived amino acids for overnight muscle protein synthesis in older men. Twenty healthy, older [69 ± 1 (SE) yr] men were subjected to 24 h of bed rest, starting at 8:00 AM. In the evening, volunteers were subjected to 70-min 1-legged NMES, while the other leg served as nonstimulated control (CON). Immediately following NMES, 40 g of intrinsically l-[1- 13 C]-phenylalanine labeled protein was ingested prior to sleep. Blood samples were taken throughout the night, and muscle biopsies were obtained from both legs in the evening and the following morning (8 h after protein ingestion) to assess dietary protein-derived l-[1- 13 C]-phenylalanine enrichments in myofibrillar protein. Plasma phenylalanine concentrations and plasma l-[1- 13 C]-phenylalanine enrichments increased significantly following protein ingestion and remained elevated for up to 6 h after protein ingestion (P < 0.05). During overnight sleep, myofibrillar protein-bound l-[1- 13 C]-phenylalanine enrichments (MPE) increased to a greater extent in the stimulated compared with the control leg (0.0344 ± 0.0019 vs. 0.0297 ± 0.0016 MPE, respectively; P < 0.01), representing 18 ± 6% greater incorporation of presleep protein-derived amino acids in the NMES compared with CON leg. In conclusion, application of NMES prior to presleep protein feeding stimulates the use of dietary protein-derived amino acids for overnight muscle protein synthesis in older men. Neuromuscular electrical stimulation (NMES) as well as presleep dietary protein ingestion represent effective strategies to stimulate muscle protein synthesis rates. Here we demonstrate that in older men after a day of bed rest, the application of NMES prior to presleep protein feeding stimulates the use of dietary protein-derived amino acids for overnight muscle protein synthesis by 18% compared with presleep protein feeding only. Copyright © 2017 the American Physiological Society.

  4. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials

    PubMed Central

    Hutton, Brian; Núñez-Beltrán, Amparo; Page, Matthew J.; Ridao, Manuel; Macías Saint-Gerons, Diego; Catalá, Miguel A.; Tabarés-Seisdedos, Rafael; Moher, David

    2017-01-01

    Background Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents. Methods and findings We performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants and their combination showed the best profile of acceptability. Stimulants and non-stimulants seemed well tolerated. Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and clonidine seemed significantly more efficacious than placebo. Methylphenidate and amphetamine seemed more efficacious than atomoxetine and guanfacine. Methylphenidate and clonidine seemed better accepted than placebo and atomoxetine. Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed. There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine. Overall findings were limited by the clinical and methodological heterogeneity, small sample sizes of trials, short-term follow-up, and the absence of high-quality evidence; consequently, results should be interpreted with caution. Conclusions Clinical differences may exist between the pharmacological and non-pharmacological treatment used for the management of ADHD. Uncertainties about therapies and the balance between benefits, costs and potential harms should be considered before starting treatment. There is an urgent need for high-quality randomised trials of the multiple treatments for ADHD in children and adolescents. PROSPERO, number CRD42014015008. PMID:28700715

  5. The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials.

    PubMed

    Catalá-López, Ferrán; Hutton, Brian; Núñez-Beltrán, Amparo; Page, Matthew J; Ridao, Manuel; Macías Saint-Gerons, Diego; Catalá, Miguel A; Tabarés-Seisdedos, Rafael; Moher, David

    2017-01-01

    Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents. We performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants and their combination showed the best profile of acceptability. Stimulants and non-stimulants seemed well tolerated. Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and clonidine seemed significantly more efficacious than placebo. Methylphenidate and amphetamine seemed more efficacious than atomoxetine and guanfacine. Methylphenidate and clonidine seemed better accepted than placebo and atomoxetine. Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed. There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine. Overall findings were limited by the clinical and methodological heterogeneity, small sample sizes of trials, short-term follow-up, and the absence of high-quality evidence; consequently, results should be interpreted with caution. Clinical differences may exist between the pharmacological and non-pharmacological treatment used for the management of ADHD. Uncertainties about therapies and the balance between benefits, costs and potential harms should be considered before starting treatment. There is an urgent need for high-quality randomised trials of the multiple treatments for ADHD in children and adolescents. PROSPERO, number CRD42014015008.

  6. Network effects of deep brain stimulation

    PubMed Central

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

    2015-01-01

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

  7. Brown adipose tissue responds to cold and adrenergic stimulation by induction of FGF21.

    PubMed

    Chartoumpekis, Dionysios V; Habeos, Ioannis G; Ziros, Panos G; Psyrogiannis, Agathoklis I; Kyriazopoulou, Venetsana E; Papavassiliou, Athanasios G

    2011-01-01

    Fibroblast growth factor-21 (FGF21) is a pleiotropic protein involved in glucose, lipid metabolism and energy homeostasis, with main tissues of expression being the liver and adipose tissue. Brown adipose tissue (BAT) is responsible for cold-induced thermogenesis in rodents. The role of FGF21 in BAT biology has not been investigated. In the present study, wild-type C57BL/6J mice as well as a brown adipocyte cell line were used to explore the potential role of cold exposure and β3-adrenergic stimulation in the expression of FGF21 in BAT. Our results demonstrate that short-term exposure to cold, as well as β3-adrenergic stimulation, causes a significant induction of FGF21 mRNA levels in BAT, without a concomitant increase in FGF21 plasma levels. This finding opens new routes for the potential use of pharmaceuticals that could induce FGF21 and, hence, activate BAT thermogenesis.

  8. Economic impact of ovarian stimulation with corifollitropin alfa versus conventional daily gonadotropins in oocyte donors: a randomized study.

    PubMed

    Cruz, María; Alamá, Pilar; Muñoz, Manuel; Collado, Diana; Blanes, Carlos; Solbes, Enrique; Requena, Antonio

    2017-06-01

    Assisted reproductive technologies are well-established treatments for many types of subfertility representing substantial economic and healthcare implications for patients, healthcare providers and society as a whole. In order to optimize outcomes according to the type of gonadotrophins within an oocyte donor programme, we performed an economic evaluation based on data collected in a multicentre, prospective, randomized study within three private clinics belonging to the IVI Group. Results showed no relevant between-group differences in the clinical variables. According to the economic analysis, ovarian stimulation with corifollitropin alfa increased the overall cost of the treatment as well as the cost per retrieved and effective oocyte, although the differences were not statistically significant. In conclusion, cost savings can be achieved using cheaper gonadotrophins during ovarian stimulation. The cost of corifollitropin alfa compared with recombinant FSH and highly purified human menopausal gonadotrophin should be considered when making treatment decisions. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  9. Bacterial community diversity in a low-permeability oil reservoir and its potential for enhancing oil recovery.

    PubMed

    Xiao, Meng; Zhang, Zhong-Zhi; Wang, Jing-Xiu; Zhang, Guang-Qing; Luo, Yi-Jing; Song, Zhao-Zheng; Zhang, Ji-Yuan

    2013-11-01

    The diversity of indigenous bacterial community and the functional species in the water samples from three production wells of a low permeability oil reservoir was investigated by high-throughput sequencing technology. The potential of application of indigenous bacteria for enhancing oil recovery was evaluated by examination of the effect of bacterial stimulation on the formation water-oil-rock surface interactions and micromodel test. The results showed that production well 88-122 had the most diverse bacterial community and functional species. The broth of indigenous bacteria stimulated by an organic nutrient activator at aerobic condition changed the wettability of the rock surface from oil-wet to water-wet. Micromodel test results showed that flooding using stimulated indigenous bacteria following water flooding improved oil recovery by 6.9% and 7.7% in fractured and unfractured micromodels, respectively. Therefore, the zone of low permeability reservoir has a great potential for indigenous microbial enhanced oil recovery. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Deep Brain Stimulation of the Memory Circuit: Improving Cognition in Alzheimer's Disease.

    PubMed

    Posporelis, Sotirios; David, Anthony S; Ashkan, Keyoumars; Shotbolt, Paul

    2018-05-26

    Deep brain stimulation (DBS) is an effective invasive treatment for a wide range of neurological and psychiatric disorders. Neurosurgically implanted electrodes deliver stimulation of pre-programmed amplitude, frequency, and pulse width within deep brain structures; those settings can be adjusted at a later stage according to individual needs for optimal response. This results in variable effects dependent on the targeted region. An established treatment for movement disorders, the effectiveness of DBS in dementia remains under investigation. Translational studies have uncovered a pro-cognitive effect mediated by changes on cellular as well as network level. Several groups have attempted to examine the benefits of DBS in Alzheimer's disease; differences in inclusion criteria and methodology make generalization of results difficult. This review aims to summarize all completed and ongoing human studies of DBS in Alzheimer's disease. The results are classified by targeted anatomical structure. Future directions, as well as economical and ethical arguments, are explored in the final section.

  11. Neuropathic Pain Causes Pyramidal Neuronal Hyperactivity in the Anterior Cingulate Cortex.

    PubMed

    Zhao, Ruohe; Zhou, Hang; Huang, Lianyan; Xie, Zhongcong; Wang, Jing; Gan, Wen-Biao; Yang, Guang

    2018-01-01

    The anterior cingulate cortex (ACC) is thought to be important for acute pain perception as well as the development of chronic pain after peripheral nerve injury. Nevertheless, how ACC neurons respond to sensory stimulation under chronic pain states is not well understood. Here, we used an in vivo two-photon imaging technique to monitor the activity of individual neurons in the ACC of awake, head restrained mice. Calcium imaging in the dorsal ACC revealed robust somatic activity in layer 5 (L5) pyramidal neurons in response to peripheral noxious stimuli, and the degree of evoked activity was correlated with the intensity of noxious stimulation. Furthermore, the activation of ACC neurons occurred bilaterally upon noxious stimulation to either contralateral or ipsilateral hind paws. Notably, with nerve injury-induced neuropathic pain in one limb, L5 pyramidal neurons in both sides of the ACC showed enhanced activity in the absence or presence of pain stimuli. These results reveal hyperactivity of L5 pyramidal neurons in the bilateral ACC during the development of neuropathic pain.

  12. Effects of hydrocortisone treatment and whole-body irradiation on mouse lymphocyte stimulation in vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ruehl, H.; Vogt, W.; Ruehl, U.

    Whole-body gamma irradiation was found to reduce the number of nucleated cells in the thymus and the spleen of C57B1 mice to the same extent as hydrocortisone treatment. Equal numbers of thymus and spleen cells from either hydrocortisone-treated or irradiated e cultured and stimulated with various mitogens. An increased stimulation of DNA synthesis by PHA. Con A, and PWM was found in thymus and spleen cells after hydrocortisone treatment as well as after whole-body irradiation. In contrast, the response to LPS, known as a typical B- cell mitogen, was not affected by any of the procedures. (auth)

  13. The effect of optokinetic stimulation on daytime sleepiness

    NASA Technical Reports Server (NTRS)

    Leslie, K. R.; Stickgold, R.; Dizio, P.; Lackner, J. R.; Hobson, J. A.

    1997-01-01

    This study examined the effect of optokinetic stimulation on objective sleepiness, as measured by the Multiple Sleep Latency Test (MSLT). The Nightcap, a portable sleep monitor, was used in a novel way to perform MSLTs, as well as record sleep in the home. Subjects wore the Nightcap for seven consecutive nights. On days 3 and 5 of the protocol, subjects came into the lab for an MSLT. On the experimental day, subjects underwent 10 minutes optokinetic stimulation (OKS), resulting in moderate motion sickness prior to each MSLT trial. Although subjects in the OKS condition reported significantly more drowsiness than controls, this did not result in significantly reduced sleep latencies.

  14. Enhancement by oxotremorine of acetylcholine release from the rat phrenic nerve.

    PubMed Central

    Das, M; Ganguly, D K; Vedasiromoni, J R

    1978-01-01

    Oxotremorine (10.5 micron) produced a paralytic effect on twitch responses of rat diaphragm in vitro to direct and indirect stimulation. 2 The paralytic effect of oxotremorine was absent when the diaphragm was stimulated directly in the presence of hemicholinium-3 (0.42 mM), at a time when twitch responses to indirect stimulation ceased completely. 3 Oxotremorine, at two different pharmacologically active doses, strikingly increased the resting as well as electrically evoked release of acetylcholine into the bathing fluid from the phrenic nerve-diaphragm preparation. 4 This presynaptic effect of oxotremorine may explain its pharmacological effects at the cholinergic synapses studied so far. PMID:203356

  15. Highly specific detection of H2O2-dependent luminol chemiluminescence in stimulated human leukocytes using polyvinyl films.

    PubMed

    Moriguchi, K; Ohno, N; Ogawa, T; Hirai, K

    1999-01-01

    When human polymorphonuclear leukocytes (PMN) were attached to glass coverslips, cells always spread and formed reactive oxygen species prior to any experimental stimulation. To avoid this, a polyvinylidine chloride film was used as an inactive substance to place the cells. Cells engaged in phagocytosis on the film exhibited a specific H2O2-mediated luminol chemiluminescence (LCL) at the cell-particle interface; the cells stimulated with 12-O-tetradecanoylphorbol-13-acetate became aggregated and the LCL was observed at the cell-cell contact. These results corresponded well with those obtained by an electron microscopic H2O2-demonstration method.

  16. Precision rodent whisker stimulator with integrated servo-locked control and displacement measurement.

    PubMed

    Walker, Jennifer L; Monjaraz-Fuentes, Fernanda; Pedrow, Christi R; Rector, David M

    2011-03-15

    We developed a high speed voice coil based whisker stimulator that delivers precise deflections of a single whisker or group of whiskers in a repeatable manner. The device is miniature, quiet, and inexpensive to build. Multiple stimulators fit together for independent stimulation of four or more whiskers. The system can be used with animals under anesthesia as well as awake animals with head-restraint, and does not require trimming the whiskers. The system can deliver 1-2 mm deflections in 2 ms resulting in velocities up to 900 mm/s to attain a wide range of evoked responses. Since auditory artifacts can influence behavioral studies using whisker stimulation, we tested potential effects of auditory noise by recording somatosensory evoked potentials (SEP) with varying auditory click levels, and with/without 80 dBa background white noise. We found that auditory clicks as low as 40 dBa significantly influence the SEP. With background white noise, auditory clicks as low as 50 dBa were still detected in components of the SEP. For behavioral studies where animals must learn to respond to whisker stimulation, these sounds must be minimized. Together, the stimulator and data system can be used for psychometric vigilance tasks, mapping of the barrel cortex and other electrophysiological paradigms. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Electrical stimulation in the treatment of pain.

    PubMed

    Rushton, David N

    2002-05-20

    To review the published literature concerning the treatment of painful conditions using devices that deliver electrical stimulation to nervous structures. The review briefly surveys the results obtained using surface electrodes ("TENS") as well as implanted devices. The method used is a critical review of the important published literature up to mid-1999. References were obtained using Medline and the keywords "pain", together with "electrical", "stimulation", "neurostimulation" or "TENS". Electrical stimulation has been found to be of potential benefit in the management of a range of painful conditions. Adequately controlled trials of electrical stimulation are often difficult to achieve. Implanted devices tend to be used in the more severe intractable pain conditions. It is likely that there is more than one mechanism of action. The mechanisms of action are however still often poorly understood, even though historically theoretical and experimental advances in the understanding of pain mechanisms prompted the development of clinical systems and the institution of clinical studies. TENS has proved to be remarkably safe, and provides significant analgesia in about half of patients experiencing moderate predictable pain. Implanted devices can be more effective, but they carry a risk of device failure, implant infection or surgical complication, and are reserved for the more severe intractable chronic pains. The main implanted devices used clinically are the spinal cord stimulator and the deep brain stimulator.

  18. Antidromic propagation of action potentials in branched axons: implications for the mechanisms of action of deep brain stimulation.

    PubMed

    Grill, Warren M; Cantrell, Meredith B; Robertson, Matthew S

    2008-02-01

    Electrical stimulation of the central nervous system creates both orthodromically propagating action potentials, by stimulation of local cells and passing axons, and antidromically propagating action potentials, by stimulation of presynaptic axons and terminals. Our aim was to understand how antidromic action potentials navigate through complex arborizations, such as those of thalamic and basal ganglia afferents-sites of electrical activation during deep brain stimulation. We developed computational models to study the propagation of antidromic action potentials past the bifurcation in branched axons. In both unmyelinated and myelinated branched axons, when the diameters of each axon branch remained under a specific threshold (set by the antidromic geometric ratio), antidromic propagation occurred robustly; action potentials traveled both antidromically into the primary segment as well as "re-orthodromically" into the terminal secondary segment. Propagation occurred across a broad range of stimulation frequencies, axon segment geometries, and concentrations of extracellular potassium, but was strongly dependent on the geometry of the node of Ranvier at the axonal bifurcation. Thus, antidromic activation of axon terminals can, through axon collaterals, lead to widespread activation or inhibition of targets remote from the site of stimulation. These effects should be included when interpreting the results of functional imaging or evoked potential studies on the mechanisms of action of DBS.

  19. Acoustic Events and “Optophonic” Cochlear Responses Induced by Pulsed Near-Infrared LASER

    PubMed Central

    Maier, Hannes; Richter, Claus-Peter; Kral, Andrej

    2012-01-01

    Optical stimulation of neural tissue within the cochlea was described as a possible alternative to electrical stimulation. Most optical stimulation was performed with pulsed lasers operating with near-infrared (NIR) light and in thermal confinement. Under these conditions, the coexistence of laser-induced optoacoustic stimulation of the cochlea (“optophony”) has not been analyzed yet. This study demonstrates that pulsed 1850-nm laser light used for neural stimulation also results in sound pressure levels up to 62 dB peak-to-peak equivalent sound pressure level (SPL) in air. The sound field was confined to a small volume along the laser beam. In dry nitrogen, laser-induced acoustic events disappeared. Hydrophone measurements demonstrated pressure waves for laser fibers immersed in water. In hearing rats, laser-evoked signals were recorded from the cochlea without targeting neural tissue. The signals showed a two-domain response differing in amplitude and latency functions, as well as sensitivity to white-noise masking. The first component had characteristics of a cochlear microphonic potential, and the second component was characteristic for a compound action potential. The present data demonstrate that laser-evoked acoustic events can stimulate a hearing cochlea. Whenever optical stimulation is used, care must be taken to distinguish between such “optophony” and the true optoneural response. PMID:21278011

  20. Visual cortex responses reflect temporal structure of continuous quasi-rhythmic sensory stimulation.

    PubMed

    Keitel, Christian; Thut, Gregor; Gross, Joachim

    2017-02-01

    Neural processing of dynamic continuous visual input, and cognitive influences thereon, are frequently studied in paradigms employing strictly rhythmic stimulation. However, the temporal structure of natural stimuli is hardly ever fully rhythmic but possesses certain spectral bandwidths (e.g. lip movements in speech, gestures). Examining periodic brain responses elicited by strictly rhythmic stimulation might thus represent ideal, yet isolated cases. Here, we tested how the visual system reflects quasi-rhythmic stimulation with frequencies continuously varying within ranges of classical theta (4-7Hz), alpha (8-13Hz) and beta bands (14-20Hz) using EEG. Our findings substantiate a systematic and sustained neural phase-locking to stimulation in all three frequency ranges. Further, we found that allocation of spatial attention enhances EEG-stimulus locking to theta- and alpha-band stimulation. Our results bridge recent findings regarding phase locking ("entrainment") to quasi-rhythmic visual input and "frequency-tagging" experiments employing strictly rhythmic stimulation. We propose that sustained EEG-stimulus locking can be considered as a continuous neural signature of processing dynamic sensory input in early visual cortices. Accordingly, EEG-stimulus locking serves to trace the temporal evolution of rhythmic as well as quasi-rhythmic visual input and is subject to attentional bias. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Short pauses in thalamic deep brain stimulation promote tremor and neuronal bursting.

    PubMed

    Swan, Brandon D; Brocker, David T; Hilliard, Justin D; Tatter, Stephen B; Gross, Robert E; Turner, Dennis A; Grill, Warren M

    2016-02-01

    We conducted intraoperative measurements of tremor during DBS containing short pauses (⩽50 ms) to determine if there is a minimum pause duration that preserves tremor suppression. Nine subjects with ET and thalamic DBS participated during IPG replacement surgery. Patterns of DBS included regular 130 Hz stimulation interrupted by 0, 15, 25 or 50 ms pauses. The same patterns were applied to a model of the thalamic network to quantify effects of pauses on activity of model neurons. All patterns of DBS decreased tremor relative to 'off'. Patterns with pauses generated less tremor reduction than regular high frequency DBS. The model revealed that rhythmic burst-driver inputs to thalamus were masked during DBS, but pauses in stimulation allowed propagation of bursting activity. The mean firing rate of bursting-type model neurons as well as the firing pattern entropy of model neurons were both strongly correlated with tremor power across stimulation conditions. The temporal pattern of stimulation influences the efficacy of thalamic DBS. Pauses in stimulation resulted in decreased tremor suppression indicating that masking of pathological bursting is a mechanism of thalamic DBS for tremor. Pauses in stimulation decreased the efficacy of open-loop DBS for suppression of tremor. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Optimization of geothermal well trajectory in order to minimize borehole failure

    NASA Astrophysics Data System (ADS)

    Dahrabou, A.; Valley, B.; Ladner, F.; Guinot, F.; Meier, P.

    2017-12-01

    In projects based on Enhanced Geothermal System (EGS) principle, deep boreholes are drilled to low permeability rock masses. As part of the completion operations, the permeability of existing fractures in the rock mass is enhanced by injecting large volumes of water. These stimulation treatments aim at achieving enough water circulation for heat extraction at commercial rates which makes the stimulation operations critical to the project success. The accurate placement of the stimulation treatments requires well completion with effective zonal isolation, and wellbore stability is a prerequisite to all zonal isolation techniques, be it packer sealing or cement placement. In this project, a workflow allowing a fast decision-making process for selecting an optimal well trajectory for EGS projects is developed. In fact, the well is first drilled vertically then based on logging data which are costly (100 KCHF/day), the direction in which the strongly deviated borehole section will be drilled needs to be determined in order to optimize borehole stability and to intersect the highest number of fractures that are oriented favorably for stimulation. The workflow applies to crystalline rock and includes an uncertainty and risk assessment framework. An initial sensitivity study was performed to identify the most influential parameters on borehole stability. The main challenge in these analyses is that the strength and stress profiles are unknown independently. Calibration of a geomechanical model on the observed borehole failure has been performed using data from the Basel Geothermal well BS-1. In a first approximation, a purely elastic-static analytical solution in combination with a purely cohesive failure criterion were used as it provides the most consistent prediction across failure indicators. A systematic analysis of the uncertainty on all parameters was performed to assess the reliability of the optimal trajectory selection. To each drilling scenario, failure probability and the associated risks, are computed stochastically. In addition, model uncertainty is assessed by confronting various failure modelling approaches to the available failure data from the Basel Project. Together, these results form the basis of an integrated workflow optimizing geothermal (EGS) well trajectory.

  3. Electronic approaches to restoration of sight

    NASA Astrophysics Data System (ADS)

    Goetz, G. A.; Palanker, D. V.

    2016-09-01

    Retinal prostheses are a promising means for restoring sight to patients blinded by the gradual atrophy of photoreceptors due to retinal degeneration. They are designed to reintroduce information into the visual system by electrically stimulating surviving neurons in the retina. This review outlines the concepts and technologies behind two major approaches to retinal prosthetics: epiretinal and subretinal. We describe how the visual system responds to electrical stimulation. We highlight major differences between direct encoding of the retinal output with epiretinal stimulation, and network-mediated response with subretinal stimulation. We summarize results of pre-clinical evaluation of prosthetic visual functions in- and ex vivo, as well as the outcomes of current clinical trials of various retinal implants. We also briefly review alternative, non-electronic, approaches to restoration of sight to the blind, and conclude by suggesting some perspectives for future advancement in the field.

  4. Electronic Approaches to Restoration of Sight

    PubMed Central

    Goetz, G A; Palanker, D V

    2016-01-01

    Retinal prostheses are a promising means for restoring sight to patients blinded by the gradual atrophy of photoreceptors due to retinal degeneration. They are designed to reintroduce information into the visual system by electrically stimulating surviving neurons in the retina. This review outlines the concepts and technologies behind two major approaches to retinal prosthetics: epiretinal and subretinal. We describe how the visual system responds to electrical stimulation. We highlight major differences between direct encoding of the retinal output with epiretinal stimulation, and network-mediated response with subretinal stimulation. We summarize results of pre-clinical evaluation of prosthetic visual functions in- and ex-vivo, as well as the outcomes of current clinical trials of various retinal implants. We also briefly review alternative, non-electronic, approaches to restoration of sight to the blind, and conclude by suggesting some perspectives for future advancement in the field. PMID:27502748

  5. Pharyngeal dysesthesia in refractory complex partial epilepsy: new seizure or adverse effect of vagal nerve stimulation?

    PubMed

    Akman, Cigdem; Riviello, James J; Madsen, Joseph R; Bergin, Ann M

    2003-06-01

    Sensory symptoms are commonly seen in association with focal epilepsy, but viscerosensory auras, such as pharyngeal dysesthesias, are rarely the main clinical manifestation. With the introduction of vagal nerve stimulation (VNS) for medically refractory epilepsy, viscerosensory symptoms commonly occur as an adverse effect of VNS. Voice alterations (hoarseness or tremulousness), local neck or throat pain, and cough are the most common adverse effects seen during active stimulation (on-time). Numbness of the throat, neck, or chin, as well as a tingling sensation of the neck and throat is directly related to stimulation intensity. We present a case in which recurrent pharyngeal sensations caused a diagnostic dilemma and in which monitoring the VNS artifact during video/EEG and correlating this with clinical symptoms helped determine the etiology of the recurrent sensory symptoms.

  6. Effect of Variation in the Burst Mode and Carrier Frequency of High Intensity Electrical Stimulation on Muscle Fatigue and Pain Perception of Healthy Subjects

    DTIC Science & Technology

    1988-10-22

    Soderlund, K. (1986). Biochemistry of muscle fatigue. Biomedica Brochimica Acta, 45, 97-106. Huskisson, E. C. (1983). Visual analogue scales. In R. Melzack...stimulation. IT 7-t -Hs53, Ui#4£sizy o3 Ktucy, Lexington, Kentucky. Luttgens, K. and Wells, K. F. (1933). Kinesiology (7th ed.). Philadelonia: Dryden Press

  7. Nonlinear dynamics, chaos and complex cardiac arrhythmias

    NASA Technical Reports Server (NTRS)

    Glass, L.; Courtemanche, M.; Shrier, A.; Goldberger, A. L.

    1987-01-01

    Periodic stimulation of a nonlinear cardiac oscillator in vitro gives rise to complex dynamics that is well described by one-dimensional finite difference equations. As stimulation parameters are varied, a large number of different phase-locked and chaotic rhythms is observed. Similar rhythms can be observed in the intact human heart when there is interaction between two pacemaker sites. Simplified models are analyzed, which show some correspondence to clinical observations.

  8. Recent Advances in Narrowband Stimulated Electromagnetic Emission NSEE Investigations at HAARP and EISCAT

    NASA Astrophysics Data System (ADS)

    Scales, Wayne

    2016-07-01

    Investigation of stimulated radiation, commonly known as Stimulated Electromagnetic Emissions (SEE), produced by the interaction of high-power, High Frequency HF radiowaves with the ionospheric plasma has been a vibrant area of research since the early 1980's. Substantial diagnostic information about ionospheric plasma characteristics, dynamics, and turbulence can be obtained from the frequency spectrum of the stimulated radiation. During the past several decades, so-called wideband SEE (WSEE) which exists in a frequency band of ±100 KHz or so of the transmit wave frequency (which is several MHz) has been investigated relatively thoroughly. Upgrades both in transmitter power and diagnostic receiver frequency sensitivity at major ionosphere interaction facilities (i.e. HAARP and EISCAT) have allowed new breakthroughs in the ability to study a plethora of processes associated with the ionospheric plasma during these active experiments. A primary advance is in observations of so-called narrowband SEE (NSEE) which exists roughly within ±1 kHz of the transmit wave frequency. NSEE investigation has opened the door for a potentially powerful tool for aeronomy investigations as well. An overview of several important new results associated with NSEE are discussed in this presentation, including observations, theory, computational modeling, as well as implications to new diagnostics of space plasma physics occurring during ionospheric interaction experiments.

  9. Effects of intermittent theta burst stimulation on spasticity after spinal cord injury.

    PubMed

    Nardone, Raffaele; Langthaler, Patrick B; Orioli, Andrea; Höller, Peter; Höller, Yvonne; Frey, Vanessa N; Brigo, Francesco; Trinka, Eugen

    2017-01-01

    Spasticity is a common disorder in patients with spinal cord injury (SCI). The aim of this study was to investigate whether intermittent theta burst stimulation (iTBS), a safe, non-invasive and well-tolerated protocol of excitatory repetitive transcranial magnetic stimulation (rTMS), is effective in modulating spasticity in SCI patients. In this randomized, double-blind, crossover, sham-controlled study, ten subjects with incomplete cervical or thoracic SCI received 10 days of daily sessions of real or sham iTBS. The H/M amplitude ratio of the Soleus H reflex, the amplitude of the motor evoked potentials (MEPs) at rest and during background contraction, as well as Modified Ashworth Scale (MAS) and the Spinal Cord Injury Assessment Tool for Spasticity (SCAT) were compared before and after the stimulation protocols. Patients receiving real iTBS showed significant increased resting and active MEPs amplitude and a significant reduction of the H/M amplitude ratio. In these patients also the MAS and SCAT scores were significantly reduced after treatment. These changes persisted up to 1 week after the end of the iTBS treatment, and were not observed under the sham-TBS condition. These findings suggest that iTBS may be a promising therapeutic tool for the spasticity in SCI patients.

  10. Molecular adjuvants based on nonpyrogenic lipophilic derivatives of norAbuMDP/GMDP formulated in nanoliposomes: stimulation of innate and adaptive immunity.

    PubMed

    Knotigová, Pavlína Turánek; Zyka, Daniel; Mašek, Josef; Kovalová, Anna; Křupka, Michal; Bartheldyová, Eliška; Kulich, Pavel; Koudelka, Štěpán; Lukáč, Róbert; Kauerová, Zuzana; Vacek, Antonín; Horynová, Milada Stuchlová; Kozubík, Alois; Miller, Andrew D; Fekete, Ladislav; Kratochvílová, Irena; Ježek, Jan; Ledvina, Miroslav; Raška, Milan; Turánek, Jaroslav

    2015-04-01

    The aim of this work was to demonstrate an immunostimulatory and adjuvant effect of new apyrogenic lipophilic derivatives of norAbuMDP and norAbuGMDP formulated in nanoliposomes. Nanoliposomes and metallochelating nanoliposomes were prepared by lipid film hydration and extrusion methods. The structure of the liposomal formulation was studied by electron microscopy, AF microscopy, and dynamic light scattering. Sublethal and lethal γ-irradiation mice models were used to demonstrate stimulation of innate immune system. Recombinant Hsp90 antigen (Candida albicans) bound onto metallochelating nanoliposomes was used for immunisation of mice to demonstrate adjuvant activities of tested compounds. Safety and stimulation of innate and adaptive immunity were demonstrated on rabbits and mice. The liposomal formulation of norAbuMDP/GMDP was apyrogenic in rabbit test and lacking any side effect in vivo. Recovery of bone marrow after sublethal γ-irradiation as well as increased survival of mice after lethal irradiation was demonstrated. Enhancement of specific immune response was demonstrated for some derivatives incorporated in metallochelating nanoliposomes with recombinant Hsp90 protein antigen. Liposomal formulations of new lipophilic derivatives of norAbuMDP/GMDP proved themselves as promising adjuvants for recombinant vaccines as well as immunomodulators for stimulation of innate immunity and bone-marrow recovery after chemo/radio therapy of cancer.

  11. Role of glycogenolysis in stimulation of ATP release from cultured mouse astrocytes by transmitters and high K+ concentrations.

    PubMed

    Xu, Junnan; Song, Dan; Bai, Qiufang; Zhou, Lijun; Cai, Liping; Hertz, Leif; Peng, Liang

    2014-01-13

    This study investigates the role of glycogenolysis in stimulated release of ATP as a transmitter from astrocytes. Within the last 20 years our understanding of brain glycogenolysis has changed from it being a relatively uninteresting process to being a driving force for essential brain functions like production of transmitter glutamate and homoeostasis of potassium ions (K+) after their release from excited neurons. Simultaneously, the importance of astrocytic handling of adenosine, its phosphorylation to ATP and release of some astrocytic ATP, located in vesicles, as an important transmitter has also become to be realized. Among the procedures stimulating Ca2+-dependent release of vesicular ATP are exposure to such transmitters as glutamate and adenosine, which raise intra-astrocytic Ca2+ concentration, or increase of extracellular K+ to a depolarizing level that opens astrocytic L-channels for Ca2+ and thereby also increase intra-astrocytic Ca2+ concentration, a prerequisite for glycogenolysis. The present study has confirmed and quantitated stimulated ATP release from well differentiated astrocyte cultures by glutamate, adenosine or elevated extracellular K+ concentrations, measured by a luciferin/luciferase reaction. It has also shown that this release is virtually abolished by an inhibitor of glycogenolysis as well as by inhibitors of transmitter-mediated signaling or of L-channel opening by elevated K+ concentrations.

  12. Bioglass promotes wound healing by affecting gap junction connexin 43 mediated endothelial cell behavior.

    PubMed

    Li, Haiyan; He, Jin; Yu, Hongfei; Green, Colin R; Chang, Jiang

    2016-04-01

    It is well known that gap junctions play an important role in wound healing, and bioactive glass (BG) has been shown to help healing when applied as a wound dressing. However, the effects of BG on gap junctional communication between cells involved in wound healing is not well understood. We hypothesized that BG may be able to affect gap junction mediated cell behavior to enhance wound healing. Therefore, we set out to investigate the effects of BG on gap junction related behavior of endothelial cells in order to elucidate the mechanisms through which BG is operating. In in vitro studies, BG ion extracts prevented death of human umbilical vein endothelial cells (HUVEC) following hypoxia in a dose dependent manner, possibly through connexin hemichannel modulation. In addition, BG showed stimulatory effects on gap junction communication between HUVECs and upregulated connexin43 (Cx43) expression. Furthermore, BG prompted expression of vascular endothelial growth factor and basic fibroblast growth factor as well as their receptors, and vascular endothelial cadherin in HUVECs, all of which are beneficial for vascularization. In vivo wound healing results showed that the wound closure of full-thickness excisional wounds of rats was accelerated by BG with reduced inflammation during initial stages of healing and stimulated angiogenesis during the proliferation stage. Therefore, BG can stimulate wound healing through affecting gap junctions and gap junction related endothelial cell behaviors, including prevention of endothelial cell death following hypoxia, stimulation of gap junction communication and upregulation of critical vascular growth factors, which contributes to the enhancement of angiogenesis in the wound bed and finally to accelerate wound healing. Although many studies have reported that BG stimulates angiogenesis and wound healing, this work reveals the relationship between BG and gap junction connexin 43 mediated endothelial cell behavior and elucidates one of the possible mechanisms through which BG stimulates wound healing. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Neuro-muscular transmission in blood vessels: phasic and tonic components. An in-vitro study of mesenteric arteries of the rat.

    PubMed

    Sjöblom-Widfeldt, N

    1990-01-01

    For many years noradrenaline was considered to be the exclusive transmitter released from sympathetic nerves. However, during recent years both ATP and NPY have been suggested to be co-transmitters to noradrenaline in these nerves. The present study aimed to investigate the functional relationship between these suggested transmitters during nerve stimulation with different frequencies and in different extracellular calcium concentrations. Also the importance of the pattern of nerve stimulation and the potentiation of the neurogenic response after a period of high-frequency nerve stimulation were investigated. Contractions caused by nerve stimulation and applied agonists were investigated in segments of small mesenteric arteries from rat. The biophysical, electrophysiological, and pharmacological properties of these vessels are well characterized in previous studies. The rapid contraction caused by a single nerve stimulus, the "single twitch", and the initial, phasic contraction caused by high-frequency nerve stimulation were only slightly affected by alpha-adrenoceptor blockade with prazosin, whereas the tonic response to high-frequency stimulation was markedly reduced. The phasic responses and those to low-frequency nerve stimulation thus appear to be due mainly to a non-adrenergic transmitter. After inhibiting the response to exogenous ATP by alpha beta-methylene ATP, the response to single impulses and to low-frequency nerve stimulation were markedly reduced, while those to high-frequency stimulation were unaffected. This suggests that ATP acts as a true transmitter in sympathetic nerves, being responsible mainly for rapid responses to low-frequency stimulation, and for the initial part of responses to high-frequency stimulation. When alpha beta-methylene ATP and prazosin were given in combination, no contraction was obtained during nerve stimulation at any frequency. However, if in this situation a contraction was induced by e.g. exogenous vasopressin, field stimulation caused a further, slow contraction. This additional response was undoubtedly neurogenic, but required high-frequency nerve stimulation. The response to nerve stimulation was found to be calcium-dependent, the calcium-dependency being more pronounced at low than at high stimulation frequencies. A continuous, high-frequency (8-16 Hz) nerve stimulation could greatly (5-15 fold) enhance the response to subsequent low-frequency nerve stimulation. This potentiation increased with the frequency of the conditioning stimulation and, within limits, with the number of impulses delivered. Also the extracellular calcium concentration during the conditioning stimulation determined the magnitude of the potentiation. This post-tetanic potentiation has many characteristics in common with the post-tetanic potentiation studied in the central and somatomotor nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)

  14. Modeling extracellular electrical stimulation: I. Derivation and interpretation of neurite equations.

    PubMed

    Meffin, Hamish; Tahayori, Bahman; Grayden, David B; Burkitt, Anthony N

    2012-12-01

    Neuroprosthetic devices, such as cochlear and retinal implants, work by directly stimulating neurons with extracellular electrodes. This is commonly modeled using the cable equation with an applied extracellular voltage. In this paper a framework for modeling extracellular electrical stimulation is presented. To this end, a cylindrical neurite with confined extracellular space in the subthreshold regime is modeled in three-dimensional space. Through cylindrical harmonic expansion of Laplace's equation, we derive the spatio-temporal equations governing different modes of stimulation, referred to as longitudinal and transverse modes, under types of boundary conditions. The longitudinal mode is described by the well-known cable equation, however, the transverse modes are described by a novel ordinary differential equation. For the longitudinal mode, we find that different electrotonic length constants apply under the two different boundary conditions. Equations connecting current density to voltage boundary conditions are derived that are used to calculate the trans-impedance of the neurite-plus-thin-extracellular-sheath. A detailed explanation on depolarization mechanisms and the dominant current pathway under different modes of stimulation is provided. The analytic results derived here enable the estimation of a neurite's membrane potential under extracellular stimulation, hence bypassing the heavy computational cost of using numerical methods.

  15. Intra-accumbens baclofen, but not muscimol, increases second order instrumental responding for food reward in rats.

    PubMed

    Pulman, Kim G T; Somerville, Elizabeth M; Clifton, Peter G

    2012-01-01

    Stimulation of either GABA(A) or GABA(B) receptors within the nucleus accumbens shell strongly enhances food intake in rats. However the effects of subtype-selective stimulation of GABA receptors on instrumental responses for food reward are less well characterized. Here we contrast the effects of the GABA(A) receptor agonist muscimol and GABA(B) receptor agonist baclofen on instrumental responding for food using a second order reinforcement schedule. Bilateral intra-accumbens administration of baclofen (220-440 pmol) stimulated responding but a higher dose (660 pmol) induced stereotyped oral behaviour that interfered with responding. Baclofen (220-660 pmol) also stimulated intake of freely available chow. Muscimol (220-660 pmol) was without effect on responding for food on this schedule but did stimulate intake of freely available chow. Unilateral administration of either baclofen or muscimol (220 pmol) induced similar patterns of c-fos immunoreactivity in several hypothalamic sites but differed in its induction in the central nucleus of the amygdala. We conclude that stimulation of GABA(A) or GABA(B) receptors in the nucleus accumbens shell of rats produces clearly distinguishable effects on operant responding for food.

  16. Utility of a tripolar stimulating electrode for eliciting dopamine release in the rat striatum.

    PubMed

    Bergstrom, B P; Garris, P A

    1999-03-01

    The present study evaluated tripolar stimulating electrodes for eliciting dopamine release in the rat brain in vivo. Stimulating electrodes were placed either in the medial forebrain bundle or in the ventral mesencephalon associated with the ventral tegmental area and substantia nigra. The concentration of extracellular dopamine was monitored in dopamine terminal fields at 100-ms intervals using fast-scan cyclic voltammetry at carbon-fiber microelectrodes. To characterize the stimulated area, recordings were collected in several striatal regions including the caudate putamen and the core and shell of the nucleus accumbens. The tripolar electrode was equally effective in stimulating dopamine release in medial and lateral regions of the striatum. In contrast, responses evoked by a bipolar electrode were typically greater in one mediolateral edge versus the other. The added size of the tripolar electrode did not appear to cause complications as signals were stable over the course of the experiment (3 h). Subsets of mesostriatal dopamine neurons could also be selectively activated using the tripolar electrode in excellent agreement with previously described topography. Taken together, these results suggested that the tripolar stimulating electrode is well suited for studying the regulation of midbrain dopamine neurons in vivo.

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  18. Influence of the on-line ELF-EMF stimulation on the electrophysiological properties of the rat hippocampal CA1 neurons in vitro

    NASA Astrophysics Data System (ADS)

    Zheng, Yu; Ma, Wei; Dong, Lei; Dou, Jun-rong; Gao, Yang; Xue, Jing

    2017-10-01

    The extremely low frequency electromagnetic fields (ELF-EMFs) have been shown to have an environmentally negative effect on humans' health; however, its treatment effect is beneficial for patients suffering from neurological disorders. Despite this success, the application of ELF-EMF has exceeded in the understanding of its internal mechanism. Recently, it was found that on-line magnetic stimulation may offer advantages over off-line magnetic exposure and has proven to be effective in activating the prefrontal cortex pyramidal neurons in vitro. Here, we perform computational simulations of the stimulation coils in COMSOL modeling to describe the uniformity of the distribution of the on-line magnetic field. Interestingly, the modeling data and actual measurements showed that the densities of the magnetic flux that was generated by the on-line stimulation coils were similar. The on-line magnetic stimulator induced sodium channel currents as well as field excitatory postsynaptic potentials of the rat hippocampal CA1 neurons and successfully demonstrated its extensive applications to activate neuronal tissue. These findings further raise the possibility that the instrument of on-line magnetic stimulation may be an effective alternative for studies in the field of bioelectromagnetics.

  19. Vaccination with Irradiated Tumor Cells Engineered to Secrete Murine Granulocyte-Macrophage Colony-Stimulating Factor Stimulates Potent, Specific, and Long-Lasting Anti-Tumor Immunity

    NASA Astrophysics Data System (ADS)

    Dranoff, Glenn; Jaffee, Elizabeth; Lazenby, Audrey; Golumbek, Paul; Levitsky, Hyam; Brose, Katja; Jackson, Valerie; Hamada, Hirofumi; Pardoll, Drew; Mulligan, Richard C.

    1993-04-01

    To compare the ability of different cytokines and other molecules to enhance the immunogenicity of tumor cells, we generated 10 retroviruses encoding potential immunomodulators and studied the vaccination properties of murine tumor cells transduced by the viruses. Using a B16 melanoma model, in which irradiated tumor cells alone do not stimulate significant anti-tumor immunity, we found that irradiated tumor cells expressing murine granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated potent, long-lasting, and specific anti-tumor immunity, requiring both CD4^+ and CD8^+ cells. Irradiated cells expressing interleukins 4 and 6 also stimulated detectable, but weaker, activity. In contrast to the B16 system, we found that in a number of other tumor models, the levels of anti-tumor immunity reported previously in cytokine gene transfer studies involving live, transduced cells could be achieved through the use of irradiated cells alone. Nevertheless, manipulation of the vaccine or challenge doses made it possible to demonstrate the activity of murine GM-CSF in those systems as well. Overall, our results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines.

  20. Effect of bilateral stimulation of the subthalamic nucleus on different speech subsystems in patients with Parkinson's disease.

    PubMed

    Pützer, Manfred; Barry, William J; Moringlane, Jean Richard

    2008-12-01

    The effect of deep brain stimulation on the two speech-production subsystems, articulation and phonation, of nine Parkinsonian patients is examined. Production parameters (stop closure voicing; stop closure, VOT, vowel) in fast syllable-repetitions were defined and measured and quantitative, objective metrics of vocal fold function were obtained during vowel production. Speech material was recorded for patients (with and without stimulation) and for a reference group of healthy control speakers. With stimulation, precision of the glottal and supraglottal articulation as well as the phonatory function is reduced for some individuals, whereas for other individuals an improvement is observed. Importantly, the improvement or deterioration is determined not only on the basis of the direction of parameter change but also on the individuals' position relative to the healthy control data. This study also notes differences within an individual in the effects of stimulation on the two speech subsystems. These findings qualify the value of global statements about the effect of neurostimulatory operations on Parkinsonian patients. They also underline the importance of careful consideration of individual differences in the effect of deep brain stimulation on different speech subsystems.

  1. The inability of phosphatidylinositol 3-kinase activation to stimulate GLUT4 translocation indicates additional signaling pathways are required for insulin-stimulated glucose uptake.

    PubMed

    Isakoff, S J; Taha, C; Rose, E; Marcusohn, J; Klip, A; Skolnik, E Y

    1995-10-24

    Recent experimental evidence has focused attention to the role of two molecules, insulin receptor substrate 1 (IRS-1) and phosphatidylinositol 3-kinase (PI3-kinase), in linking the insulin receptor to glucose uptake; IRS-1 knockout mice are insulin resistant, and pharmacological inhibitors of PI3-kinase block insulin-stimulated glucose uptake. To investigate the role of PI3-kinase and IRS-1 in insulin-stimulated glucose uptake we examined whether stimulation of insulin-sensitive cells with platelet-derived growth factor (PDGF) or with interleukin 4 (IL-4) stimulates glucose uptake; the activated PDGF receptor (PDGFR) directly binds and activates PI3-kinase, whereas the IL-4 receptor (IL-4R) activates PI3-kinase via IRS-1 or the IRS-1-related molecule 4PS. We found that stimulation of 3T3-L1 adipocytes with PDGF resulted in tyrosine phosphorylation of the PDGFR and activation of PI3-kinase in these cells. To examine whether IL-4 stimulates glucose uptake, L6 myoblasts were engineered to overexpress GLUT4 as well as both chains of the IL-4R (L6/IL-4R/GLUT4); when these L6/IL-4R/GLUT4 myoblasts were stimulated with IL-4, IRS-1 became tyrosine phosphorylated and associated with PI3-kinase. Although PDGF and IL-4 can activate PI3-kinase in the respective cell lines, they do not possess insulin's ability to stimulate glucose uptake and GLUT4 translocation to the plasma membrane. These findings indicate that activation of PI3-kinase is not sufficient to stimulate GLUT4 translocation to the plasma membrane. We postulate that activation of a second signaling pathway by insulin, distinct from PI3-kinase, is necessary for the stimulation of glucose uptake in insulin-sensitive cells.

  2. Mechanisms of reflex bladder activation by pudendal afferents

    PubMed Central

    Woock, John P.; Yoo, Paul B.

    2011-01-01

    Activation of pudendal afferents can evoke bladder contraction or relaxation dependent on the frequency of stimulation, but the mechanisms of reflex bladder excitation evoked by pudendal afferent stimulation are unknown. The objective of this study was to determine the contributions of sympathetic and parasympathetic mechanisms to bladder contractions evoked by stimulation of the dorsal nerve of the penis (DNP) in α-chloralose anesthetized adult male cats. Bladder contractions were evoked by DNP stimulation only above a bladder volume threshold equal to 73 ± 12% of the distension-evoked reflex contraction volume threshold. Bilateral hypogastric nerve transection (to eliminate sympathetic innervation of the bladder) or administration of propranolol (a β-adrenergic antagonist) decreased the stimulation-evoked and distension-evoked volume thresholds by −25% to −39%. Neither hypogastric nerve transection nor propranolol affected contraction magnitude, and robust bladder contractions were still evoked by stimulation at volume thresholds below the distension-evoked volume threshold. As well, inhibition of distention-evoked reflex bladder contractions by 10 Hz stimulation of the DNP was preserved following bilateral hypogastric nerve transection. Administration of phentolamine (an α-adrenergic antagonist) increased stimulation-evoked and distension-evoked volume thresholds by 18%, but again, robust contractions were still evoked by stimulation at volumes below the distension-evoked threshold. These results indicate that sympathetic mechanisms contribute to establishing the volume dependence of reflex contractions but are not critical to the excitatory pudendal to bladder reflex. A strong correlation between the magnitude of stimulation-evoked bladder contractions and bladder volume supports that convergence of pelvic afferents and pudendal afferents is responsible for bladder excitation evoked by pudendal afferents. Further, abolition of stimulation-evoked bladder contractions following administration of hexamethonium bromide confirmed that contractions were generated by pelvic efferent activation via the pelvic ganglion. These findings indicate that pudendal afferent stimulation evokes bladder contractions through convergence with pelvic afferents to increase pelvic efferent activity. PMID:21068196

  3. The role of nerve monitoring to predict postoperative recurrent laryngeal nerve function in thyroid and parathyroid surgery.

    PubMed

    Eid, Issam; Miller, Frank R; Rowan, Stephanie; Otto, Randal A

    2013-10-01

    To determine the role and efficacy of intraoperative recurrent laryngeal nerve (RLN) stimulation in the prediction of early and permanent postoperative nerve function in thyroid and parathyroid surgery. A retrospective review of thyroid and parathyroid surgeries was performed with calculation of sensitivity and specificity of the response of intraoperative stimulation for different pathological groups. Normal electromyography (EMG) response with 0.5 mAmp stimulation was considered a positive stimulation response with postoperative function determined by laryngoscopy. No EMG response at >1-2 mAmps was considered a negative response. The rates of early and permanent paralysis, as well as sensitivity, specificity, and positive and negative predictive values for postoperative nerve function were calculated for separate pathological groups. The number of nerves at risk analyzed was 909. The overall early and permanent paralysis rates were 3.1% and 1.2%, respectively, with the highest rate being for Grave's disease cases. The overall sensitivity was 98.4%. The specificity was lower at 62.5% but acceptable in thyroid carcinoma and Grave's disease patients. The majority of nerves with a positive stimulation result and postoperative paralysis on laryngoscopy recovered function in 3 to 12 weeks, showing positive stimulation to be a good predictor of eventual recovery. Stimulation of the RLN during thyroid and parathyroid surgery is a useful tool in predicting postoperative RLN function. The sensitivity of stimulation is high, showing positive stimulation to be an excellent predictor of normal nerve function. Negative stimulation is more predictive of paralysis in cases of thyroid carcinoma and Grave's disease. 2b. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  4. Transcranial Alternating Current Stimulation (tACS) Enhances Mental Rotation Performance during and after Stimulation

    PubMed Central

    Kasten, Florian H.; Herrmann, Christoph S.

    2017-01-01

    Transcranial alternating current stimulation (tACS) has been repeatedly demonstrated to modulate endogenous brain oscillations in a frequency specific manner. Thus, it is a promising tool to uncover causal relationships between brain oscillations and behavior or perception. While tACS has been shown to elicit a physiological aftereffect for up to 70 min, it remains unclear whether the effect can still be elicited if subjects perform a complex task interacting with the stimulated frequency band. In addition, it has not yet been investigated whether the aftereffect is behaviorally relevant. In the current experiment, participants performed a Shepard-like mental rotation task for 80 min. After 10 min of baseline measurement, participants received either 20 min of tACS at their individual alpha frequency (IAF) or sham stimulation (30 s tACS in the beginning of the stimulation period). Afterwards another 50 min of post-stimulation EEG were recorded. Task performance and EEG were acquired during the whole experiment. While there were no effects of tACS on reaction times or event-related-potentials (ERPs), results revealed an increase in mental rotation performance in the stimulation group as compared to sham both during and after stimulation. This was accompanied by increased ongoing alpha power and coherence as well as event-related-desynchronization (ERD) in the alpha band in the stimulation group. The current study demonstrates a behavioral and physiological aftereffect of tACS in parallel. This indicates that it is possible to elicit aftereffects of tACS during tasks interacting with the alpha band. Therefore, the tACS aftereffect is suitable to achieve an experimental manipulation. PMID:28197084

  5. Linking physics with physiology in TMS: a sphere field model to determine the cortical stimulation site in TMS.

    PubMed

    Thielscher, Axel; Kammer, Thomas

    2002-11-01

    A fundamental problem of transcranial magnetic stimulation (TMS) is determining the site and size of the stimulated cortical area. In the motor system, the most common procedure for this is motor mapping. The obtained two-dimensional distribution of coil positions with associated muscle responses is used to calculate a center of gravity on the skull. However, even in motor mapping the exact stimulation site on the cortex is not known and only rough estimates of its size are possible. We report a new method which combines physiological measurements with a physical model used to predict the electric field induced by the TMS coil. In four subjects motor responses in a small hand muscle were mapped with 9-13 stimulation sites at the head perpendicular to the central sulcus in order to keep the induced current direction constant in a given cortical region of interest. Input-output functions from these head locations were used to determine stimulator intensities that elicit half-maximal muscle responses. Based on these stimulator intensities the field distribution on the individual cortical surface was calculated as rendered from anatomical MR data. The region on the cortical surface in which the different stimulation sites produced the same electric field strength (minimal variance, 4.2 +/- 0.8%.) was determined as the most likely stimulation site on the cortex. In all subjects, it was located at the lateral part of the hand knob in the motor cortex. Comparisons of model calculations with the solutions obtained in this manner reveal that the stimulated cortex area innervating the target muscle is substantially smaller than the size of the electric field induced by the coil. Our results help to resolve fundamental questions raised by motor mapping studies as well as motor threshold measurements.

  6. Low-intensity repetitive magnetic stimulation lowers action potential threshold and increases spike firing in layer 5 pyramidal neurons in vitro.

    PubMed

    Tang, Alexander D; Hong, Ivan; Boddington, Laura J; Garrett, Andrew R; Etherington, Sarah; Reynolds, John N J; Rodger, Jennifer

    2016-10-29

    Repetitive transcranial magnetic stimulation (rTMS) has become a popular method of modulating neural plasticity in humans. Clinically, rTMS is delivered at high intensities to modulate neuronal excitability. While the high-intensity magnetic field can be targeted to stimulate specific cortical regions, areas adjacent to the targeted area receive stimulation at a lower intensity and may contribute to the overall plasticity induced by rTMS. We have previously shown that low-intensity rTMS induces molecular and structural plasticity in vivo, but the effects on membrane properties and neural excitability have not been investigated. Here we investigated the acute effect of low-intensity repetitive magnetic stimulation (LI-rMS) on neuronal excitability and potential changes on the passive and active electrophysiological properties of layer 5 pyramidal neurons in vitro. Whole-cell current clamp recordings were made at baseline prior to subthreshold LI-rMS (600 pulses of iTBS, n=9 cells from 7 animals) or sham (n=10 cells from 9 animals), immediately after stimulation, as well as 10 and 20min post-stimulation. Our results show that LI-rMS does not alter passive membrane properties (resting membrane potential and input resistance) but hyperpolarises action potential threshold and increases evoked spike-firing frequency. Increases in spike firing frequency were present throughout the 20min post-stimulation whereas action potential (AP) threshold hyperpolarization was present immediately after stimulation and at 20min post-stimulation. These results provide evidence that LI-rMS alters neuronal excitability of excitatory neurons. We suggest that regions outside the targeted region of high-intensity rTMS are susceptible to neuromodulation and may contribute to rTMS-induced plasticity. Copyright © 2016 IBRO. All rights reserved.

  7. Prevalence and Correlates of Prescription Stimulant Use, Misuse, Use Disorders, and Motivations for Misuse Among Adults in the United States.

    PubMed

    Compton, Wilson M; Han, Beth; Blanco, Carlos; Johnson, Kimberly; Jones, Christopher M

    2018-04-16

    The authors sought to simultaneously examine the prevalence and correlates of prescription stimulant use, misuse, use disorders, and motivations for misuse in the U.S. adult population. This was a nationally representative household population study of adults age 18 or older from the 2015 and 2016 National Surveys on Drug Use and Health (N=102,000). Measurements included prescription stimulant use, use without misuse, misuse without use disorders, and misuse with use disorders, as well as sociodemographic characteristics, health conditions, and mental health factors. Among U.S. adults, 6.6% (annual average) used prescription stimulants overall; 4.5% used without misuse, 1.9% misused without use disorders, and 0.2% had use disorders. Adults with past-year prescription stimulant use disorders did not differ from those with misuse without use disorders in any of the examined sociodemographic characteristics and in many of the examined substance use problems. The most commonly reported motivations for misuse were to help be alert or concentrate (56.3%). The most likely source of misused prescription stimulants was by obtaining them free from friends or relatives (56.9%). More frequent prescription stimulant misuse and use disorder were associated with an increased likelihood of obtaining medications from physicians or from drug dealers or strangers and less likelihood of obtaining them from friends or relatives. Approximately 16.0 million U.S. adults used prescription stimulants in the preceding year (annual average), 5.0 million misused prescription stimulants without use disorders, and 0.4 million had use disorders. Cognitive enhancement was the most commonly reported reason for misusing prescription stimulants. Patients who are using their medication for cognitive enhancement or diverting their medication to others present a high risk.

  8. Dose-Dependent Effects of Theta Burst rTMS on Cortical Excitability and Resting-State Connectivity of the Human Motor System

    PubMed Central

    Nettekoven, Charlotte; Volz, Lukas J.; Kutscha, Martha; Pool, Eva-Maria; Rehme, Anne K.; Eickhoff, Simon B.; Fink, Gereon R.

    2014-01-01

    Theta burst stimulation (TBS), a specific protocol of repetitive transcranial magnetic stimulation (rTMS), induces changes in cortical excitability that last beyond stimulation. TBS-induced aftereffects, however, vary between subjects, and the mechanisms underlying these aftereffects to date remain poorly understood. Therefore, the purpose of this study was to investigate whether increasing the number of pulses of intermittent TBS (iTBS) (1) increases cortical excitability as measured by motor-evoked potentials (MEPs) and (2) alters functional connectivity measured using resting-state fMRI, in a dose-dependent manner. Sixteen healthy, human subjects received three serially applied iTBS blocks of 600 pulses over the primary motor cortex (M1 stimulation) and the parieto-occipital vertex (sham stimulation) to test for dose-dependent iTBS effects on cortical excitability and functional connectivity (four sessions in total). iTBS over M1 increased MEP amplitudes compared with sham stimulation after each stimulation block. Although the increase in MEP amplitudes did not differ between the first and second block of M1 stimulation, we observed a significant increase after three blocks (1800 pulses). Furthermore, iTBS enhanced resting-state functional connectivity between the stimulated M1 and premotor regions in both hemispheres. Functional connectivity between M1 and ipsilateral dorsal premotor cortex further increased dose-dependently after 1800 pulses of iTBS over M1. However, no correlation between changes in MEP amplitudes and functional connectivity was detected. In summary, our data show that increasing the number of iTBS stimulation blocks results in dose-dependent effects at the local level (cortical excitability) as well as at a systems level (functional connectivity) with a dose-dependent enhancement of dorsal premotor cortex-M1 connectivity. PMID:24828639

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

    PubMed

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

    2014-01-01

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

  10. Spinal cord stimulation for the treatment of chronic back pain patients: 500-Hz vs. 1000-Hz burst stimulation.

    PubMed

    Van Havenbergh, Tony; Vancamp, Tim; Van Looy, Pieter; Vanneste, Sven; De Ridder, Dirk

    2015-01-01

    Spinal cord stimulation is a commonly used, safe, and effective procedure applied for medically intractable failed back surgery syndrome, as well as other neuropathic pain syndromes. Recently, a novel stimulation paradigm called burst stimulation has been developed that is paresthesia-free and has a more pronounced suppressive effect on neuropathic pain. Fifteen patients who were being treated with burst spinal cord stimulation for failed back surgery syndrome participated in an open-label trial to verify whether their pain suppression could be further ameliorated by changing the burst pattern. Burst stimulation with packets of five electrical pulses delivered at 500 Hz with 1000-μsec pulse width 40 times per second was changed to burst mode delivering five spikes at 1000 Hz with 500-μsec pulse width 40 times a second. As the amplitudes did not differ between the two groups, the total delivery of current to the spinal cord was not different between the two modes of burst stimulation. Scores on visual analog scales for pain and paresthesia, the Pain Catastrophizing Scale, the Pain Vigilance and Awareness Questionnaire, and the Short Form 36 quality of life measurement were compared between the two modes of burst stimulation. [Correction added on 06 Feb 2015, after first online publication: this paragraph has been revised to signify the comparison of amplitudes between two groups] No statistically significant differences were found between the two modes of stimulation. The results suggest that increasing the frequency from 500 to 1000 Hz while keeping the pulse width constant does not add any extra benefit in suppressing pain. Further studies should verify whether increasing the frequency above 1000 Hz has a similar lack of effect. © 2014 International Neuromodulation Society.

  11. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Increased Energy Demand during Adrenergic Receptor Stimulation Contributes to Ca(2+) Wave Generation.

    PubMed

    Bovo, Elisa; Mazurek, Stefan R; de Tombe, Pieter P; Zima, Aleksey V

    2015-10-20

    While β-adrenergic receptor (β-AR) stimulation ensures adequate cardiac output during stress, it can also trigger life-threatening cardiac arrhythmias. We have previously shown that proarrhythmic Ca(2+) waves during β-AR stimulation temporally coincide with augmentation of reactive oxygen species (ROS) production. In this study, we tested the hypothesis that increased energy demand during β-AR stimulation plays an important role in mitochondrial ROS production and Ca(2+)-wave generation in rabbit ventricular myocytes. We found that β-AR stimulation with isoproterenol (0.1 μM) decreased the mitochondrial redox potential and the ratio of reduced to oxidated glutathione. As a result, β-AR stimulation increased mitochondrial ROS production. These metabolic changes induced by isoproterenol were associated with increased sarcoplasmic reticulum (SR) Ca(2+) leak and frequent diastolic Ca(2+) waves. Inhibition of cell contraction with the myosin ATPase inhibitor blebbistatin attenuated oxidative stress as well as spontaneous SR Ca(2+) release events during β-AR stimulation. Furthermore, we found that oxidative stress induced by β-AR stimulation caused the formation of disulfide bonds between two ryanodine receptor (RyR) subunits, referred to as intersubunit cross-linking. Preventing RyR cross-linking with N-ethylmaleimide decreased the propensity of Ca(2+) waves induced by β-AR stimulation. These data suggest that increased energy demand during sustained β-AR stimulation weakens mitochondrial antioxidant defense, causing ROS release into the cytosol. By inducing RyR intersubunit cross-linking, ROS can increase SR Ca(2+) leak to the critical level that can trigger proarrhythmic Ca(2+) waves. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  13. Illegal drugs and delinquency.

    PubMed

    Kirschbaum, Katrin M; Grigoleit, Lisa; Hess, Cornelius; Madea, Burkhard; Musshoff, Frank

    2013-03-10

    An interrelation between consumption of illegal drugs and committing an indictable offence has been repeatedly discussed in literature. In a retrospective study serum concentrations of illegal and legal drugs as well as data originating from police reports and examinations by physicians taking blood from individuals being suspected to be under the influence of drugs were evaluated. Results from 4816 cases were available. Property offences were the most frequent type (36%) as well as consumption of cannabinoids (55%). Psychophysiological conditions of consumers were compared with according serum concentrations. Close correlations between stimulating drugs and violence associated crime could not be found. Stimulated as well as sedated behaviour occurring following the consumption of various drugs might be the reason for no clear correlation between types of offence and consumed illegal or legal drugs in this study. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Deep brain stimulation of the pedunculopontine nucleus for treatment of gait and balance disorder in progressive supranuclear palsy: Effects of frequency modulations and clinical outcome.

    PubMed

    Galazky, Imke; Kaufmann, Jörn; Lorenzl, Stefan; Ebersbach, Georg; Gandor, Florin; Zaehle, Tino; Specht, Sylke; Stallforth, Sabine; Sobieray, Uwe; Wirkus, Edyta; Casjens, Franziska; Heinze, Hans-Jochen; Kupsch, Andreas; Voges, Jürgen

    2018-05-01

    The pedunculopontine nucleus has been suggested as a potential deep brain stimulation target for axial symptoms such as gait and balance impairment in idiopathic Parkinson's disease as well as atypical Parkinsonian disorders. Seven consecutive patients with progressive supranuclear palsy received bilateral pedunculopontine nucleus deep brain stimulation. Inclusion criteria comprised of the clinical diagnosis of progressive supranuclear palsy, a levodopa-resistant gait and balance disorder, age <75 years, and absence of dementia or major psychiatric co-morbidities. Effects of stimulation frequencies at 8, 20, 60 and 130 Hz on motor scores and gait were assessed. Motor scores were followed up for two years postoperatively. Activities of daily living, frequency of falls, health-related quality of life, cognition and mood at 12 months were compared to baseline parameters. Surgical and stimulation related adverse events were assessed. Bilateral pedunculopontine nucleus deep brain stimulation at 8 Hz significantly improved axial motor symptoms and cyclic gait parameters, while high frequency stimulation did not ameliorate gait and balance but improved hypokinesia. This improvement however did not translate into clinically relevant benefits. Frequency of falls was not reduced. Activities of daily living, quality of life and frontal cognitive functions declined, while mood remained unchanged. Bilateral pedunculopontine nucleus deep brain stimulation in progressive supranuclear palsy generates frequency-dependent effects with improvement of cyclic gait parameters at low frequency and amelioration of hypokinesia at high frequency stimulation. However, these effects do not translate into a clinically important improvement. Copyright © 2018. Published by Elsevier Ltd.

  15. The Social Context of “Do-It-Yourself” Brain Stimulation: Neurohackers, Biohackers, and Lifehackers

    PubMed Central

    Wexler, Anna

    2017-01-01

    The “do-it-yourself” (DIY) brain stimulation movement began in earnest in late 2011, when lay individuals began building stimulation devices and applying low levels of electricity to their heads for self-improvement purposes. To date, scholarship on the home use of brain stimulation has focused on characterizing the practices of users via quantitative and qualitative studies, and on analyzing related ethical and regulatory issues. In this perspective piece, however, I take the opposite approach: rather than viewing the home use of brain stimulation on its own, I argue that it must be understood within the context of other DIY and citizen science movements. Seen in this light, the home use of brain stimulation is only a small part of the “neurohacking” movement, which is comprised of individuals attempting to optimize their brains to achieve enhanced performance. Neurohacking itself is an offshoot of the “life hacking” (or “quantified self”) movement, in which individuals self-track minute aspects of their daily lives in order to enhance productivity or performance. Additionally, the home or DIY use of brain stimulation is in many ways parallel to the DIY Biology (or “biohacking”) movement, which seeks to democratize tools of scientific experimentation. Here, I describe the place of the home use of brain stimulation with regard to neurohackers, lifehackers, and biohackers, and suggest that a policy approach for the home use of brain stimulation should have an appreciation both of individual motivations as well as the broader social context of the movement itself. PMID:28539877

  16. A novel device for the study of somatosensory information processing

    PubMed Central

    Holden, Jameson K.; Nguyen, Richard H.; Francisco, Eric M.; Zhang, Zheng; Dennis, Robert G.; Tommerdahl, Mark

    2012-01-01

    Current methods for applying multi-site vibratory stimuli to the skin typically involve the use of multiple, individual vibrotactile stimulators. Limitations of such an arrangement include difficulty with both positioning the stimuli as well as ensuring that stimuli are delivered in a synchronized and deliberate manner. Previously, we reported a two-site tactile stimulator that was developed in order to solve these problems (Tannan et al., 2007a). Due to both the success of that novel stimulator and the limitations that were inherent in that device, we designed and fabricated a four-site stimulator that provides a number of advantages over the previous version. First, the device can stimulate four independent skin sites and is primarily designed for stimulating the digit tips. Second, the positioning of the probe tips has been re-designed to provide better ergonomic hand placement. Third, the device is much more portable than the previously-reported stimulator. Fourth, the stimulator head has a much smaller footprint on the table or surface where it resides. To demonstrate the capacity of the device for delivering tactile stimulation at four independent sites, a finger agnosia protocol, in the presence and absence of conditioning stimuli, was conducted on seventeen healthy control subjects. The study demonstrated that with increasing amplitudes of vibrotactile conditioning stimuli concurrent with the agnosia test, inaccuracies of digit identification increased, particularly at digits D3 and D4. The results are consistent with prior studies that implicated synchronization of adjacent and near-adjacent cortical ensembles with conditioning stimuli in impacting TOJ performance (Tommerdahl et al., 2007). PMID:22155443

  17. Functional magnetic resonance imaging of the human spinal cord during vibration stimulation of different dermatomes.

    PubMed

    Lawrence, Jane M; Stroman, Patrick W; Kollias, Spyros S

    2008-03-01

    We investigated noninvasively areas of the healthy human spinal cord that become active in response to vibration stimulation of different dermatomes using functional magnetic resonance imaging (fMRI). The objectives of this study were to: (1) examine the patterns of consistent activity in the spinal cord during vibration stimulation of the skin, and (2) investigate the rostrocaudal distribution of active pixels when stimulation was applied to different dermatomes. FMRI of the cervical and lumbar spinal cord of seven healthy human subjects was carried out during vibration stimulation of six different dermatomes. In separate experiments, vibratory stimulation (about 50 Hz) was applied to the right biceps, wrist, palm, patella, Achilles tendon and left palm. The segmental distribution of activity observed by fMRI corresponded well with known spinal cord neuroanatomy. The peak number of active pixels was observed at the expected level of the spinal cord with some activity in the adjacent segments. The rostrocaudal distribution of activity was observed to correspond to the dermatome being stimulated. Cross-sectional localization of activity was primarily in dorsal areas but also spread into ventral and intermediate areas of the gray matter and a distinct laterality ipsilateral to the stimulated limb was not observed. We demonstrated that fMRI can detect a dermatome-dependent pattern of spinal cord activity during vibratory stimulation and can be used as a passive stimulus for the noninvasive assessment of the functional integrity of the human spinal cord. Demonstration of cross-sectional selectivity of the activation awaits further methodological and experimental refinements.

  18. Misuse of Prescribed Stimulant Medication for ADHD and Associated Patterns of Substance Use: Preliminary Analysis Among College Students

    PubMed Central

    Sepúlveda, Dalissa R.; Thomas, Lisl M.; McCabe, Sean Esteban; Cranford, James A.; Boyd, Carol J.; Teter, Christian J.

    2012-01-01

    Objectives To explore the prevalence and characteristics associated with college students who misuse their prescribed stimulants for attention-deficit hyperactivity disorder (ADHD) and examine diversion and substance use behaviors as a function of misuse. Methods Cohort of 55 past-year prescribed stimulant users was identified from a random sample (n = 1738) at a large Midwestern research university following the self-administration of a web-based survey. An index was created to assess misuse of prescribed stimulants (i.e., Misuse Index). Results Of 55 college students who reported past-year use of prescribed stimulants for ADHD, 22 (40%) endorsed at least one item on the misuse index. The most frequently endorsed misuse items were used too much (36%), self-reported misuse (19%), and intentionally used with alcohol or other drugs (19%). Misusers of prescribed stimulant medication were more likely to report cigarette smoking (p = 0.022), binge drinking (p = 0.022), illicit use of cocaine (p = 0.032), and screen positive on the Drug Abuse Screening test (DAST-10) criteria (p = 0.002). The bivariate odds ratio for the DAST-10 findings was 8.4 (95% CI: 2.0–34.6). Diversion of prescribed stimulants was common (36%) and occurred more frequently among stimulant misusers (57%; p = 0.008). Conclusion There is a strong relationship between misuse of prescribed stimulants for ADHD and substance use behaviors, as well as other deleterious behaviors such as diversion. These findings suggest the need for close screening, assessment, and therapeutic monitoring of medication use in the college population. PMID:22095577

  19. [Significance of CRF and dopamine receptors in amygdala for reinforcing effects of opiates and opioids on self-stimulation of lateral hypothalamus in rats].

    PubMed

    Shabanov, P D; Lebedev, A A; Liubimov, A V; Kornilov, V A

    2011-01-01

    Bipolar electrodes were implanted in the lateral hypothalamus in a group of 44 Wistar male rats in order to study self-stimulation reaction in the Skinner box. Simultaneously, microcanules were implanted into the central nucleus of the amygdala to inject the drugs (1 microl per injection). The blockade of corticoliberin (CRF) receptors (astressin, 1 microg) or Na+influx currents (xycaine or lidocain 1 microg) by the intrastructural administration of drugs into the amygdala decreased self-stimulation reaction of the lateral hypothalamus in rats by 29-55%. The inhibition of D1 and D2 dopamine receptors in the amygdala with SCH23390 (1 microg) or sulpiride (1 microg) respectively, also reduced self-stimulation but to a lower degree. On the background of blockade of CRF (astressin) and dopamine (sulpiride) receptors as well as sodium influx ionic currents (lidocain) in the amygdala neurons, psychomotor stimulant amphetamine (1 mg/kg) and barbiturate sodium ethaminal (5 mg/kg) retained their psychoactivating effect on self-stimulation (+30-37%), while fentanyl (0.1 mg/kg) and leu-enkephaline (0.1 mg/kg) did not produce this effect. Fentanyl moderately activated self-stimulation only after the blockade of D1 dopamine receptors with SCH23390. After the blockade of CRF receptors, leu-enkephaline strengthened its depressant effect on self-stimulation reaction (-89%). Therefore, if the modulating action of amygdala on the hypothalamus is eliminated, the enhancing effects of opiates (fentanyl) and opioids (leu-encephaline) are blocked, but the effects of psychomotor stimulant amphetamine and barbiturate sodium ethaminal are retained.

  20. Neurocognitive Enhancement or Impairment? A Systematic Meta-Analysis of Prescription Stimulant Effects on Processing Speed, Decision-Making, Planning, and Cognitive Perseveration

    PubMed Central

    Marraccini, Marisa E.; Weyandt, Lisa L.; Rossi, Joseph S.; Gudmundsdottir, Bergljot Gyda

    2016-01-01

    Increasing numbers of adults, particularly college students, are misusing prescription stimulants primarily for cognitive/academic enhancement, so it is critical to explore whether empirical findings support neurocognitive benefits of prescription stimulants. Previous meta-analytic studies have supported small benefits from prescription stimulants for the cognitive domains of inhibitory control and memory; however, no meta-analytic studies have examined the effects on processing speed or the potential impairment on other domains of cognition, including planning, decision-making, and cognitive perseveration. Therefore, the present study conducted a meta-analysis of the available literature examining the effects of prescription stimulants on specific measures of processing speed, planning, decision-making, and cognitive perseveration among healthy adult populations. The meta-analysis results indicated a positive influence of prescription stimulant medication on processing speed accuracy, with an overall mean effect size of g = 0.282 (95% CI 0.077, 0.488; n = 345). Neither improvements nor impairments were revealed for planning time, planning accuracy, advantageous decision-making, or cognitive perseveration; however findings are limited by the small number of studies examining these outcomes. Findings support that prescription stimulant medication may indeed act as a neurocognitive enhancer for accuracy measures of processing speed without impeding other areas of cognition. Considering that adults are already engaging in illegal use of prescription stimulants for academic enhancement, as well as the potential for stimulant misuse to have serious side effects, the establishment of public policies informed by interdisciplinary research surrounding this issue, whether restrictive or liberal, is of critical importance. PMID:27454675

  1. Neuropsychological Functioning in College Students Who Misuse Prescription Stimulants

    PubMed Central

    Wilens, Timothy; Carrellas, Nicholas W.; Martelon, MaryKate; Yule, Amy M.; Fried, Ronna; Anselmo, Rayce; McCabe, Sean E.

    2017-01-01

    Background and Objectives Relatively little is known about the neuropsychological profiles of college students who misuse prescription stimulant medications. Methods Data presented are from college students aged 18 to 28 years who misused prescription stimulants prescribed for attention-deficit/hyperactivity disorder and controls (no prescription stimulant misuse). Students were assessed neuropsychologically using the self-report Behavioral Rating Inventory of Executive Functioning (BRIEF-A), the Cambridge Automated Neuropsychological Test and Battery (CANTAB), and other tests of cognitive functioning. The analyses included 198 controls (age 20.7 ± 2.6 years) and 100 prescription stimulant misusers (age 20.7 ± 1.7 years). Results On the BRIEF-A, misusers were more likely than controls to endorse greater dysfunction on 8 of 12 measures including Inhibition, Self Monitor, Initiation, Working Memory, and Plan/Organize, when adjusting for race and sex (all p’s <0.05). Similarly, when dichotomizing the BRIEF-A as abnormal (T score ≥ 65), misusers had more abnormalities on 5 of 9 subscales, as well as all major indices (p’s<0.05). Misusers also performed worse on several subtests of the CANTAB and standardized cognitive battery (p’s <0.05). A proxy of prescription stimulant misuse frequency was positively correlated with greater executive dysfunction on the BRIEF-A. Discussion and Conclusions These data demonstrate elevated risk for neuropsychological dysfunction among students who misuse prescription stimulants compared to non-misusing peers. The presence of ADHD contributed significantly to these cognitive findings. Students who misuse prescription stimulants should be screened for neuropsychological dysfunction. Scientific Significance These data may better elucidate the neuropsychological profile of college-aged prescription stimulant misusers. PMID:28494131

  2. Epitope mapping of tsh receptor-blocking antibodies in Graves' disease that appear during pregnancy.

    PubMed

    Kung, A W; Lau, K S; Kohn, L D

    2001-08-01

    Spontaneous remission of Graves' disease during pregnancy is thought to be due to a reduction of thyroid-stimulating antibody activity. We suspected, however, that a broader change in TSH receptor antibody characteristics might play an important role in modulating disease activity during pregnancy. We measured TSH binding inhibitory Ig, thyroid-stimulating antibody, and thyroid stimulating-blocking antibody activities in 13 pregnant Graves' disease patients at first, second, and third trimesters and 4 months postpartum. To measure and epitope-map thyroid-stimulating antibody and thyroid stimulating-blocking antibody activities, we used CHO cells transfected with wild-type human TSH receptor or with several TSH receptor-LH/hCG receptor chimeras: Mc1+2, Mc2, and Mc4. These chimeric cells have their respective TSH receptor residues 9-165, 90-165, and 261-370 substituted with equivalent residues of the LH/hCG receptor. Overall thyroid-stimulating antibody decreased, whereas thyroid stimulating-blocking antibody increased progressively during pregnancy. TSH binding inhibitory Ig fluctuated in individual patients, but overall the activities remained statistically unchanged. Thyroid stimulating-blocking antibody appeared in subjects who were either negative for thyroid-stimulating antibody or whose thyroid-stimulating antibody activity increased or decreased during pregnancy. Epitope mapping showed that the thyroid-stimulating antibodies were mainly directed against residues 9-165 of the N-terminus of the TSH receptor extracellular domain. All thyroid stimulating-blocking antibodies had blocking activities against residues 261-370 of the C-terminus of the ectodomain. However, the majority of the thyroid stimulating-blocking antibodies had a hybrid conformational epitope directed against N-terminal residues 9-89 or 90-165 as well. Despite a change in the activity level, we did not observe any change in the epitope of either the stimulatory or blocking Abs as pregnancy advanced. In conclusion, a change in the specificity of TSH receptor antibody from stimulatory to blocking activity was observed during pregnancy, and the appearance of thyroid stimulating-blocking antibody may contribute to the remission of Graves' disease during pregnancy.

  3. Spin state switching of metal complexes by visible light or hard X-rays.

    PubMed

    Unruh, Daniel; Homenya, Patrick; Kumar, Manish; Sindelar, Ralf; Garcia, Yann; Renz, Franz

    2016-09-28

    Electromagnetic stimuli of spin crossover compounds restricted to UV-vis light irradiation for many years could be recently extended to X-ray excitation. This review covers a large variety of light-induced effects, as well as recent analogues stimulated by X-ray irradiation which have not yet been reviewed. The focus is also on multistable multinuclear spin crossover compounds which are the subject of lively discussions within the spin crossover community. Their spin transition often occurs incompletely and with different switching mechanisms. In this review, we recall a predicted sequential switching induced thermally as well as a concerted stimulation mechanism by light irradiation for these interesting multifunctional materials.

  4. Electrochemical synthesis of mesoporous gold films toward mesospace-stimulated optical properties

    NASA Astrophysics Data System (ADS)

    Li, Cuiling; Dag, Ömer; Dao, Thang Duy; Nagao, Tadaaki; Sakamoto, Yasuhiro; Kimura, Tatsuo; Terasaki, Osamu; Yamauchi, Yusuke

    2015-03-01

    Mesoporous gold (Au) films with tunable pores are expected to provide fascinating optical properties stimulated by the mesospaces, but they have not been realized yet because of the difficulty of controlling the Au crystal growth. Here, we report a reliable soft-templating method to fabricate mesoporous Au films using stable micelles of diblock copolymers, with electrochemical deposition advantageous for precise control of Au crystal growth. Strong field enhancement takes place around the center of the uniform mesopores as well as on the walls between the pores, leading to the enhanced light scattering as well as surface-enhanced Raman scattering (SERS), which is understandable, for example, from Babinet principles applied for the reverse system of nanoparticle ensembles.

  5. Potential Experimental Topics for EGS Collab Experiment 3

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johnston, Henry; Mattson, Earl; Blankenship, Douglas

    To facilitate the success of FORGE, the DOE GTO has initiated a new research effort, the EGS Collab project, which will utilize readily accessible underground facilities that can refine our understanding of rock mass response to stimulation and provide a test bed at intermediate (~10 m) scale for the validation of thermal-hydrological-mechanical-chemical modeling approaches as well as novel monitoring tools. The first two EGS Experiments 1 and 2 are planned be performed under different stress/fracture conditions, and will evaluate different stimulation processes: Experiment 1 will focus on hydrofracturing of a competent rock mass, while Experiment 2 will concentrate on hydroshearingmore » of a rock mass that contains natural fractures. Experiment 3 is scheduled to begin in 2019 will build off the lessons learned in Experiments 1 and 2 and will investigate alternate stimulation and operation methods to improve heat extraction in an EGS reservoir. This paper evaluates potential experiments that could potentially be conducted in Experiment 3. The two technical parameters defining energy extracted from EGS reservoirs with the highest economic uncertainty and risk are the production well flow rates and the reservoir thermal drawdown rate. A review of historical and currently on-going EGS studies has identified that over 1/2 of the projects have identified heat extraction challenges during their operation associated with these two parameters as well as some additional secondary issues. At present, no EGS reservoir has continuously produced flow rates on the order of 80 kg/s. Short circuiting (i.e. early thermal breakthrough) has been identified in numerous cases. In addition, working fluid loss (i.e. the difference between the injected fluid mass and the extracted fluid mass as compared to the injected mass) has been as high as 90%. Finally, the engineering aspects of operating a true EGS multi-fracture reservoir such as repairing/modifying fractures and controlling working fluid fluxes within multiple fractures for the effective EGS fracture management has not been sufficiently studied. To examine issues such as these, EGS Collab Experiment 3 may be conducted in the testbeds prepared for Experiments 1 and 2 by improving the previously performed stimulations, or conducted at a new site performing new stimulations with alternate method. Potential experiments may include using different stimulation and working fluids, evaluating different stimulation methods, using proppants to enhance permeability, and other high-risk high-reward methods that can be evaluated at the 10-m scale environment.« less

  6. Rock specific hydraulic fracturing and matrix acidizing to enhance a geothermal system — Concepts and field results

    NASA Astrophysics Data System (ADS)

    Zimmermann, Günter; Blöcher, Guido; Reinicke, Andreas; Brandt, Wulf

    2011-04-01

    Enhanced geothermal systems (EGS) are engineered reservoirs developed to extract economic amounts of heat from low permeability and/or porosity geothermal resources. To enhance the productivity of reservoirs, a site specific concept is necessary to actively make reservoir conditions profitable using specially adjusted stimulation treatments, such as multi fracture concepts and site specific well path design. The results of previously performed stimulation treatments in the geothermal research well GtGrSk4/05 at Groß Schönebeck, Germany are presented. The reservoir is located at a 4100-4300 m depth within the Lower Permian of the NE German Basin with a bottom-hole temperature of 150 °C. The reservoir rock is classified by two lithological units from bottom to top: volcanic rocks (andesitic rocks) and siliciclastics ranging from conglomerates to fine-grained sandstones (fluvial sediments). The stimulation treatments included multiple hydraulic stimulations and an acid treatment. In order to initiate a cross-flow from the sandstone layer, the hydraulic stimulations were performed in different depth sections (two in the sandstone section and one in the underlying volcanic section). In low permeability volcanic rocks, a cyclic hydraulic fracturing treatment was performed over 6 days in conjunction with adding quartz in low concentrations to maintain a sustainable fracture performance. Flow rates of up to 150 l/s were realized, and a total of 13,170 m 3 of water was injected. A hydraulic connection to the sandstone layer was successfully achieved in this way. However, monitoring of the water level in the offsetting well EGrSk3/90, which is 475 m apart at the final depth, showed a very rapid water level increase due to the stimulation treatment. This can be explained by a connected fault zone within the volcanic rocks. Two gel-proppant treatments were performed in the slightly higher permeability sandstones to obtain long-term access to the reservoir rocks. During each treatment, a total of 100 ton of high strength proppants was injected with 500 m 3 of cross-linked gel. The subsequent production test in conjunction with flowmeter logging showed an improvement of productivity by a factor of more than 4. Due to assumed residual drilling mud (constituents: calcite, dolomite, and aragonite) in the near-wellbore vicinity, an acid matrix stimulation was performed thereafter using a coil tubing unit. The following nitrogen lift test demonstrated another increase of productivity by 30-50% to an overall increase by a factor of 5.5-6.2.

  7. Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance

    PubMed Central

    Lile, Joshua A.; Stoops, William W.; Glaser, Paul E.A.; Hays, Lon R.; Rush, Craig R.

    2015-01-01

    Background Medications development for methamphetamine dependence is ongoing, but no widely accepted, effective pharmacotherapy has been identified. Previous studies have demonstrated neurobiological perturbations to central GABAA activity following chronic stimulant use, and that positive modulation of GABAA receptors attenuates the neurochemical and behavioral response to stimulant drugs such as methamphetamine. Therefore, GABAA modulators could be useful as pharmacotherapies for stimulant-use disorders. Methods This study tested the hypothesis that intranasal methamphetamine would be safe and well tolerated during maintenance on extended-release alprazolam (XR), and that the effects of methamphetamine would be attenuated. Eight non-treatment-seeking, stimulant-dependent individuals completed an inpatient experiment in which ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) were administered after four days of alprazolam XR maintenance (0 and 1 mg/day). Results Intranasal methamphetamine produced prototypical effects (e.g., increased positive subjective ratings and elevated cardiovascular signs). The combination of intranasal methamphetamine and alprazolam XR was safe and well tolerated. Alprazolam XR produced small, but orderly, reductions in some of the subjective effects of methamphetamine, and performance impairment. Conclusions The present results demonstrate that methamphetamine use during alprazolam XR treatment would not pose a significant safety risk. Given the potential of GABAA positive modulators to manage certain aspects of stimulant abuse and dependence (i.e., drug-induced seizures, anxiety and stress), but the relatively small impact on the acute abuse-related effects of methamphetamine observed here, additional research with GABAA positive modulators is warranted, but should consider their use as an adjunct component of combination behavioral and/or drug treatment. PMID:21737214

  8. Mechanical Stimulation (Pulsed Electromagnetic Fields “PEMF” and Extracorporeal Shock Wave Therapy “ESWT”) and Tendon Regeneration: A Possible Alternative

    PubMed Central

    Rosso, Federica; Bonasia, Davide E.; Marmotti, Antonio; Cottino, Umberto; Rossi, Roberto

    2015-01-01

    The pathogenesis of tendon degeneration and tendinopathy is still partially unclear. However, an active role of metalloproteinases (MMP), growth factors, such as vascular endothelial growth factor (VEGF) and a crucial role of inflammatory elements and cytokines was demonstrated. Mechanical stimulation may play a role in regulation of inflammation. In vitro studies demonstrated that both pulsed electromagnetic fields (PEMF) and extracorporeal shock wave therapy (ESWT) increased the expression of pro-inflammatory cytokine such as interleukin (IL-6 and IL-10). Moreover, ESWT increases the expression of growth factors, such as transforming growth factor β(TGF-β), (VEGF), and insulin-like growth factor 1 (IGF1), as well as the synthesis of collagen I fibers. These pre-clinical results, in association with several clinical studies, suggest a potential effectiveness of ESWT for tendinopathy treatment. Recently PEMF gained popularity as adjuvant for fracture healing and bone regeneration. Similarly to ESWT, the mechanical stimulation obtained using PEMFs may play a role for treatment of tendinopathy and for tendon regeneration, increasing in vitro TGF-β production, as well as scleraxis and collagen I gene expression. In this manuscript the rational of mechanical stimulations and the clinical studies on the efficacy of extracorporeal shock wave (ESW) and PEMF will be discussed. However, no clear evidence of a clinical value of ESW and PEMF has been found in literature with regards to the treatment of tendinopathy in human, so further clinical trials are needed to confirm the promising hypotheses concerning the effectiveness of ESWT and PEMF mechanical stimulation. PMID:26617513

  9. Acupuncture mobilizes the brain's default mode and its anti-correlated network in healthy subjects.

    PubMed

    Hui, Kathleen K S; Marina, Ovidiu; Claunch, Joshua D; Nixon, Erika E; Fang, Jiliang; Liu, Jing; Li, Ming; Napadow, Vitaly; Vangel, Mark; Makris, Nikos; Chan, Suk-Tak; Kwong, Kenneth K; Rosen, Bruce R

    2009-09-01

    Previous work has shown that acupuncture stimulation evokes deactivation of a limbic-paralimbic-neocortical network (LPNN) as well as activation of somatosensory brain regions. This study explores the activity and functional connectivity of these regions during acupuncture vs. tactile stimulation and vs. acupuncture associated with inadvertent sharp pain. Acupuncture during 201 scans and tactile stimulation during 74 scans for comparison at acupoints LI4, ST36 and LV3 was monitored with fMRI and psychophysical response in 48 healthy subjects. Clusters of deactivated regions in the medial prefrontal, medial parietal and medial temporal lobes as well as activated regions in the sensorimotor and a few paralimbic structures can be identified during acupuncture by general linear model analysis and seed-based cross correlation analysis. Importantly, these clusters showed virtual identity with the default mode network and the anti-correlated task-positive network in response to stimulation. In addition, the amygdala and hypothalamus, structures not routinely reported in the default mode literature, were frequently involved in acupuncture. When acupuncture induced sharp pain, the deactivation was attenuated or became activated instead. Tactile stimulation induced greater activation of the somatosensory regions but less extensive deactivation of the LPNN. These results indicate that the deactivation of the LPNN during acupuncture cannot be completely explained by the demand of attention that is commonly proposed in the default mode literature. Our results suggest that acupuncture mobilizes the anti-correlated functional networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response.

  10. Responses of neurons in the caudal medullary lateral tegmental field to visceral inputs and vestibular stimulation in vertical planes

    PubMed Central

    Moy, Jennifer D.; Miller, Daniel J.; Catanzaro, Michael F.; Boyle, Bret M.; Ogburn, Sarah W.; Cotter, Lucy A.; McCall, Andrew A.

    2012-01-01

    The dorsolateral reticular formation of the caudal medulla, or the lateral tegmental field (LTF), has been classified as the brain's “vomiting center”, as well as an important region in regulating sympathetic outflow. We examined the responses of LTF neurons in cats to rotations of the body that activate vestibular receptors, as well as to stimulation of baroreceptors (through mechanical stretch of the carotid sinus) and gastrointestinal receptors (through the intragastric administration of the emetic compound copper sulfate). Approximately half of the LTF neurons exhibited graviceptive responses to vestibular stimulation, similar to primary afferents innervating otolith organs. The other half of the neurons had complex responses, including spatiotemporal convergence behavior, suggesting that they received convergent inputs from a variety of vestibular receptors. Neurons that received gastrointestinal and baroreceptor inputs had similar complex responses to vestibular stimulation; such responses are expected for neurons that contribute to the generation of motion sickness. LTF units with convergent baroreceptor and vestibular inputs may participate in producing the cardiovascular system components of motion sickness, such as the changes in skin blood flow that result in pallor. The administration of copper sulfate often modulated the gain of responses of LTF neurons to vestibular stimulation, particularly for units whose spontaneous firing rate was altered by infusion of drug (median of 459%). The present results raise the prospect that emetic signals from the gastrointestinal tract modify the processing of vestibular inputs by LTF neurons, thereby affecting the probability that vomiting will occur as a consequence of motion sickness. PMID:22955058

  11. What saccadic eye movements tell us about TMS-induced neuromodulation of the DLPFC and mood changes: a pilot study in bipolar disorders.

    PubMed

    Beynel, Lysianne; Chauvin, Alan; Guyader, Nathalie; Harquel, Sylvain; Szekely, David; Bougerol, Thierry; Marendaz, Christian

    2014-01-01

    The study assumed that the antisaccade (AS) task is a relevant psychophysical tool to assess (i) short-term neuromodulation of the dorsolateral prefrontal cortex (DLPFC) induced by intermittent theta burst stimulation (iTBS); and (ii) mood change occurring during the course of the treatment. Saccadic inhibition is known to strongly involve the DLPFC, whose neuromodulation with iTBS requires less stimulation time and lower stimulation intensity, as well as results in longer aftereffects than the conventional repetitive transcranial magnetic stimulation (rTMS). Active or sham iTBS was applied every day for 3 weeks over the left DLPFC of 12 drug-resistant bipolar depressed patients. To assess the iTBS-induced short-term neuromodulation, the saccadic task was performed just before (S1) and just after (S2) the iTBS session, the first day of each week. Mood was evaluated through Montgomery and Asberg Depression Rating Scale (MADRS) scores and the difference in scores between the beginning and the end of treatment was correlated with AS performance change between these two periods. As expected, only patients from the active group improved their performance from S1 to S2 and mood improvement was significantly correlated with AS performance improvement. In addition, the AS task also discriminated depressive bipolar patients from healthy control subjects. Therefore, the AS task could be a relevant and useful tool for clinicians to assess if the Transcranial magnetic stimulation (TMS)-induced short-term neuromodulation of the DLPFC occurs as well as a "trait vs. state" objective marker of depressive mood disorder.

  12. Stimulating the cerebellum affects visuomotor adaptation but not intermanual transfer of learning

    PubMed Central

    Block, Hannah; Celnik, Pablo

    2013-01-01

    When systematic movement errors occur, the brain responds with a systematic change in motor behavior. This type of adaptive motor learning can transfer intermanually; adaptation of movements of the right hand in response to training with a perturbed visual signal (visuomotor adaptation) may carry over to the left hand. While visuomotor adaptation has been studied extensively, it is unclear whether the cerebellum, a structure involved in adaptation, is important for intermanual transfer as well. We addressed this question with three experiments in which subjects reached with their right hands as a 30° visuomotor rotation was introduced. Subjects received anodal or sham transcranial direct current stimulation (tDCS) on the trained (Experiment 1) or untrained (Experiment 2) hemisphere of the cerebellum, or, for comparison, motor cortex (M1). After the training period, subjects reached with their left hand, without visual feedback, to assess intermanual transfer of learning aftereffects. Stimulation of the right cerebellum caused faster adaptation, but none of the stimulation sites affected transfer. To ascertain whether cerebellar stimulation would increase transfer if subjects learned faster as well as a larger amount, in Experiment 3 anodal and sham cerebellar groups experienced a shortened training block such that the anodal group learned more than sham. Despite the difference in adaptation magnitude, transfer was similar across these groups, although smaller than in Experiment 1. Our results suggest that intermanual transfer of visuomotor learning does not depend on cerebellar activity, and that the number of movements performed at plateau is an important predictor of transfer. PMID:23625383

  13. Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach

    PubMed Central

    Karamintziou, Sofia D.; Custódio, Ana Luísa; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stéphan; Stathis, Pantelis G.; Tagaris, George A.; Sakas, Damianos E.; Polychronaki, Georgia E.; Tsirogiannis, George L.; David, Olivier; Nikita, Konstantina S.

    2017-01-01

    Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson’s disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications. PMID:28222198

  14. 1-Oleoyl-2-acetylglycerol stimulates 5-lipoxygenase activity via a putative (phospho)lipid binding site within the N-terminal C2-like domain.

    PubMed

    Hörnig, Christina; Albert, Dana; Fischer, Lutz; Hörnig, Michael; Rådmark, Olof; Steinhilber, Dieter; Werz, Oliver

    2005-07-22

    5-Lipoxygenase (5-LO) catalysis is positively regulated by Ca2+ ions and phospholipids that both act via the N-terminal C2-like domain of 5-LO. Previously, we have shown that 1-oleoyl-2-acetylglycerol (OAG) functions as an agonist for human polymorphonuclear leukocytes (PMNL) in stimulating 5-LO product formation. Here we have demonstrated that OAG directly stimulates 5-LO catalysis in vitro. In the absence of Ca2+ (chelated using EDTA), OAG strongly and concentration-dependently stimulated crude 5-LO in 100,000 x g supernatants as well as purified 5-LO enzyme from PMNL. Also, the monoglyceride 1-O-oleyl-rac-glycerol and 1,2-dioctanoyl-sn-glycerol were effective, whereas various phospholipids did not stimulate 5-LO. However, in the presence of Ca2+, OAG caused no stimulation of 5-LO. Also, phospholipids or cellular membranes abolished the effects of OAG. As found previously for Ca2+, OAG renders 5-LO activity resistant against inhibition by glutathione peroxidase activity, and this effect of OAG is reversed by phospholipids. Intriguingly, a 5-LO mutant lacking tryptophan residues (Trp-13, -75, and -102) important for the binding of the 5-LO C2-like domain to phospholipids was not stimulated by OAG. We conclude that OAG directly stimulates 5-LO by acting at a phospholipid binding site located within the C2-like domain.

  15. Different Movement of Hyolaryngeal Structures by Various Application of Electrical Stimulation in Normal Individuals

    PubMed Central

    Kim, Sae Hyun; Oh, Byung-Mo; Han, Tae Ryun; Jeong, Ho Joong

    2015-01-01

    Objective To identify the differences in the movement of the hyoid bone and the vocal cord with and without electrical stimulation in normal subjects. Methods Two-dimensional motion analysis using a videofluoroscopic swallowing study with and without electrical stimulation was performed. Surface electrical stimulation was applied during swallowing using electrodes placed at three different locations on each subject. All subjects were analyzed three times using the following electrode placements: with one pair of electrodes on the suprahyoid muscles and a second pair on the infrahyoid muscles (SI); with placement of the electrode pairs on only the infrahyoid muscles (IO); and with the electrode pairs placed vertically on the suprahyoid and infrahyoid muscles (SIV). Results The main outcomes of this study demonstrated an initial downward displacement as well as different movements of the hyoid bone with the three electrode placements used for electrical stimulation. The initial positions of the hyoid bone with the SI and IO placements resulted in an inferior and anterior displaced position. During swallowing, the hyoid bone moved in a more superior and less anterior direction, resulting in almost the same peak position compared with no electrical stimulation. Conclusion These results demonstrate that electrical stimulation caused an initial depression of the hyoid bone, which had nearly the same peak position during swallowing. Electrical stimulation during swallowing was not dependent on the position of the electrode on the neck, such as on the infrahyoid or on both the suprahyoid and infrahyoid muscles. PMID:26361589

  16. Electrical foot stimulation and implications for the prevention of venous thromboembolic disease.

    PubMed

    Kaplan, Robert E; Czyrny, James J; Fung, Tat S; Unsworth, John D; Hirsh, Jack

    2002-08-01

    Venous stasis caused by immobility is an important risk factor for deep vein thrombosis following surgery and lower limb trauma, in bed-ridden medical patients, and in high-risk long distance air travelers. A safe and convenient method for reducing venous stasis would be useful in patients while in hospital and after discharge during their rehabilitation. 49 healthy subjects aged 51-76 were seated for 4 hours during which they received mild electrical stimulation of the calf, or sole of the foot (plantar muscles). Popliteal and femoral venous blood flow velocities were measured via doppler ultrasound. The non-stimulated lower extremity served as the simultaneous control. Subjects completed a questionnaire regarding their acceptance and tolerance of the electrical stimulation. There was a significant increase in venous femoral and popliteal blood flow for both calf (p < 0.035, p < 0.003), and plantar muscles (p < 0.0001, p < 0.009) on the stimulated side compared to the unstimulated side. The magnitude of the effect was similar for calf and plantar muscle stimulation. Subjects did not find the experience uncomfortable, and would use an electrical stimulator if told by their physician that they were at risk for developing blood clots. Mild electrical stimulation of the feet, as well as the calf, is a safe effective and convenient method for counteracting venous stasis and therefore has the potential to reduce the risk of deep vein thrombosis and pulmonary embolism for subjects who are immobilized.

  17. Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease.

    PubMed

    Grafton, S T; Turner, R S; Desmurget, M; Bakay, R; Delong, M; Vitek, J; Crutcher, M

    2006-04-25

    To test whether therapeutic unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to normalization in the pattern of brain activation during movement execution and control of movement extent. Six patients with PD were imaged off medication by PET during performance of a visually guided tracking task with the DBS voltage programmed for therapeutic (effective) or subtherapeutic (ineffective) stimulation. Data from patients with PD during ineffective stimulation were compared with a group of 13 age-matched control subjects to identify sites with abnormal patterns of activation. Conjunction analysis was used to identify those areas in patients with PD where activity normalized when they were treated with effective stimulation. For movement execution, effective DBS caused an increase of activation in the supplementary motor area (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation also induced reductions of movement related "overactivity" compared with healthy subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent with the notion that many areas are recruited to compensate for ineffective motor initiation. Normalization of activity related to the control of movement extent was associated with reductions of activity in primary motor cortex, SMA, and basal ganglia. Effective subthalamic nucleus stimulation leads to task-specific modifications with appropriate recruitment of motor areas as well as widespread, nonspecific reductions of compensatory or competing cortical activity.

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

    PubMed

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

    2016-07-01

    Adaptive deep brain stimulation (aDBS) uses feedback from brain signals to guide stimulation. A recent acute trial of unilateral aDBS showed that aDBS can lead to substantial improvements in contralateral hemibody Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and may be superior to conventional continuous DBS in Parkinson's disease (PD). We test whether potential benefits are retained with bilateral aDBS and in the face of concurrent medication. We applied bilateral aDBS in 4 patients with PD undergoing DBS of the subthalamic nucleus. aDBS was delivered bilaterally with independent triggering of stimulation according to the amplitude of β activity at the corresponding electrode. Mean stimulation voltage was 3.0±0.1 volts. Motor assessments consisted of double-blinded video-taped motor UPDRS scores that included both limb and axial features. UPDRS scores were 43% (p=0.04; Cohen's d=1.62) better with aDBS than without stimulation. Motor improvement with aDBS occurred despite an average time on stimulation (ToS) of only 45%. Levodopa was well tolerated during aDBS and led to further reductions in ToS. Bilateral aDBS can improve both axial and limb symptoms and can track the need for stimulation across drug states. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. [Effect of biological electric stimulation on free muscle transfer].

    PubMed

    Yuang, F; Guan, W; Cao, Y

    1997-01-01

    The rectus femoris muscles of rabbits were used as muscle model. The electrical stimulation which resembled the normal motor-unit activity was used to observe its effects on free transferred muscle. After three months, the moist muscle weight (MW), its maximum cross-section area, its contractility and its histochemical characteristics were examined. The results showed that the function and morphology of the muscles were well preserved. These findings might encourage its clinical application.

  20. Myogenic Growth Factor Present in Skeletal Muscle is Purified by Heparin-Affinity Chromatography

    NASA Astrophysics Data System (ADS)

    Kardami, Elissavet; Spector, Dennis; Strohman, Richard C.

    1985-12-01

    A myogenic growth factor has been purified from a skeletal muscle, the anterior latissimus dorsi, of adult chickens. In the range of 1-10 ng, this factor stimulates DNA synthesis as well as protein and muscle-specific myosin accumulation in myogenic cell cultures. Purification is achieved through binding of the factor to heparin. The factor is distinct from transferrin and works synergistically with transferrin in stimulating myogenesis in vitro.

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

    PubMed

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

    2013-10-02

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

  2. The Tympanic Membrane Motion in Forward and Reverse Middle-Ear Sound Transmission

    NASA Astrophysics Data System (ADS)

    Cheng, Jeffrey Tao; Harrington, Ellery; Horwitz, Rachelle; Furlong, Cosme; Rosowski, John J.

    2011-11-01

    Sound-induced displacement of the tympanic membrane (TM) is the first stage in the forward transformation of environmental sound to sound within the inner ear, while displacement of the TM induced by mechanical motions of the ossicular chain is the last stage in the reverse transformation of sound generated within the inner ear to clinically valuable otoacoustic emissions (OAEs). In this study, we use stroboscopic holographic interferometry to study motions of the human cadaveric TM evoked by both forward and reverse stimuli. During forward acoustic stimulation, pure tones from 500 to 10000 Hz are used to stimulate the TM, while reverse stimulation is produced by direct mechanical stimulation of the ossicular chain. The TM surface motions in response to both forward and reverse stimuli show differences and similarities, including the modal motion patterns at specific frequencies as well as the presence and directions of traveling waves on the TM surface.

  3. Not Just "Study Drugs" for the Rich: Stimulants as Moral Tools for Creating Opportunities for Socially Disadvantaged Students.

    PubMed

    Ray, Keisha Shantel

    2016-06-01

    An argument in the cognitive enhancement literature is that using stimulants in populations of healthy but socially disadvantaged individuals mistakenly attributes pathology to nonpathological individuals who experience social inequalities. As the argument goes, using stimulants as cognitive-enhancing drugs to solve the social problem of poorly educated students in inadequate schools misattributes the problem as an individual medical problem, when it is really a collective sociopolitical problem. I challenge this argument on the grounds that not all types of enhancement have to be explained in medical terms, but rather at least one conception of enhancement can be explained in social terms-opportunity maintenance. Therefore, I propose that as a moral requirement we ought to explore whether stimulants could be a means of remedying underprivileged children's experiences of social inequalities that are borne from inadequate schools for the sake of increasing their chances for opportunities and well-being.

  4. Optically stimulated luminescence dosimetry with gypsum wallboard (drywall).

    PubMed

    Thompson, Jeroen W; Burdette, Kevin E; Inrig, Elizabeth L; Dewitt, Regina; Mistry, Rajesh; Rink, W Jack; Boreham, Douglas R

    2010-09-01

    Gypsum wallboard (drywall) represents an attractive target for retrospective dosimetry by optically stimulated luminescence (OSL) in the event of a radiological accident or malicious use of nuclear material. In this study, wallboard is shown to display a radiation-induced luminescence signal (RIS) as well as a natural background signal (NS), which is comparable in intensity to the RIS. Excitation and emission spectra show that maximum luminescence intensity is obtained for stimulation with blue light-emitting diodes (470 nm) and for detection in the ultraviolet region (290-370 nm). It is necessary to decrease the optical stimulation power dramatically in order to adequately separate the RIS from the interfering background signal. The necessary protocols are developed for accurately measuring the absorbed dose as low as 500 mGy and demonstrate that the RIS decays logarithmically with storage time, with complete erasure expected within 1-4 d.

  5. Use of G-CSF-stimulated marrow in allogeneic hematopoietic stem cell transplantation settings: a comprehensive review.

    PubMed

    Chang, Ying-Jun; Huang, Xiao-Jun

    2011-01-01

    In recent years, several researchers have unraveled the previously unrecognized effects of granulocyte colony-stimulating factor (G-CSF) on hematopoiesis and the immune cell functions of bone marrow in healthy donors. In human leukocyte antigen-matched or haploidentical transplant settings, available data have established the safety of using G-CSF-stimulated bone marrow grafts, as well as the ability of this source to produce rapid and sustained engraftment. Interestingly, G-CSF-primed bone marrow transplants could capture the advantages of blood stem cell transplants, without the increased risk of chronic graft-versus-host disease that is associated with blood stem cell transplants. This review summarizes the growing body of evidence that supports the use of G-CSF-stimulated bone marrow grafts as an alternative stem cell source in allogeneic hematopoietic stem cell transplantation. © 2010 John Wiley & Sons A/S.

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

    PubMed Central

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

    2017-01-01

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

  7. A Numerical Study of Factors Affecting Fracture-Fluid Cleanup and Produced Gas/Water in Marcellus Shale: Part II

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Seales, Maxian B.; Dilmore, Robert; Ertekin, Turgay

    Horizontal wells combined with successful multistage-hydraulic-fracture treatments are currently the most-established method for effectively stimulating and enabling economic development of gas-bearing organic-rich shale formations. Fracture cleanup in the stimulated reservoir volume (SRV) is critical to stimulation effectiveness and long-term well performance. But, fluid cleanup is often hampered by formation damage, and post-fracture well performance frequently falls to less than expectations. A systematic study of the factors that hinder fracture-fluid cleanup in shale formations can help optimize fracture treatments and better quantify long-term volumes of produced water and gas. Fracture-fluid cleanup is a complex process influenced by mutliphase flow through porousmore » media (relative permeability hysteresis, capillary pressure), reservoir-rock and -fluid properties, fracture-fluid properties, proppant placement, fracture-treatment parameters, and subsequent flowback and field operations. Changing SRV and fracture conductivity as production progresses further adds to the complexity of this problem. Numerical simulation is the best and most-practical approach to investigate such a complicated blend of mechanisms, parameters, their interactions, and subsequent effect on fracture-fluid cleanup and well deliverability. Here, a 3D, two-phase, dual-porosity model was used to investigate the effect of mutliphase flow, proppant crushing, proppant diagenesis, shut-in time, reservoir-rock compaction, gas slippage, and gas desorption on fracture-fluid cleanup and well performance in Marcellus Shale. Our findings have shed light on the factors that substantially constrain efficient fracture-fluid cleanup in gas shales, and we have provided guidelines for improved fracture-treatment designs and water management.« less

  8. Methodology for assessing quantities of water and proppant injection, and water production associated with development of continuous petroleum accumulations

    USGS Publications Warehouse

    Haines, Seth S.

    2015-07-13

    The quantities of water and hydraulic fracturing proppant required for producing petroleum (oil, gas, and natural gas liquids) from continuous accumulations, and the quantities of water extracted during petroleum production, can be quantitatively assessed using a probabilistic approach. The water and proppant assessment methodology builds on the U.S. Geological Survey methodology for quantitative assessment of undiscovered technically recoverable petroleum resources in continuous accumulations. The U.S. Geological Survey assessment methodology for continuous petroleum accumulations includes fundamental concepts such as geologically defined assessment units, and probabilistic input values including well-drainage area, sweet- and non-sweet-spot areas, and success ratio within the untested area of each assessment unit. In addition to petroleum-related information, required inputs for the water and proppant assessment methodology include probabilistic estimates of per-well water usage for drilling, cementing, and hydraulic-fracture stimulation; the ratio of proppant to water for hydraulic fracturing; the percentage of hydraulic fracturing water that returns to the surface as flowback; and the ratio of produced water to petroleum over the productive life of each well. Water and proppant assessments combine information from recent or current petroleum assessments with water- and proppant-related input values for the assessment unit being studied, using Monte Carlo simulation, to yield probabilistic estimates of the volume of water for drilling, cementing, and hydraulic fracture stimulation; the quantity of proppant for hydraulic fracture stimulation; and the volumes of water produced as flowback shortly after well completion, and produced over the life of the well.

  9. A Numerical Study of Factors Affecting Fracture-Fluid Cleanup and Produced Gas/Water in Marcellus Shale: Part II

    DOE PAGES

    Seales, Maxian B.; Dilmore, Robert; Ertekin, Turgay; ...

    2017-04-01

    Horizontal wells combined with successful multistage-hydraulic-fracture treatments are currently the most-established method for effectively stimulating and enabling economic development of gas-bearing organic-rich shale formations. Fracture cleanup in the stimulated reservoir volume (SRV) is critical to stimulation effectiveness and long-term well performance. But, fluid cleanup is often hampered by formation damage, and post-fracture well performance frequently falls to less than expectations. A systematic study of the factors that hinder fracture-fluid cleanup in shale formations can help optimize fracture treatments and better quantify long-term volumes of produced water and gas. Fracture-fluid cleanup is a complex process influenced by mutliphase flow through porousmore » media (relative permeability hysteresis, capillary pressure), reservoir-rock and -fluid properties, fracture-fluid properties, proppant placement, fracture-treatment parameters, and subsequent flowback and field operations. Changing SRV and fracture conductivity as production progresses further adds to the complexity of this problem. Numerical simulation is the best and most-practical approach to investigate such a complicated blend of mechanisms, parameters, their interactions, and subsequent effect on fracture-fluid cleanup and well deliverability. Here, a 3D, two-phase, dual-porosity model was used to investigate the effect of mutliphase flow, proppant crushing, proppant diagenesis, shut-in time, reservoir-rock compaction, gas slippage, and gas desorption on fracture-fluid cleanup and well performance in Marcellus Shale. Our findings have shed light on the factors that substantially constrain efficient fracture-fluid cleanup in gas shales, and we have provided guidelines for improved fracture-treatment designs and water management.« less

  10. Effect of short peptides on expression of signaling molecules in organotypic pineal cell culture.

    PubMed

    Khavinson, V Kh; Linkova, N S; Chalisova, N I; Dudkov, A V; Koncevaya, E A

    2011-11-01

    We demonstrated the influence of short peptides on the expression of signaling molecules in organotypic culture of the pineal gland from 3-month-old rats. Peptides Ala-Glu-Asp-Gly and Lys-Glu-Asp stimulate the expression of proliferative protein Ki-67 in pineal gland culture. These peptides as well as Glu-Asp-Arg and Lys-Glu do not affect the expression of apoptosis marker AIF. The synthesis of transcription factor CGRP by pinealocytes was stimulated only by Ala-Glu-Asp-Gly. Thus, peptide Ala-Glu-Asp-Gly tissue-specifically stimulates proliferative and secretory activities of pinealocytes, which can be used for recovery of pineal gland functions at the molecular level.

  11. The Importance of Accuracy, Stimulating writing, and Relevance in Middle School Science Textbook Writing

    NASA Astrophysics Data System (ADS)

    Hubisz, John

    2004-05-01

    While accuracy in Middle School science texts is most important, the texts should also read well, stimulating the student to want to go on, and the material must be relevant to the subject at hand as the typical student is not yet prepared to ignore that which is irrelevant. We know that children will read if the material is of interest (witness The Lord of the Rings and the Harry Potter book sales) and so we must write in a way that stimulates the student to want to examine the subject further and eliminate that which adds nothing to the discipline. Examples of the good and the bad will be presented.

  12. [Methods of brain stimulation based on weak electric current--future tool for the clinician?].

    PubMed

    Kotilainen, Tuukka; Lehto, Soili M

    2016-01-01

    Methods of brain stimulation based on a weak electric current are non-invasive neuromodulation techniques. They include transcranial direct current, alternating current and random noise stimulation. These methods modify the membrane potential of neurons without triggering the action potential, and have been successfully utilized to influence cognition and regulation of emotions in healthy experimental subjects. In clinical studies, indications of the efficacy of these techniques have been obtained in the treatment of depression, schizophrenia, memory disorders and pain as well as in stroke rehabilitation. It is hoped that these techniques will become established as part of the care and rehabilitation of psychiatric and neurologic patients in the future.

  13. Methylphenidate Abuse and Psychiatric Side Effects

    PubMed Central

    Morton, W. Alexander; Stockton, Gwendolyn G.

    2000-01-01

    Methylphenidate is a central nervous system stimulant drug that has become the primary drug of choice in treating attention-deficit/hyperactivity disorder in children. Side effects are usually mild and are generally well tolerated by patients. Along with increases in prescribing frequency, the potential for abuse has increased. Intranasal abuse produces effects rapidly that are similar to the effects of cocaine in both onset and type. The clinical picture of stimulant abuse produces a wide array of psychiatric symptoms. There is little in the literature to differentiate methylphenidate from other stimulants when they are abused. The need for education of all involved with the use of methylphenidate is discussed to help prevent an increasing pattern of methylphenidate abuse. PMID:15014637

  14. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Gaoming; Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Normal University, Fuzhou 350007; Gao, Fei

    Multiple stimulated emission fluorescence photoacoustic (MSEF-PA) phenomenon is demonstrated in this letter. Under simultaneous illumination of pumping light and stimulated emission light, the fluorescence emission process is speeded up by the stimulated emission effect. This leads to nonlinear enhancement of photoacoustic signal while the quantity of absorbed photons is more than that of fluorescent molecules illuminated by pumping light. The electronic states' specificity of fluorescent molecular can also be labelled by the MSEF-PA signals, which can potentially be used to obtain fluorescence excitation spectrum in deep scattering tissue with nonlinearly enhanced photoacoustic detection. In this preliminary study, the fluorescence excitationmore » spectrum is reconstructed by MSEF-PA signals through sweeping the wavelength of exciting light, which confirms the theoretical derivation well.« less

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

    PubMed

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

    2018-01-01

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

  16. [Thoracic surgery for patients with bronchial asthma].

    PubMed

    Iyoda, A; Satoh, Y

    2012-07-01

    Thoracic surgery poses a risk for complications in the respiratory system. In particular, for patients with bronchial asthma, we need to care for perioperative complications because it is well known that these patients frequently have respiratory complications after surgery, and they may have bronchial spasms during surgery. If we can get good control of their bronchial asthma, we can usually perform surgery for these patients without limitations. For safe postoperative care, it is desirable that these patients have stable asthma conditions that are well-controlled before surgery, as thoracic surgery requires intrabronchial intubation for anesthesia and sometimes bronchial resection. These stimulations to the bronchus do not provide for good conditions because of the risk of bronchial spasm. Therefore, we should use the same agents that are used to control bronchial asthma if it is already well controlled. If it is not, we have to administer a β₂ stimulator, aminophylline, or steroidal agents for good control. Isoflurane or sevoflurane are effective for the safe control of anesthesia during surgery, and we should use a β₂ stimulator, with or without inhalation, or steroidal agents after surgery. It is important to understand that we can perform thoracic surgery for asthma patients if we can provide perioperative control of bronchial asthma, although these patients still have severe risks.

  17. Stimulants of Toll-like receptor (TLR)-2 and TLR-4 are abundant in certain minimally-processed vegetables.

    PubMed

    Erridge, Clett

    2011-06-01

    Stimulants of the innate immune receptors Toll-like receptor (TLR)-2 and TLR4 have been shown to promote insulin resistance and atherosclerosis in animal models of these diseases. As minimally processed vegetables (MPV) can contain a relatively large bacterial load compared to other foodstuffs, we aimed to quantify the abundance of stimulants of TLR2 and TLR4 in MPV using a transfection-based bioassay calibrated with Escherichia coli LPS and the synthetic lipopeptide Pam(3)CSK(4). Of 5 classes of MPV and 3 classes of related vegetable products considered to be likely to contain a high microbial load, diced onion and bean sprouts contained the highest levels of stimulants of TLR2 (up to 18.5 μg Pam(3)CSK(4)-equivalents per g) and TLR4 (up to 11.4 μg LPS-equivalents per g). By contrast, the majority of fresh whole vegetables examined reproducibly contained minimal or undetectable levels of TLR2- or TLR4-stimulants. The accumulation of TLR-stimulants in MPVs correlated well with growth of enterobacterial spoilage organisms. In conclusion, the modern trend towards eating minimally processed vegetables rather than whole foods is likely to be associated with increased oral exposure to stimulants of TLR2 and TLR4. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Intensive gait training with rhythmic auditory stimulation in individuals with chronic hemiparetic stroke: a pilot randomized controlled study.

    PubMed

    Cha, Yuri; Kim, Young; Hwang, Sujin; Chung, Yijung

    2014-01-01

    Motor relearning protocols should involve task-oriented movement, focused attention, and repetition of desired movements. To investigate the effect of intensive gait training with rhythmic auditory stimulation on postural control and gait performance in individuals with chronic hemiparetic stroke. Twenty patients with chronic hemiparetic stroke participated in this study. Subjects in the Rhythmic auditory stimulation training group (10 subjects) underwent intensive gait training with rhythmic auditory stimulation for a period of 6 weeks (30 min/day, five days/week), while those in the control group (10 subjects) underwent intensive gait training for the same duration. Two clinical measures, Berg balance scale and stroke specific quality of life scale, and a 2-demensional gait analysis system, were used as outcome measure. To provide rhythmic auditory stimulation during gait training, the MIDI Cuebase musical instrument digital interface program and a KM Player version 3.3 was utilized for this study. Intensive gait training with rhythmic auditory stimulation resulted in significant improvement in scores on the Berg balance scale, gait velocity, cadence, stride length and double support period in affected side, and stroke specific quality of life scale compared with the control group after training. Findings of this study suggest that intensive gait training with rhythmic auditory stimulation improves balance and gait performance as well as quality of life, in individuals with chronic hemiparetic stroke.

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

    NASA Technical Reports Server (NTRS)

    Koehne, Jessica E.

    2016-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Koehne, Jessica E.

    2016-01-01

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

  1. Functional connectivity and activity of white matter in somatosensory pathways under tactile stimulations.

    PubMed

    Wu, Xi; Yang, Zhipeng; Bailey, Stephen K; Zhou, Jiliu; Cutting, Laurie E; Gore, John C; Ding, Zhaohua

    2017-05-15

    Functional MRI has proven to be effective in detecting neural activity in brain cortices on the basis of blood oxygenation level dependent (BOLD) contrast, but has relatively poor sensitivity for detecting neural activity in white matter. To demonstrate that BOLD signals in white matter are detectable and contain information on neural activity, we stimulated the somatosensory system and examined distributions of BOLD signals in related white matter pathways. The temporal correlation profiles and frequency contents of BOLD signals were compared between stimulation and resting conditions, and between relevant white matter fibers and background regions, as well as between left and right side stimulations. Quantitative analyses show that, overall, MR signals from white matter fiber bundles in the somatosensory system exhibited significantly greater temporal correlations with the primary sensory cortex and greater signal power during tactile stimulations than in a resting state, and were stronger than corresponding measurements for background white matter both during stimulations and in a resting state. The temporal correlation and signal power under stimulation were found to be twice those observed from the same bundle in a resting state, and bore clear relations with the side of stimuli. These indicate that BOLD signals in white matter fibers encode neural activity related to their functional roles connecting cortical volumes, which are detectable with appropriate methods. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Application of describing function analysis to a model of deep brain stimulation.

    PubMed

    Davidson, Clare Muireann; de Paor, Annraoi M; Lowery, Madeleine M

    2014-03-01

    Deep brain stimulation effectively alleviates motor symptoms of medically refractory Parkinson's disease, and also relieves many other treatment-resistant movement and affective disorders. Despite its relative success as a treatment option, the basis of its efficacy remains elusive. In Parkinson's disease, increased functional connectivity and oscillatory activity occur within the basal ganglia as a result of dopamine loss. A correlative relationship between pathological oscillatory activity and the motor symptoms of the disease, in particular bradykinesia, rigidity, and tremor, has been established. Suppression of the oscillations by either dopamine replacement or DBS also correlates with an improvement in motor symptoms. DBS parameters are currently chosen empirically using a "trial and error" approach, which can be time-consuming and costly. The work presented here amalgamates concepts from theories of neural network modeling with nonlinear control engineering to describe and analyze a model of synchronous neural activity and applied stimulation. A theoretical expression for the optimum stimulation parameters necessary to suppress oscillations is derived. The effect of changing stimulation parameters (amplitude and pulse duration) on induced oscillations is studied in the model. Increasing either stimulation pulse duration or amplitude enhanced the level of suppression. The predicted parameters were found to agree well with clinical measurements reported in the literature for individual patients. It is anticipated that the simplified model described may facilitate the development of protocols to aid optimum stimulation parameter choice on a patient by patient basis.

  3. Application of noninvasive brain stimulation for post-stroke dysphagia rehabilitation.

    PubMed

    Wang, Zhuo; Song, Wei-Qun; Wang, Liang

    2017-02-01

    Noninvasive brain stimulation (NIBS), commonly consisting of transcranial magnetic stimulation (TMS), transcranial direct-current stimulation (tDCS), as well as paired associative stimulation (PAS), has attracted increased interest and been applied experimentally in the treatment of post-stroke dysphagia (PSD). This review presented a synopsis of the current research for the application of NIBS on PSD. The intention here was to understand the current research progress and limitations in this field and to stimulate potential research questions not yet investigated for the application of NIBS on patients with PSD. Here we successively reviewed advances of repetitive TMS (rTMS), tDCS, and PAS techniques on both healthy participants and PSD patients in three aspects, including scientific researches about dysphagia mechanism, applied studies about stimulation parameters, and clinical trials about their therapeutic effects. The techniques of NIBS, especially rTMS, have been used by the researchers to explore the different mechanisms between swallowing recovery and extremity rehabilitation. The key findings included the important role of intact hemisphere reorganization for PSD recovery, and the use of NIBS on the contra-lesional side as a therapeutic potential for dysphagia rehabilitation. Though significant results were achieved in most studies by using NIBS on swallowing rehabilitation, it is still difficult to draw conclusions for the efficacy of these neurostimulation techniques, considering the great disparities between studies. Copyright © 2016. Published by Elsevier Taiwan.

  4. A functional electrical stimulation system for human walking inspired by reflexive control principles.

    PubMed

    Meng, Lin; Porr, Bernd; Macleod, Catherine A; Gollee, Henrik

    2017-04-01

    This study presents an innovative multichannel functional electrical stimulation gait-assist system which employs a well-established purely reflexive control algorithm, previously tested in a series of bipedal walking robots. In these robots, ground contact information was used to activate motors in the legs, generating a gait cycle similar to that of humans. Rather than developing a sophisticated closed-loop functional electrical stimulation control strategy for stepping, we have instead utilised our simple reflexive model where muscle activation is induced through transfer functions which translate sensory signals, predominantly ground contact information, into motor actions. The functionality of the functional electrical stimulation system was tested by analysis of the gait function of seven healthy volunteers during functional electrical stimulation-assisted treadmill walking compared to unassisted walking. The results demonstrated that the system was successful in synchronising muscle activation throughout the gait cycle and was able to promote functional hip and ankle movements. Overall, the study demonstrates the potential of human-inspired robotic systems in the design of assistive devices for bipedal walking.

  5. Experimental studies of gastric dysfunction in motion sickness: The effect of gastric and vestibular stimulation on the vagal and splanchnic gastric efferents

    NASA Technical Reports Server (NTRS)

    Niijima, A.; Jiang, Z. Y.; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    The experiments were conducted in anaesthetized rats. In the first part of the experiments, the effect of CuSO4 on the afferent activity in the gastric branch of the vagus nerve was investigated. Gastric perfusion of CuSO4 solution (0.04 percent and 0.08 percent) provoked an increase in afferent activity. In the second part of the experiments, the reflex effects of gastric perfusion of CuSO4 solution, repetitive stimulation of the gastric vagus nerve, and caloric stimulation of the right vestibular apparatus (5-18 C water) on gastric autonomic outflow were investigated. The results of these experiments showed that these three different types of stimulation caused an inhibition in efferent activity of the gastric vagus nerve and a slight activation of the splanchnic gastric efferents. The summation of the effect of each stimulation was also observed. These results, therefore, provide evidence for a possible integrative inhibitory function of the vagal gastric center as well as an excitatory function of gastric sympathetic motoneurons in relation to motion sickness.

  6. Treating Clinical Depression with Repetitive Deep Transcranial Magnetic Stimulation Using the Brainsway H1-coil.

    PubMed

    Feifel, David; Pappas, Katherine

    2016-10-04

    Repetitive transcranial magnetic stimulation (rTMS) is an emerging non-pharmacological approach to treating many brain-based disorders. rTMS uses electromagnetic coils to stimulate areas of the brain non-invasively. Deep transcranial magnetic stimulation (dTMS) with the Brainsway H1-coil system specifically is a type of rTMS indicated for treating patients with major depressive disorder (MDD) who are resistant to medication. The unique H1-coil design of this device is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. dTMS is considered to be low-risk and well tolerated, making it a viable treatment option for people who have not responded to medication or psychotherapy trials for their depression. Randomized, sham-control studies have demonstrated that dTMS produces significantly greater improvement in depressive symptoms than sham dTMS treatment in patients with major depression that has not responded to antidepressant medication. In this paper, we will review the methodology for treating major depression with dTMS using an H1-coil.

  7. Single embryo transfer: the role of natural cycle/minimal stimulation IVF in the future.

    PubMed

    Nygren, Karl-Gösta

    2007-05-01

    There are several good reasons to assume that single embryo transfer (SET) eventually will become the norm internationally in IVF treatments. A tendency is clearly visible, as demonstrated in the latest IVF World Report. The Nordic countries and Belgium have been leading the way. Sweden at present has 70% SET, with 5% twins and a pregnancy rate per transfer remaining constant at about 30%. As a consequence, recent data show a drastic reduction of the risk of prematurity and therefore of child morbidity and perinatal mortality. It is now time to discuss alternatives to the current clinical policy of quite an aggressive ovarian stimulation in settings where SET is the norm. When and at what proportion could natural cycle/soft stimulation be used? What group of patients would benefit? What will the consequences be in terms of efficacy, safety, cost, time and quality of life? Selection of the most beneficial, rather than the most aggressive, ovarian stimulation protocol by clinicians and by the couples themselves in the future may well include a much wider use of natural cycle/soft stimulation in IVF.

  8. EMMPRIN Is Secreted by Human Uterine Epithelial Cells in Microvesicles and Stimulates Metalloproteinase Production by Human Uterine Fibroblast Cells

    PubMed Central

    Dayger, C. A.; Mehrotra, P.; Belton, R. J.; Nowak, R. A.

    2012-01-01

    Endometrial remodeling is a physiological process involved in the gynecological disease, endometriosis. Tissue remodeling is directed by uterine fibroblast production of matrix metalloproteinases (MMPs). Several MMPs are regulated directly by the protein extracellular matrix metalloproteinase inducer (EMMPRIN) and also by proinflammatory cytokines such as interleukin (IL)1-α/β. We hypothesized that human uterine epithelial cells (HESs) secrete intact EMMPRIN to stimulate MMPs. Microvesicles from HES cell-conditioned medium (CM) expressed intact EMMPRIN protein. Treatment of HES cells with estradiol or phorbyl 12-myristate-13-acetate increased the release of EMMPRIN-containing microvesicles. The HES CM stimulated MMP-1, -2, and -3 messenger RNA levels in human uterine fibroblasts (HUFs) and EMMPRIN immunodepletion from HES-cell concentrated CM reduced MMP stimulation (P < .05). Treatment of HUF cells with low concentrations of IL-1β/α stimulated MMP production (P < .05). These results indicate that HES cells regulate MMP production by HUF cells by secretion of EMMPRIN, in response to ovarian hormones, proinflammatory cytokines as well as activation of protein kinase C. PMID:22729071

  9. EMMPRIN is secreted by human uterine epithelial cells in microvesicles and stimulates metalloproteinase production by human uterine fibroblast cells.

    PubMed

    Braundmeier, A G; Dayger, C A; Mehrotra, P; Belton, R J; Nowak, R A

    2012-12-01

    Endometrial remodeling is a physiological process involved in the gynecological disease, endometriosis. Tissue remodeling is directed by uterine fibroblast production of matrix metalloproteinases (MMPs). Several MMPs are regulated directly by the protein extracellular matrix metalloproteinase inducer (EMMPRIN) and also by proinflammatory cytokines such as interleukin (IL)1-α/β. We hypothesized that human uterine epithelial cells (HESs) secrete intact EMMPRIN to stimulate MMPs. Microvesicles from HES cell-conditioned medium (CM) expressed intact EMMPRIN protein. Treatment of HES cells with estradiol or phorbyl 12-myristate-13-acetate increased the release of EMMPRIN-containing microvesicles. The HES CM stimulated MMP-1, -2, and -3 messenger RNA levels in human uterine fibroblasts (HUFs) and EMMPRIN immunodepletion from HES-cell concentrated CM reduced MMP stimulation (P < .05). Treatment of HUF cells with low concentrations of IL-1β/α stimulated MMP production (P < .05). These results indicate that HES cells regulate MMP production by HUF cells by secretion of EMMPRIN, in response to ovarian hormones, proinflammatory cytokines as well as activation of protein kinase C.

  10. Retinal stimulation strategies to restore vision: Fundamentals and systems.

    PubMed

    Yue, Lan; Weiland, James D; Roska, Botond; Humayun, Mark S

    2016-07-01

    Retinal degeneration, a leading cause of blindness worldwide, is primarily characterized by the dysfunctional/degenerated photoreceptors that impair the ability of the retina to detect light. Our group and others have shown that bioelectronic retinal implants restore useful visual input to those who have been blind for decades. This unprecedented approach of restoring sight demonstrates that patients can adapt to new visual input, and thereby opens up opportunities to not only improve this technology but also develop alternative retinal stimulation approaches. These future improvements or new technologies could have the potential of selectively stimulating specific cell classes in the inner retina, leading to improved visual resolution and color vision. In this review we will detail the progress of bioelectronic retinal implants and future devices in this genre as well as discuss other technologies such as optogenetics, chemical photoswitches, and ultrasound stimulation. We will discuss the principles, biological aspects, technology development, current status, clinical outcomes/prospects, and challenges for each approach. The review will cover functional imaging documented cortical responses to retinal stimulation in blind patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. The influence of functional electrical stimulation on hand motor recovery in stroke patients: a review.

    PubMed

    Quandt, Fanny; Hummel, Friedhelm C

    2014-01-01

    Neuromuscular stimulation has been used as one potential rehabilitative treatment option to restore motor function and improve recovery in patients with paresis. Especially stroke patients who often regain only limited hand function would greatly benefit from a therapy that enhances recovery and restores movement. Multiple studies investigated the effect of functional electrical stimulation on hand paresis, the results however are inconsistent. Here we review the current literature on functional electrical stimulation on hand motor recovery in stroke patients. We discuss the impact of different parameters such as stage after stoke, degree of impairment, spasticity and treatment protocols on the functional outcome. Importantly, we outline the results from recent studies investigating the cortical effects elicited by functional electrical stimulation giving insights into the underlying mechanisms responsible for long-term treatment effects. Bringing together the findings from present research it becomes clear that both, treatment outcomes as well as the neurophysiologic mechanisms causing functional recovery, vary depending on patient characteristics. In order to develop unified treatment guidelines it is essential to conduct homogenous studies assessing the impact of different parameters on rehabilitative success.

  12. The influence of functional electrical stimulation on hand motor recovery in stroke patients: a review

    PubMed Central

    2014-01-01

    Neuromuscular stimulation has been used as one potential rehabilitative treatment option to restore motor function and improve recovery in patients with paresis. Especially stroke patients who often regain only limited hand function would greatly benefit from a therapy that enhances recovery and restores movement. Multiple studies investigated the effect of functional electrical stimulation on hand paresis, the results however are inconsistent. Here we review the current literature on functional electrical stimulation on hand motor recovery in stroke patients. We discuss the impact of different parameters such as stage after stoke, degree of impairment, spasticity and treatment protocols on the functional outcome. Importantly, we outline the results from recent studies investigating the cortical effects elicited by functional electrical stimulation giving insights into the underlying mechanisms responsible for long-term treatment effects. Bringing together the findings from present research it becomes clear that both, treatment outcomes as well as the neurophysiologic mechanisms causing functional recovery, vary depending on patient characteristics. In order to develop unified treatment guidelines it is essential to conduct homogenous studies assessing the impact of different parameters on rehabilitative success. PMID:25276333

  13. Evaluation of Intradural Stimulation Efficiency and Selectivity in a Computational Model of Spinal Cord Stimulation

    PubMed Central

    Howell, Bryan; Lad, Shivanand P.; Grill, Warren M.

    2014-01-01

    Spinal cord stimulation (SCS) is an alternative or adjunct therapy to treat chronic pain, a prevalent and clinically challenging condition. Although SCS has substantial clinical success, the therapy is still prone to failures, including lead breakage, lead migration, and poor pain relief. The goal of this study was to develop a computational model of SCS and use the model to compare activation of neural elements during intradural and extradural electrode placement. We constructed five patient-specific models of SCS. Stimulation thresholds predicted by the model were compared to stimulation thresholds measured intraoperatively, and we used these models to quantify the efficiency and selectivity of intradural and extradural SCS. Intradural placement dramatically increased stimulation efficiency and reduced the power required to stimulate the dorsal columns by more than 90%. Intradural placement also increased selectivity, allowing activation of a greater proportion of dorsal column fibers before spread of activation to dorsal root fibers, as well as more selective activation of individual dermatomes at different lateral deviations from the midline. Further, the results suggest that current electrode designs used for extradural SCS are not optimal for intradural SCS, and a novel azimuthal tripolar design increased stimulation selectivity, even beyond that achieved with an intradural paddle array. Increased stimulation efficiency is expected to increase the battery life of implantable pulse generators, increase the recharge interval of rechargeable implantable pulse generators, and potentially reduce stimulator volume. The greater selectivity of intradural stimulation may improve the success rate of SCS by mitigating the sensitivity of pain relief to malpositioning of the electrode. The outcome of this effort is a better quantitative understanding of how intradural electrode placement can potentially increase the selectivity and efficiency of SCS, which, in turn, provides predictions that can be tested in future clinical studies assessing the potential therapeutic benefits of intradural SCS. PMID:25536035

  14. Brain stimulation in posttraumatic stress disorder

    PubMed Central

    Novakovic, Vladan; Sher, Leo; Lapidus, Kyle A.B.; Mindes, Janet; A.Golier, Julia; Yehuda, Rachel

    2011-01-01

    Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in reducing anxiety, findings that may suggest possible utility in relieving PTSD-associated anxiety. Treatment of animal models of PTSD with DBS suggests potential human benefit. Additional research and novel treatment options for PTSD are urgently needed. The potential usefulness of brain stimulation in treating PTSD deserves further exploration. PMID:22893803

  15. Changes and challenges: managing ADHD in a fast-paced world.

    PubMed

    Manos, Michael J; Tom-Revzon, Catherine; Bukstein, Oscar G; Crismon, M Lynn

    2007-11-01

    Attention-deficit/hyperactivity disorder (ADHD) impairs the lives of both children and adults. Undiagnosed and untreated, ADHD may have serious lifelong consequences. Research has identified diagnostic clues, neurotransmitter pathways, and psychiatric comorbidities related to ADHD, as well as effective pharmacologic, behavioral, and psychosocial interventions. Stimulant agents have been the foundation of ADHD therapy for more than 50 years. Availability of new extended-release (XR or ER) and longer-acting (LA) formulations and novel agents allows for wider and more individualized treatment choices. Side effects of stimulants are generally mild, short lived, and responsive to adjustments in dosage or timing. Outcomes in ADHD treatment can be improved with the use of clear treatment guidelines and tools to aid clinicians in implementing them efficiently and effectively. The Texas Children's Medication Algorithm Project (CMAP) provides a system of algorithm-driven treatment decisions that is evidence based and easy to implement. To (1) review the psychological components of attention, the neurotransmitter pathways associated with ADHD, and the array of therapeutic options for ADHD, with an emphasis on the most recent introductions to the therapeutic armamentarium; (2) discuss the rare psychiatric and cardiovascular side effects associated with stimulants; (3) review abuse liability, comorbidities, and suggested approaches to these issues; and (4) review the development and use of CMAP and offer resources for its implementation in clinical practice. The pathophysiology of ADHD is linked to dysfunction of fronto-subcortical networks and dysregulation of dopaminergic, noradrenergic, and nicotinic neurotransmitter systems. An additive effect of multiple genes as well as environmental influences contributes to the clinical picture. Treatment with stimulants and nonstimulants has proven effective in different subgroups, with the effectiveness of specific agents most likely related to the primary neurotransmitter involved. Availability of XR, ER, LA, and transdermal stimulant formulations, as well as alternative nonstimulant agents, offers new options for the pharmacotherapy of ADHD. Major concerns associated with abuse liability of stimulants have been allayed by the availability of ER formulations, which have reduced reinforcing effects associated with short-acting preparations. Medication outcomes in ADHD can be enhanced by the use of evidence-based algorithms such as CMAP. Keys to success are adequate initial assessment and diagnosis, the use of sustained-release products, sufficient dose titration, and the use of clinical rating scales with feedback from caregivers and teachers. Optimal treatment outcomes can be achieved by appropriate pharmacotherapy combined with psychosocial interventions.

  16. Active and passive seismic imaging of a hydraulic fracture in diatomite

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vinegar, H.J.; Wills, P.B.; De Martini, D.C.

    1992-01-01

    This paper reports on a comprehensive set of experiments including remote- and treatment-well microseismic monitoring, interwell shear-wave shadowing, and surface tiltmeter arrays, that was used to monitor the growth of a hydraulic fracture in the Belridge diatomite. To obtain accurate measurements, and extensive subsurface network of geophones was cemented spanning the diatomite formation in three closely spaced observation wells around the well to be fracture treated. Data analysis indicates that the minifracture and main hydraulic fracture stimulations resulted in a nearly vertical fracture zone (striking N26{degrees}E) vertically segregated into two separate elements, the uppermost of which grew 60 ft abovemore » the perforated interval. The interwell seismic effects are consistent with a side process zone of reduced shear velocity, which remote-well microseismic data independently suggest may be as wide as 40 ft. The experiments indicate complicated processes occurring during hydraulic fracturing that have significant implications for stimulation, waterflooding, in fill drilling, and EOR. These processes are neither well understood nor included in current hydraulic fracture models.« less

  17. Vagus nerve stimulation therapy in partial epilepsy: a review.

    PubMed

    Panebianco, Mariangela; Zavanone, Chiara; Dupont, Sophie; Restivo, Domenico A; Pavone, Antonino

    2016-09-01

    Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked epileptic seizures. The majority of people given a diagnosis of epilepsy have a good prognosis, but 20-30 % will develop drug-resistant epilepsy. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with medically refractory epilepsy. It consists of chronic intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator (Neuro-Cybernetic Prosthesis). In 1997, the Food and Drug Administration approved VNS as adjunctive treatment for medically refractory partial-onset seizures in adults and adolescents. This article reviews the literature from 1988 to nowadays. We discuss thoroughly the anatomy and physiology of vagus nerve and the potential mechanisms of actions and clinical applications involved in VNS therapy, as well as the management, safety, tolerability and effectiveness of VNS therapy. VNS for partial seizures appears to be an effective and well tolerated treatment in adult and pediatric patients. People noted improvements in feelings of well-being, alertness, memory and thinking skills, as well as mood. The adverse effect profile is substantially different from the adverse effect profile associated with antiepileptic drugs, making VNS a potential alternative for patients with difficulty tolerating antiepileptic drug adverse effects. Despite the passing years and the advent of promising neuromodulation technologies, VNS remains an efficacy treatment for people with medically refractory epilepsy. Past and ongoing investigations in other indications have provided signals of the therapeutic potential in a wide variety of conditions.

  18. DOE Office of Scientific and Technical Information (OSTI.GOV)

    J. Ford Brett; Robert V. Westermark

    This Technical Quarterly Report is for the reporting period March 31, 2002 to June 30, 2002. The report provides details of the work done on the project entitled ''Enhanced Oil Recovery with Downhole Vibration Stimulation in Osage County Oklahoma''. The project is divided into nine separate tasks. Several of the tasks are being worked on simultaneously, while other tasks are dependent on earlier tasks being completed. The vibration stimulation Well 111-W-27 is located in section 8 T26N R6E of the North Burbank Unit (NBU), Osage County Oklahoma. It was drilled to 3090-feet cored, logged, cased and cemented. The rig movedmore » off August 6, 2001. Phillips Petroleum Co. has performed several core studies on the cores recovered from the test well. Standard porosity, permeability and saturation measurements have been conducted. In addition Phillips has prepared a Core Petrology Report, detailing the lithology, stratigraphy and sedimentology for Well 111-W27, NBU. Phillips has also conducted the sonic stimulation core tests, the final sonic stimulation report has not yet been released. Calumet Oil Company, the operator of the NBU, began collecting both production and injection wells information to establish a baseline for the project in the pilot field test area since May 2001. The original 7-inch Downhole Vibration Tool (DHVT) has been thoroughly tested and it has been concluded that it needs to be redesigned. An engineering firm from Fayetteville AR has been retained to assist in developing a new design for the DHVT. The project participants requested from the DOE, a no-cost extension for the project through December 31, 2002. The no-cost extension amendment to the contract was signed during this reporting period. A technical paper SPE 75254 ''Enhanced Oil Recovery with Downhole Vibration Stimulation, Osage County, Oklahoma'' was presented at the 2002 SPE/DOE Thirteenth Symposium on Improved Oil Recovery, in Tulsa OK, April 17, 2002. A one-day short course was conducted at the SPE/DOE Thirteenth Symposium on Improved Oil Recovery in Tulsa, OK, April 13-14, 2002. Dan Maloney, Phillips and Bob Westermark, OGCI, Brett Davidson and Tim Spanos, Prism Production Technologies, were the instructors. The sixteen attendees also participated in the half-day field trip to the test facility near Tulsa.« less

  19. Modulation of Experimental Herpes Encephalitis-Associated Neurotoxicity through Sulforaphane Treatment

    PubMed Central

    Schachtele, Scott J.; Hu, Shuxian; Lokensgard, James R.

    2012-01-01

    Reactive oxygen species (ROS) produced by brain-infiltrating macrophages and neutrophils, as well as resident microglia, are pivotal to pathogen clearance during viral brain infection. However, unchecked free radical generation is also responsible for damage to and cytotoxicity of critical host tissue bystander to primary infection. These unwanted effects of excessive ROS are combated by local cellular production of antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutathione peroxidase 1 (Gpx1). In this study, we showed that experimental murine herpes encephalitis triggered robust ROS production, as well as an opposing upregulation of the antioxidants HO-1 and Gpx1. This antioxidant response was insufficient to prevent tissue damage, neurotoxicity, and mortality associated with viral brain infection. Previous studies corroborate our data supporting astrocytes as the major antioxidant producer in brain cell cultures exposed to HSV-1 stimulated microglia. We hypothesized that stimulating opposing antioxidative responses in astrocytes, as well as neurons, would mitigate the effects of ROS-mediated neurotoxicity both in vitro and during viral brain infection in vivo. Here, we demonstrate that the addition of sulforaphane, a potent stimulator of antioxidant responses, enhanced HO-1 and Gpx1 expression in astrocytes through the activation of nuclear factor-E2-related factor 2 (Nrf2). Additionally, sulforaphane treatment was found to be effective in reducing neurotoxicity associated with HSV-stimulated microglial ROS production. Finally, intraperitoneal injections of sulforaphane into mice during active HSV infection reduced neuroinflammation via a decrease in brain-infiltrating leukocytes, macrophage- and neutrophil-produced ROS, and MHCII-positive, activated microglia. These data support a key role for astrocyte-produced antioxidants in modulating oxidative stress and neuronal damage in response to viral infection. PMID:22558388

  20. Chasing Tics in the Human Brain: Development of Open, Scheduled and Closed Loop Responsive Approaches to Deep Brain Stimulation for Tourette Syndrome

    PubMed Central

    Martinez-Ramirez, Daniel; Rossi, Peter J.; Peng, Zhongxing; Gunduz, Aysegul; Okun, Michael S.

    2015-01-01

    Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome. PMID:25851890

  1. The Stimuli-Actions-Effects-Responses (SAER)-framework for exploring perceived relationships between private and public climate change adaptation in agriculture.

    PubMed

    Mitter, Hermine; Schönhart, Martin; Larcher, Manuela; Schmid, Erwin

    2018-03-01

    Empirical findings on actors' roles and responsibilities in the climate change adaptation process are rare even though cooperation between private and public actors is perceived important to foster adaptation in agriculture. We therefore developed the framework SAER (Stimuli-Actions-Effects-Responses) to investigate perceived relationships between private and public climate change adaptation in agriculture at regional scale. In particular, we explore agricultural experts' perceptions on (i) climatic and non-climatic factors stimulating private adaptation, (ii) farm adaption actions, (iii) potential on-farm and off-farm effects from adaptation, and (iv) the relationships between private and public adaptation. The SAER-framework is built on a comprehensive literature review and empirical findings from semi-structured interviews with agricultural experts from two case study regions in Austria. We find that private adaptation is perceived as incremental, systemic or transformational. It is typically stimulated by a mix of bio-physical and socio-economic on-farm and off-farm factors. Stimulating factors related to climate change are perceived of highest relevance for systemic and transformational adaptation whereas already implemented adaptation is mostly perceived to be incremental. Perceived effects of private adaptation are related to the environment, weather and climate, quality and quantity of agricultural products as well as human, social and economic resources. Our results also show that public adaptation can influence factors stimulating private adaptation as well as adaptation effects through the design and development of the legal, policy and organizational environment as well as the provision of educational, informational, financial, and technical infrastructure. Hence, facilitating existing and new collaborations between private and public actors may enable farmers to adapt effectively to climate change. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. [Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing].

    PubMed

    Uvnas-Moberg, Kerstin; Petersson, Maria

    2005-01-01

    The neuroendocrine and physiological systems related to pain and stress have long been subjected to study. More recently, the corresponding systems promoting anti-stress and restoration have also come into focus. It is not only important to investigate the mechanisms underlying disease but also to examine the physiological and psychological mechanisms which protect and heal the body and soul. The nonapeptide oxytocin, originally known to stimulate labour and milk ejection, appears to play an important role in this regard. Oxytocin can induce anti-stress-like effects such as reduction of blood pressure and cortisol levels. It increases pain thresholds, exerts an anxiolytic-like effect and stimulates various types of positive social interaction. In addition, it promotes growth and healing. Repeated exposure to oxytocin causes long-lasting effects by influencing the activity of other transmitter systems, a pattern which makes oxytocin potentially clinically relevant. Oxytocin can be released by various types of non-noxious sensory stimulation, for example by touch and warmth. Ingestion of food triggers oxytocin release by activation of vagal afferents. Most likely, oxytocin can also be released by stimulation of other senses such as olfaction, as well as by certain types of sound and light. In addition, purely psychological mechanisms may trigger the release of oxytocin. This means that positive interaction involving touch and psychological support may be health-promoting. The social interaction of daily life, as well as a positive environment, continuously activate this system. In addition, various types of psychotherapy involving transfer of support, warmth and empathy are likely to induce similar effects, which thus contribute to the positive effects of these kinds of therapies.

  3. Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms

    PubMed Central

    Soto, Cristina; Canedo, Antonio

    2011-01-01

    Abstract Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3–4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5–2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain. PMID:21746779

  4. Intracellular recordings of subnucleus reticularis dorsalis neurones revealed novel electrophysiological properties and windup mechanisms.

    PubMed

    Soto, Cristina; Canedo, Antonio

    2011-09-01

    Aδ- and/or C-fibre nociceptive inputs drive subnucleus reticularis dorsalis (SRD) neurones projecting to a variety of regions including the spinal cord and the nucleus reticularis gigantocellularis (NRGc), but their electrophysiological properties are largely unknown. Here we intracellularly recorded the SRD neuronal responses to injection of polarising current pulses as well as to electrical stimulation of the cervical spinal posterior quadrant (PQ) and the NRGc. Three different classes of neurones with distinct electrophysiological properties were found: type I were characterised by the absence of a fast postspike hyperpolarisation, type II by the presence of a postspike hyperpolarisation followed by a depolarisation resembling low threshold calcium spikes (LTSs), and type III (lacking LTSs) had a fast postspike hyperpolarisation deinactivating A-like potassium channels leading to enlarged interspike intervals. All three classes generated depolarising sags to hyperpolarising current pulses and showed 3-4.5 Hz subthreshold oscillatory activity leading to windup when intracellularly injecting low-frequency repetitive depolarising pulses as well as in response to 0.5-2 Hz NRGc and PQ electrical stimulation. About half of the 132 sampled neurones responded antidromically to NRGc stimulation with more than 65% of the NRGc-antidromic cells, pertaining to all three types, also responding antidromically to PQ stimulation. NRGc stimulation induced exclusively excitatory first-synaptic-responses whilst PQ stimulation induced first-response excitation in most cases, but inhibitory postsynaptic potentials in a few type II and type III neurones not projecting to the spinal cord that also displayed cumulative inhibitory effects (inverse windup). The results show that SRD cells (i) can actively regulate different temporal firing patterns due to their intrinsic electrophysiological properties, (ii) generate windup upon gradual membrane depolarisation produced by low-frequency intracellular current injection and by C-fibre tonic input, both processes leading subthreshold oscillations to threshold, and (iii) collateralise to the NRGc and the spinal cord, potentially providing simultaneous regulation of ascending noxious information and motor reactions to pain.

  5. Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS

    PubMed Central

    Edwards, Dylan; Cortes, Mar; Datta, Abhishek; Minhas, Preet; Wassermann, Eric M.; Bikson, Marom

    2015-01-01

    Transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost, well-tolerated technique producing lasting modulation of cortical excitability. Behavioral and therapeutic outcomes of tDCS are linked to the targeted brain regions, but there is little evidence that current reaches the brain as intended. We aimed to: (1) validate a computational model for estimating cortical electric fields in human transcranial stimulation, and (2) assess the magnitude and spread of cortical electric field with a novel High-Definition tDCS (HD-tDCS) scalp montage using a 4×1-Ring electrode configuration. In three healthy adults, Transcranial Electrical Stimulation (TES) over primary motor cortex (M1) was delivered using the 4×1 montage (4× cathode, surrounding a single central anode; montage radius ~3 cm) with sufficient intensity to elicit a discrete muscle twitch in the hand. The estimated current distribution in M1 was calculated using the individualized MRI-based model, and compared with the observed motor response across subjects. The response magnitude was quantified with stimulation over motor cortex as well as anterior and posterior to motor cortex. In each case the model data were consistent with the motor response across subjects. The estimated cortical electric fields with the 4×1 montage were compared (area, magnitude, direction) for TES and tDCS in each subject. We provide direct evidence in humans that TES with a 4×1-Ring configuration can activate motor cortex and that current does not substantially spread outside the stimulation area. Computational models predict that both TES and tDCS waveforms using the 4×1-Ring configuration generate electric fields in cortex with comparable gross current distribution, and preferentially directed normal (inward) currents. The agreement of modeling and experimental data for both current delivery and focality support the use of the HD-tDCS 4×1-Ring montage for cortically targeted neuromodulation. PMID:23370061

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

    PubMed

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

    2017-07-01

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

  7. Higher-order power harmonics of pulsed electrical stimulation modulates corticospinal contribution of peripheral nerve stimulation.

    PubMed

    Chen, Chiun-Fan; Bikson, Marom; Chou, Li-Wei; Shan, Chunlei; Khadka, Niranjan; Chen, Wen-Shiang; Fregni, Felipe

    2017-03-03

    It is well established that electrical-stimulation frequency is crucial to determining the scale of induced neuromodulation, particularly when attempting to modulate corticospinal excitability. However, the modulatory effects of stimulation frequency are not only determined by its absolute value but also by other parameters such as power at harmonics. The stimulus pulse shape further influences parameters such as excitation threshold and fiber selectivity. The explicit role of the power in these harmonics in determining the outcome of stimulation has not previously been analyzed. In this study, we adopted an animal model of peripheral electrical stimulation that includes an amplitude-adapted pulse train which induces force enhancements with a corticospinal contribution. We report that the electrical-stimulation-induced force enhancements were correlated with the amplitude of stimulation power harmonics during the amplitude-adapted pulse train. In an exploratory analysis, different levels of correlation were observed between force enhancement and power harmonics of 20-80 Hz (r = 0.4247, p = 0.0243), 100-180 Hz (r = 0.5894, p = 0.0001), 200-280 Hz (r = 0.7002, p < 0.0001), 300-380 Hz (r = 0.7449, p < 0.0001), 400-480 Hz (r = 0.7906, p < 0.0001), 500-600 Hz (r = 0.7717, p < 0.0001), indicating a trend of increasing correlation, specifically at higher order frequency power harmonics. This is a pilot, but important first demonstration that power at high order harmonics in the frequency spectrum of electrical stimulation pulses may contribute to neuromodulation, thus warrant explicit attention in therapy design and analysis.

  8. Acute effects of unilateral whole body vibration training on single leg vertical jump height and symmetry in healthy men.

    PubMed

    Shin, Seungho; Lee, Kyeongjin; Song, Changho

    2015-12-01

    [Purpose] The aim of the present study was to investigate the acute effects of unilateral whole body vibration training on height and symmetry of the single leg vertical jump in healthy men. [Subjects] Thirty males with no history of lower limb dysfunction participated in this study. [Methods] The participants were randomly allocated to one of three groups: the unilateral vibratory stimulation group (n=10), bilateral vibratory stimulation group (n=10), and, no vibratory stimulation group (n=10). The subjects in the unilateral and bilateral stimulation groups participated in one session of whole body vibration training at 26 Hz for 3 min. The no vibratory stimulation group subjects underwent the same training for 3 min without whole body vibration. All participants performed the single leg vertical jump for each lower limb, to account for the strong and weak sides. The single leg vertical jump height and symmetry were measured before and after the intervention. [Results] The single leg vertical jump height of the weak lower limb significantly improved in the unilateral vibratory stimulation group, but not in the other groups. The single leg vertical jump height of the strong lower limb significantly improved in the bilateral vibratory stimulation group, but not in the other groups. The single leg vertical jump symmetry significantly improved in the unilateral vibratory stimulation group, but not in the other groups. [Conclusion] Therefore, the present study found that the effects of whole body vibration training were different depending on the type of application. To improve the single leg vertical jump height in the weak lower limbs as well as limb symmetry, unilateral vibratory stimulation might be more desirable.

  9. Influence of extremely low frequency, low energy electromagnetic fields and combined mechanical stimulation on chondrocytes in 3-D constructs for cartilage tissue engineering.

    PubMed

    Hilz, Florian M; Ahrens, Philipp; Grad, Sibylle; Stoddart, Martin J; Dahmani, Chiheb; Wilken, Frauke L; Sauerschnig, Martin; Niemeyer, Philipp; Zwingmann, Jörn; Burgkart, Rainer; von Eisenhart-Rothe, Rüdiger; Südkamp, Norbert P; Weyh, Thomas; Imhoff, Andreas B; Alini, Mauro; Salzmann, Gian M

    2014-02-01

    Articular cartilage, once damaged, has very low regenerative potential. Various experimental approaches have been conducted to enhance chondrogenesis and cartilage maturation. Among those, non-invasive electromagnetic fields have shown their beneficial influence for cartilage regeneration and are widely used for the treatment of non-unions, fractures, avascular necrosis and osteoarthritis. One very well accepted way to promote cartilage maturation is physical stimulation through bioreactors. The aim of this study was the investigation of combined mechanical and electromagnetic stress affecting cartilage cells in vitro. Primary articular chondrocytes from bovine fetlock joints were seeded into three-dimensional (3-D) polyurethane scaffolds and distributed into seven stimulated experimental groups. They either underwent mechanical or electromagnetic stimulation (sinusoidal electromagnetic field of 1 mT, 2 mT, or 3 mT; 60 Hz) or both within a joint-specific bioreactor and a coil system. The scaffold-cell constructs were analyzed for glycosaminoglycan (GAG) and DNA content, histology, and gene expression of collagen-1, collagen-2, aggrecan, cartilage oligomeric matrix protein (COMP), Sox9, proteoglycan-4 (PRG-4), and matrix metalloproteinases (MMP-3 and -13). There were statistically significant differences in GAG/DNA content between the stimulated versus the control group with highest levels in the combined stimulation group. Gene expression was significantly higher for combined stimulation groups versus static control for collagen 2/collagen 1 ratio and lower for MMP-13. Amongst other genes, a more chondrogenic phenotype was noticed in expression patterns for the stimulated groups. To conclude, there is an effect of electromagnetic and mechanical stimulation on chondrocytes seeded in a 3-D scaffold, resulting in improved extracellular matrix production. © 2013 Wiley Periodicals, Inc.

  10. Nonmedical Use of Prescription ADHD Stimulants and Preexisting Patterns of Drug Abuse

    PubMed Central

    Sweeney, Christine T.; Sembower, Mark A.; Ertischek, Michelle D.; Shiffman, Saul; Schnoll, Sidney H.

    2013-01-01

    Multidrug use is well documented among nonmedical users of prescription stimulants. We sought to provide insight into the drug use patterns of those reporting nonmedical use of prescription attention-deficit hyperactivity disorder (ADHD) stimulants in an attempt to discern whether such use is a first step in a pattern of drug-abusing behavior or, conversely, is a later development accompanied or preceded by a history of drug abuse. A cross-sectional, population-based survey of the U.S. civilian, non-institutionalized population aged 12 years and older was analyzed for lifetime nonmedical use of prescription ADHD stimulants, lifetime nonmedical use of another prescription drug, illicit drug use, and drug use initiation patterns. This included 443,041 respondents from the 2002–2009 National Survey on Drug Use and Health. Lifetime nonmedical use of prescription ADHD stimulants was reported by 3.4% of those aged 12 years and older. Of these, 95.3% also reported use of an illicit drug (i.e., marijuana, cocaine/crack, heroin, hallucinogens, inhalants) or nonmedical use of another prescription drug (i.e., tranquilizers, pain relievers, or sedatives), and such use preceded nonmedical use of prescription ADHD stimulants in 77.6% of cases. On average, 2.40 drugs were used prior to the first nonmedical use of prescription ADHD stimulants. These data suggest that nonmedical use of prescription ADHD stimulants is not commonly an initiating factor leading to the nonmedical use of other prescription medications or abuse of illicit drugs. Rather, nonmedical use of prescription ADHD stimulants appears to be adopted by individuals already engaged in broader patterns of drug abuse and misuse. PMID:23480243

  11. Phospholemman is not required for the acute stimulation of Na⁺-K⁺-ATPase α₂-activity during skeletal muscle fatigue.

    PubMed

    Manoharan, Palanikumar; Radzyukevich, Tatiana L; Hakim Javadi, Hesamedin; Stiner, Cory A; Landero Figueroa, Julio A; Lingrel, Jerry B; Heiny, Judith A

    2015-12-15

    The Na(+)-K(+)-ATPase α2-isoform in skeletal muscle is rapidly stimulated during muscle use and plays a critical role in fatigue resistance. The acute mechanisms that stimulate α2-activity are not completely known. This study examines whether phosphorylation of phospholemman (PLM/FXYD1), a regulatory subunit of Na(+)-K(+)-ATPase, plays a role in the acute stimulation of α2 in working muscles. Mice lacking PLM (PLM KO) have a normal content of the α2-subunit and show normal exercise capacity, in contrast to the greatly reduced exercise capacity of mice that lack α2 in the skeletal muscles. Nerve-evoked contractions in vivo did not induce a change in total PLM or PLM phosphorylated at Ser63 or Ser68, in either WT or PLM KO. Isolated muscles of PLM KO mice maintain contraction and resist fatigue as well as wild type (WT). Rb(+) transport by the α2-Na(+)-K(+)-ATPase is stimulated to the same extent in contracting WT and contracting PLM KO muscles. Phosphorylation of sarcolemmal membranes prepared from WT but not PLM KO skeletal muscles stimulates the activity of both α1 and α2 in a PLM-dependent manner. The stimulation occurs by an increase in Na(+) affinity without significant change in Vmax and is more effective for α1 than α2. These results demonstrate that phosphorylation of PLM is capable of stimulating the activity of both isozymes in skeletal muscle; however, contractile activity alone is not sufficient to induce PLM phosphorylation. Importantly, acute stimulation of α2, sufficient to support exercise and oppose fatigue, does not require PLM or its phosphorylation. Copyright © 2015 the American Physiological Society.

  12. Facilitatory non-invasive brain stimulation in older adults: the effect of stimulation type and duration on the induction of motor cortex plasticity.

    PubMed

    Puri, Rohan; Hinder, Mark R; Canty, Alison J; Summers, Jeffery J

    2016-12-01

    Despite holding significant promise for counteracting the deleterious effects of ageing on cognitive and motor function, little is known of the effects of facilitatory non-invasive brain stimulation (NBS) techniques on corticospinal excitability (CSE) in older adults. Thirty-three older adults (≥60 years) participated in four NBS sessions on separate days, receiving 10- and 20-min anodal transcranial direct current stimulation (atDCS), and 300 and 600 pulses of intermittent theta burst stimulation (iTBS) over the left M1. Motor-evoked potentials measured in the contralateral hand served as a measure of CSE before and for 30 min following each NBS intervention. At the group level, generalized post-stimulation CSE increases were observed (p < 0.001) with no significant differences between the two durations of each stimulation type (atDCS: p = 0.5; iTBS: p = 0.9). For individuals exhibiting overall facilitatory change to atDCS ('responders', n = 10), 20-min atDCS resulted in longer lasting CSE facilitation than 10 min. No such difference was observed between the two iTBS protocols. Considerable variability was observed inter-individually, where 52-58 % of the cohort exhibited the expected facilitation after each of the NBS protocols-as well as intra-individually, where 45-48 % of the cohort maintained consistent post-stimulation responses across the varying durations and types of stimulation. In conclusion, as shown previously in young adults, older adults demonstrate substantial variability in response to different facilitatory NBS protocols. Studies to assess the intra-individual reliability of these protocols are critical to progress towards translation of appropriate protocols (i.e. those that elicit the greatest response for each individual) into clinical practice.

  13. Neurocognitive enhancement or impairment? A systematic meta-analysis of prescription stimulant effects on processing speed, decision-making, planning, and cognitive perseveration.

    PubMed

    Marraccini, Marisa E; Weyandt, Lisa L; Rossi, Joseph S; Gudmundsdottir, Bergljot Gyda

    2016-08-01

    Increasing numbers of adults, particularly college students, are misusing prescription stimulants primarily for cognitive/academic enhancement, so it is critical to explore whether empirical findings support neurocognitive benefits of prescription stimulants. Previous meta-analytic studies have supported small benefits from prescription stimulants for the cognitive domains of inhibitory control and memory; however, no meta-analytic studies have examined the effects on processing speed or the potential impairment on other domains of cognition, including planning, decision-making, and cognitive perseveration. Therefore, the present study conducted a meta-analysis of the available literature examining the effects of prescription stimulants on specific measures of processing speed, planning, decision-making, and cognitive perseveration among healthy adult populations. The meta-analysis results indicated a positive influence of prescription stimulant medication on processing speed accuracy, with an overall mean effect size of g = 0.282 (95% CI [0.077, 0.488]; n = 345). Neither improvements nor impairments were revealed for planning time, planning accuracy, advantageous decision-making, or cognitive perseveration; however, findings are limited by the small number of studies examining these outcomes. Findings support that prescription stimulant medication may indeed act as a neurocognitive enhancer for accuracy measures of processing speed without impeding other areas of cognition. Considering that adults are already engaging in illegal use of prescription stimulants for academic enhancement, as well as the potential for stimulant misuse to have serious side effects, the establishment of public policies informed by interdisciplinary research surrounding this issue, whether restrictive or liberal, is of critical importance. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  14. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy.

    PubMed

    Morrell, Martha J

    2011-09-27

    This multicenter, double-blind, randomized controlled trial assessed the safety and effectiveness of responsive cortical stimulation as an adjunctive therapy for partial onset seizures in adults with medically refractory epilepsy. A total of 191 adults with medically intractable partial epilepsy were implanted with a responsive neurostimulator connected to depth or subdural leads placed at 1 or 2 predetermined seizure foci. The neurostimulator was programmed to detect abnormal electrocorticographic activity. One month after implantation, subjects were randomized 1:1 to receive stimulation in response to detections (treatment) or to receive no stimulation (sham). Efficacy and safety were assessed over a 12-week blinded period and a subsequent 84-week open-label period during which all subjects received responsive stimulation. Seizures were significantly reduced in the treatment (-37.9%, n = 97) compared to the sham group (-17.3%, n = 94; p = 0.012) during the blinded period and there was no difference between the treatment and sham groups in adverse events. During the open-label period, the seizure reduction was sustained in the treatment group and seizures were significantly reduced in the sham group when stimulation began. There were significant improvements in overall quality of life (p < 0.02) and no deterioration in mood or neuropsychological function. Responsive cortical stimulation reduces the frequency of disabling partial seizures, is associated with improvements in quality of life, and is well-tolerated with no mood or cognitive effects. Responsive stimulation may provide another adjunctive treatment option for adults with medically intractable partial seizures. This study provides Class I evidence that responsive cortical stimulation is effective in significantly reducing seizure frequency for 12 weeks in adults who have failed 2 or more antiepileptic medication trials, 3 or more seizures per month, and 1 or 2 seizure foci.

  15. The effect of pulse width and contact configuration on paresthesia coverage in spinal cord stimulation.

    PubMed

    Holsheimer, Jan; Buitenweg, Jan R; Das, John; de Sutter, Paul; Manola, Ljubomir; Nuttin, Bart

    2011-05-01

    In spinal cord stimulation for the management of chronic, intractable pain, a satisfactory analgesic effect can be obtained only when the stimulation-induced paresthesias cover all painful body areas completely or partially. To investigate the effect of stimulus pulse width (PW) and contact configuration (CC) on the area of paresthesia (PA), perception threshold (VPT), discomfort threshold (VDT), and usage range (UR) in spinal cord stimulation. Chronic pain patients were tested during a follow-up visit. They were stimulated monopolarly and with the CC giving each patient the best analgesia. VPT, VDT, and UR were determined for PWs of 90, 210, and 450 microseconds. The paresthesia contours at VDT were drawn on a body map and digitized; PA was calculated; and its anatomic composition was described. The effects of PW and CC on PA, VPT, VDT, and UR were tested statistically. Twenty-four of 31 tests with low thoracic stimulation and 8 of 9 tests with cervical stimulation gave a significant extension of PA at increasing PW. In 14 of 18 tests (low thoracic), a caudal extension was obtained (primarily in L5-S2). In cervical stimulation the extension was predominantly caudal as well. In contrast to VPT and VDT, UR is not significantly different when stimulating with any CC. PA extends caudally with increasing PW. The mechanism includes that the larger and smaller dorsal column fibers have a different mediolateral distribution and that smaller dorsal column fibers have a smaller UR and can be activated only when PW is sufficiently large. A similar effect of CC on PA is unlikely as long as electrodes with a large intercontact distance are applied.

  16. Illicit Stimulant Use Is Associated with Abnormal Substantia Nigra Morphology in Humans

    PubMed Central

    Todd, Gabrielle; Noyes, Carolyn; Flavel, Stanley C.; Della Vedova, Chris B.; Spyropoulos, Peter; Chatterton, Barry; Berg, Daniela; White, Jason M.

    2013-01-01

    Use of illicit stimulants such as methamphetamine, cocaine, and ecstasy is an increasing health problem. Chronic use can cause neurotoxicity in animals and humans but the long-term consequences are not well understood. The aim of the current study was to investigate the long-term effect of stimulant use on the morphology of the human substantia nigra. We hypothesised that history of illicit stimulant use is associated with an abnormally bright and enlarged substantia nigra (termed ‘hyperechogenicity’) when viewed with transcranial sonography. Substantia nigra morphology was assessed in abstinent stimulant users (n = 36; 31±9 yrs) and in two groups of control subjects: non-drug users (n = 29; 24±5 yrs) and cannabis users (n = 12; 25±7 yrs). Substantia nigra morphology was viewed with transcranial sonography and the area of echogenicity at the anatomical site of the substantia nigra was measured at its greatest extent. The area of substantia nigra echogenicity was significantly larger in the stimulant group (0.273±0.078 cm2) than in the control (0.201±0.054 cm2; P<0.001) and cannabis (0.202±0.045 cm2; P<0.007) groups. 53% of stimulant users exhibited echogenicity that exceeded the 90th percentile for the control group. The results of the current study suggest that individuals with a history of illicit stimulant use exhibit abnormal substantia nigra morphology. Substantia nigra hyperechogenicity is a strong risk factor for developing Parkinson's disease later in life and further research is required to determine if the observed abnormality in stimulant users is associated with a functional deficit of the nigro-striatal system. PMID:23418568

  17. Transcranial direct current stimulation can enhance working memory in Huntington's disease.

    PubMed

    Eddy, Clare M; Shapiro, Kimron; Clouter, Andrew; Hansen, Peter C; Rickards, Hugh E

    2017-07-03

    Transcranial direct current stimulation (tDCS) combined with a cognitive task can enhance targeted aspects of cognitive functioning in clinical populations. The movement disorder Huntington's disease (HD) is associated with progressive cognitive impairment. Deficits in working memory (WM) can be apparent early in the disease and impact functional capacity. We investigated whether tDCS combined with cognitive training could improve WM in patients with HD, and if baseline clinical or cognitive measures may predict efficacy. Twenty participants with HD completed this crossover trial, undergoing 1.5mA anodal tDCS over left dorsolateral prefrontal cortex and sham stimulation on separate visits. Participants and assessor were blinded to condition order, which was randomised across participants. All participants completed baseline clinical and cognitive assessments. Pre- and post-stimulation tasks included digit reordering, computerised n-back tests and a Stroop task. During 15min of tDCS/sham stimulation, participants practiced 1- and 2-back WM tasks. Participants exhibited an increase in WM span on the digit re-ordering span task from pre- to post-stimulation after tDCS, but not after sham stimulation. Gains in WM were positively related to motor symptom ratings and negatively associated with verbal fluency scores. Patients with more severe motor symptoms showed greatest improvement, suggesting that motor symptom ratings may help identify patients who are most likely to benefit from tDCS. Dorsolateral prefrontal tDCS appears well tolerated in HD and enhances WM span compared to sham stimulation. Our findings strongly encourage further investigation of the extent to which tDCS combined with cognitive training could enhance everyday function in HD. ClinicalTrials.gov; NCT02216474 Brain stimulation in Movement Disorders; https://clinicaltrials.gov/ct2/show/NCT02216474. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance--The U.S. E-37 Trial.

    PubMed

    Fisher, Robert S; Afra, Pegah; Macken, Micheal; Minecan, Daniela N; Bagić, Anto; Benbadis, Selim R; Helmers, Sandra L; Sinha, Saurabh R; Slater, Jeremy; Treiman, David; Begnaud, Jason; Raman, Pradheep; Najimipour, Bita

    2016-02-01

    The Automatic Stimulation Mode (AutoStim) feature of the Model 106 Vagus Nerve Stimulation (VNS) Therapy System stimulates the left vagus nerve on detecting tachycardia. This study evaluates performance, safety of the AutoStim feature during a 3-5-day Epilepsy Monitoring Unit (EMU) stay and long- term clinical outcomes of the device stimulating in all modes. The E-37 protocol (NCT01846741) was a prospective, unblinded, U.S. multisite study of the AspireSR(®) in subjects with drug-resistant partial onset seizures and history of ictal tachycardia. VNS Normal and Magnet Modes stimulation were present at all times except during the EMU stay. Outpatient visits at 3, 6, and 12 months tracked seizure frequency, severity, quality of life, and adverse events. Twenty implanted subjects (ages 21-69) experienced 89 seizures in the EMU. 28/38 (73.7%) of complex partial and secondarily generalized seizures exhibited ≥20% increase in heart rate change. 31/89 (34.8%) of seizures were treated by Automatic Stimulation on detection; 19/31 (61.3%) seizures ended during the stimulation with a median time from stimulation onset to seizure end of 35 sec. Mean duty cycle at six-months increased from 11% to 16%. At 12 months, quality of life and seizure severity scores improved, and responder rate was 50%. Common adverse events were dysphonia (n = 7), convulsion (n = 6), and oropharyngeal pain (n = 3). The Model 106 performed as intended in the study population, was well tolerated and associated with clinical improvement from baseline. The study design did not allow determination of which factors were responsible for improvements. © 2015 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

  19. An affordable optically stimulated luminescent dosimeter reader utilizing multiple excitation wavelengths.

    PubMed

    Kearfott, Kimberlee J; West, W Geoffrey

    2015-10-01

    A lower-cost optically stimulated luminescence (OSL) reader with increased flexibility for pursuing laboratory research into OSL theory and application was designed and constructed. This was achieved by using off-the-shelf optical components and higher-power light emitting diodes. The resulting reader includes more wavelengths of excitation light than current commercial readers, as well as the ability to swap out filters and other components during an experiment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Advanced stimulation technology deployment program: Sonat Exploration Company, Haynesville Formation, North Shongaloo, Red Rock Field, Columbia County, Arkansas and Webster Parish, Louisiana. Topical report, August 1995-January 1997

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Skees, J.L.; Middlebrook, M.L.; Anthony, W.L.

    1997-01-01

    The objective of this program is to transfer the core GRI advanced stimulation technologies to Sonat Exploration Company for their continued use upon completion of the program. The methodology to accomplish the objective included seminars and training schools, offset well baseline analysis, fracture treatment design optimization, real-time and post-fracture treatment evaluation and documentation of economic benefits.

  1. Annual Progress Report FY 93 (Walter Reed Army Medical Center, Department of Clinical Investigation). Clinical Investigation Program. Volume 2

    DTIC Science & Technology

    1993-01-01

    Effect of Methotrexate on Expression of Interceilular Adhesion Molecule I in Interleukin- 1 Stimulated Cultured Human Cells KEYWORDS: methotrexate...on interleukin- 1 ( IL -I) induced ICAM-l expression in cultured human fibroblasts and adenocarcinoma cells. TECHNICAL APPROACH Expression of ICAM- 1 will...incubated with IL -l to stimulate ICAM-l expression. In general, the cells responded well. ICAM- 1 was readily detectable with monoclonal antibodies and flow

  2. Human hematopoietic progenitors express erythropoietin.

    PubMed

    Stopka, T; Zivny, J H; Stopkova, P; Prchal, J F; Prchal, J T

    1998-05-15

    Erythropoietin (EPO) is a factor essential for erythroid cell proliferation, differentiation, and survival. The production of EPO by the kidneys in response to hypoxia and anemia is well documented. To determine whether EPO is also produced by hematopoietic cells, we analyzed the expression of EPO in normal human hematopoietic progenitors and in their progeny. Undifferentiated CD34(+)lin- hematopoietic progenitors do not have detectable EPO mRNA. Differentiating CD34(+) cells that are stimulated with recombinant human EPO in serum-free liquid cultures express both EPO and EPO receptor (EPOR). Because CD34(+) cells represent a heterogeneous cell population, we analyzed individual burst-forming units-erythroid (BFU-E) and nonerythroid colony-forming unit-granulocyte-macrophage colonies for EPO mRNA. Only BFU-E colonies were positive for EPO mRNA. Lysates from pooled BFU-E colonies stained positively for EPO by immunoblotting. To further confirm the intrinsic nature of erythroid EPO, we replaced extrinsic EPO in erythroid colony cultures with EPO-mimicking peptide (EMP). We show EPO expression in the EMP-stimulated BFU-Es at both mRNA and protein levels. Stimulation of bone marrow mononuclear cells (BMMCs) with EMP upregulated EPO expression. Furthermore, we found EPO and EPOR mRNAs as well as EPO protein in K562 cells, a human erythroleukemia cell line. Stimulation of K562 cells with EMP upregulated EPO expression. We suggest that EPO of erythroid origin may have a role in the regulation of erythropoiesis.

  3. Non-invasive red light optogenetic pacing and optical coherence microscopy (OCM) imaging for drosophila melanogaster (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Men, Jing; Li, Airong; Jerwick, Jason; Tanzi, Rudolph E.; Zhou, Chao

    2017-02-01

    Cardiac pacing could be a powerful tool for investigating mammalian cardiac electrical conduction systems as well as for treatment of certain cardiac pathologies. However, traditional electrical pacing using pacemaker requires an invasive surgical procedure. Electrical currents from the implanted electrodes can also cause damage to heart tissue, further restricting its utility. Optogenetic pacing has been developed as a promising, non-invasive alternative to electrical stimulation for controlling animal heart rhythms. It induces heart contractions by shining pulsed light on transgene-generated microbial opsins, which in turn activate the light gated ion channels in animal hearts. However, commonly used opsins in optogenetic pacing, such as channelrhodopsin-2 (ChR2), require short light wavelength stimulation (475 nm), which is strongly absorbed and scattered by tissue. Here, we performed optogenetic pacing by expression of recently engineered red-shifted microbial opsins, ReaChR and CsChrimson, in a well-established animal model, Drosophila melanogaster, using the 617 nm stimulation light pulses. The OCM technique enables non-invasive optical imaging of animal hearts with high speed and ultrahigh axial and transverse resolutions. We integrated a customized OCM system with the optical stimulation system to monitor the optogenetic pacing noninvasively. The use of red-sifted opsins enabled deeper penetration of simulating light at lower power, which is promising for applications of optogenetic pacing in mammalian cardiac pathology studies or clinical treatments in the future.

  4. "Green technology": Bio-stimulation by an electric field for textile reactive dye contaminated agricultural soil.

    PubMed

    Annamalai, Sivasankar; Santhanam, Manikandan; Selvaraj, Subbulakshmi; Sundaram, Maruthamuthu; Pandian, Kannan; Pazos, Marta

    2018-05-15

    The aim of the study is to degrade pollutants as well as to increase the fertility of agricultural soil by starch enhancing electrokinetic (EKA) and electro-bio-stimulation (EBS) processes. Starch solution was used as an anolyte and voltage gradient was about 0.5V/cm. The influence of bacterial mediated process was evaluated in real contaminated farming soil followed by pilot scale experiment. The in-situ formation of β-cyclodextrin from starch in the treatments had also influence on the significant removal of the pollutants from the farming soil. The conductivity of the soil was effectively reduced from 15.5dS/m to 1.5dS/m which corroborates well with the agricultural norms. The bio-stimulation was confirmed by the increase of the phosphorus content in the treated soil. Finally, phytotoxicity assays demonstrated the viability of the developed technique for soil remediation because plant germination percentage was higher in the treated soil in comparison to untreated soil. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Control of proliferation rate of N27 dopaminergic neurons using Transcranial Magnetic Stimulation orientation

    NASA Astrophysics Data System (ADS)

    Meng, Yiwen; Hadimani, Ravi; Anantharam, Vellareddy; Kanthasamy, Anumantha; Jiles, David

    2015-03-01

    Transcranial magnetic stimulation (TMS) has been used to investigate possible treatments for a variety of neurological disorders. However, the effect that magnetic fields have on neurons has not been well documented in the literature. We have investigated the effect of different orientation of magnetic field generated by TMS coils with a monophasic stimulator on the proliferation rate of N27 neuronal cells cultured in flasks and multi-well plates. The proliferation rate of neurons would increase by exposed horizontally adherent N27 cells to a magnetic field pointing upward through the neuronal proliferation layer compared with the control group. On the other hand, proliferation rate would decrease in cells exposed to a magnetic field pointing downward through the neuronal growth layer compared with the control group. We confirmed results obtained from the Trypan-blue and automatic cell counting methods with those from the CyQuant and MTS cell viability assays. Our findings could have important implications for the preclinical development of TMS treatments of neurological disorders and represents a new method to control the proliferation rate of neuronal cells.

  6. Cyclic GMP-AMP Synthase Is Required for Cell Proliferation and Inflammatory Responses in Rheumatoid Arthritis Synoviocytes.

    PubMed

    Wang, Yan; Su, Guo-Hua; Zhang, Fang; Chu, Jing-Xue; Wang, Yun-Shan

    2015-01-01

    Rheumatoid arthritis (RA) is characterized by inflammatory cell infiltration, fibroblast-like synoviocytes (FLS) invasive proliferation, and joint destruction. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. In this study, we examined whether cGAS plays a role in RA FLS. In this study, cGAS was overexpressed in RA-FLS compared with OA FLS. TNFα stimulation induced cGAS expression in RA FLS. Overexpression of cGAS promoted the proliferation and knockdown of cGAS inhibited the proliferation of RA FLS. cGAS overexpression enhanced the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. In contrast, cGAS silencing inhibited production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. These results suggest that cGAS activates the AKT and ERK pathways to promote the inflammatory response of RA FLS, and the development of strategies targeting cGAS may have therapeutic potential for human RA.

  7. Morphine 6 glucuronide stimulates nitric oxide release in mussel neural tissues: evidence for a morphine 6 glucuronide opiate receptor subtype.

    PubMed

    Mantione, K; Zhu, W; Rialas, C; Casares, F; Cadet, P; Franklin, A L; Tonnesen, J; Stefano, G B

    2002-03-01

    We have previously demonstrated that Mytilus edulis pedal ganglia contain opiate alkaloids, i.e., morphine and morphine 6 glucuronide (M6G), as well as mu opiate receptor subtype fragments exhibiting high sequence similarity to those found in mammals. Now we demonstrate that M6G stimulates pedal ganglia constitutive nitric oxide (NO) synthase (cNOS)-derived NO release at identical concentrations and to similar peak levels as morphine. However, the classic opiate antagonist, naloxone, only blocked the ability of morphine to stimulate cNOS-derived NO release and not that of M6G. CTOP, a mu-specific antagonist, blocked the ability of M6G to induce cNOS-derived NO release as well as that of morphine, suggesting that a novel mu opiate receptor was present and selective toward M6G. In examining a receptor displacement analysis, both opiate alkaloids displaced [3H]-dihydromorphine binding to the mu opiate receptor subtype. However, morphine exhibited a twofold higher affinity, again suggesting that a novel mu opiate receptor may be present.

  8. Transcranial direct current stimulation in psychiatric disorders

    PubMed Central

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

    2015-01-01

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

  9. The effects of laser immunotherapy on cancer cell migration

    NASA Astrophysics Data System (ADS)

    Bahavar, Cody F.; Zhou, Feifan; Hasanjee, Aamr M.; Layton, Elivia; Lam, Anh; Chen, Wei R.; Vaughan, Melville B.

    2016-03-01

    Laser immunotherapy (LIT) uses laser irradiation and immunological stimulation to target all types of metastases and creates a long-term tumor resistance. Glycated chitosan (GC) is the immunological stimulant used in LIT. Interestingly, GC can act as a surfactant for single-walled carbon nanotubes (SWNTs) to immunologically modify SWNTs. SWNT-GC retains the optical properties of SWNTs and the immunological functions of GC to help increase the selectivity of the laser and create a more optimal immune response. One essential aspect of understanding this immune response is knowing how laser irradiation affects cancer cells' ability to metastasize. In this experiment, a cell migration assay was performed. A 2mm circular elastomer plugs were placed at the bottom of multi-well dishes. Pre-cancerous keratinocytes, different tumor cells, and fibroblasts were then plated separately in treated wells. Once the cells reached 100% confluence, they were irradiated by either a 980nm or 805nm wavelength laser. The goal was to determine the effects of laser irradiation and immunological stimulation on cancer cell migration in vitro, paying the way to understand the mechanism of LIT in treating metastatic tumors in cancer patients.

  10. Understanding the Chinese Approach to Creative Teaching in Mathematics Classrooms

    ERIC Educational Resources Information Center

    Niu, Weihua; Zhou, Zheng; Zhou, Xinlin

    2017-01-01

    Using Amabile's componential theory of creativity as a framework, this paper analyzes how Chinese mathematics teachers achieve creative teaching through acquiring in-depth domain-specific knowledge in mathematics, developing creativity-related skills, as well as stimulating student interest in learning mathematics, through well-crafted,…

  11. Participation of the Classical Speech Areas in Auditory Long-Term Memory

    PubMed Central

    Karabanov, Anke Ninija; Paine, Rainer; Chao, Chi Chao; Schulze, Katrin; Scott, Brian; Hallett, Mark; Mishkin, Mortimer

    2015-01-01

    Accumulating evidence suggests that storing speech sounds requires transposing rapidly fluctuating sound waves into more easily encoded oromotor sequences. If so, then the classical speech areas in the caudalmost portion of the temporal gyrus (pSTG) and in the inferior frontal gyrus (IFG) may be critical for performing this acoustic-oromotor transposition. We tested this proposal by applying repetitive transcranial magnetic stimulation (rTMS) to each of these left-hemisphere loci, as well as to a nonspeech locus, while participants listened to pseudowords. After 5 minutes these stimuli were re-presented together with new ones in a recognition test. Compared to control-site stimulation, pSTG stimulation produced a highly significant increase in recognition error rate, without affecting reaction time. By contrast, IFG stimulation led only to a weak, non-significant, trend toward recognition memory impairment. Importantly, the impairment after pSTG stimulation was not due to interference with perception, since the same stimulation failed to affect pseudoword discrimination examined with short interstimulus intervals. Our findings suggest that pSTG is essential for transforming speech sounds into stored motor plans for reproducing the sound. Whether or not the IFG also plays a role in speech-sound recognition could not be determined from the present results. PMID:25815813

  12. Participation of the classical speech areas in auditory long-term memory.

    PubMed

    Karabanov, Anke Ninija; Paine, Rainer; Chao, Chi Chao; Schulze, Katrin; Scott, Brian; Hallett, Mark; Mishkin, Mortimer

    2015-01-01

    Accumulating evidence suggests that storing speech sounds requires transposing rapidly fluctuating sound waves into more easily encoded oromotor sequences. If so, then the classical speech areas in the caudalmost portion of the temporal gyrus (pSTG) and in the inferior frontal gyrus (IFG) may be critical for performing this acoustic-oromotor transposition. We tested this proposal by applying repetitive transcranial magnetic stimulation (rTMS) to each of these left-hemisphere loci, as well as to a nonspeech locus, while participants listened to pseudowords. After 5 minutes these stimuli were re-presented together with new ones in a recognition test. Compared to control-site stimulation, pSTG stimulation produced a highly significant increase in recognition error rate, without affecting reaction time. By contrast, IFG stimulation led only to a weak, non-significant, trend toward recognition memory impairment. Importantly, the impairment after pSTG stimulation was not due to interference with perception, since the same stimulation failed to affect pseudoword discrimination examined with short interstimulus intervals. Our findings suggest that pSTG is essential for transforming speech sounds into stored motor plans for reproducing the sound. Whether or not the IFG also plays a role in speech-sound recognition could not be determined from the present results.

  13. Diagnosis of polycystic ovary disease in obese women with a 24-hour hormone profile after buserelin stimulation.

    PubMed

    Hagag, P; Ben-Shlomo, A; Herzianu, I; Weiss, M

    2000-03-01

    To evaluate the 24-hour hormone response to GnRH agonist stimulation in the diagnosis of polycystic ovary disease (PCOD) in obese women. Forty-three obese PCOD patients and 23 controls were randomized to 1 mg buserelin (BSRL) stimulation (PCOD group P-1, n = 31; control group C-1, n = 12) or 0.1 mg (PCOD group P-0.1, n = 12; control group C-0.1, n = 11). Whereas following 1 mg BSRL administration, serum levels of 17 hydroxyprogesterone (17OHP), delta 4 androstenedione, estradiol (E2) and luteinizing hormone increment (delta LH) as well as the delta LH/delta follicle stimulating hormone ratio were all higher in group P-1 than in group C-1 (P < .001, < .01, < .01, = .08 and < .001, respectively), only 17OHP and E2 serum levels were higher in group P-0.1 than in group C-0.1 (P < .001, and = .01, respectively). Whereas 24-hour LH inversely correlated with body mass index (r = .37, P = .04), 24-hour hormone profile, and basal or glucose-stimulated serum insulin levels did not correlate in group P-1. The 1-mg BSRL stimulation test is a convenient diagnostic means in obesity-associated PCOD. The hormone response to BSRL administration is related to obesity, not to insulin resistance.

  14. Effects of Functional Electrical Stimulation Lower Extremity Training in Myotonic Dystrophy Type I: A Pilot Controlled Study.

    PubMed

    Cudia, Paola; Weis, Luca; Baba, Alfonc; Kiper, Pawel; Marcante, Andrea; Rossi, Simonetta; Angelini, Corrado; Piccione, Francesco

    2016-11-01

    Functional electrical stimulation (FES) is a new rehabilitative approach that combines electrical stimulation with a functional task. This pilot study evaluated the safety and effectiveness of FES lower extremity training in myotonic dystrophy type 1. This is a controlled pilot study that enrolled 20 patients with myotonic dystrophy type 1 over 2 years. Eight patients (age, 39-67 years) fulfilled the inclusion criteria. Four participants performed FES cycling training for 15 days (one daily session of 30 minutes for 5 days a week). A control group, matched for clinical and genetic variables, who had contraindications to electrical stimulation, performed 6 weeks of conventional resistance and aerobic training. The modified Medical Research Council Scale and functional assessments were performed before and after treatment. Cohen d effect size was used for statistical analysis. Functional electrical stimulation induced lower extremity training was well tolerated and resulted in a greater improvement of tibialis anterior muscle strength (d = 1,583), overall muscle strength (d = 1,723), and endurance (d = 0,626) than conventional training. Functional electrical stimulation might be considered a safe and valid tool to improve muscle function, also in muscles severely compromised in which no other restorative options are available. Confirmation of FES efficacy through further clinical trials is strongly advised.

  15. Assessing prescription stimulant use, misuse and diversion among youth 10 to 18 years of age

    PubMed Central

    Cottler, Linda B.; Striley, Catherine Woodstock; Lasopa, Sonam O.

    2018-01-01

    Purpose Assessing medical and non-medical use of stimulants and diversion is a challenge, especially among youth, with different methods for recruitment, and definitions of non-medical use and use. The field needs inexpensive, yet effective and reliable, methods of data collection to understand the prescription drug use problem. Most studies of youth are school or web-based, and conducted with teens. Recent Findings The National Monitoring of Adolescent Prescription Stimulants Study (N-MAPSS) recruited 11,048 youth 10 to 18 years of age from urban, rural and suburban areas in ten US cities using an entertainment venue intercept study. This review discusses the effectiveness of the method and results from four cross sections as well as the representativeness of the sample. Lifetime prevalence of any stimulant use was 14.8%, with rates highest among rural 16 to 18 year olds. The rate of past 30 day use was 7.3%, with over half (3.9%) non-medical use. Nearly 12% of all youth (whether a user or not) reported lifetime incoming/outgoing diversion of prescription stimulants. Summary Because no study has focused on stimulant use among youth as young as 10 and 11, this study is a landmark for future comparisons and offers a unique strategy for sampling and data collection. PMID:23896947

  16. Calcitonin gene-related peptide stimulates proliferation of human endothelial cells.

    PubMed Central

    Haegerstrand, A; Dalsgaard, C J; Jonzon, B; Larsson, O; Nilsson, J

    1990-01-01

    The effects of the vasoactive perivascular neuropeptides calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) on proliferation of cultured human umbilical vein endothelial cells (HUVECs) were investigated. CGRP was shown to increase both cell number and DNA synthesis, whereas NKA, NPY, and VIP were ineffective. 125I-labeled CGRP was shown to bind to HUVECs and this binding was displaced by addition of unlabeled CGRP, suggesting the existence of specific CGRP receptors. The effect of CGRP on formation of adenosine 3',5'-cyclic monophosphate (cAMP) and inositol phosphates (InsP), two intracellular messengers known to be involved in regulation of cell proliferation, was investigated. CGRP stimulated cAMP formation but was without effect on the formation of InsP. Proliferation, as well as cAMP formation, was also stimulated by cholera toxin. Basic fibroblast growth factor stimulated growth without affecting cAMP or InsP formation, whereas thrombin, which increased InsP formation, did not stimulate proliferation. We thus suggest that CGRP may act as a local factor stimulating proliferation of endothelial cells; that the mechanism of action is associated with cAMP formation; and that this effect of CGRP may be important for formation of new vessels during physiological and pathophysiological events such as ischemia, inflammation, and wound healing. PMID:2159144

  17. Calcitonin gene-related peptide stimulates proliferation of human endothelial cells.

    PubMed

    Haegerstrand, A; Dalsgaard, C J; Jonzon, B; Larsson, O; Nilsson, J

    1990-05-01

    The effects of the vasoactive perivascular neuropeptides calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) on proliferation of cultured human umbilical vein endothelial cells (HUVECs) were investigated. CGRP was shown to increase both cell number and DNA synthesis, whereas NKA, NPY, and VIP were ineffective. 125I-labeled CGRP was shown to bind to HUVECs and this binding was displaced by addition of unlabeled CGRP, suggesting the existence of specific CGRP receptors. The effect of CGRP on formation of adenosine 3',5'-cyclic monophosphate (cAMP) and inositol phosphates (InsP), two intracellular messengers known to be involved in regulation of cell proliferation, was investigated. CGRP stimulated cAMP formation but was without effect on the formation of InsP. Proliferation, as well as cAMP formation, was also stimulated by cholera toxin. Basic fibroblast growth factor stimulated growth without affecting cAMP or InsP formation, whereas thrombin, which increased InsP formation, did not stimulate proliferation. We thus suggest that CGRP may act as a local factor stimulating proliferation of endothelial cells; that the mechanism of action is associated with cAMP formation; and that this effect of CGRP may be important for formation of new vessels during physiological and pathophysiological events such as ischemia, inflammation, and wound healing.

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

    PubMed

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

    2010-02-01

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

  19. Psychostimulant and sensory stimulation interventions that target the reading and math deficits of students with ADHD.

    PubMed

    Zentall, Sydney S; Tom-Wright, Kinsey; Lee, Jiyeon

    2013-05-01

    The purpose of this review of students with attention deficit hyperactivity disorder (ADHD) was to summarize the following: (1) academic deficits in math and reading, (2) possible theoretical contributors to these deficits, and (3) psychostimulant interventions that target math and reading, as well as, parallel interventions involving sensory stimulation. A comprehensive examination of the literature was conducted on children with ADHD with and without co-occurring disabilities, summarizing their reading and math achievement and the effects of psychostimulant and sensory stimulant interventions on these academic areas. Students without co-occurring disabilities (ADHD-) had fewer deficits in reading than in math and than students with co-occurring disabilities (ADHD+). Furthermore, students with ADHD+ demonstrated greater responsiveness to psychostimulants through improved reading recognition and math calculations, with limited gains in literal reading comprehension. Added sensory stimulation produced differential gains for both groups in reading recognition and comprehension and in math calculations and problem solving. The efficacy of psychostimulants was documented on specific areas of achievement for the ADHD+ group, but this review did not support the administration of psychostimulants for students with ADHD-. For both groups of students, differential gains, losses, and habituation were documented in response to sensory stimulation for both subareas within reading and math, which were interpreted as support for the optimal stimulation theory.

  20. Strong-field adiabatic passage in the continuum: Electromagnetically induced transparency and stimulated Raman adiabatic passage

    NASA Astrophysics Data System (ADS)

    Eilam, A.; Shapiro, M.

    2012-01-01

    We present a fully quantum-mechanical theory of the mutual light-matter effects when two laser pulses interact with three discrete states coupled to a (quasi)continuum. Our formulation uses a single set of equations to describe the time dependence of the discrete and continuum populations, as well as pulse propagation in electromagnetically induced transparency (EIT) and stimulated Raman adiabatic passage (STIRAP) situations, for both weak and strong laser pulses. The theory gives a mechanistic picture of the “slowing down of light” and the state of spontaneously emitted photons during this process. Surprising features regarding the time dependence of material and radiative transients as well as limitations on quantum light storage and retrieval are unraveled.

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