Distinct Feedforward and Feedback Effects of Microstimulation in Visual Cortex Reveal Neural Mechanisms of Texture Segregation.

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Klink, P Christiaan; Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Roelfsema, Pieter R

2017-07-05

The visual cortex is hierarchically organized, with low-level areas coding for simple features and higher areas for complex ones. Feedforward and feedback connections propagate information between areas in opposite directions, but their functional roles are only partially understood. We used electrical microstimulation to perturb the propagation of neuronal activity between areas V1 and V4 in monkeys performing a texture-segregation task. In both areas, microstimulation locally caused a brief phase of excitation, followed by inhibition. Both these effects propagated faithfully in the feedforward direction from V1 to V4. Stimulation of V4, however, caused little V1 excitation, but it did yield a delayed suppression during the late phase of visually driven activity. This suppression was pronounced for the V1 figure representation and weaker for background representations. Our results reveal functional differences between feedforward and feedback processing in texture segregation and suggest a specific modulating role for feedback connections in perceptual organization. Copyright © 2017 Elsevier Inc. All rights reserved.

Poststroke upper-limb rehabilitation using 5 to 7 inserted microstimulators: implant procedure, safety, and efficacy for restoration of function.

Science.gov (United States)

Davis, Ross; Sparrow, Owen; Cosendai, Gregoire; Burridge, Jane H; Wulff, Christian; Turk, Ruth; Schulman, Joseph

2008-10-01

To investigate the feasibility of implanting microstimulators to deliver programmed nerve stimulation for sequenced muscle activation to recover arm-hand functions. By using a minimally invasive procedure and local anesthesia, 5 to 7 microstimulators can be safely and comfortably implanted adjacent to targeted radial nerve branches in the arm and forearm of 7 subjects with poststroke paresis. The microstimulators' position should remain stable with no tissue infection and can be programmed to produce effective personalized functional muscle activity with no discomfort for a preliminary 12-week study. Clinical testing, before and after the study, is reported in the accompanying study. Microstimulator implantations in a sterile operating room. Seven adults, with poststroke hemiparesis of 12 months or more. Under local anesthesia, a stimulating probe was inserted to identify radial nerve branches. Microstimulators were inserted by using an introducer and were retrievable for 6 days by attached suture. Each device was powered via a radiofrequency link from 2 external cuff coils connected to a control unit. To achieve low threshold values at the target sites with minimal implant discomfort. Microstimulators and external equipment were monitored over 12 weeks of exercise. Seven subjects were implanted with 41 microstimulators, 5 to 7 per subject, taking 3.5 to 6 hours. Implantation pain levels were 20% more than anticipated. No infections or microstimulator failures occurred. Mean nerve thresholds ranged between 4.0 to 7.7 microcoulomb/cm(2)/phase over 90 days, indicating that cathodes were within 2 to 4 mm of target sites. In 1 subject, 2 additional microstimulators were inserted. Microstimulators were safely implanted with no infection or failure. The system was reliable and programmed effectively to perform exercises at home for functional restoration.

Technical and surgical aspects of the sphenopalatine ganglion (SPG) microstimulator insertion procedure

DEFF Research Database (Denmark)

Assaf, A T; Hillerup, S; Rostgaard, J

2016-01-01

into the pterygopalatine fossa (PPF) is presented herein. Technical aspects include detailed descriptions of the preoperative planning using computed tomography or cone beam computed tomography scans for presurgical digital microstimulator insertion into the patient-specific anatomy and intraoperative verification......), and removal (n=5). This SPG microstimulator insertion procedure has sequelae comparable to other oral cavity procedures including tooth extractions, sinus surgery, and dental implant placement. Twenty-five of 29 subjects (86%) completing a self-assessment questionnaire indicated that the surgical effects were...

Cortical visual prostheses: from microstimulation to functional percept

Science.gov (United States)

Najarpour Foroushani, Armin; Pack, Christopher C.; Sawan, Mohamad

2018-04-01

Cortical visual prostheses are intended to restore vision by targeted electrical stimulation of the visual cortex. The perception of spots of light, called phosphenes, resulting from microstimulation of the visual pathway, suggests the possibility of creating meaningful percept made of phosphenes. However, to date electrical stimulation of V1 has still not resulted in perception of phosphenated images that goes beyond punctate spots of light. In this review, we summarize the clinical and experimental progress that has been made in generating phosphenes and modulating their associated perceptual characteristics in human and macaque primary visual cortex (V1). We focus specifically on the effects of different microstimulation parameters on perception and we analyse key challenges facing the generation of meaningful artificial percepts. Finally, we propose solutions to these challenges based on the application of supervised learning of population codes for spatial stimulation of visual cortex.

Microstimulation of area V4 has little effect on spatial attention and on perception of phosphenes evoked in area V1.

Science.gov (United States)

Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Roelfsema, Pieter R

2015-02-01

Previous transcranial magnetic stimulation (TMS) studies suggested that feedback from higher to lower areas of the visual cortex is important for the access of visual information to awareness. However, the influence of cortico-cortical feedback on awareness and the nature of the feedback effects are not yet completely understood. In the present study, we used electrical microstimulation in the visual cortex of monkeys to test the hypothesis that cortico-cortical feedback plays a role in visual awareness. We investigated the interactions between the primary visual cortex (V1) and area V4 by applying microstimulation in both cortical areas at various delays. We report that the monkeys detected the phosphenes produced by V1 microstimulation but subthreshold V4 microstimulation did not influence V1 phosphene detection thresholds. A second experiment examined the influence of V4 microstimulation on the monkeys' ability to detect the dimming of one of three peripheral visual stimuli. Again, microstimulation of a group of V4 neurons failed to modulate the monkeys' perception of a stimulus in their receptive field. We conclude that conditions exist where microstimulation of area V4 has only a limited influence on visual perception. Copyright © 2015 the American Physiological Society.

Intracortical inhibition is modulated by phase of prosthetic rehabilitation in transtibial amputees

Directory of Open Access Journals (Sweden)

Brenton eHordacre

2015-05-01

Full Text Available Reorganisation of primary motor cortex (M1 is well described in long-term lower limb amputees. In contrast cortical reorganisation during the rehabilitation period after amputation is poorly understood. Thirteen transtibial amputees and thirteen gender matched control participants of similar age were recruited. Transcranial magnetic stimulation was used to assess corticomotor and intracortical excitability of M1 bilaterally. Neurophysiological assessments were conducted at admission, prosthetic casting, first walk and discharge. Gait variability at discharge was assessed as a functional measure. Compared to controls, amputees had reduced short-latency intracortical inhibition for the ipsilateral M1 at admission (p=0.01. Analysis across rehabilitation revealed short-latency intracortical inhibition was reduced for the contralateral M1 at first walk compared to discharge (p=0.003. For the ipsilateral M1 both short and long-latency intracortical inhibition were reduced at admission (p<0.05 and prosthetic casting (p<0.02. Analysis of the neurophysiology and gait function revealed several interesting relationships. For the contralateral M1, reduced inhibition at admission (p=0.04 and first walk (p=0.05 was associated with better gait function. For the ipsilateral M1, reduced inhibition at discharge (p=0.05 was associated with poor gait function. This study characterised intracortical excitability in rehabilitating amputees. A dichotomous relationship between reduced intracortical inhibition for each M1 and gait function was observed at different times. Intracortical inhibition may be an appropriate cortical biomarker of gait function in lower limb amputees during rehabilitation, but requires further investigation. Understanding M1 intracortical excitability of amputees undertaking prosthetic rehabilitation provides insight into brain reorganisation in the sub-acute post amputation period and may guide future studies seeking to improve rehabilitation

Design and demonstration of an intracortical probe technology with tunable modulus.

Science.gov (United States)

Simon, Dustin M; Charkhkar, Hamid; St John, Conan; Rajendran, Sakthi; Kang, Tong; Reit, Radu; Arreaga-Salas, David; McHail, Daniel G; Knaack, Gretchen L; Sloan, Andrew; Grasse, Dane; Dumas, Theodore C; Rennaker, Robert L; Pancrazio, Joseph J; Voit, Walter E

2017-01-01

Intracortical probe technology, consisting of arrays of microelectrodes, offers a means of recording the bioelectrical activity from neural tissue. A major limitation of existing intracortical probe technology pertains to limited lifetime of 6 months to a year of recording after implantation. A major contributor to device failure is widely believed to be the interfacial mechanical mismatch of conventional stiff intracortical devices and the surrounding brain tissue. We describe the design, development, and demonstration of a novel functional intracortical probe technology that has a tunable Young's modulus from ∼2 GPa to ∼50 MPa. This technology leverages advances in dynamically softening materials, specifically thiol-ene/acrylate thermoset polymers, which exhibit minimal swelling of memory polymer-based multichannel intracortical probe can be fabricated, that the mechanical properties are stable for at least 2 months and that the device is capable of single unit recordings for durations up to 77 days in vivo. This novel technology, which is amenable to processes suitable for manufacturing via standard semiconductor fabrication techniques, offers the capability of softening in vivo to reduce the tissue-device modulus mismatch to ultimately improve long term viability of neural recordings. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 159-168, 2017. © 2016 Wiley Periodicals, Inc.

Cell-Targeted Optogenetics and Electrical Microstimulation Reveal the Primate Koniocellular Projection to Supra-granular Visual Cortex.

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Klein, Carsten; Evrard, Henry C; Shapcott, Katharine A; Haverkamp, Silke; Logothetis, Nikos K; Schmid, Michael C

2016-04-06

Electrical microstimulation and more recently optogenetics are widely used to map large-scale brain circuits. However, the neuronal specificity achieved with both methods is not well understood. Here we compare cell-targeted optogenetics and electrical microstimulation in the macaque monkey brain to functionally map the koniocellular lateral geniculate nucleus (LGN) projection to primary visual cortex (V1). Selective activation of the LGN konio neurons with CamK-specific optogenetics caused selective electrical current inflow in the supra-granular layers of V1. Electrical microstimulation targeted at LGN konio layers revealed the same supra-granular V1 activation pattern as the one elicited by optogenetics. Taken together, these findings establish a selective koniocellular LGN influence on V1 supra-granular layers, and they indicate comparable capacities of both stimulation methods to isolate thalamo-cortical circuits in the primate brain. Copyright © 2016 Elsevier Inc. All rights reserved.

In Vivo Demonstration of Addressable Microstimulators Powered by Rectification of Epidermically Applied Currents for Miniaturized Neuroprostheses.

Directory of Open Access Journals (Sweden)

Laura Becerra-Fajardo

Full Text Available Electrical stimulation is used in order to restore nerve mediated functions in patients with neurological disorders, but its applicability is constrained by the invasiveness of the systems required to perform it. As an alternative to implantable systems consisting of central stimulation units wired to the stimulation electrodes, networks of wireless microstimulators have been devised for fine movement restoration. Miniaturization of these microstimulators is currently hampered by the available methods for powering them. Previously, we have proposed and demonstrated a heterodox electrical stimulation method based on electronic rectification of high frequency current bursts. These bursts can be delivered through textile electrodes on the skin. This approach has the potential to result in an unprecedented level of miniaturization as no bulky parts such as coils or batteries are included in the implant. We envision microstimulators designs based on application-specific integrated circuits (ASICs that will be flexible, thread-like (diameters < 0.5 mm and not only with controlled stimulation capabilities but also with sensing capabilities for artificial proprioception. We in vivo demonstrate that neuroprostheses composed of addressable microstimulators based on this electrical stimulation method are feasible and can perform controlled charge-balanced electrical stimulation of muscles. We developed miniature external circuit prototypes connected to two bipolar probes that were percutaneously implanted in agonist and antagonist muscles of the hindlimb of an anesthetized rabbit. The electronic implant architecture was able to decode commands that were amplitude modulated on the high frequency (1 MHz auxiliary current bursts. The devices were capable of independently stimulating the target tissues, accomplishing controlled dorsiflexion and plantarflexion joint movements. In addition, we numerically show that the high frequency current bursts comply with

The difference between electrical microstimulation and direct electrical stimulation - towards new opportunities for innovative functional brain mapping?

Science.gov (United States)

Vincent, Marion; Rossel, Olivier; Hayashibe, Mitsuhiro; Herbet, Guillaume; Duffau, Hugues; Guiraud, David; Bonnetblanc, François

2016-04-01

Both electrical microstimulation (EMS) and direct electrical stimulation (DES) of the brain are used to perform functional brain mapping. EMS is applied to animal fundamental neuroscience experiments, whereas DES is performed in the operating theatre on neurosurgery patients. The objective of the present review was to shed new light on electrical stimulation techniques in brain mapping by comparing EMS and DES. There is much controversy as to whether the use of DES during wide-awake surgery is the 'gold standard' for studying the brain function. As part of this debate, it is sometimes wrongly assumed that EMS and DES induce similar effects in the nervous tissues and have comparable behavioural consequences. In fact, the respective stimulation parameters in EMS and DES are clearly different. More surprisingly, there is no solid biophysical rationale for setting the stimulation parameters in EMS and DES; this may be due to historical, methodological and technical constraints that have limited the experimental protocols and prompted the use of empirical methods. In contrast, the gap between EMS and DES highlights the potential for new experimental paradigms in electrical stimulation for functional brain mapping. In view of this gap and recent technical developments in stimulator design, it may now be time to move towards alternative, innovative protocols based on the functional stimulation of peripheral nerves (for which a more solid theoretical grounding exists).

Augmenting intracortical brain-machine interface with neurally driven error detectors

Science.gov (United States)

Even-Chen, Nir; Stavisky, Sergey D.; Kao, Jonathan C.; Ryu, Stephen I.; Shenoy, Krishna V.

2017-12-01

Objective. Making mistakes is inevitable, but identifying them allows us to correct or adapt our behavior to improve future performance. Current brain-machine interfaces (BMIs) make errors that need to be explicitly corrected by the user, thereby consuming time and thus hindering performance. We hypothesized that neural correlates of the user perceiving the mistake could be used by the BMI to automatically correct errors. However, it was unknown whether intracortical outcome error signals were present in the premotor and primary motor cortices, brain regions successfully used for intracortical BMIs. Approach. We report here for the first time a putative outcome error signal in spiking activity within these cortices when rhesus macaques performed an intracortical BMI computer cursor task. Main results. We decoded BMI trial outcomes shortly after and even before a trial ended with 96% and 84% accuracy, respectively. This led us to develop and implement in real-time a first-of-its-kind intracortical BMI error ‘detect-and-act’ system that attempts to automatically ‘undo’ or ‘prevent’ mistakes. The detect-and-act system works independently and in parallel to a kinematic BMI decoder. In a challenging task that resulted in substantial errors, this approach improved the performance of a BMI employing two variants of the ubiquitous Kalman velocity filter, including a state-of-the-art decoder (ReFIT-KF). Significance. Detecting errors in real-time from the same brain regions that are commonly used to control BMIs should improve the clinical viability of BMIs aimed at restoring motor function to people with paralysis.

sLORETA intracortical lagged coherence during breath counting in meditation-naïve participants

Directory of Open Access Journals (Sweden)

Patricia eMilz

2014-05-01

Full Text Available We investigated brain functional connectivity comparing no-task resting to breath counting (a meditation exercise but given as task without referring to meditation. Functional connectivity computed as EEG coherence between head-surface data suffers from localization ambiguity, reference dependence, and overestimation due to volume conduction. Lagged coherence between intracortical model sources addresses these criticisms. With this analysis approach, experienced meditators reportedly showed reduced coherence during meditation, meditation-naïve participants have not yet been investigated. 58-channel EEG from 23 healthy, right-handed, meditation-naïve males during resting [3 runs] and breath counting [2 runs] was computed into sLORETA time series of intracortical electrical activity in 19 regions of interest corresponding to the cortex underlying 19 scalp electrode sites, for each of the 8 independent EEG frequency bands covering 1.5-44 Hz. Intracortical lagged coherences and head-surface conventional coherences were computed between the 19 regions/sites. During breath counting compared to resting, paired t-tests corrected for multiple testing revealed 4 significantly lower intracortical lagged coherences, but 4 significantly higher head-surface conventional coherences. Lowered intracortical lagged coherences involved left BA 10 and right BAs 3, 10, 17, 40. In conclusion, intracortical lagged coherence can yield results that are inverted to those of head-surface conventional coherence. The lowered functional connectivity between cognitive control areas and sensory perception areas during meditation-type breath counting compared to resting conceivably reflects the attention to a bodily percept without cognitive reasoning. The reductions in functional connectivity were similar but not as widespread as the reductions reported during meditation in experienced meditators.

Black bears with longer disuse (hibernation) periods have lower femoral osteon population density and greater mineralization and intracortical porosity.

Science.gov (United States)

Wojda, Samantha J; Weyland, David R; Gray, Sarah K; McGee-Lawrence, Meghan E; Drummer, Thomas D; Donahue, Seth W

2013-08-01

Intracortical bone remodeling is persistent throughout life, leading to age related increases in osteon population density (OPD). Intracortical porosity also increases with age in many mammals including humans, contributing to bone fragility and fracture risk. Unbalanced bone resorption and formation during disuse (e.g., physical inactivity) also increases intracortical porosity. In contrast, hibernating bears are a naturally occurring model for the prevention of both age-related and disuse osteoporoses. Intracortical bone remodeling is decreased during hibernation, but resorption and formation remain balanced. Black bears spend 0.25-7 months in hibernation annually depending on climate and food availability. We found longer hibernating bears demonstrate lower OPD and higher cortical bone mineralization than bears with shorter hibernation durations, but we surprisingly found longer hibernating bears had higher intracortical porosity. However, bears from three different latitudes showed age-related decreases in intracortical porosity, indicating that regardless of hibernation duration, black bears do not show the disuse- or age-related increases in intracortical porosity which is typical of other animals. This ability to prevent increases in intracortical porosity likely contributes to their ability to maintain bone strength during prolonged periods of physical inactivity and throughout life. Improving our understanding of the unique bone metabolism in hibernating bears will potentially increase our ability to develop treatments for age- and disuse-related osteoporoses in humans. Copyright © 2013 Wiley Periodicals, Inc.

In Vivo Demonstration of Addressable Microstimulators Powered by Rectification of Epidermically Applied Currents for Miniaturized Neuroprostheses.

Science.gov (United States)

Becerra-Fajardo, Laura; Ivorra, Antoni

2015-01-01

Electrical stimulation is used in order to restore nerve mediated functions in patients with neurological disorders, but its applicability is constrained by the invasiveness of the systems required to perform it. As an alternative to implantable systems consisting of central stimulation units wired to the stimulation electrodes, networks of wireless microstimulators have been devised for fine movement restoration. Miniaturization of these microstimulators is currently hampered by the available methods for powering them. Previously, we have proposed and demonstrated a heterodox electrical stimulation method based on electronic rectification of high frequency current bursts. These bursts can be delivered through textile electrodes on the skin. This approach has the potential to result in an unprecedented level of miniaturization as no bulky parts such as coils or batteries are included in the implant. We envision microstimulators designs based on application-specific integrated circuits (ASICs) that will be flexible, thread-like (diameters electrical stimulation method are feasible and can perform controlled charge-balanced electrical stimulation of muscles. We developed miniature external circuit prototypes connected to two bipolar probes that were percutaneously implanted in agonist and antagonist muscles of the hindlimb of an anesthetized rabbit. The electronic implant architecture was able to decode commands that were amplitude modulated on the high frequency (1 MHz) auxiliary current bursts. The devices were capable of independently stimulating the target tissues, accomplishing controlled dorsiflexion and plantarflexion joint movements. In addition, we numerically show that the high frequency current bursts comply with safety standards both in terms of tissue heating and unwanted electro-stimulation. We demonstrate that addressable microstimulators powered by rectification of epidermically applied currents are feasible.

Using Arrays of Microelectrodes Implanted in Residual Peripheral Nerves to Provide Dextrous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis

Science.gov (United States)

2015-10-01

extended that work by investigating multiple aspects important for developing future bidirectional neural prostheses based on high-count microelectrode...Fan J M, Kao J C, Stavisky S D, Ryu S and Shenoy K 2012 A recurrent neural network for closed-loop intracortical brain-machine interface decoders J...Peripheral Nerve Interface, Prosthetic Hand, Neural Prosthesis, Sensory Feedback, Micro-stimulation, Electrophysiology, Action Potentials, Micro

Development of a polymer based fully flexible electrode tip for neuronal micro-stimulation applications

Science.gov (United States)

David, Romain; Miki, Norihisa

2017-06-01

Neural stimulation systems design is highly impacted by the overall resolution and adaptability of the device to the targeted application and area to stimulate. In this paper, we report a novel design for neural micro-stimulation electrode presenting high resolution and adaptability to any targeted area via a high flexibility. We propose the use of liquid metal micro-channels encapsulated into a polymer volume, achieving micro-stimulation pads at the tip of the channels. It presents a high degree of patternability to match different possible targeted applications, and good flexibility and mechanic properties to make it insertable and adaptable into soft tissues. A stable fabrication process, including insertion of the liquid alloy into 50 µm half-channels, the necessity of the U-shape to produce functional conductive micro-channels and the mechanical integrity of the device are discussed.

The biocompatibility, integrity, and positional stability of an injectable microstimulator for reanimation of the paralyzed larynx.

Science.gov (United States)

Zealear, D L; Garren, K C; Rodriguez, R J; Reyes, J H; Huang, S; Dokmeci, M R; Najafi, K

2001-08-01

The biocompatibility, integrity, positional stability, and potential use of hermetically sealed injectable wireless micromachined microstimulators were investigated for reanimation of the paralyzed larynx. The device, consisting of silicon and glass, has been tested and proven to be biocompatible with no evidence of pathological tissue reaction or rejection up to one-year implantation in the rat dorsum and canine larynx. By one month, each unit was encapsulated by a thin membrane, which thickened to form a fibrous layer of less than 500 microm at 6-12 months. The microstimulators demonstrated long-term in vivo durability: the hermetic seal of only one in ten devices was breached. Once implanted, migration of the device varied from 0 to 3 cm, depending upon the extent of surgical dissection. No discernable migration was noted when the tissue dissection was minimal. Studies utilizing a modified device equipped with electrodes indicated that migration was nominal with sufficient positional stability to ensure activation of target muscles for glottis opening. This study supported the feasibility of using a microstimulator for reanimation of paralyzed laryngeal muscles that open the airway during breathing. This innovative approach to treatment would alleviate the need for a tracheotomy or surgical resection of the vocal fold.

Intra-cortical excitability in healthy human subjects after tongue training

DEFF Research Database (Denmark)

Baad-Hansen, Lene; Blicher, Jakob; Lapitskaya, Natallia

2009-01-01

Training of specific muscles causes plastic changes in corticomotor pathways which may underlie the effect of various clinical rehabilitation procedures. The paired pulse transcranial magnetic stimulation (ppTMS) technique can be used to assess short interval intra-cortical inhibitory (SICI...... tongue muscles. In tongue motor cortex, bilateral SICI (P training. There were no significant effects of training on single MEPs or SICI/ICF (P > 0.063). The success rate improved during training (P ...) and intra-cortical facilitatory (ICF) networks. This study examined changes in SICI and ICF in tongue motor cortex after tongue training in 11 healthy volunteers using ppTMS. Paired pulse TMS was applied to the 'hot-spot' for the tongue motor cortex and motor-evoked potentials (MEPs) were recorded from...

Eliciting Naturalistic Cortical Responses with a Sensory Prosthesis via Optimized Microstimulation

Science.gov (United States)

2016-08-12

Eliciting naturalistic cortical responses with a sensory prosthesis via optimized microstimulation John S Choi1, Austin J Brockmeier2, David B...applied to single electrodes in the ventral caudal thalamus evoke percepts that are both place and modality-specific, and yet ‘unnatural’ in feeling ...information on touch parameters, they do so with the same timing, as would be expected for a biomimetic sensory prosthesis . The discriminability of natural

A low-power bidirectional telemetry device with a near-field charging feature for a cardiac microstimulator.

Science.gov (United States)

Shuenn-Yuh Lee; Chih-Jen Cheng; Ming-Chun Liang

2011-08-01

In this paper, wireless telemetry using the near-field coupling technique with round-wire coils for an implanted cardiac microstimulator is presented. The proposed system possesses an external powering amplifier and an internal bidirectional microstimulator. The energy of the microstimulator is provided by a rectifier that can efficiently charge a rechargeable device. A fully integrated regulator and a charge pump circuit are included to generate a stable, low-voltage, and high-potential supply voltage, respectively. A miniature digital processor includes a phase-shift-keying (PSK) demodulator to decode the transmission data and a self-protective system controller to operate the entire system. To acquire the cardiac signal, a low-voltage and low-power monitoring analog front end (MAFE) performs immediate threshold detection and data conversion. In addition, the pacing circuit, which consists of a pulse generator (PG) and its digital-to-analog (D/A) controller, is responsible for stimulating heart tissue. The chip was fabricated by Taiwan Semiconductor Manufacturing Company (TSMC) with 0.35-μm complementary metal-oxide semiconductor technology to perform the monitoring and pacing functions with inductively powered communication. Using a model with lead and heart tissue on measurement, a -5-V pulse at a stimulating frequency of 60 beats per minute (bpm) is delivered while only consuming 31.5 μW of power.

Impaired intracortical transmission in G2019S leucine rich-repeat kinase Parkinson patients.

Science.gov (United States)

Ponzo, Viviana; Di Lorenzo, Francesco; Brusa, Livia; Schirinzi, Tommaso; Battistini, Stefania; Ricci, Claudia; Sambucci, Manolo; Caltagirone, Carlo; Koch, Giacomo

2017-05-01

A mutation in leucine-rich repeat kinase 2 is the most common cause of hereditary Parkinson's disease (PD), yet the neural mechanisms and the circuitry potentially involved are poorly understood. We used different transcranial magnetic stimulation protocols to explore in the primary motor cortex the activity of intracortical circuits and cortical plasticity (long-term potentiation) in patients with the G2019S leucine-rich repeat kinase 2 gene mutation when compared with idiopathic PD patients and age-matched healthy subjects. Paired pulse transcranial magnetic stimulation was used to investigate short intracortical inhibition and facilitation and short afferent inhibition. Intermittent theta burst stimulation, a form of repetitive transcranial magnetic stimulation, was used to test long-term potentiation-like cortical plasticity. Leucine-rich repeat kinase 2 and idiopathic PD were tested both in ON and in OFF l-dopa therapy. When compared with idiopathic PD and healthy subjects, leucine-rich repeat kinase 2 PD patients showed a remarkable reduction of short intracortical inhibition in both ON and in OFF l-dopa therapy. This reduction was paralleled by an increase of intracortical facilitation in OFF l-dopa therapy. Leucine-rich repeat kinase 2 PD showed abnormal long-term potentiation-like cortical plasticity in ON l-dopa therapy. The motor cortex in leucine-rich repeat kinase 2 mutated PD patients is strongly disinhibited and hyperexcitable. These abnormalities could be a result of an impairment of inhibitory (gamma-Aminobutyric acid) transmission eventually related to altered neurotransmitter release. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Lens Accommodation, Ocular Convergence and the Brain(Physiology of Vision)

OpenAIRE

坂東, 武彦; 戸田, 春男; 安藤, 誠男; 高木, 峰夫; 吉沢, 豊久; 原, 直人; Bando, Takehiko; Toda, Haruo; Ando, Tomoo; Takagi, Mineo; Yoshizawa, Toyohisa; Hara, Naoto

1993-01-01

Experimental findings obtained by our group were reviewed, and functional significance of the visual association cortex in controlling lens accommodation and ocular convergence was discussed. By intracortical microstimulation in an extrastriate visual area in the cat, lens accommodation and vergence eye movement were evoked. In the same cortical area, a group of neurons was also activated in correlation with lens accommodation or ocular convergence. In addition, after the lesion in this area,...

Short-interval and long-interval intracortical inhibition of TMS-evoked EEG potentials.

Science.gov (United States)

Premoli, Isabella; Király, Julia; Müller-Dahlhaus, Florian; Zipser, Carl M; Rossini, Pierre; Zrenner, Christoph; Ziemann, Ulf; Belardinelli, Paolo

2018-03-15

Inhibition in the human motor cortex can be probed by means of paired-pulse transcranial magnetic stimulation (ppTMS) at interstimulus intervals of 2-3 ms (short-interval intracortical inhibition, SICI) or ∼100 ms (long-interval intracortical inhibition, LICI). Conventionally, SICI and LICI are recorded as motor evoked potential (MEP) inhibition in the hand muscle. Pharmacological experiments indicate that they are mediated by GABAA and GABAB receptors, respectively. SICI and LICI of TMS-evoked EEG potentials (TEPs) and their pharmacological properties have not been systematically studied. Here, we sought to examine SICI by ppTMS-evoked compared to single-pulse TMS-evoked TEPs, to investigate its pharmacological manipulation and to compare SICI with our previous results on LICI. PpTMS-EEG was applied to the left motor cortex in 16 healthy subjects in a randomized, double-blind placebo-controlled crossover design, testing the effects of a single oral dose 20 mg of diazepam, a positive modulator at the GABAA receptor, vs. 50 mg of the GABAB receptor agonist baclofen on SICI of TEPs. We found significant SICI of the N100 and P180 TEPs prior to drug intake. Diazepam reduced SICI of the N100 TEP, while baclofen enhanced it. Compared to our previous ppTMS-EEG results on LICI, the SICI effects on TEPs, including their drug modulation, were largely analogous. Findings suggest a similar interaction of paired-pulse effects on TEPs irrespective of the interstimulus interval. Therefore, SICI and LICI as measured with TEPs cannot be directly derived from SICI and LICI measured with MEPs, but may offer novel insight into paired-pulse responses recorded directly from the brain rather than muscle. Copyright © 2018 Elsevier Inc. All rights reserved.

Microstimulation of the lumbar DRG recruits primary afferent neurons in localized regions of lower limb.

Science.gov (United States)

Ayers, Christopher A; Fisher, Lee E; Gaunt, Robert A; Weber, Douglas J

2016-07-01

Patterned microstimulation of the dorsal root ganglion (DRG) has been proposed as a method for delivering tactile and proprioceptive feedback to amputees. Previous studies demonstrated that large- and medium-diameter afferent neurons could be recruited separately, even several months after implantation. However, those studies did not examine the anatomical localization of sensory fibers recruited by microstimulation in the DRG. Achieving precise recruitment with respect to both modality and receptive field locations will likely be crucial to create a viable sensory neuroprosthesis. In this study, penetrating microelectrode arrays were implanted in the L5, L6, and L7 DRG of four isoflurane-anesthetized cats instrumented with nerve cuff electrodes around the proximal and distal branches of the sciatic and femoral nerves. A binary search was used to find the recruitment threshold for evoking a response in each nerve cuff. The selectivity of DRG stimulation was characterized by the ability to recruit individual distal branches to the exclusion of all others at threshold; 84.7% (n = 201) of the stimulation electrodes recruited a single nerve branch, with 9 of the 15 instrumented nerves recruited selectively. The median stimulation threshold was 0.68 nC/phase, and the median dynamic range (increase in charge while stimulation remained selective) was 0.36 nC/phase. These results demonstrate the ability of DRG microstimulation to achieve selective recruitment of the major nerve branches of the hindlimb, suggesting that this approach could be used to drive sensory input from localized regions of the limb. This sensory input might be useful for restoring tactile and proprioceptive feedback to a lower-limb amputee. Copyright © 2016 the American Physiological Society.

Intracortical inhibitory and excitatory circuits in subjects with minimal hepatic encephalopathy: a TMS study.

Science.gov (United States)

Nardone, Raffaele; De Blasi, Pierpaolo; Höller, Yvonne; Brigo, Francesco; Golaszewski, Stefan; Frey, Vanessa N; Orioli, Andrea; Trinka, Eugen

2016-10-01

Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy (HE) and affects up to 80 % of patients with liver cirrhosis. By definition, MHE is characterized by psychomotor slowing and subtle cognitive deficits,  but obvious clinical manifestations are lacking. Given its covert nature, MHE is often underdiagnosed. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the HE. We investigated motor cortex excitability in 15 patients with MHE and in 15 age-matched age-matched cirrhotic patients without MHE; the resting motor threshold, the short-interval intracortical inhibition (SICI) and the intracortical facilitation (ICF) were examined. Paired-pulse TMS revealed significant increased SICI and reduced ICF in the patients with MHE. These findings may reflect abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. In particular, the results suggest a shift in the balance between intracortical inhibitory and excitatory mechanisms towards a net increase of inhibitory neurotransmission. Together with other neurophysiological (in particular EEG) and neuroimaging techniques, TMS may thus provide early markers of cerebral dysfunction in cirrhotic patients with MHE.

Neuronal responses to tactile stimuli and tactile sensations evoked by microstimulation in the human thalamic principal somatic sensory nucleus (ventral caudal).

Science.gov (United States)

Schmid, Anne-Christine; Chien, Jui-Hong; Greenspan, Joel D; Garonzik, Ira; Weiss, Nirit; Ohara, Shinji; Lenz, Frederick Arthur

2016-06-01

The normal organization and plasticity of the cutaneous core of the thalamic principal somatosensory nucleus (ventral caudal, Vc) have been studied by single-neuron recordings and microstimulation in patients undergoing awake stereotactic operations for essential tremor (ET) without apparent somatic sensory abnormality and in patients with dystonia or chronic pain secondary to major nervous system injury. In patients with ET, most Vc neurons responded to one of the four stimuli, each of which optimally activates one mechanoreceptor type. Sensations evoked by microstimulation were similar to those evoked by the optimal stimulus only among rapidly adapting neurons. In patients with ET, Vc was highly segmented somatotopically, and vibration, movement, pressure, and sharp sensations were usually evoked by microstimulation at separate sites in Vc. In patients with conditions including spinal cord transection, amputation, or dystonia, RFs were mismatched with projected fields more commonly than in patients with ET. The representation of the border of the anesthetic area (e.g., stump) or of the dystonic limb was much larger than that of the same part of the body in patients with ET. This review describes the organization and reorganization of human Vc neuronal activity in nervous system injury and dystonia and then proposes basic mechanisms. Copyright © 2016 the American Physiological Society.

Neural control of finger movement via intracortical brain-machine interface

Science.gov (United States)

Irwin, Z. T.; Schroeder, K. E.; Vu, P. P.; Bullard, A. J.; Tat, D. M.; Nu, C. S.; Vaskov, A.; Nason, S. R.; Thompson, D. E.; Bentley, J. N.; Patil, P. G.; Chestek, C. A.

2017-12-01

Objective. Intracortical brain-machine interfaces (BMIs) are a promising source of prosthesis control signals for individuals with severe motor disabilities. Previous BMI studies have primarily focused on predicting and controlling whole-arm movements; precise control of hand kinematics, however, has not been fully demonstrated. Here, we investigate the continuous decoding of precise finger movements in rhesus macaques. Approach. In order to elicit precise and repeatable finger movements, we have developed a novel behavioral task paradigm which requires the subject to acquire virtual fingertip position targets. In the physical control condition, four rhesus macaques performed this task by moving all four fingers together in order to acquire a single target. This movement was equivalent to controlling the aperture of a power grasp. During this task performance, we recorded neural spikes from intracortical electrode arrays in primary motor cortex. Main results. Using a standard Kalman filter, we could reconstruct continuous finger movement offline with an average correlation of ρ  =  0.78 between actual and predicted position across four rhesus macaques. For two of the monkeys, this movement prediction was performed in real-time to enable direct brain control of the virtual hand. Compared to physical control, neural control performance was slightly degraded; however, the monkeys were still able to successfully perform the task with an average target acquisition rate of 83.1%. The monkeys’ ability to arbitrarily specify fingertip position was also quantified using an information throughput metric. During brain control task performance, the monkeys achieved an average 1.01 bits s-1 throughput, similar to that achieved in previous studies which decoded upper-arm movements to control computer cursors using a standard Kalman filter. Significance. This is, to our knowledge, the first demonstration of brain control of finger-level fine motor skills. We believe

Long-interval intracortical inhibition as biomarker for epilepsy : a transcranial magnetic stimulation study

NARCIS (Netherlands)

Bauer, Prisca R.; de Goede, Annika A.; Stern, William M.; Pawley, Adam D.; Chowdhury, Fahmida A.; Helling, Robert M.; Bouet, Romain; Kalitzin, Stiliyan N.; Visser, Gerhard H.; Sisodiya, Sanjay M.; Rothwell, John C.; Richardson, Mark P.; van Putten, Michel J.A.M.; Sander, Josemir W.

2018-01-01

Cortical excitability, as measured by transcranial magnetic stimulation combined with electromyography, is a potential biomarker for the diagnosis and follow-up of epilepsy. We report on long-interval intracortical inhibition data measured in four different centres in healthy controls (n = 95),

Decoder calibration with ultra small current sample set for intracortical brain-machine interface

Science.gov (United States)

Zhang, Peng; Ma, Xuan; Chen, Luyao; Zhou, Jin; Wang, Changyong; Li, Wei; He, Jiping

2018-04-01

Objective. Intracortical brain-machine interfaces (iBMIs) aim to restore efficient communication and movement ability for paralyzed patients. However, frequent recalibration is required for consistency and reliability, and every recalibration will require relatively large most current sample set. The aim in this study is to develop an effective decoder calibration method that can achieve good performance while minimizing recalibration time. Approach. Two rhesus macaques implanted with intracortical microelectrode arrays were trained separately on movement and sensory paradigm. Neural signals were recorded to decode reaching positions or grasping postures. A novel principal component analysis-based domain adaptation (PDA) method was proposed to recalibrate the decoder with only ultra small current sample set by taking advantage of large historical data, and the decoding performance was compared with other three calibration methods for evaluation. Main results. The PDA method closed the gap between historical and current data effectively, and made it possible to take advantage of large historical data for decoder recalibration in current data decoding. Using only ultra small current sample set (five trials of each category), the decoder calibrated using the PDA method could achieve much better and more robust performance in all sessions than using other three calibration methods in both monkeys. Significance. (1) By this study, transfer learning theory was brought into iBMIs decoder calibration for the first time. (2) Different from most transfer learning studies, the target data in this study were ultra small sample set and were transferred to the source data. (3) By taking advantage of historical data, the PDA method was demonstrated to be effective in reducing recalibration time for both movement paradigm and sensory paradigm, indicating a viable generalization. By reducing the demand for large current training data, this new method may facilitate the application

Comparative pathogenesis of radium-induced intracortical bone lesions in humans and beagles

International Nuclear Information System (INIS)

Pool, R.R.; Morgan, J.P.; Parks, N.J.; Farnham, J.E.; Littman, M.S.

1982-01-01

An interlaboratory research team from our Laboratory and the Center for Human Radiobiology at Argonne National Laboratory has performed an initial comparison of intracortical lesions in the long bones of dog and man following chronic radium deposition in the skeleton. The sequential radiographic appearance and morphology of radiation osteodystrophy is discussed. The role of osteodystrohy in the evaluation of bone tumors in the dog is examined

Correlation of mRNA Expression and Signal Variability in Chronic Intracortical Electrodes.

Science.gov (United States)

Falcone, Jessica D; Carroll, Sheridan L; Saxena, Tarun; Mandavia, Dev; Clark, Alexus; Yarabarla, Varun; Bellamkonda, Ravi V

2018-01-01

The goal for this research was to identify molecular mechanisms that explain animal-to-animal variability in chronic intracortical recordings. Microwire electrodes were implanted into Sprague Dawley rats at an acute (1 week) and a chronic (14 weeks) time point. Weekly recordings were conducted, and action potentials were evoked in the barrel cortex by deflecting the rat's whiskers. At 1 and 14 weeks, tissue was collected, and mRNA was extracted. mRNA expression was compared between 1 and 14 weeks using a high throughput multiplexed qRT-PCR. Pearson correlation coefficients were calculated between mRNA expression and signal-to-noise ratios at 14 weeks. At 14 weeks, a positive correlation between signal-to-noise ratio (SNR) and NeuN and GFAP mRNA expression was observed, indicating a relationship between recording strength and neuronal population, as well as reactive astrocyte activity. The inflammatory state around the electrode interface was evaluated using M1-like and M2-like markers. Expression for both M1-like and M2-like mRNA markers remained steady from 1 to 14 weeks. Anti-inflammatory markers, CD206 and CD163, however, demonstrated a significant positive correlation with SNR quality at 14 weeks. VE-cadherin, a marker for adherens junctions, and PDGFR-β, a marker for pericytes, both partial representatives of blood-brain barrier health, had a positive correlation with SNR at 14 weeks. Endothelial adhesion markers revealed a significant increase in expression at 14 weeks, while CD45, a pan-leukocyte marker, significantly decreased at 14 weeks. No significant correlation was found for either the endothelial adhesion or pan-leukocyte markers. A positive correlation between anti-inflammatory and blood-brain barrier health mRNA markers with electrophysiological efficacy of implanted intracortical electrodes has been demonstrated. These data reveal potential mechanisms for further evaluation to determine potential target mechanisms to improve

Implications of chronic daily anti-oxidant administration on the inflammatory response to intracortical microelectrodes

Science.gov (United States)

Potter-Baker, Kelsey A.; Stewart, Wade G.; Tomaszewski, William H.; Wong, Chun T.; Meador, William D.; Ziats, Nicholas P.; Capadona, Jeffrey R.

2015-08-01

Objective. Oxidative stress events have been implicated to occur and facilitate multiple failure modes of intracortical microelectrodes. The goal of the present study was to evaluate the ability of a sustained concentration of an anti-oxidant and to reduce oxidative stress-mediated neurodegeneration for the application of intracortical microelectrodes. Approach. Non-functional microelectrodes were implanted into the cortex of male Sprague Dawley rats for up to sixteen weeks. Half of the animals received a daily intraperitoneal injection of the natural anti-oxidant resveratrol, at 30 mg kg-1. The study was designed to investigate the biodistribution of the resveratrol, and the effects on neuroinflammation/neuroprotection following device implantation. Main results. Daily maintenance of a sustained range of resveratrol throughout the implantation period resulted in fewer degenerating neurons in comparison to control animals at both two and sixteen weeks post implantation. Initial and chronic improvements in neuronal viability in resveratrol-dosed animals were correlated with significant reductions in local superoxide anion accumulation around the implanted device at two weeks after implantation. Controls, receiving only saline injections, were also found to have reduced amounts of accumulated superoxide anion locally and less neurodegeneration than controls at sixteen weeks post-implantation. Despite observed benefits, thread-like adhesions were found between the liver and diaphragm in resveratrol-dosed animals. Significance. Overall, our chronic daily anti-oxidant dosing scheme resulted in improvements in neuronal viability surrounding implanted microelectrodes, which could result in improved device performance. However, due to the discovery of thread-like adhesions, further work is still required to optimize a chronic anti-oxidant dosing regime for the application of intracortical microelectrodes.

Paired-Pulse TMS and Fine-Wire Recordings Reveal Short-Interval Intracortical Inhibition and Facilitation of Deep Multifidus Muscle Fascicles.

Directory of Open Access Journals (Sweden)

Hugo Massé-Alarie

Full Text Available Paired-pulse transcranial magnetic stimulation (ppTMS is used to probe inhibitory and excitatory networks within the primary motor cortex (M1. These mechanisms are identified for limb muscles but it is unclear whether they share properties with trunk muscles. The aim was to determine whether it was possible to test the intracortical inhibition and facilitation of the deep multifidus muscle fascicles (DM and at which inter-stimulus intervals (ISI.In ten pain-free individuals, TMS was applied over M1 and motor evoked potentials (MEP were recorded using fine-wire electrodes in DM. MEPs were conditioned with subthreshold stimuli at ISIs of 1 to 12 ms to test short-interval intracortical inhibition (SICI and at 15 ms for long-interval intracortical facilitation. Short-interval facilitation (SICF was tested using 1-ms ISI.SICI of DM was consistently obtained with ISI of 1-, 3-, 4- and 12-ms. Facilitation of DM MEP was only identified using SICF paradigm.A similar pattern of MEP modulation with ISI changes for deep trunk and limb muscles implies that M1 networks share some functional properties.The ppTMS paradigm presents a potential to determine how M1 inhibitory and excitatory mechanisms participate in brain re-organization in back pain that affects control of trunk muscles.

Intracortical chondroblastoma mimicking intra-articular osteoid osteoma

Energy Technology Data Exchange (ETDEWEB)

Ishida, Tsuyoshi; Mukai, Kiyoshi [First Department of Pathology, Tokyo Medical University, Shinjuku 6-1-1, Shinjuku-ku, Tokyo 160-8402 (Japan); Goto, Takahiro [Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, Tokyo (Japan); Motoi, Noriko [Department of Pathology, Toranomon Hospital, Tokyo (Japan)

2002-10-01

We report a case of intra-articular intracortical chondroblastoma of the femoral condyle which radiologically appeared to be osteoid osteoma. A 19-year-old woman presented with a 3-year history of gradually increasing pain in the right knee and had been on nonsteroidal anti-inflammatory drugs for pain relief. Laboratory data were within normal limits. Radiographs showed a well-demarcated lucent lesion in the medial condyle of the right femur. A nidus-like lesion with calcifications and a sclerotic rim located in the cortex was imaged by computed tomography scan. Magnetic resonance imaging revealed bone marrow edema and soft tissue swelling around the lesion, with low signal intensity of the nidus-like lesion on both T1- and T2-weighted images. The lesion was excised en bloc and the histological diagnosis of chondroblastoma was made. A mild inflammatory reaction was observed in the bone marrow and synovium around the tumor. The chondroblastoma cells were shown to express cyclooxygenase-2 with immunohistochemistry. (orig.)

The Effect of the Elimination of Micromotion and Tissue Strain on Intracortical Device Performance

Science.gov (United States)

2017-10-01

evoked by short term and chronic implantation of non-softening, moderately softening, and softening shape memory polymer (SMP)-based intracortical...Does probe softening improve the surrounding tissue response and recording performance of the device? The short term impact will be on the scientific...community through publications and presentations. Over the long term , the core technology has exceptional promise for translation into the clinic. SMP

A critical review of cell culture strategies for modelling intracortical brain implant material reactions.

Science.gov (United States)

Gilmour, A D; Woolley, A J; Poole-Warren, L A; Thomson, C E; Green, R A

2016-06-01

The capacity to predict in vivo responses to medical devices in humans currently relies greatly on implantation in animal models. Researchers have been striving to develop in vitro techniques that can overcome the limitations associated with in vivo approaches. This review focuses on a critical analysis of the major in vitro strategies being utilized in laboratories around the world to improve understanding of the biological performance of intracortical, brain-implanted microdevices. Of particular interest to the current review are in vitro models for studying cell responses to penetrating intracortical devices and their materials, such as electrode arrays used for brain computer interface (BCI) and deep brain stimulation electrode probes implanted through the cortex. A background on the neural interface challenge is presented, followed by discussion of relevant in vitro culture strategies and their advantages and disadvantages. Future development of 2D culture models that exhibit developmental changes capable of mimicking normal, postnatal development will form the basis for more complex accurate predictive models in the future. Although not within the scope of this review, innovations in 3D scaffold technologies and microfluidic constructs will further improve the utility of in vitro approaches. Copyright © 2016 Elsevier Ltd. All rights reserved.

Patients in a vegetative state following traumatic brain injury display a reduced intracortical modulation.

Science.gov (United States)

Bagnato, Sergio; Boccagni, Cristina; Sant'Angelo, Antonino; Prestandrea, Caterina; Rizzo, Silvia; Galardi, Giuseppe

2012-10-01

Patients in coma who fail to wake develop a condition known as a vegetative state (VS). While we know that some cortical activities exist in patients in VS, it remains unclear whether interneuronal modulation can be abnormal in the cerebral cortex of these patients. The aim of the study was to evaluate the inhibitory and excitatory interneuronal circuits in patients in VS following a traumatic brain injury. Cortical excitability was studied in 5 VS patients and in 10 healthy subjects using paired pulses transcranial magnetic stimulation (TMS). Resting motor threshold and intracortical inhibition and facilitation at short intervals (2 and 10 ms, respectively) were evaluated. Two patients were studied again after their level of consciousness transitioned into a minimally conscious state (MCS). Both intracortical inhibition and facilitation were significantly reduced in patients compared to healthy subjects (p<0.05). In addition, these results did not significantly change in the 2 patients who evolved into a MCS. This is the first report showing an abnormal cortical excitability in patients in VS. Our findings suggest a pathophysiological base for future work aiming to restore the lack of interneuronal transmission in patients in VS. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Spatial and temporal characteristics of V1 microstimulation during chronic implantation of a microelectrode array in a behaving macaque

Science.gov (United States)

Davis, T. S.; Parker, R. A.; House, P. A.; Bagley, E.; Wendelken, S.; Normann, R. A.; Greger, B.

2012-12-01

Objective. It has been hypothesized that a vision prosthesis capable of evoking useful visual percepts can be based upon electrically stimulating the primary visual cortex (V1) of a blind human subject via penetrating microelectrode arrays. As a continuation of earlier work, we examined several spatial and temporal characteristics of V1 microstimulation. Approach. An array of 100 penetrating microelectrodes was chronically implanted in V1 of a behaving macaque monkey. Microstimulation thresholds were measured using a two-alternative forced choice detection task. Relative locations of electrically-evoked percepts were measured using a memory saccade-to-target task. Main results. The principal finding was that two years after implantation we were able to evoke behavioural responses to electric stimulation across the spatial extent of the array using groups of contiguous electrodes. Consistent responses to stimulation were evoked at an average threshold current per electrode of 204 ± 49 µA (mean ± std) for groups of four electrodes and 91 ± 25 µA for groups of nine electrodes. Saccades to electrically-evoked percepts using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with groups having an average separation of 1.6 ± 0.3 mm (mean ± std) in cortex and 1.0° ± 0.2° in visual space. Significance. These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a cortically-based vision prosthesis for the blind using penetrating microelectrodes.

Relative contributions of intracortical and thalamo-cortical processes in the generation of alpha rhythms, revealed by partial coherence analysis

NARCIS (Netherlands)

Lopes da Silva, F.H.; Vos, J.E.; Mooibroek, J.; Rotterdam, A. van

1980-01-01

The thalamo-cortical relationships of alpha rhythms have been analysed in dogs using partial coherence function analysis. The objective was to clarify how far the large intracortical coherence commonly recorded between different cortical sites could depend on a common thalamic site. It was found

Neural Interfaces for Intracortical Recording: Requirements, Fabrication Methods, and Characteristics.

Science.gov (United States)

Szostak, Katarzyna M; Grand, Laszlo; Constandinou, Timothy G

2017-01-01

Implantable neural interfaces for central nervous system research have been designed with wire, polymer, or micromachining technologies over the past 70 years. Research on biocompatible materials, ideal probe shapes, and insertion methods has resulted in building more and more capable neural interfaces. Although the trend is promising, the long-term reliability of such devices has not yet met the required criteria for chronic human application. The performance of neural interfaces in chronic settings often degrades due to foreign body response to the implant that is initiated by the surgical procedure, and related to the probe structure, and material properties used in fabricating the neural interface. In this review, we identify the key requirements for neural interfaces for intracortical recording, describe the three different types of probes-microwire, micromachined, and polymer-based probes; their materials, fabrication methods, and discuss their characteristics and related challenges.

Intracortical excitability in patients with relapsing-remitting and secondary progressive multiple sclerosis.

Science.gov (United States)

Conte, A; Lenzi, D; Frasca, V; Gilio, F; Giacomelli, E; Gabriele, M; Bettolo, C Marini; Iacovelli, E; Pantano, P; Pozzilli, C; Inghilleri, M

2009-06-01

We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing-remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients' TMS findings and magnetic resonance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.

Intracortical inhibition in the soleus muscle is reduced during the control of upright standing in both young and old adults

NARCIS (Netherlands)

Papegaaij, Selma; Baudry, Stéphane; Négyesi, János; Taube, Wolfgang; Hortobagyi, Tibor

Purpose In a previous study, we reported that a short-interval intracortical inhibition (SICI) decreases in old but not in young adults when standing on foam vs. a rigid surface. Here, we examined if such an age by task difficulty interaction in motor cortical excitability also occurs in easier

Neural Interfaces for Intracortical Recording: Requirements, Fabrication Methods, and Characteristics

Directory of Open Access Journals (Sweden)

Katarzyna M. Szostak

2017-12-01

Full Text Available Implantable neural interfaces for central nervous system research have been designed with wire, polymer, or micromachining technologies over the past 70 years. Research on biocompatible materials, ideal probe shapes, and insertion methods has resulted in building more and more capable neural interfaces. Although the trend is promising, the long-term reliability of such devices has not yet met the required criteria for chronic human application. The performance of neural interfaces in chronic settings often degrades due to foreign body response to the implant that is initiated by the surgical procedure, and related to the probe structure, and material properties used in fabricating the neural interface. In this review, we identify the key requirements for neural interfaces for intracortical recording, describe the three different types of probes—microwire, micromachined, and polymer-based probes; their materials, fabrication methods, and discuss their characteristics and related challenges.

Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with osteogenesis imperfecta.

Science.gov (United States)

Albert, Carolyne; Jameson, John; Smith, Peter; Harris, Gerald

2014-09-01

Osteogenesis imperfecta is a genetic disorder resulting in bone fragility. The mechanisms behind this fragility are not well understood. In addition to characteristic bone mass deficiencies, research suggests that bone material properties are compromised in individuals with this disorder. However, little data exists regarding bone properties beyond the microstructural scale in individuals with this disorder. Specimens were obtained from long bone diaphyses of nine children with osteogenesis imperfecta during routine osteotomy procedures. Small rectangular beams, oriented longitudinally and transversely to the diaphyseal axis, were machined from these specimens and elastic modulus, yield strength, and maximum strength were measured in three-point bending. Intracortical vascular porosity, bone volume fraction, osteocyte lacuna density, and volumetric tissue mineral density were determined by synchrotron micro-computed tomography, and relationships among these mechanical properties and structural parameters were explored. Modulus and strength were on average 64-68% lower in the transverse vs. longitudinal beams (Posteogenesis imperfecta. Results confirm that these properties are anisotropic. Elevated vascular porosity was observed in most specimens, and this parameter was associated with reduced bone material strength. These results offer insight toward understanding bone fragility and the role of intracortical porosity on the strength of bone tissue in children with osteogenesis imperfecta. Copyright © 2014 Elsevier Inc. All rights reserved.

Deep-brain electrical microstimulation is an effective tool to explore functional characteristics of somatosensory neurons in the rat brain.

Directory of Open Access Journals (Sweden)

Han-Jia Jiang

Full Text Available In neurophysiology researches, peripheral stimulation is used along with recordings of neural activities to study the processing of somatosensory signals in the brain. However, limited precision of peripheral stimulation makes it difficult to activate the neuron with millisecond resolution and study its functional properties in this scale. Also, tissue/receptor damage that could occur in some experiments often limits the amount of responses that can be recorded and hence reduces data reproducibility. To overcome these limitations, electrical microstimulation (ES of the brain could be used to directly and more precisely evoke neural responses. For this purpose, a deep-brain ES protocol for rat somatosensory relay neurons was developed in this study. Three male Wistar rats were used in the experiment. The ES was applied to the thalamic region responsive to hindpaw tactile stimulation (TS via a theta glass microelectrode. The resulting ES-evoked cortical responses showed action potentials and thalamocortical relay latencies very similar to those evoked by TS. This result shows that the developed deep-brain ES protocol is an effective tool to bypass peripheral tissue for in vivo functional analysis of specific types of somatosensory neurons. This protocol could be readily applied in researches of nociception and other somatosensory systems to allow more extensive exploration of the neural functional networks.

Intracortical stiffness of mid-diaphysis femur bovine bone: lacunar-canalicular based homogenization numerical solutions and microhardness measurements.

Science.gov (United States)

Hage, Ilige S; Hamade, Ramsey F

2017-09-01

Microscale lacunar-canalicular (L-C) porosity is a major contributor to intracortical bone stiffness variability. In this work, such variability is investigated experimentally using micro hardness indentation tests and numerically using a homogenization scheme. Cross sectional rings of cortical bones are cut from the middle tubular part of bovine femur long bone at mid-diaphysis. A series of light microscopy images are taken along a line emanating from the cross-section center starting from the ring's interior (endosteum) ring surface toward the ring's exterior (periosteum) ring surface. For each image in the line, computer vision analysis of porosity is conducted employing an image segmentation methodology based on pulse coupled neural networks (PCNN) recently developed by the authors. Determined are size and shape of each of the lacunar-canalicular (L-C) cortical micro constituents: lacunae, canaliculi, and Haversian canals. Consequently, it was possible to segment and quantify the geometrical attributes of all individual segmented pores leading to accurate determination of derived geometrical measures such as L-C cortical pores' total porosity (pore volume fraction), (elliptical) aspect ratio, orientation, location, and number of pores in secondary and primary osteons. Porosity was found to be unevenly (but linearly) distributed along the interior and exterior regions of the intracortical bone. The segmented L-C porosity data is passed to a numerical microscale-based homogenization scheme, also recently developed by the authors, that analyses a composite made up of lamella matrix punctuated by multi-inclusions and returns corresponding values for longitudinal and transverse Young's modulus (matrix stiffness) for these micro-sized spatial locations. Hence, intracortical stiffness variability is numerically quantified using a combination of computer vision program and numerical homogenization code. These numerically found stiffness values of the homogenization

PTH treatment activates intracortical bone remodeling in patients with hypoparathyroidism

DEFF Research Database (Denmark)

Sikjær, Tanja Tvistholm; Rejnmark, Lars; Thomsen, Jesper Skovhus

2017-01-01

Hypoparathyroidism (hypoPT) is characterized by a state of low bone turnover and high BMD. We have previously shown that hypoPT patients treated with PTH(1-84) for six months have highly increased bone turnover markers and a decrease in aBMD at the hip and spine(1). The present study aims...... to investigate the effect of PTH(1-84) on cortical bone and intracortical bone remodeling in hypoPT. The study was conducted on 20 transiliac bone biopsies from hypoPT patients after six months of treatment with either PTH(1-84) 100 µg s.c./day N=10 or placebo N=10. The groups were age- (±6 years) and gender...... and diameter were measured. Cortical porosity and pore density did not differ between groups, but PTH treatment had a marked effect on the remodeling status of the pores. The percentage of pores undergoing remodeling was higher in the PTH-group than in placebo-group reported as median values (IQR[25-75%]) (52...

HCN channels segregate stimulation‐evoked movement responses in neocortex and allow for coordinated forelimb movements in rodents

Science.gov (United States)

Farrell, Jordan S.; Palmer, Laura A.; Singleton, Anna C.; Pittman, Quentin J.; Teskey, G. Campbell

2016-01-01

Key points The present study tested whether HCN channels contribute to the organization of motor cortex and to skilled motor behaviour during a forelimb reaching task.Experimental reductions in HCN channel signalling increase the representation of complex multiple forelimb movements in motor cortex as assessed by intracortical microstimulation.Global HCN1KO mice exhibit reduced reaching accuracy and atypical movements during a single‐pellet reaching task relative to wild‐type controls.Acute pharmacological inhibition of HCN channels in forelimb motor cortex decreases reaching accuracy and increases atypical movements during forelimb reaching. Abstract The mechanisms by which distinct movements of a forelimb are generated from the same area of motor cortex have remained elusive. Here we examined a role for HCN channels, given their ability to alter synaptic integration, in the expression of forelimb movement responses during intracortical microstimulation (ICMS) and movements of the forelimb on a skilled reaching task. We used short‐duration high‐resolution ICMS to evoke forelimb movements following pharmacological (ZD7288), experimental (electrically induced cortical seizures) or genetic approaches that we confirmed with whole‐cell patch clamp to substantially reduce I h current. We observed significant increases in the number of multiple movement responses evoked at single sites in motor maps to all three experimental manipulations in rats or mice. Global HCN1 knockout mice were less successful and exhibited atypical movements on a skilled‐motor learning task relative to wild‐type controls. Furthermore, in reaching‐proficient rats, reaching accuracy was reduced and forelimb movements were altered during infusion of ZD7288 within motor cortex. Thus, HCN channels play a critical role in the separation of overlapping movement responses and allow for successful reaching behaviours. These data provide a novel mechanism for the encoding of multiple

A proposed intracortical visual prosthesis image processing system.

Science.gov (United States)

Srivastava, N R; Troyk, P

2005-01-01

It has been a goal of neuroprosthesis researchers to develop a system, which could provide artifical vision to a large population of individuals with blindness. It has been demonstrated by earlier researches that stimulating the visual cortex area electrically can evoke spatial visual percepts, i.e. phosphenes. The goal of visual cortex prosthesis is to stimulate the visual cortex area and generate a visual perception in real time to restore vision. Even though the normal working of the visual system is not been completely understood, the existing knowledge has inspired research groups to develop strategies to develop visual cortex prosthesis which can help blind patients in their daily activities. A major limitation in this work is the development of an image proceessing system for converting an electronic image, as captured by a camera, into a real-time data stream for stimulation of the implanted electrodes. This paper proposes a system, which will capture the image using a camera and use a dedicated hardware real time image processor to deliver electrical pulses to intracortical electrodes. This system has to be flexible enough to adapt to individual patients and to various strategies of image reconstruction. Here we consider a preliminary architecture for this system.

Influence of Waveform and Current Direction on Short-Interval Intracortical Facilitation

DEFF Research Database (Denmark)

Delvendahl, Igor; Lindemann, Hannes; Jung, Nikolai H

2014-01-01

-posterior (AP) current direction (AP-AP or PA-PA), whereas current direction was reversed between first and second pulse for half-sine paired-pulse stimulation (PA-AP and AP-PA). RESULTS: Monophasic AP-AP stimulation resulted in stronger early SICF at 1.4 ms relative to late SICF at 2.8 and 4.4 ms, whereas...... monophasic PA-PA stimulation produced SICF of comparable size at all three peaks. With half-sine stimulation the third SICF peak was reduced for PA-AP current orientation compared with AP-PA. CONCLUSION: SICF elicited using monophasic as well as half-sine pulses is affected by current direction at clearly......BACKGROUND: Transcranial magnetic stimulation (TMS) of the human primary motor hand area (M1-HAND) can produce multiple descending volleys in fast-conducting corticospinal neurons, especially so-called indirect waves (I-waves) resulting from trans-synaptic excitation. Facilitatory interaction...

An intra-neural microstimulation system for ultra-high field magnetic resonance imaging and magnetoencephalography.

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Glover, Paul M; Watkins, Roger H; O'Neill, George C; Ackerley, Rochelle; Sanchez-Panchuelo, Rosa; McGlone, Francis; Brookes, Matthew J; Wessberg, Johan; Francis, Susan T

2017-10-01

Intra-neural microstimulation (INMS) is a technique that allows the precise delivery of low-current electrical pulses into human peripheral nerves. Single unit INMS can be used to stimulate individual afferent nerve fibres during microneurography. Combining this with neuroimaging allows the unique monitoring of central nervous system activation in response to unitary, controlled tactile input, with functional magnetic resonance imaging (fMRI) providing exquisite spatial localisation of brain activity and magnetoencephalography (MEG) high temporal resolution. INMS systems suitable for use within electrophysiology laboratories have been available for many years. We describe an INMS system specifically designed to provide compatibility with both ultra-high field (7T) fMRI and MEG. Numerous technical and safety issues are addressed. The system is fully analogue, allowing for arbitrary frequency and amplitude INMS stimulation. Unitary recordings obtained within both the MRI and MEG screened-room environments are comparable with those obtained in 'clean' electrophysiology recording environments. Single unit INMS (current met. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Cortical topography of intracortical inhibition influences the speed of decision making.

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Wilimzig, Claudia; Ragert, Patrick; Dinse, Hubert R

2012-02-21

The neocortex contains orderly topographic maps; however, their functional role remains controversial. Theoretical studies have suggested a role in minimizing computational costs, whereas empirical studies have focused on spatial localization. Using a tactile multiple-choice reaction time (RT) task before and after the induction of perceptual learning through repetitive sensory stimulation, we extend the framework of cortical topographies by demonstrating that the topographic arrangement of intracortical inhibition contributes to the speed of human perceptual decision-making processes. RTs differ among fingers, displaying an inverted U-shaped function. Simulations using neural fields show the inverted U-shaped RT distribution as an emergent consequence of lateral inhibition. Weakening inhibition through learning shortens RTs, which is modeled through topographically reorganized inhibition. Whereas changes in decision making are often regarded as an outcome of higher cortical areas, our data show that the spatial layout of interaction processes within representational maps contributes to selection and decision-making processes.

The aging motor system as a model for plastic changes of GABA-mediated intracortical inhibition and their behavioral relevance.

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Heise, Kirstin-F; Zimerman, Maximo; Hoppe, Julia; Gerloff, Christian; Wegscheider, Karl; Hummel, Friedhelm C

2013-05-22

Since GABAA-mediated intracortical inhibition has been shown to underlie plastic changes throughout the lifespan from development to aging, here, the aging motor system was used as a model to analyze the interdependence of plastic alterations within the inhibitory motorcortical network and level of behavioral performance. Double-pulse transcranial magnetic stimulation (dpTMS) was used to examine inhibition by means of short-interval intracortical inhibition (SICI) of the contralateral primary motor cortex in a sample of 64 healthy right-handed human subjects covering a wide range of the adult lifespan (age range 20-88 years, mean 47.6 ± 20.7, 34 female). SICI was evaluated during resting state and in an event-related condition during movement preparation in a visually triggered simple reaction time task. In a subgroup (N = 23), manual motor performance was tested with tasks of graded dexterous demand. Weak resting-state inhibition was associated with an overall lower manual motor performance. Better event-related modulation of inhibition correlated with better performance in more demanding tasks, in which fast alternating activation of cortical representations are necessary. Declining resting-state inhibition was associated with weakened event-related modulation of inhibition. Therefore, reduced resting-state inhibition might lead to a subsequent loss of modulatory capacity, possibly reflecting malfunctioning precision in GABAAergic neurotransmission; the consequence is an inevitable decline in motor function.

Long-term stability of intracortical recordings using perforated and arrayed Parylene sheath electrodes

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Hara, Seth A.; Kim, Brian J.; Kuo, Jonathan T. W.; Lee, Curtis D.; Meng, Ellis; Pikov, Victor

2016-12-01

Objective. Acquisition of reliable and robust neural recordings with intracortical neural probes is a persistent challenge in the field of neuroprosthetics. We developed a multielectrode array technology to address chronic intracortical recording reliability and present in vivo recording results. Approach. The 2 × 2 Parylene sheath electrode array (PSEA) was microfabricated and constructed from only Parylene C and platinum. The probe includes a novel three-dimensional sheath structure, perforations, and bioactive coatings that improve tissue integration and manage immune response. Coatings were applied using a sequential dip-coating method that provided coverage over the entire probe surface and interior of the sheath structure. A sharp probe tip taper facilitated insertion with minimal trauma. Fabricated probes were subject to examination by optical and electron microscopy and electrochemical testing prior to implantation. Main results. 1 × 2 arrays were successfully fabricated on wafer and then packaged together to produce 2 × 2 arrays. Then, probes having electrode sites with adequate electrochemical properties were selected. A subset of arrays was treated with bioactive coatings to encourage neuronal growth and suppress inflammation and another subset of arrays was implanted in conjunction with a virally mediated expression of Caveolin-1. Arrays were attached to a custom-made insertion shuttle to facilitate precise insertion into the rat motor cortex. Stable electrophysiological recordings were obtained during the period of implantation up to 12 months. Immunohistochemical evaluation of cortical tissue around individual probes indicated a strong correlation between the electrophysiological performance of the probes and histologically observable proximity of neurons and dendritic sprouting. Significance. The PSEA demonstrates the scalability of sheath electrode technology and provides higher electrode count and density to access a greater volume for recording

Decoding of intended saccade direction in an oculomotor brain-computer interface

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Jia, Nan; Brincat, Scott L.; Salazar-Gómez, Andrés F.; Panko, Mikhail; Guenther, Frank H.; Miller, Earl K.

2017-08-01

Objective. To date, invasive brain-computer interface (BCI) research has largely focused on replacing lost limb functions using signals from the hand/arm areas of motor cortex. However, the oculomotor system may be better suited to BCI applications involving rapid serial selection from spatial targets, such as choosing from a set of possible words displayed on a computer screen in an augmentative and alternative communication (AAC) application. Here we aimed to demonstrate the feasibility of a BCI utilizing the oculomotor system. Approach. We developed a chronic intracortical BCI in monkeys to decode intended saccadic eye movement direction using activity from multiple frontal cortical areas. Main results. Intended saccade direction could be decoded in real time with high accuracy, particularly at contralateral locations. Accurate decoding was evident even at the beginning of the BCI session; no extensive BCI experience was necessary. High-frequency (80-500 Hz) local field potential magnitude provided the best performance, even over spiking activity, thus simplifying future BCI applications. Most of the information came from the frontal and supplementary eye fields, with relatively little contribution from dorsolateral prefrontal cortex. Significance. Our results support the feasibility of high-accuracy intracortical oculomotor BCIs that require little or no practice to operate and may be ideally suited for ‘point and click’ computer operation as used in most current AAC systems.

On the Nature of the Intrinsic Connectivity of the Cat Motor Cortex: Evidence for a Recurrent Neural Network Topology

DEFF Research Database (Denmark)

Capaday, Charles; Ethier, C; Brizzi, L

2009-01-01

and functional significance of the intrinsic horizontal connections between neurons in the motor cortex (MCx) remain to be clarified. To further elucidate the nature of this intracortical connectivity pattern, experiments were done on the MCx of three cats. The anterograde tracer biocytin was ejected......Capaday C, Ethier C, Brizzi L, Sik A, van Vreeswijk C, Gingras D. On the nature of the intrinsic connectivity of the cat motor cortex: evidence for a recurrent neural network topology. J Neurophysiol 102: 2131-2141, 2009. First published July 22, 2009; doi: 10.1152/jn.91319.2008. The details...... iontophoretically in layers II, III, and V. Some 30-50 neurons within a radius of similar to 250 mu m were thus stained. The functional output of the motor cortical point at which biocytin was injected, and of the surrounding points, was identified by microstimulation and electromyographic recordings. The axonal...

The effect of the anodal transcranial direct current stimulation over the cerebellum on the motor cortex excitability.

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Ates, Mehlika Panpalli; Alaydin, Halil Can; Cengiz, Bulent

2018-04-25

This study was designed to investigate whether the cerebellum has an inhibitory effect on motor cortical excitability. Sixteen healthy adults (age range, 25-50 years, five female) participated in the study. Anodal cerebellar transcranial direct current stimulation (a-cTDCS) was used to modulate cerebellar excitability. A-cTDCS was given for 20 min at 1 mA intensity. The automatic threshold tracking method was used to investigate cortical excitability. Resting motor threshold (RMT), short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF), intracortical facilitation (ICF), and the input output curve (I-O curve) were motor cortical excitability parameters. a-cTDCS caused a reduction in overall SICI and the reduced SICF for interstimulus intervals (ISIs) to 2.4-4.4 ms. a-cTDCS has no effect on ICF, RMT, and the I-O curve. There were no significant changes in any of these cortical excitability parameters after sham cTDCS. Results of the study indicate that a-cTDCS has a dual (both inhibitory and excitatory) effect on motor cortical excitability, rather than a simple inhibitory effect. The cerebellum modulates both the inhibitory and facilitatory activities of motor cortex (M1) and suggest that cerebello-cerebral motor connectivity is more complex than solely inhibitory or facilitatory connections. Copyright © 2018 Elsevier Inc. All rights reserved.

Glassy carbon MEMS for novel origami-styled 3D integrated intracortical and epicortical neural probes

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Goshi, Noah; Castagnola, Elisa; Vomero, Maria; Gueli, Calogero; Cea, Claudia; Zucchini, Elena; Bjanes, David; Maggiolini, Emma; Moritz, Chet; Kassegne, Sam; Ricci, Davide; Fadiga, Luciano

2018-06-01

We report on a novel technology for microfabricating 3D origami-styled micro electro-mechanical systems (MEMS) structures with glassy carbon (GC) features and a supporting polymer substrate. GC MEMS devices that open to form 3D microstructures are microfabricated from GC patterns that are made through pyrolysis of polymer precursors on high-temperature resisting substrates like silicon or quartz and then transferring the patterned devices to a flexible substrate like polyimide followed by deposition of an insulation layer. The devices on flexible substrate are then folded into 3D form in an origami-fashion. These 3D MEMS devices have tunable mechanical properties that are achieved by selectively varying the thickness of the polymeric substrate and insulation layers at any desired location. This technology opens new possibilities by enabling microfabrication of a variety of 3D GC MEMS structures suited to applications ranging from biochemical sensing to implantable microelectrode arrays. As a demonstration of the technology, a neural signal recording microelectrode array platform that integrates both surface (cortical) and depth (intracortical) GC microelectrodes onto a single flexible thin-film device is introduced. When the device is unfurled, a pre-shaped shank of polyimide automatically comes off the substrate and forms the penetrating part of the device in a 3D fashion. With the advantage of being highly reproducible and batch-fabricated, the device introduced here allows for simultaneous recording of electrophysiological signals from both the brain surface (electrocorticography—ECoG) and depth (single neuron). Our device, therefore, has the potential to elucidate the roles of underlying neurons on the different components of µECoG signals. For in vivo validation of the design capabilities, the recording sites are coated with a poly(3,4-ethylenedioxythiophene)—polystyrene sulfonate—carbon nanotube composite, to improve the electrical conductivity of the

Brain computer interface learning for systems based on electrocorticography and intracortical microelectrode arrays.

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Hiremath, Shivayogi V; Chen, Weidong; Wang, Wei; Foldes, Stephen; Yang, Ying; Tyler-Kabara, Elizabeth C; Collinger, Jennifer L; Boninger, Michael L

2015-01-01

A brain-computer interface (BCI) system transforms neural activity into control signals for external devices in real time. A BCI user needs to learn to generate specific cortical activity patterns to control external devices effectively. We call this process BCI learning, and it often requires significant effort and time. Therefore, it is important to study this process and develop novel and efficient approaches to accelerate BCI learning. This article reviews major approaches that have been used for BCI learning, including computer-assisted learning, co-adaptive learning, operant conditioning, and sensory feedback. We focus on BCIs based on electrocorticography and intracortical microelectrode arrays for restoring motor function. This article also explores the possibility of brain modulation techniques in promoting BCI learning, such as electrical cortical stimulation, transcranial magnetic stimulation, and optogenetics. Furthermore, as proposed by recent BCI studies, we suggest that BCI learning is in many ways analogous to motor and cognitive skill learning, and therefore skill learning should be a useful metaphor to model BCI learning.

Acute human brain responses to intracortical microelectrode arrays: Challenges and future prospects

Directory of Open Access Journals (Sweden)

Eduardo eFernandez

2014-07-01

Full Text Available The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons. As more and more patients benefit from these approaches, the interest in neural interfaces has grown significantly and a new generation of penetrating microelectrode arrays are providing unprecedented access to the neurons of the CNS. These microelectrodes have active tip dimensions that are similar in size to neurons and because they penetrate the nervous system, they provide selective access to these cells (within a few microns. However, the very long-term viability of chronically implanted microelectrodes and the capability of recording the same spiking activity over long time periods still remain to be established and confirmed in human studies. Here we review the main responses to acute implantation of microelectrode arrays, and emphasize that it will become essential to control the neural tissue damage induced by these intracortical microelectrodes in order to achieve the high clinical potentials accompanying this technology.

Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates

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Barrese, James C.; Aceros, Juan; Donoghue, John P.

2016-04-01

Objective. Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. Approach. We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. Main results. SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. Significance. These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does

Potential for thermal damage to the blood–brain barrier during craniotomy: implications for intracortical recording microelectrodes

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Shoffstall, Andrew J.; Paiz, Jen E.; Miller, David M.; Rial, Griffin M.; Willis, Mitchell T.; Menendez, Dhariyat M.; Hostler, Stephen R.; Capadona, Jeffrey R.

2018-06-01

Objective. Our objective was to determine how readily disruption of the blood–brain barrier (BBB) occurred as a result of bone drilling during a craniotomy to implant microelectrodes in rat cortex. While the phenomenon of heat production during bone drilling is well known, practices to evade damage to the underlying brain tissue are inconsistently practiced and reported in the literature. Approach. We conducted a review of the intracortical microelectrode literature to summarize typical approaches to mitigate drill heating during rodent craniotomies. Post mortem skull-surface and transient brain-surface temperatures were experimentally recorded using an infrared camera and thermocouple, respectively. A number of drilling conditions were tested, including varying drill speed and continuous versus intermittent contact. In vivo BBB permeability was assayed 1 h after the craniotomy procedure using Evans blue dye. Main results. Of the reviewed papers that mentioned methods to mitigate thermal damage during craniotomy, saline irrigation was the most frequently cited (in six of seven papers). In post mortem tissues, we observed increases in skull-surface temperature ranging from  +3 °C to  +21 °C, dependent on drill speed. In vivo, pulsed-drilling (2 s-on/2 s-off) and slow-drilling speeds (1000 r.p.m.) were the most effective methods we studied to mitigate heating effects from drilling, while inconclusive results were obtained with saline irrigation. Significance. Neuroinflammation, initiated by damage to the BBB and perpetuated by the foreign body response, is thought to play a key role in premature failure of intracortical recording microelectrodes. This study demonstrates the extreme sensitivity of the BBB to overheating caused by bone drilling. To avoid damage to the BBB, the authors recommend that craniotomies be drilled with slow speeds and/or with intermittent drilling with complete removal of the drill from the skull during ‘off’ periods. While

Synthetic tactile perception induced by transcranial alternating-current stimulation can substitute for natural sensory stimulus in behaving rabbits.

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Márquez-Ruiz, Javier; Ammann, Claudia; Leal-Campanario, Rocío; Ruffini, Giulio; Gruart, Agnès; Delgado-García, José M

2016-01-21

The use of brain-derived signals for controlling external devices has long attracted the attention from neuroscientists and engineers during last decades. Although much effort has been dedicated to establishing effective brain-to-computer communication, computer-to-brain communication feedback for "closing the loop" is now becoming a major research theme. While intracortical microstimulation of the sensory cortex has already been successfully used for this purpose, its future application in humans partly relies on the use of non-invasive brain stimulation technologies. In the present study, we explore the potential use of transcranial alternating-current stimulation (tACS) for synthetic tactile perception in alert behaving animals. More specifically, we determined the effects of tACS on sensory local field potentials (LFPs) and motor output and tested its capability for inducing tactile perception using classical eyeblink conditioning in the behaving animal. We demonstrated that tACS of the primary somatosensory cortex vibrissa area could indeed substitute natural stimuli during training in the associative learning paradigm.

Functional organization of the insula and inner perisylvian regions

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Jezzini, Ahmad; Caruana, Fausto; Stoianov, Ivilin; Gallese, Vittorio; Rizzolatti, Giacomo

2012-01-01

In the last few years, the insula has been the focus of many brain-imaging studies, mostly devoted to clarify its role in emotions and social communication. Physiological data, however, on which one may ground these correlative findings are almost totally lacking. Here, we investigated the functional properties of the insular cortex in behaving monkeys using intracortical microstimulation. Behavioral responses and heart rate changes were recorded. The results showed that the insula is functionally formed by two main subdivisions: (i) a sensorimotor field occupying the caudal–dorsal portion of the insula and appearing as an extension of the parietal lobe; and (ii) a mosaic of orofacial motor programs located in the anterior and centroventral insula sector. These programs show a progressive shift from dorsally located nonemotional motor programs (ingestive activity) to ventral ones laden with emotional and communicative content. The relationship between ingestive and other behaviors is discussed in an evolutionary perspective. PMID:22647599

Beyond intuitive anthropomorphic control: recent achievements using brain computer interface technologies

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Pohlmeyer, Eric A.; Fifer, Matthew; Rich, Matthew; Pino, Johnathan; Wester, Brock; Johannes, Matthew; Dohopolski, Chris; Helder, John; D'Angelo, Denise; Beaty, James; Bensmaia, Sliman; McLoughlin, Michael; Tenore, Francesco

2017-05-01

Brain-computer interface (BCI) research has progressed rapidly, with BCIs shifting from animal tests to human demonstrations of controlling computer cursors and even advanced prosthetic limbs, the latter having been the goal of the Revolutionizing Prosthetics (RP) program. These achievements now include direct electrical intracortical microstimulation (ICMS) of the brain to provide human BCI users feedback information from the sensors of prosthetic limbs. These successes raise the question of how well people would be able to use BCIs to interact with systems that are not based directly on the body (e.g., prosthetic arms), and how well BCI users could interpret ICMS information from such devices. If paralyzed individuals could use BCIs to effectively interact with such non-anthropomorphic systems, it would offer them numerous new opportunities to control novel assistive devices. Here we explore how well a participant with tetraplegia can detect infrared (IR) sources in the environment using a prosthetic arm mounted camera that encodes IR information via ICMS. We also investigate how well a BCI user could transition from controlling a BCI based on prosthetic arm movements to controlling a flight simulator, a system with different physical dynamics than the arm. In that test, the BCI participant used environmental information encoded via ICMS to identify which of several upcoming flight routes was the best option. For both tasks, the BCI user was able to quickly learn how to interpret the ICMSprovided information to achieve the task goals.

Brain Computer Interface Learning for Systems Based on Electrocorticography and Intracortical Microelectrode Arrays

Directory of Open Access Journals (Sweden)

Shivayogi V Hiremath

2015-06-01

Full Text Available A brain-computer interface (BCI system transforms neural activity into control signals for external devices in real time. A BCI user needs to learn to generate specific cortical activity patterns to control external devices effectively. We call this process BCI learning, and it often requires significant effort and time. Therefore, it is important to study this process and develop novel and efficient approaches to accelerate BCI learning. This article reviews major approaches that have been used for BCI learning, including computer-assisted learning, co-adaptive learning, operant conditioning, and sensory feedback. We focus on BCIs based on electrocorticography and intracortical microelectrode arrays for restoring motor function. This article also explores the possibility of brain modulation techniques in promoting BCI learning, such as electrical cortical stimulation, transcranial magnetic stimulation, and optogenetics. Furthermore, as proposed by recent BCI studies, we suggest that BCI learning is in many ways analogous to motor and cognitive skill learning, and therefore skill learning should be a useful metaphor to model BCI learning.

Influence of position and stimulation parameters on intracortical inhibition and facilitation in human tongue motor cortex

DEFF Research Database (Denmark)

Kothari, Mohit; Svensson, Peter; Nielsen, Jørgen Feldbæk

Paired-pulse transcranial magnetic stimulation (ppTMS) can be used to assess short-interval intracortical inhibitory (SICI) and facilitatory (ICF) networks. The aim of the study was to examine the influence of body positions (recline and supine), inter-stimulus intervals (ISI) between the test...... recorded from contralateral tongue muscles. In study 1, single pulse and three ppTMS ISIs: 2, 10, 15 ms were applied 8 times each in three blocks (TS: 120%, 140% and 160% of resting motor threshold (rMT); CS: 80% of rMT) in two different body positions (recline and supine) randomly. In study 2, single...... pulse and four ppTMS ISIs: 2, 2.5, 3, 3.5 ms were applied 8 times each in randomized order in two blocks (CS: 70% and 80% of rMT; TS: 120% of rMT). There was a significant effect of body position (P=0.049), TS intensities (P

Progressive motor cortex functional reorganization following 6-hydroxydopamine lesioning in rats.

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Viaro, Riccardo; Morari, Michele; Franchi, Gianfranco

2011-03-23

Many studies have attempted to correlate changes of motor cortex activity with progression of Parkinson's disease, although results have been controversial. In the present study we used intracortical microstimulation (ICMS) combined with behavioral testing in 6-hydroxydopamine hemilesioned rats to evaluate the impact of dopamine depletion on movement representations in primary motor cortex (M1) and motor behavior. ICMS allows for motor-effective stimulation of corticofugal neurons in motor areas so as to obtain topographic movements representations based on movement type, area size, and threshold currents. Rats received unilateral 6-hydroxydopamine in the nigrostriatal bundle, causing motor impairment. Changes in M1 were time dependent and bilateral, although stronger in the lesioned than the intact hemisphere. Representation size and threshold current were maximally impaired at 15 d, although inhibition was still detectable at 60-120 d after lesion. Proximal forelimb movements emerged at the expense of the distal ones. Movement lateralization was lost mainly at 30 d after lesion. Systemic L-3,4-dihydroxyphenylalanine partially attenuated motor impairment and cortical changes, particularly in the caudal forelimb area, and completely rescued distal forelimb movements. Local application of the GABA(A) antagonist bicuculline partially restored cortical changes, particularly in the rostral forelimb area. The local anesthetic lidocaine injected into the M1 of the intact hemisphere restored movement lateralization in the lesioned hemisphere. This study provides evidence for motor cortex remodeling after unilateral dopamine denervation, suggesting that cortical changes were associated with dopamine denervation, pathogenic intracortical GABA inhibition, and altered interhemispheric activity.

Influence of position and stimulation parameters on intracortical inhibition and facilitation in human tongue motor cortex

DEFF Research Database (Denmark)

Kothari, Mohit; Svensson, Peter; Nielsen, Jørgen Feldbæk

2014-01-01

Paired-pulse transcranial magnetic stimulation (ppTMS) can be used to assess short-interval intracortical inhibitory (SICI) and facilitatory (ICF) networks. Many methodological parameters may however influence the outcome. The aim of the study was to examine the influence of body positions (recline...... motor cortex and motor evoked potentials (MEPs) were recorded from contralateral tongue muscles. In study 1, single pulse and three ppTMS ISIs: 2, 10, 15 ms were applied 8 times each in three blocks (TS: 120%, 140% and 160% of resting motor threshold (rMT); CS: 80% of rMT) in two different body...... positions (recline and supine) randomly. In study 2, single pulse and four ppTMS ISIs: 2, 2.5, 3, 3.5 ms were applied 8 times each in randomized order in two blocks (CS: 70% and 80% of rMT; TS: 120% of rMT). There was a significant effect of body position (P=0.049), TS intensities (P

A fast intracortical brain-machine interface with patterned optogenetic feedback.

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Abbasi, Aamir; Goueytes, Dorian; Shulz, Daniel E; Ego-Stengel, Valerie; Estebanez, Luc

2018-04-04

The development of brain-machine interfaces (BMIs) brings a new perspective to patients with a loss of autonomy. By combining online recordings of brain activity with a decoding algorithm, patients can learn to control a robotic arm in order to perform simple actions. However, in contrast to the vast amounts of somatosensory information channeled by limbs to the brain, current BMIs are devoid of touch and force sensors. Patients must therefore rely solely on vision and audition, which are maladapted to the control of a prosthesis. In contrast, in a healthy limb, somatosensory inputs alone can efficiently guide the handling of a fragile object, or ensure a smooth trajectory. We have developed a BMI in the mouse that includes a rich artificial somatosensory-like cortical feedback. Our setup includes online recordings of the activity of multiple neurons in the whisker primary motor cortex (vM1), and delivers feedback simultaneously via a low-latency, high-refresh rate and spatially structured photo-stimulation of the whisker primary somatosensory cortex (vS1), based on a mapping obtained by intrinsic imaging. We demonstrate the operation of the loop and show that mice can detect the neuronal spiking in vS1 triggered by the photo-stimulations. Finally, we show that the mice can learn a behavioral task relying only on the artificial inputs and outputs of the closed-loop BMI. This is the first motor BMI that includes a short-latency, intracortical, somatosensory-like feedback. It will be a useful platform to discover efficient cortical feedback schemes towards future human BMI applications. Creative Commons Attribution license.

Proactive modulation of long-interval intracortical inhibition during response inhibition

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Cowie, Matthew J.; MacDonald, Hayley J.; Cirillo, John

2016-01-01

Daily activities often require sudden cancellation of preplanned movement, termed response inhibition. When only a subcomponent of a whole response must be suppressed (required here on Partial trials), the ensuing component is markedly delayed. The neural mechanisms underlying partial response inhibition remain unclear. We hypothesized that Partial trials would be associated with nonselective corticomotor suppression and that GABAB receptor-mediated inhibition within primary motor cortex might be responsible for the nonselective corticomotor suppression contributing to Partial trial response delays. Sixteen right-handed participants performed a bimanual anticipatory response inhibition task while single- and paired-pulse transcranial magnetic stimulation was delivered to elicit motor evoked potentials in the left first dorsal interosseous muscle. Lift times, amplitude of motor evoked potentials, and long-interval intracortical inhibition were examined across the different trial types (Go, Stop-Left, Stop-Right, Stop-Both). Go trials produced a tight distribution of lift times around the target, whereas those during Partial trials (Stop-Left and Stop-Right) were substantially delayed. The modulation of motor evoked potential amplitude during Stop-Right trials reflected anticipation, suppression, and subsequent reinitiation of movement. Importantly, suppression was present across all Stop trial types, indicative of a “default” nonselective inhibitory process. Compared with blocks containing only Go trials, inhibition increased when Stop trials were introduced but did not differ between trial types. The amount of inhibition was positively correlated with lift times during Stop-Right trials. Tonic levels of inhibition appear to be proactively modulated by task context and influence the speed at which unimanual responses occur after a nonselective “brake” is applied. PMID:27281744

Structural bases of intracortical processes underlying the synchronization of epileptic potentials in the sensorimotor areas of the neocortex in rats.

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Pasikova, N V; Marchenko, V G; Kositsyn, N S

2001-01-01

Studies in long-term isolated areas of the rat neocortex were performed to investigate the dynamics of the numbers and areas of nerve cell bodies in layer V and to compare these data with the degree of synchronization of epileptic discharges evoked by application of penicillin. Decreases in the number of pyramidal neurons with body areas of 200-350 microm2 in isolated strips after maintenance for 30 and 90 days led to decreases in the degree of synchronization of epileptiform potentials. Large pyramidal neurons are known to have long horizontal axon collaterals, spreading into layers V and VI of the neocortex. It is suggested that the neural networks formed by large pyramidal neurons by means of their long horizontal collaterals mediate the process of intracortical synchronization.

A cognitive neuroprosthetic that uses cortical stimulation for somatosensory feedback

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Klaes, Christian; Shi, Ying; Kellis, Spencer; Minxha, Juri; Revechkis, Boris; Andersen, Richard A.

2014-10-01

Objective. Present day cortical brain-machine interfaces (BMIs) have made impressive advances using decoded brain signals to control extracorporeal devices. Although BMIs are used in a closed-loop fashion, sensory feedback typically is visual only. However medical case studies have shown that the loss of somesthesis in a limb greatly reduces the agility of the limb even when visual feedback is available. Approach. To overcome this limitation, this study tested a closed-loop BMI that utilizes intracortical microstimulation to provide ‘tactile’ sensation to a non-human primate. Main result. Using stimulation electrodes in Brodmann area 1 of somatosensory cortex (BA1) and recording electrodes in the anterior intraparietal area, the parietal reach region and dorsal area 5 (area 5d), it was found that this form of feedback can be used in BMI tasks. Significance. Providing somatosensory feedback has the poyential to greatly improve the performance of cognitive neuroprostheses especially for fine control and object manipulation. Adding stimulation to a BMI system could therefore improve the quality of life for severely paralyzed patients.

In vivo demonstration of injectable microstimulators based on charge-balanced rectification of epidermically applied currents

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Ivorra, Antoni; Becerra-Fajardo, Laura; Castellví, Quim

2015-12-01

Objective. It is possible to develop implantable microstimulators whose actuation principle is based on rectification of high-frequency (HF) current bursts supplied through skin electrodes. This has been demonstrated previously by means of devices consisting of a single diode. However, previous single diode devices caused dc currents which made them impractical for clinical applications. Here flexible thread-like stimulation implants which perform charge balance are demonstrated in vivo. Approach. The implants weigh 40.5 mg and they consist of a 3 cm long tubular silicone body with a diameter of 1 mm, two electrodes at opposite ends, and, within the central section of the body, an electronic circuit made up of a diode, two capacitors, and a resistor. In the present study, each implant was percutaneously introduced through a 14 G catheter into either the gastrocnemius muscle or the cranial tibial muscle of a rabbit hindlimb. Then stimulation was performed by delivering HF bursts (amplitude pair of textile electrodes strapped around the hindlimb and either isometric plantarflexion or dorsiflexion forces were recorded. Stimulation was also assayed 1, 2 and 4 weeks after implantation. Main results. The implants produced bursts of rectified current whose mean value was of a few mA and were capable of causing local neuromuscular stimulation. The implants were well-tolerated during the 4 weeks. Significance. Existing power supply methods, and, in particular inductive links, comprise stiff and bulky parts. This hinders the development of minimally invasive implantable devices for neuroprostheses based on electrical stimulation. The proposed methodology is intended to relieving such bottleneck. In terms of mass, thinness, and flexibility, the demonstrated implants appear to be unprecedented among the intramuscular stimulation implants ever assayed in vertebrates.

Model-based analysis and control of a network of basal ganglia spiking neurons in the normal and Parkinsonian states

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Liu, Jianbo; Khalil, Hassan K.; Oweiss, Karim G.

2011-08-01

Controlling the spatiotemporal firing pattern of an intricately connected network of neurons through microstimulation is highly desirable in many applications. We investigated in this paper the feasibility of using a model-based approach to the analysis and control of a basal ganglia (BG) network model of Hodgkin-Huxley (HH) spiking neurons through microstimulation. Detailed analysis of this network model suggests that it can reproduce the experimentally observed characteristics of BG neurons under a normal and a pathological Parkinsonian state. A simplified neuronal firing rate model, identified from the detailed HH network model, is shown to capture the essential network dynamics. Mathematical analysis of the simplified model reveals the presence of a systematic relationship between the network's structure and its dynamic response to spatiotemporally patterned microstimulation. We show that both the network synaptic organization and the local mechanism of microstimulation can impose tight constraints on the possible spatiotemporal firing patterns that can be generated by the microstimulated network, which may hinder the effectiveness of microstimulation to achieve a desired objective under certain conditions. Finally, we demonstrate that the feedback control design aided by the mathematical analysis of the simplified model is indeed effective in driving the BG network in the normal and Parskinsonian states to follow a prescribed spatiotemporal firing pattern. We further show that the rhythmic/oscillatory patterns that characterize a dopamine-depleted BG network can be suppressed as a direct consequence of controlling the spatiotemporal pattern of a subpopulation of the output Globus Pallidus internalis (GPi) neurons in the network. This work may provide plausible explanations for the mechanisms underlying the therapeutic effects of deep brain stimulation (DBS) in Parkinson's disease and pave the way towards a model-based, network level analysis and closed

An online brain-machine interface using decoding of movement direction from the human electrocorticogram

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Milekovic, Tomislav; Fischer, Jörg; Pistohl, Tobias; Ruescher, Johanna; Schulze-Bonhage, Andreas; Aertsen, Ad; Rickert, Jörn; Ball, Tonio; Mehring, Carsten

2012-08-01

A brain-machine interface (BMI) can be used to control movements of an artificial effector, e.g. movements of an arm prosthesis, by motor cortical signals that control the equivalent movements of the corresponding body part, e.g. arm movements. This approach has been successfully applied in monkeys and humans by accurately extracting parameters of movements from the spiking activity of multiple single neurons. We show that the same approach can be realized using brain activity measured directly from the surface of the human cortex using electrocorticography (ECoG). Five subjects, implanted with ECoG implants for the purpose of epilepsy assessment, took part in our study. Subjects used directionally dependent ECoG signals, recorded during active movements of a single arm, to control a computer cursor in one out of two directions. Significant BMI control was achieved in four out of five subjects with correct directional decoding in 69%-86% of the trials (75% on average). Our results demonstrate the feasibility of an online BMI using decoding of movement direction from human ECoG signals. Thus, to achieve such BMIs, ECoG signals might be used in conjunction with or as an alternative to intracortical neural signals.

Feedback control policies employed by people using intracortical brain-computer interfaces

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Willett, Francis R.; Pandarinath, Chethan; Jarosiewicz, Beata; Murphy, Brian A.; Memberg, William D.; Blabe, Christine H.; Saab, Jad; Walter, Benjamin L.; Sweet, Jennifer A.; Miller, Jonathan P.; Henderson, Jaimie M.; Shenoy, Krishna V.; Simeral, John D.; Hochberg, Leigh R.; Kirsch, Robert F.; Bolu Ajiboye, A.

2017-02-01

Objective. When using an intracortical BCI (iBCI), users modulate their neural population activity to move an effector towards a target, stop accurately, and correct for movement errors. We call the rules that govern this modulation a ‘feedback control policy’. A better understanding of these policies may inform the design of higher-performing neural decoders. Approach. We studied how three participants in the BrainGate2 pilot clinical trial used an iBCI to control a cursor in a 2D target acquisition task. Participants used a velocity decoder with exponential smoothing dynamics. Through offline analyses, we characterized the users’ feedback control policies by modeling their neural activity as a function of cursor state and target position. We also tested whether users could adapt their policy to different decoder dynamics by varying the gain (speed scaling) and temporal smoothing parameters of the iBCI. Main results. We demonstrate that control policy assumptions made in previous studies do not fully describe the policies of our participants. To account for these discrepancies, we propose a new model that captures (1) how the user’s neural population activity gradually declines as the cursor approaches the target from afar, then decreases more sharply as the cursor comes into contact with the target, (2) how the user makes constant feedback corrections even when the cursor is on top of the target, and (3) how the user actively accounts for the cursor’s current velocity to avoid overshooting the target. Further, we show that users can adapt their control policy to decoder dynamics by attenuating neural modulation when the cursor gain is high and by damping the cursor velocity more strongly when the smoothing dynamics are high. Significance. Our control policy model may help to build better decoders, understand how neural activity varies during active iBCI control, and produce better simulations of closed-loop iBCI movements.

High performance communication by people with paralysis using an intracortical brain-computer interface

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Pandarinath, Chethan; Nuyujukian, Paul; Blabe, Christine H; Sorice, Brittany L; Saab, Jad; Willett, Francis R; Hochberg, Leigh R

2017-01-01

Brain-computer interfaces (BCIs) have the potential to restore communication for people with tetraplegia and anarthria by translating neural activity into control signals for assistive communication devices. While previous pre-clinical and clinical studies have demonstrated promising proofs-of-concept (Serruya et al., 2002; Simeral et al., 2011; Bacher et al., 2015; Nuyujukian et al., 2015; Aflalo et al., 2015; Gilja et al., 2015; Jarosiewicz et al., 2015; Wolpaw et al., 1998; Hwang et al., 2012; Spüler et al., 2012; Leuthardt et al., 2004; Taylor et al., 2002; Schalk et al., 2008; Moran, 2010; Brunner et al., 2011; Wang et al., 2013; Townsend and Platsko, 2016; Vansteensel et al., 2016; Nuyujukian et al., 2016; Carmena et al., 2003; Musallam et al., 2004; Santhanam et al., 2006; Hochberg et al., 2006; Ganguly et al., 2011; O’Doherty et al., 2011; Gilja et al., 2012), the performance of human clinical BCI systems is not yet high enough to support widespread adoption by people with physical limitations of speech. Here we report a high-performance intracortical BCI (iBCI) for communication, which was tested by three clinical trial participants with paralysis. The system leveraged advances in decoder design developed in prior pre-clinical and clinical studies (Gilja et al., 2015; Kao et al., 2016; Gilja et al., 2012). For all three participants, performance exceeded previous iBCIs (Bacher et al., 2015; Jarosiewicz et al., 2015) as measured by typing rate (by a factor of 1.4–4.2) and information throughput (by a factor of 2.2–4.0). This high level of performance demonstrates the potential utility of iBCIs as powerful assistive communication devices for people with limited motor function. Clinical Trial No: NCT00912041 DOI: http://dx.doi.org/10.7554/eLife.18554.001 PMID:28220753

Effects of a Finger Tapping Fatiguing Task on M1-Intracortical Inhibition and Central Drive to the Muscle.

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Madrid, Antonio; Madinabeitia-Mancebo, Elena; Cudeiro, Javier; Arias, Pablo

2018-06-19

The central drive to the muscle reduces when muscle force wanes during sustained MVC, and this is generally considered the neurophysiological footprint of central fatigue. The question is if force loss and the failure of central drive to the muscle are responsible mechanisms of fatigue induced by un-resisted repetitive movements. In various experimental blocks, we validated a 3D-printed hand-fixation system permitting the execution of finger-tapping and maximal voluntary contractions (MVC). Subsequently, we checked the suitability of the system to test the level of central drive to the muscle and developed an algorithm to test it at the MVC force plateau. Our main results show that the maximum rate of finger-tapping dropped at 30 s, while the excitability of inhibitory M1-intracortical circuits and corticospinal excitability increased (all by approximately 15%). Furthermore, values obtained immediately after finger-tapping showed that MVC force and the level of central drive to the muscle remained unchanged. Our data suggest that force and central drive to the muscle are not determinants of fatigue induced by short-lasting un-resisted repetitive finger movements, even in the presence of increased inhibition of the motor cortex. According to literature, this profile might be different in longer-lasting, more complex and/or resisted repetitive movements.

Alpha and gamma oscillations characterize feedback and feedforward processing in monkey visual cortex.

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van Kerkoerle, Timo; Self, Matthew W; Dagnino, Bruno; Gariel-Mathis, Marie-Alice; Poort, Jasper; van der Togt, Chris; Roelfsema, Pieter R

2014-10-07

Cognitive functions rely on the coordinated activity of neurons in many brain regions, but the interactions between cortical areas are not yet well understood. Here we investigated whether low-frequency (α) and high-frequency (γ) oscillations characterize different directions of information flow in monkey visual cortex. We recorded from all layers of the primary visual cortex (V1) and found that γ-waves are initiated in input layer 4 and propagate to the deep and superficial layers of cortex, whereas α-waves propagate in the opposite direction. Simultaneous recordings from V1 and downstream area V4 confirmed that γ- and α-waves propagate in the feedforward and feedback direction, respectively. Microstimulation in V1 elicited γ-oscillations in V4, whereas microstimulation in V4 elicited α-oscillations in V1, thus providing causal evidence for the opposite propagation of these rhythms. Furthermore, blocking NMDA receptors, thought to be involved in feedback processing, suppressed α while boosting γ. These results provide new insights into the relation between brain rhythms and cognition.

Effect of early and late rehabilitation onset in a chronic rat model of ischemic stroke- assessment of motor cortex signaling and gait functionality over time.

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Nielsen, Rasmus K; Samson, Katrine L; Simonsen, Daniel; Jensen, Winnie

2013-11-01

The aim of the present study was to investigate the effects of ischemic stroke and onset of subsequent rehabilitation of gait function in rats. Nine male Sprague-Dawley rats were instrumented with a 16-channel intracortical (IC) electrode array. An ischemic stroke was induced within the hindlimb area of the left motor cortex. The rehabilitation consisted of a repetitive training paradigm over 28 days, initiated on day one ("Early-onset", 5 rats) and on day seven, ("Late-onset", 4 rats). Data were obtained from IC microstimulation tests, treadmill walking tests, and beam walking tests. Results revealed an expansion of the hindlimb representation within the motor cortex area and an increased amount of cortical firing rate modulation for the "Early-onset" group but not for the "Late-onset" group. Kinematic data revealed a significant change for both intervention groups. However, this difference was larger for the "Early-onset" group. Results from the beam walking test showed functional performance deficits following stroke which returned to pre-stroke level after the rehabilitative training. The results from the present study indicate the existence of a critical time period following stroke where onset of rehabilitative training may be more effective and related to a higher degree of true recovery.

The Functional Organization and Cortical Connections of Motor Cortex in Squirrels

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Cooke, Dylan F.; Padberg, Jeffrey; Zahner, Tony

2012-01-01

Despite extraordinary diversity in the rodent order, studies of motor cortex have been limited to only 2 species, rats and mice. Here, we examine the topographic organization of motor cortex in the Eastern gray squirrel (Sciurus carolinensis) and cortical connections of motor cortex in the California ground squirrel (Spermophilus beecheyi). We distinguish a primary motor area, M1, based on intracortical microstimulation (ICMS), myeloarchitecture, and patterns of connectivity. A sensorimotor area between M1 and the primary somatosensory area, S1, was also distinguished based on connections, functional organization, and myeloarchitecture. We term this field 3a based on similarities with area 3a in nonrodent mammals. Movements are evoked with ICMS in both M1 and 3a in a roughly somatotopic pattern. Connections of 3a and M1 are distinct and suggest the presence of a third far rostral field, termed “F,” possibly involved in motor processing based on its connections. We hypothesize that 3a is homologous to the dysgranular zone (DZ) in S1 of rats and mice. Our results demonstrate that squirrels have both similar and unique features of M1 organization compared with those described in rats and mice, and that changes in 3a/DZ borders appear to have occurred in both lineages. PMID:22021916

Late emergence of the vibrissa direction selectivity map in the rat barrel cortex.

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Kremer, Yves; Léger, Jean-François; Goodman, Dan; Brette, Romain; Bourdieu, Laurent

2011-07-20

In the neocortex, neuronal selectivities for multiple sensorimotor modalities are often distributed in topographical maps thought to emerge during a restricted period in early postnatal development. Rodent barrel cortex contains a somatotopic map for vibrissa identity, but the existence of maps representing other tactile features has not been clearly demonstrated. We addressed the issue of the existence in the rat cortex of an intrabarrel map for vibrissa movement direction using in vivo two-photon imaging. We discovered that the emergence of a direction map in rat barrel cortex occurs long after all known critical periods in the somatosensory system. This map is remarkably specific, taking a pinwheel-like form centered near the barrel center and aligned to the barrel cortex somatotopy. We suggest that this map may arise from intracortical mechanisms and demonstrate by simulation that the combination of spike-timing-dependent plasticity at synapses between layer 4 and layer 2/3 and realistic pad stimulation is sufficient to produce such a map. Its late emergence long after other classical maps suggests that experience-dependent map formation and refinement continue throughout adult life.

Investigating the Efficacy of Novel TrkB Agonists to Augment Stroke Recovery

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Warraich, Zuha

Stroke remains the leading cause of adult disability in developed countries. Most survivors live with residual motor impairments that severely diminish independence and quality of life. After stroke, the only accepted treatment for these patients is motor rehabilitation. However, the amount and kind of rehabilitation required to induce clinically significant improvements in motor function is rarely given due to the constraints of our current health care system. Research reported in this dissertation contributes towards developing adjuvant therapies that may augment the impact of motor rehabilitation and improve functional outcome. These studies have demonstrated reorganization of maps within motor cortex as a function of experience in both healthy and brain-injured animals by using intracortical microstimulation technique. Furthermore, synaptic plasticity has been identified as a key neural mechanism in directing motor map plasticity, evidenced by restoration of movement representations within the spared cortical tissue accompanied by increase in synapse number translating into motor improvement after stroke. There is increasing evidence that brain-derived neurotrophic factor (BDNF) modulates synaptic and morphological plasticity in the developing and mature nervous system. Unfortunately, BDNF itself is a poor candidate because of its short half-life, low penetration through the blood brain barrier, and activating multiple receptor units, p75 and TrkB on the neuronal membrane. In order to circumvent this problem efficacy of two recently developed novel TrkB agonists, LM22A-4 and 7,8-dihydroxyflavone, that actively penetrate the blood brain barrier and enhance functional recovery. Findings from these dissertation studies indicate that administration of these pharmacological compounds, accompanied by motor rehabilitation provide a powerful therapeutic tool for stroke recovery.

Resistive and reactive changes to the impedance of intracortical microelectrodes can be mitigated with polyethylene glycol under acute in vitro and in vivo settings

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Salah eSommakia

2014-08-01

Full Text Available The reactive response of brain tissue to implantable intracortical microelectrodes is thought to negatively affect their recordable signal quality and impedance, resulting in unreliable longitudinal performance. The relationship between the progression of the reactive tissue into a glial scar and the decline in device performance is unclear. We show that exposure to a model protein solution in vitro and acute implantation result in both resistive and capacitive changes to electrode impedance, rather than purely resistive changes. We also show that applying 4000 MW polyethylene glycol (PEG prevents impedance increases in vitro, and reduces the percent change in impedance in vivo following implantation. Our results highlight the importance of considering the contributions of non-cellular components to the decline in neural microelectrode performance, and present a proof of concept for using a simple dip-coated PEG film to modulate changes in microelectrode impedance.

Saccadic interception of a moving visual target after a spatiotemporal perturbation.

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Fleuriet, Jérome; Goffart, Laurent

2012-01-11

Animals can make saccadic eye movements to intercept a moving object at the right place and time. Such interceptive saccades indicate that, despite variable sensorimotor delays, the brain is able to estimate the current spatiotemporal (hic et nunc) coordinates of a target at saccade end. The present work further tests the robustness of this estimate in the monkey when a change in eye position and a delay are experimentally added before the onset of the saccade and in the absence of visual feedback. These perturbations are induced by brief microstimulation in the deep superior colliculus (dSC). When the microstimulation moves the eyes in the direction opposite to the target motion, a correction saccade brings gaze back on the target path or very near. When it moves the eye in the same direction, the performance is more variable and depends on the stimulated sites. Saccades fall ahead of the target with an error that increases when the stimulation is applied more caudally in the dSC. The numerous cases of compensation indicate that the brain is able to maintain an accurate and robust estimate of the location of the moving target. The inaccuracies observed when stimulating the dSC that encodes the visual field traversed by the target indicate that dSC microstimulation can interfere with signals encoding the target motion path. The results are discussed within the framework of the dual-drive and the remapping hypotheses.

Linear distributed source modeling of local field potentials recorded with intra-cortical electrode arrays.

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Rikkert Hindriks

Full Text Available Planar intra-cortical electrode (Utah arrays provide a unique window into the spatial organization of cortical activity. Reconstruction of the current source density (CSD underlying such recordings, however, requires "inverting" Poisson's equation. For inter-laminar recordings, this is commonly done by the CSD method, which consists in taking the second-order spatial derivative of the recorded local field potentials (LFPs. Although the CSD method has been tremendously successful in mapping the current generators underlying inter-laminar LFPs, its application to planar recordings is more challenging. While for inter-laminar recordings the CSD method seems reasonably robust against violations of its assumptions, is it unclear as to what extent this holds for planar recordings. One of the objectives of this study is to characterize the conditions under which the CSD method can be successfully applied to Utah array data. Using forward modeling, we find that for spatially coherent CSDs, the CSD method yields inaccurate reconstructions due to volume-conducted contamination from currents in deeper cortical layers. An alternative approach is to "invert" a constructed forward model. The advantage of this approach is that any a priori knowledge about the geometrical and electrical properties of the tissue can be taken into account. Although several inverse methods have been proposed for LFP data, the applicability of existing electroencephalographic (EEG and magnetoencephalographic (MEG inverse methods to LFP data is largely unexplored. Another objective of our study therefore, is to assess the applicability of the most commonly used EEG/MEG inverse methods to Utah array data. Our main conclusion is that these inverse methods provide more accurate CSD reconstructions than the CSD method. We illustrate the inverse methods using event-related potentials recorded from primary visual cortex of a macaque monkey during a motion discrimination task.

Changes in corticomotor excitability and intracortical inhibition of the primary motor cortex forearm area induced by anodal tDCS.

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Xue Zhang

Full Text Available OBJECTIVE: Previous studies have investigated how tDCS over the primary motor cortex modulates excitability in the intrinsic hand muscles. Here, we tested if tDCS changes corticomotor excitability and/or cortical inhibition when measured in the extensor carpi radialis (ECR and if these aftereffects can be successfully assessed during controlled muscle contraction. METHODS: We implemented a double blind cross-over design in which participants (n = 16 completed two sessions where the aftereffects of 20 min of 1 mA (0.04 mA/cm2 anodal vs sham tDCS were tested in a resting muscle, and two more sessions where the aftereffects of anodal vs sham tDCS were tested in an active muscle. RESULTS: Anodal tDCS increased corticomotor excitability in ECR when aftereffects were measured with a low-level controlled muscle contraction. Furthermore, anodal tDCS decreased short interval intracortical inhibition but only when measured at rest and after non-responders (n = 2 were removed. We found no changes in the cortical silent period. CONCLUSION: These findings suggest that targeting more proximal muscles in the upper limb with anodal tDCS is achievable and corticomotor excitability can be assessed in the presence of a low-level controlled contraction of the target muscle.

Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats

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Tong-Chun Wen

2018-04-01

Full Text Available After injury to the corticospinal tract (CST in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy.

Early and late changes in the distal forelimb representation of the supplementary motor area after injury to frontal motor areas in the squirrel monkey.

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Eisner-Janowicz, Ines; Barbay, Scott; Hoover, Erica; Stowe, Ann M; Frost, Shawn B; Plautz, Erik J; Nudo, Randolph J

2008-09-01

Neuroimaging studies in stroke survivors have suggested that adaptive plasticity occurs following stroke. However, the complex temporal dynamics of neural reorganization after injury make the interpretation of functional imaging studies equivocal. In the present study in adult squirrel monkeys, intracortical microstimulation (ICMS) techniques were used to monitor changes in representational maps of the distal forelimb in the supplementary motor area (SMA) after a unilateral ischemic infarct of primary motor (M1) and premotor distal forelimb representations (DFLs). In each animal, ICMS maps were derived at early (3 wk) and late (13 wk) postinfarct stages. Lesions resulted in severe deficits in motor abilities on a reach and retrieval task. Limited behavioral recovery occurred and plateaued at 3 wk postinfarct. At both early and late postinfarct stages, distal forelimb movements could still be evoked by ICMS in SMA at low current levels. However, the size of the SMA DFL changed after the infarct. In particular, wrist-forearm representations enlarged significantly between early and late stages, attaining a size substantially larger than the preinfarct area. At the late postinfarct stage, the expansion in the SMA DFL area was directly proportional to the absolute size of the lesion. The motor performance scores were positively correlated to the absolute size of the SMA DFL at the late postinfarct stage. Together, these data suggest that, at least in squirrel monkeys, descending output from M1 and dorsal and ventral premotor cortices is not necessary for SMA representations to be maintained and that SMA motor output maps undergo delayed increases in representational area after damage to other motor areas. Finally, the role of SMA in recovery of function after such lesions remains unclear because behavioral recovery appears to precede neurophysiological map changes.

Whisker motor cortex reorganization after superior colliculus output suppression in adult rats.

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Veronesi, Carlo; Maggiolini, Emma; Franchi, Gianfranco

2013-10-01

The effect of unilateral superior colliculus (SC) output suppression on the ipsilateral whisker motor cortex (WMC) was studied at different time points after tetrodotoxin and quinolinic acid injections, in adult rats. The WMC output was assessed by mapping the movement evoked by intracortical microstimulation (ICMS) and by recording the ICMS-evoked electromyographic (EMG) responses from contralateral whisker muscles. At 1 h after SC injections, the WMC showed: (i) a strong decrease in contralateral whisker sites, (ii) a strong increase in ipsilateral whisker sites and in ineffective sites, and (iii) a strong increase in threshold current values. At 6 h after injections, the WMC size had shrunk to 60% of the control value and forelimb representation had expanded into the lateral part of the normal WMC. Thereafter, the size of the WMC recovered, returning to nearly normal 12 h later (94% of control) and persisted unchanged over time (1-3 weeks). The ICMS-evoked EMG response area decreased at 1 h after SC lesion and had recovered its baseline value 12 h later. Conversely, the latency of ICMS-evoked EMG responses had increased by 1 h and continued to increase for as long as 3 weeks following the lesion. These findings provide physiological evidence that SC output suppression persistently withdrew the direct excitatory drive from whisker motoneurons and induced changes in the WMC. We suggest that the changes in the WMC are a form of reversible short-term reorganization that is induced by SC lesion. The persistent latency increase in the ICMS-evoked EMG response suggested that the recovery of basic WMC excitability did not take place with the recovery of normal explorative behaviour. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats.

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Wen, Tong-Chun; Lall, Sophia; Pagnotta, Corey; Markward, James; Gupta, Disha; Ratnadurai-Giridharan, Shivakeshavan; Bucci, Jacqueline; Greenwald, Lucy; Klugman, Madelyne; Hill, N Jeremy; Carmel, Jason B

2018-01-01

After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy.

Restoring tactile and proprioceptive sensation through a brain interface.

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Tabot, Gregg A; Kim, Sung Shin; Winberry, Jeremy E; Bensmaia, Sliman J

2015-11-01

Somatosensation plays a critical role in the dexterous manipulation of objects, in emotional communication, and in the embodiment of our limbs. For upper-limb neuroprostheses to be adopted by prospective users, prosthetic limbs will thus need to provide sensory information about the position of the limb in space and about objects grasped in the hand. One approach to restoring touch and proprioception consists of electrically stimulating neurons in somatosensory cortex in the hopes of eliciting meaningful sensations to support the dexterous use of the hands, promote their embodiment, and perhaps even restore the affective dimension of touch. In this review, we discuss the importance of touch and proprioception in everyday life, then describe approaches to providing artificial somatosensory feedback through intracortical microstimulation (ICMS). We explore the importance of biomimicry--the elicitation of naturalistic patterns of neuronal activation--and that of adaptation--the brain's ability to adapt to novel sensory input, and argue that both biomimicry and adaptation will play a critical role in the artificial restoration of somatosensation. We also propose that the documented re-organization that occurs after injury does not pose a significant obstacle to brain interfaces. While still at an early stage of development, sensory restoration is a critical step in transitioning upper-limb neuroprostheses from the laboratory to the clinic. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of streptozotocin-induced diabetes on motor representations in the motor cortex and corticospinal tract in rats.

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Muramatsu, Ken; Ikutomo, Masako; Tamaki, Toru; Shimo, Satoshi; Niwa, Masatoshi

2018-02-01

Motor disorders in patients with diabetes are associated with diabetic peripheral neuropathy, which can lead to symptoms such as lower extremity weakness. However, it is unclear whether central motor system disorders can disrupt motor function in patients with diabetes. In a streptozotocin-induced rat model of type 1 diabetes, we used intracortical microstimulation to evaluate motor representations in the motor cortex, recorded antidromic motor cortex responses to spinal cord stimulation to evaluate the function of corticospinal tract (CST) axons, and used retrograde labeling to evaluate morphological alterations of CST neurons. The diabetic rats exhibited size reductions in the hindlimb area at 4 weeks and in trunk and forelimb areas after 13 weeks, with the hindlimb and trunk area reductions being the most severe. Other areas were unaffected. Additionally, we observed reduced antidromic responses in CST neurons with axons projecting to lumbar spinal segments (CST-L) but not in those with axons projecting to cervical segments (CST-C). This was consistent with the observation that retrograde-labeled CST-L neurons were decreased in number following tracer injection into the spinal cord in diabetic animals but that CST-C neurons were preserved. These results show that diabetes disrupts the CST system components controlling hindlimb and trunk movement. This disruption may contribute to lower extremity weakness in patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Complete reorganization of the motor cortex of adult rats following long-term spinal cord injuries.

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Tandon, Shashank; Kambi, Niranjan; Mohammed, Hisham; Jain, Neeraj

2013-07-01

Understanding brain reorganization following long-term spinal cord injuries is important for optimizing recoveries based on residual function as well as developing brain-controlled assistive devices. Although it has been shown that the motor cortex undergoes partial reorganization within a few weeks after peripheral and spinal cord injuries, it is not known if the motor cortex of rats is capable of large-scale reorganization after longer recovery periods. Here we determined the organization of the rat (Rattus norvegicus) motor cortex at 5 or more months after chronic lesions of the spinal cord at cervical levels using intracortical microstimulation. The results show that, in the rats with the lesions, stimulation of neurons in the de-efferented forelimb motor cortex no longer evokes movements of the forelimb. Instead, movements of the body parts in the adjacent representations, namely the whiskers and neck were evoked. In addition, at many sites, movements of the ipsilateral forelimb were observed at threshold currents. The extent of representations of the eye, jaw and tongue movements was unaltered by the lesion. Thus, large-scale reorganization of the motor cortex leads to complete filling-in of the de-efferented cortex by neighboring representations following long-term partial spinal cord injuries at cervical levels in adult rats. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Long-term neuroplasticity of the face primary motor cortex and adjacent somatosensory cortex induced by tooth loss can be reversed following dental implant replacement in rats.

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Avivi-Arber, Limor; Lee, Jye-Chang; Sood, Mandeep; Lakschevitz, Flavia; Fung, Michelle; Barashi-Gozal, Maayan; Glogauer, Michael; Sessle, Barry J

2015-11-01

Tooth loss is common, and exploring the neuroplastic capacity of the face primary motor cortex (face-M1) and adjacent primary somatosensory cortex (face-S1) is crucial for understanding how subjects adapt to tooth loss and their prosthetic replacement. The aim was to test if functional reorganization of jaw and tongue motor representations in the rat face-M1 and face-S1 occurs following tooth extraction, and if subsequent dental implant placement can reverse this neuroplasticity. Rats (n = 22) had the right maxillary molar teeth extracted under local and general anesthesia. One month later, seven rats had dental implant placement into healed extraction sites. Naive rats (n = 8) received no surgical treatment. Intracortical microstimulation (ICMS) and recording of evoked jaw and tongue electromyographic responses were used to define jaw and tongue motor representations at 1 month (n = 8) or 2 months (n = 7) postextraction, 1 month postimplant placement, and at 1-2 months in naive rats. There were no significant differences across study groups in the onset latencies of the ICMS-evoked responses (P > 0.05), but in comparison with naive rats, tooth extraction caused a significant (P rats. These novel findings suggest that face-M1 and adjacent face-S1 may play a role in adaptive mechanisms related to tooth loss and their replacement with dental implants. © 2015 Wiley Periodicals, Inc.

Implantation of Neural Probes in the Brain Elicits Oxidative Stress

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Evon S. Ereifej

2018-02-01

Full Text Available Clinical implantation of intracortical microelectrodes has been hindered, at least in part, by the perpetual inflammatory response occurring after device implantation. The neuroinflammatory response observed after device implantation has been correlated to oxidative stress that occurs due to neurological injury and disease. However, there has yet to be a definitive link of oxidative stress to intracortical microelectrode implantation. Thus, the objective of this study is to give direct evidence of oxidative stress following intracortical microelectrode implantation. This study also aims to identify potential molecular targets to attenuate oxidative stress observed postimplantation. Here, we implanted adult rats with silicon non-functional microelectrode probes for 4 weeks and compared the oxidative stress response to no surgery controls through postmortem gene expression analysis and qualitative histological observation of oxidative stress markers. Gene expression analysis results at 4 weeks postimplantation indicated that EH domain-containing 2, prion protein gene (Prnp, and Stearoyl-Coenzyme A desaturase 1 (Scd1 were all significantly higher for animals implanted with intracortical microelectrode probes compared to no surgery control animals. To the contrary, NADPH oxidase activator 1 (Noxa1 relative gene expression was significantly lower for implanted animals compared to no surgery control animals. Histological observation of oxidative stress showed an increased expression of oxidized proteins, lipids, and nucleic acids concentrated around the implant site. Collectively, our results reveal there is a presence of oxidative stress following intracortical microelectrode implantation compared to no surgery controls. Further investigation targeting these specific oxidative stress linked genes could be beneficial to understanding potential mechanisms and downstream therapeutics that can be utilized to reduce oxidative stress-mediated damage

Reorganization of Motor Cortex by Vagus Nerve Stimulation Requires Cholinergic Innervation.

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Hulsey, Daniel R; Hays, Seth A; Khodaparast, Navid; Ruiz, Andrea; Das, Priyanka; Rennaker, Robert L; Kilgard, Michael P

2016-01-01

Vagus nerve stimulation (VNS) paired with forelimb training drives robust, specific reorganization of movement representations in the motor cortex. The mechanisms that underlie VNS-dependent enhancement of map plasticity are largely unknown. The cholinergic nucleus basalis (NB) is a critical substrate in cortical plasticity, and several studies suggest that VNS activates cholinergic circuitry. We examined whether the NB is required for VNS-dependent enhancement of map plasticity in the motor cortex. Rats were trained to perform a lever pressing task and then received injections of the immunotoxin 192-IgG-saporin to selectively lesion cholinergic neurons of the NB. After lesion, rats underwent five days of motor training during which VNS was paired with successful trials. At the conclusion of behavioral training, intracortical microstimulation was used to document movement representations in motor cortex. VNS paired with forelimb training resulted in a substantial increase in the representation of proximal forelimb in rats with an intact NB compared to untrained controls. NB lesions prevent this VNS-dependent increase in proximal forelimb area and result in representations similar to untrained controls. Motor performance was similar between groups, suggesting that differences in forelimb function cannot account for the difference in proximal forelimb representation. Together, these findings indicate that the NB is required for VNS-dependent enhancement of plasticity in the motor cortex and may provide insight into the mechanisms that underlie the benefits of VNS therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Output Properties of the Cortical Hindlimb Motor Area in Spinal Cord-Injured Rats.

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Frost, Shawn B; Dunham, Caleb L; Barbay, Scott; Krizsan-Agbas, Dora; Winter, Michelle K; Guggenmos, David J; Nudo, Randolph J

2015-11-01

The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9-T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia. Although movements could be evoked using ICMS in the forelimb area with relatively low current levels, no movements or electromyographical responses could be evoked from ICMS in the HLA in any of the injured rats. During the same procedure, electrophysiological recordings were obtained with a single-shank, 16-channel Michigan probe (Neuronexus) to monitor activity. Neural spikes were discriminated using principle component analysis. Neural activity (action potentials) was collected and digitized for a duration of 5 min. Despite the inability to evoke movement from stimulation of cortex, robust single-unit activity could be recorded reliably from hindlimb motor cortex in SCI rats. Activity in the motor cortex of SCI rats was significantly higher compared with uninjured rats, and increased in hindlimb and forelimb motor cortex by similar amounts. These results demonstrate that in a rat model of thoracic SCI, an increase in single-unit cortical activity can be reliably recorded for several weeks post-injury.

Forelimb training drives transient map reorganization in ipsilateral motor cortex.

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Pruitt, David T; Schmid, Ariel N; Danaphongse, Tanya T; Flanagan, Kate E; Morrison, Robert A; Kilgard, Michael P; Rennaker, Robert L; Hays, Seth A

2016-10-15

Skilled motor training results in reorganization of contralateral motor cortex movement representations. The ipsilateral motor cortex is believed to play a role in skilled motor control, but little is known about how training influences reorganization of ipsilateral motor representations of the trained limb. To determine whether training results in reorganization of ipsilateral motor cortex maps, rats were trained to perform the isometric pull task, an automated motor task that requires skilled forelimb use. After either 3 or 6 months of training, intracortical microstimulation (ICMS) mapping was performed to document motor representations of the trained forelimb in the hemisphere ipsilateral to that limb. Motor training for 3 months resulted in a robust expansion of right forelimb representation in the right motor cortex, demonstrating that skilled motor training drives map plasticity ipsilateral to the trained limb. After 6 months of training, the right forelimb representation in the right motor cortex was significantly smaller than the representation observed in rats trained for 3 months and similar to untrained controls, consistent with a normalization of motor cortex maps. Forelimb map area was not correlated with performance on the trained task, suggesting that task performance is maintained despite normalization of cortical maps. This study provides new insights into how the ipsilateral cortex changes in response to skilled learning and may inform rehabilitative strategies to enhance cortical plasticity to support recovery after brain injury. Copyright © 2016 Elsevier B.V. All rights reserved.

High-order motor cortex in rats receives somatosensory inputs from the primary motor cortex via cortico-cortical pathways.

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Kunori, Nobuo; Takashima, Ichiro

2016-12-01

The motor cortex of rats contains two forelimb motor areas; the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to correspond to the premotor and/or supplementary motor cortices of primates, which are higher-order motor areas that receive somatosensory inputs, it is unknown whether the RFA of rats receives somatosensory inputs in the same manner. To investigate this issue, voltage-sensitive dye (VSD) imaging was used to assess the motor cortex in rats following a brief electrical stimulation of the forelimb. This procedure was followed by intracortical microstimulation (ICMS) mapping to identify the motor representations in the imaged cortex. The combined use of VSD imaging and ICMS revealed that both the CFA and RFA received excitatory synaptic inputs after forelimb stimulation. Further evaluation of the sensory input pathway to the RFA revealed that the forelimb-evoked RFA response was abolished either by the pharmacological inactivation of the CFA or a cortical transection between the CFA and RFA. These results suggest that forelimb-related sensory inputs would be transmitted to the RFA from the CFA via the cortico-cortical pathway. Thus, the present findings imply that sensory information processed in the RFA may be used for the generation of coordinated forelimb movements, which would be similar to the function of the higher-order motor cortex in primates. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

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

2013-04-01

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

Intraskeletal variation in human cortical osteocyte lacunar density: Implications for bone quality assessment

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Randee L. Hunter

2016-12-01

.N was able to predict 61.8% of variation in osteocyte lacunar number (Ot.Lc.N in the rib. The femur and radius also demonstrated significant relationships between these variables (R2 = 0.560 and 0.397 respectively. The results from this study indicate that although the femur, radius and rib may be experiencing systemically influenced declines in osteocyte lacunar density, there may be differential effects at each anatomical site potentially due to age related changes in mechanical loading. With decreasing osteocyte lacunar density in each element, intracortical porosity increased with likely direct impacts on gross bone strength. This study provides a foundation upon which to build interpretations of osteocyte lacunar density values and their effect on differential fracture risk for aging individuals. Keywords: Osteocyte, Osteocyte lacunar density, Cortical bone, Intracortical porosity, Bone quality

Transcranial magnetic stimulation provides means to assess cortical plasticity and excitability in humans with fragile X syndrome and autism spectrum disorder

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Lindsay M Oberman

2010-06-01

Full Text Available Fragile X Syndrome (FXS is the most common heritable cause of intellectual disability. In vitro electrophysiologic data from mouse models of FXS suggest that loss of Fragile X Mental Retardation Protein (FMRP affects intracortical excitability and synaptic plasticity. Specifically, the cortex appears hyperexcitable, and use-dependent long-term potentiation (LTP and long-term depression (LTD of synaptic strength are abnormal. Though animal models provide important information, FXS and other neurodevelopmental disorders are human diseases and as such translational research to evaluate cortical excitability and plasticity must be applied in the human. Transcranial magnetic stimulation (TMS paradigms have recently been developed to noninvasively investigate cortical excitability using paired-pulse stimulation, as well as LTP- and LTD-like synaptic plasticity in response to theta burst stimulation (TBS in vivo in the human. TBS applied on consecutive days can be used to measure metaplasticity (the ability of the synapse to undergo a second plastic change following a recent induction of plasticity. The current study investigated intracortical inhibition, plasticity and metaplasticity in full mutation females with FXS, participants with autism spectrum disorders (ASD, and neurotypical controls. Results suggest that intracortical inhibition is normal in participants with FXS, while plasticity and metaplasticity appear abnormal. ASD participants showed abnormalities in plasticity and metaplasticity, as well as heterogeneity in intracortical inhibition. Our findings highlight the utility of noninvasive neurophysiological measures to translate insights from animal models to humans with neurodevelopmental disorders, and thus provide direct confirmation of cortical dysfunction in patients with FXS and ASD.

Trunk Robot Rehabilitation Training with Active Stepping Reorganizes and Enriches Trunk Motor Cortex Representations in Spinal Transected Rats

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Oza, Chintan S.

2015-01-01

Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. PMID:25948267

Plasticity of orientation preference maps in the visual cortex of adult cats

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Godde, Ben; Leonhardt, Ralph; Cords, Sven M.; Dinse, Hubert R.

2002-01-01

In contrast to the high degree of experience-dependent plasticity usually exhibited by cortical representational maps, a number of experiments performed in visual cortex suggest that the basic layout of orientation preference maps is only barely susceptible to activity-dependent modifications. In fact, most of what we know about activity-dependent plasticity in adults comes from experiments in somatosensory, auditory, or motor cortex. Applying a stimulation protocol that has been proven highly effective in other cortical areas, we demonstrate here that enforced synchronous cortical activity induces major changes of orientation preference maps (OPMs) in adult cats. Combining optical imaging of intrinsic signals and electrophysiological single-cell recordings, we show that a few hours of intracortical microstimulation (ICMS) lead to an enlargement of the cortical representational zone at the ICMS site and an extensive restructuring of the entire OPM layout up to several millimeters away, paralleled by dramatic changes of pinwheel numbers and locations. At the single-cell level, we found that the preferred orientation was shifted toward the orientation of the ICMS site over a region of up to 4 mm. Our results show that manipulating the synchronicity of cortical activity locally without invoking training, attention, or reinforcement, OPMs undergo large-scale reorganization reminiscent of plastic changes observed for nonvisual cortical maps. However, changes were much more widespread and enduring. Such large-scale restructuring of the visual cortical networks indicates a substantial capability for activity-dependent plasticity of adult visual cortex and may provide the basis for cognitive learning processes. PMID:11959906

Exponential current pulse generation for efficient very high-impedance multisite stimulation.

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Ethier, S; Sawan, M

2011-02-01

We describe in this paper an intracortical current-pulse generator for high-impedance microstimulation. This dual-chip system features a stimuli generator and a high-voltage electrode driver. The stimuli generator produces flexible rising exponential pulses in addition to standard rectangular stimuli. This novel stimulation waveform is expected to provide superior energy efficiency for action potential triggering while releasing less toxic reduced ions in the cortical tissues. The proposed fully integrated electrode driver is used as the output stage where high-voltage supplies are generated on-chip to significantly increase the voltage compliance for stimulation through high-impedance electrode-tissue interfaces. The stimuli generator has been implemented in 0.18-μm CMOS technology while a 0.8-μm CMOS/DMOS process has been used to integrate the high-voltage output stage. Experimental results show that the rectangular pulses cover a range of 1.6 to 167.2 μA with a DNL and an INL of 0.098 and 0.163 least-significant bit, respectively. The maximal dynamic range of the generated exponential reaches 34.36 dB at full scale within an error of ± 0.5 dB while all of its parameters (amplitude, duration, and time constant) are independently programmable over wide ranges. This chip consumes a maximum of 88.3 μ W in the exponential mode. High-voltage supplies of 8.95 and -8.46 V are generated by the output stage, boosting the voltage swing up to 13.6 V for a load as high as 100 kΩ.

Reliability in the location of hindlimb motor representations in Fischer-344 rats: laboratory investigation.

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Frost, Shawn B; Iliakova, Maria; Dunham, Caleb; Barbay, Scott; Arnold, Paul; Nudo, Randolph J

2013-08-01

The purpose of the present study was to determine the feasibility of using a common laboratory rat strain for reliably locating cortical motor representations of the hindlimb. Intracortical microstimulation techniques were used to derive detailed maps of the hindlimb motor representations in 6 adult Fischer-344 rats. The organization of the hindlimb movement representation, while variable across individual rats in topographic detail, displayed several commonalities. The hindlimb representation was positioned posterior to the forelimb motor representation and posterolateral to the motor trunk representation. The areal extent of the hindlimb representation across the cortical surface averaged 2.00 ± 0.50 mm(2). Superimposing individual maps revealed an overlapping area measuring 0.35 mm(2), indicating that the location of the hindlimb representation can be predicted reliably based on stereotactic coordinates. Across the sample of rats, the hindlimb representation was found 1.25-3.75 mm posterior to the bregma, with an average center location approximately 2.6 mm posterior to the bregma. Likewise, the hindlimb representation was found 1-3.25 mm lateral to the midline, with an average center location approximately 2 mm lateral to the midline. The location of the cortical hindlimb motor representation in Fischer-344 rats can be reliably located based on its stereotactic position posterior to the bregma and lateral to the longitudinal skull suture at midline. The ability to accurately predict the cortical localization of functional hindlimb territories in a rodent model is important, as such animal models are being increasingly used in the development of brain-computer interfaces for restoration of function after spinal cord injury.

Different functional reorganization of motor cortex after transfer of the contralateral C7 to different recipient nerves in young rats with total brachial plexus root avulsion.

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Pan, Feng; Wei, Hai-feng; Chen, Liang; Gu, Yu-dong

2012-12-07

Clinically, contralateral C7 transfer is used for nerve reconstruction in brachial plexus injuries. Postoperatively, synchronous motions at the donor limb are noteworthy. This study studied if different recipient nerves influenced transhemispheric functional reorganization of motor cortex after this procedure. 90 young rats with total root avulsion of the brachial plexus were divided into groups 1-3 of contralateral C7 transfer to anterior division of the upper trunk, to both the musculocutaneous and median nerves, and to the median nerve, respectively. After reinnervation of target muscles, number of sites for forelimb representations in bilateral motor cortices was determined by intracortical microstimulation at 1.5, 3, 6, 9, and 12 months postoperatively. At nine months, transhemispheric reorganization of nerves neurotized by contralateral C7 was fulfilled in four of six rats in group 1, one of six in group 2 and none in group 3, respectively; at 12 months, that was fulfilled in five of six in group 1, four of six in groups 2 and 3, respectively. Logistic regression analysis showed that rate of fulfilled transhemispheric reorganization in group 1 was 12.19 times that in group 3 (95% CI 0.006-0.651, p=0.032). At 12 months, number of sites for hindlimb representations which had encroached upon original forelimb representations on the uninjured side was statistically more in group 3 than in group 2 (t=9.5, pmotor cortex than that to median nerve alone in rats. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Two whisker motor areas in the rat cortex: evidence from thalamocortical connections.

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Mohammed, Hisham; Jain, Neeraj

2014-02-15

In primates, the motor cortex consists of at least seven different areas, which are involved in movement planning, coordination, initiation, and execution. However, for rats, only the primary motor cortex has been well described. A rostrally located second motor area has been proposed, but its extent, organization, and even definitive existence remain uncertain. Only a rostral forelimb area (RFA) has been definitively described, besides few reports of a rostral hindlimb area. We have previously proposed existence of a second whisker area, which we termed the rostral whisker area (RWA), based on its differential response to intracortical microstimulation compared with the caudal whisker area (CWA) in animals under deep anesthesia (Tandon et al. [2008] Eur J Neurosci 27:228). To establish that RWA is distinct from the caudally contiguous CWA, we determined sources of thalamic inputs to the two proposed whisker areas. Sources of inputs to RFA, caudal forelimb area (CFA), and caudal hindlimb region were determined for comparison. The results show that RWA and CWA can be distinguished based on differences in their thalamic inputs. RWA receives major projections from mediodorsal and ventromedial nuclei, whereas the major projections to CWA are from the ventral anterior, ventrolateral, and posterior nuclei. Moreover, the thalamic nuclei that provide major inputs to RWA are the same as for RFA, and the nuclei projecting to CWA are same as for CFA. The results suggest that rats have a second rostrally located motor area with RWA and RFA as its constituents. Copyright © 2013 Wiley Periodicals, Inc.

Combinatorial Motor Training Results in Functional Reorganization of Remaining Motor Cortex after Controlled Cortical Impact in Rats.

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Combs, Hannah L; Jones, Theresa A; Kozlowski, Dorothy A; Adkins, DeAnna L

2016-04-15

Cortical reorganization subsequent to post-stroke motor rehabilitative training (RT) has been extensively examined in animal models and humans. However, similar studies focused on the effects of motor training after traumatic brain injury (TBI) are lacking. We previously reported that after a moderate/severe TBI in adult male rats, functional improvements in forelimb use were accomplished only with a combination of skilled forelimb reach training and aerobic exercise, with or without nonimpaired forelimb constraint. Thus, the current study was designed to examine the relationship between functional motor cortical map reorganization after experimental TBI and the behavioral improvements resulting from this combinatorial rehabilitative regime. Adult male rats were trained to proficiency on a skilled reaching task, received a unilateral controlled cortical impact (CCI) over the forelimb area of the caudal motor cortex (CMC). Three days post-CCI, animals began RT (n = 13) or no rehabilitative training (NoRT) control procedures (n = 13). The RT group participated in daily skilled reach training, voluntary aerobic exercise, and nonimpaired forelimb constraint. This RT regimen significantly improved impaired forelimb reaching success and normalized reaching strategies, consistent with previous findings. RT also enlarged the area of motor cortical wrist representation, derived by intracortical microstimulation, compared to NoRT. These findings indicate that sufficient RT can greatly improve motor function and improve the functional integrity of remaining motor cortex after a moderate/severe CCI. When compared with findings from stroke models, these findings also suggest that more intense RT may be needed to improve motor function and remodel the injured cortex after TBI.

The Effect of Lesion Size on the Organization of the Ipsilesional and Contralesional Motor Cortex.

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Touvykine, Boris; Mansoori, Babak K; Jean-Charles, Loyda; Deffeyes, Joan; Quessy, Stephan; Dancause, Numa

2016-03-01

Recovery of hand function following lesions in the primary motor cortex (M1) is associated with a reorganization of premotor areas in the ipsilesional hemisphere, and this reorganization depends on the size of the lesion. It is not clear how lesion size affects motor representations in the contralesional hemisphere and how the effects in the 2 hemispheres compare. Our goal was to study how lesion size affects motor representations in the ipsilesional and contralesional hemispheres. In rats, we induced lesions of different sizes in the caudal forelimb area (CFA), the equivalent of M1. The effective lesion volume in each animal was quantified histologically. Behavioral recovery was evaluated with the Montoya Staircase task for 28 days after the lesion. Then, the organization of the CFA and the rostral forelimb area (RFA)--the putative premotor area in rats--in the 2 cerebral hemispheres was studied with intracortical microstimulation mapping techniques. The distal forelimb representation in the RFA of both the ipsilesional and contralesional hemispheres was positively correlated with the size of the lesion. In contrast, lesion size had no effect on the contralesional CFA, and there was no relationship between movement representations in the 2 hemispheres. Finally, only the contralesional RFA was negatively correlated with chronic motor deficits of the paretic forelimb. Our data show that lesion size has comparable effects on motor representations in premotor areas of both hemispheres and suggest that the contralesional premotor cortex may play a greater role in the recovery of the paretic forelimb following large lesions. © The Author(s) 2015.

Detection of independent functional networks during music listening using electroencephalogram and sLORETA-ICA.

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Jäncke, Lutz; Alahmadi, Nsreen

2016-04-13

The measurement of brain activation during music listening is a topic that is attracting increased attention from many researchers. Because of their high spatial accuracy, functional MRI measurements are often used for measuring brain activation in the context of music listening. However, this technique faces the issues of contaminating scanner noise and an uncomfortable experimental environment. Electroencephalogram (EEG), however, is a neural registration technique that allows the measurement of neurophysiological activation in silent and more comfortable experimental environments. Thus, it is optimal for recording brain activations during pleasant music stimulation. Using a new mathematical approach to calculate intracortical independent components (sLORETA-IC) on the basis of scalp-recorded EEG, we identified specific intracortical independent components during listening of a musical piece and scales, which differ substantially from intracortical independent components calculated from the resting state EEG. Most intracortical independent components are located bilaterally in perisylvian brain areas known to be involved in auditory processing and specifically in music perception. Some intracortical independent components differ between the music and scale listening conditions. The most prominent difference is found in the anterior part of the perisylvian brain region, with stronger activations seen in the left-sided anterior perisylvian regions during music listening, most likely indicating semantic processing during music listening. A further finding is that the intracortical independent components obtained for the music and scale listening are most prominent in higher frequency bands (e.g. beta-2 and beta-3), whereas the resting state intracortical independent components are active in lower frequency bands (alpha-1 and theta). This new technique for calculating intracortical independent components is able to differentiate independent neural networks associated

[The Ability to Successfully Perform Different Kinds of Cognitive Activity Is Reflected in the Topological Features of Intracortical Interactions (Sex Differences in Boys and Girls Aged 5-6 Years)].

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Panasevich, E A; Tsitseroshin, M N

2015-01-01

We studied the correlation of intellectual development according to The Wechsler Intelligence Scale for Children (WISC test) with the spatial organization of resting EEG in 52 children aged 5-6 years. It was found that the patterns of interregional interactions of different parts of the cortex which correspond with the best performance in the subtests in boys (n = 23) and girls (n = 29) have significant topological differences. In girls, successful subtest performance positively correlated to a greater extent with interhemispheric interactions; in boys--long longitudinal rostral-caudal interactions between various regions of the cortex. The results showed that there are important gender differences in the spatial organization of brain activity associated with the performance of different cognitive activities in preschool children. The successful performance of various subtests by boys required considerable variability in the organization of spatial patterns of interregional interactions; on the contrary, the spatial structure of these patterns in girls was relatively invariable. Obviously, for the successful performance of various cognitive activities at this age in boys, the cortex need to form highly specialized organization of intracortical interactions, while in girls the brain uses relatively similar reorganization of interactions. The data suggest that 5-6-year-old boys and girls use different cognitive strategies when performing the same subtests of the WISC test.

Blood oxygenation level dependent signal and neuronal adaptation to optogenetic and sensory stimulation in somatosensory cortex in awake animals.

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Aksenov, Daniil P; Li, Limin; Miller, Michael J; Wyrwicz, Alice M

2016-11-01

The adaptation of neuronal responses to stimulation, in which a peak transient response is followed by a sustained plateau, has been well-studied. The blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal has also been shown to exhibit adaptation on a longer time scale. However, some regions such as the visual and auditory cortices exhibit significant BOLD adaptation, whereas other such as the whisker barrel cortex may not adapt. In the sensory cortex a combination of thalamic inputs and intracortical activity drives hemodynamic changes, although the relative contributions of these components are not entirely understood. The aim of this study is to assess the role of thalamic inputs vs. intracortical processing in shaping BOLD adaptation during stimulation in the somatosensory cortex. Using simultaneous fMRI and electrophysiology in awake rabbits, we measured BOLD, local field potentials (LFPs), single- and multi-unit activity in the cortex during whisker and optogenetic stimulation. This design allowed us to compare BOLD and haemodynamic responses during activation of the normal thalamocortical sensory pathway (i.e., both inputs and intracortical activity) vs. the direct optical activation of intracortical circuitry alone. Our findings show that whereas LFP and multi-unit (MUA) responses adapted, neither optogenetic nor sensory stimulation produced significant BOLD adaptation. We observed for both paradigms a variety of excitatory and inhibitory single unit responses. We conclude that sensory feed-forward thalamic inputs are not primarily responsible for shaping BOLD adaptation to stimuli; but the single-unit results point to a role in this behaviour for specific excitatory and inhibitory neuronal sub-populations, which may not correlate with aggregate neuronal activity. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

High Working Memory Load Increases Intracortical Inhibition in Primary Motor Cortex and Diminishes the Motor Affordance Effect.

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Freeman, Scott M; Itthipuripat, Sirawaj; Aron, Adam R

2016-05-18

of the motor affordance while working memory load was varied. We observed a typical motor affordance signature when working memory load was low; however, it was abolished when load was high. Further, there was increased intracortical inhibition in primary motor cortex under high working memory load. This suggests that being in a state of high cognitive load "sets" the motor system to be imperturbable to distracting motor influences. This makes a novel link between working memory load and the balance of excitatory/inhibitory activity in the motor cortex and potentially has implications for disorders of impulsivity. Copyright © 2016 the authors 0270-6474/16/365544-12$15.00/0.

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

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Daniel P Spiegel

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

Evidence for increased glutamatergic cortical facilitation in children and adolescents with major depressive disorder.

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Croarkin, Paul E; Nakonezny, Paul A; Husain, Mustafa M; Melton, Tabatha; Buyukdura, Jeylan S; Kennard, Betsy D; Emslie, Graham J; Kozel, F Andrew; Daskalakis, Zafiris J

2013-03-01

Converging lines of evidence implicate the glutamate and γ-aminobutyric acid neurotransmitter systems in the pathophysiology of major depressive disorder. Transcranial magnetic stimulation cortical excitability and inhibition paradigms have been used to assess cortical glutamatergic and γ-aminobutyric acid-mediated tone in adults with major depressive disorder, but not in children and adolescents. To compare measures of cortical excitability and inhibition with 4 different paradigms in a group of children and adolescents with major depressive disorder vs healthy controls. Cross-sectional study examining medication-free children and adolescents (aged 9-17 years) with major depressive disorder compared with healthy controls. Cortical excitability was assessed with motor threshold and intracortical facilitation measures. Cortical inhibition was measured with cortical silent period and intracortical inhibition paradigms. University-based child and adolescent psychiatry clinic and neurostimulation laboratory. Twenty-four participants with major depressive disorder and 22 healthy controls matched for age and sex. Patients with major depressive disorder were medication naive and had moderate to severe symptoms based on an evaluation with a child and adolescent psychiatrist and scores on the Children's Depression Rating Scale-Revised. Motor threshold, intracortical facilitation, cortical silent period, and intracortical inhibition. Compared with healthy controls, depressed patients had significantly increased intracortical facilitation at interstimulus intervals of 10 and 15 milliseconds bilaterally. There were no significant group differences in cortical inhibition measures. These findings suggest that major depressive disorder in children and adolescents is associated with increased intracortical facilitation and excessive glutamatergic activity.

Inhibition of the cluster of differentiation 14 innate immunity pathway with IAXO-101 improves chronic microelectrode performance

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Hermann, John K.; Ravikumar, Madhumitha; Shoffstall, Andrew J.; Ereifej, Evon S.; Kovach, Kyle M.; Chang, Jeremy; Soffer, Arielle; Wong, Chun; Srivastava, Vishnupriya; Smith, Patrick; Protasiewicz, Grace; Jiang, Jingle; Selkirk, Stephen M.; Miller, Robert H.; Sidik, Steven; Ziats, Nicholas P.; Taylor, Dawn M.; Capadona, Jeffrey R.

2018-04-01

Objective. Neuroinflammatory mechanisms are hypothesized to contribute to intracortical microelectrode failures. The cluster of differentiation 14 (CD14) molecule is an innate immunity receptor involved in the recognition of pathogens and tissue damage to promote inflammation. The goal of the study was to investigate the effect of CD14 inhibition on intracortical microelectrode recording performance and tissue integration. Approach. Mice implanted with intracortical microelectrodes in the motor cortex underwent electrophysiological characterization for 16 weeks, followed by endpoint histology. Three conditions were examined: (1) wildtype control mice, (2) knockout mice lacking CD14, and (3) wildtype control mice administered a small molecule inhibitor to CD14 called IAXO-101. Main results. The CD14 knockout mice exhibited acute but not chronic improvements in intracortical microelectrode performance without significant differences in endpoint histology. Mice receiving IAXO-101 exhibited significant improvements in recording performance over the entire 16 week duration without significant differences in endpoint histology. Significance. Full removal of CD14 is beneficial at acute time ranges, but limited CD14 signaling is beneficial at chronic time ranges. Innate immunity receptor inhibition strategies have the potential to improve long-term intracortical microelectrode performance.

Reliability in the Location of Hindlimb Motor Representations in Fischer-344 Rats

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Frost, Shawn B.; Iliakova, Maria; Dunham, Caleb; Barbay, Scott; Arnold, Paul; Nudo, Randolph J.

2014-01-01

Object The purpose of the present study was to determine the feasibility of using a common laboratory rat strain for locating cortical motor representations of the hindlimb reliably. Methods Intracortical Microstimulation (ICMS) techniques were used to derive detailed maps of the hindlimb motor representations in six adult Fischer-344 rats. Results The organization of the hindlimb movement representation, while variable across individuals in topographic detail, displayed several commonalities. The hindlimb representation was positioned posterior to the forelimb motor representation and postero-lateral to the motor trunk representation. The areal extent of the hindlimb representation across the cortical surface averaged 2.00 +/− 0.50 mm2. Superimposing individual maps revealed an overlapping area measuring 0.35 mm2, indicating that the location of the hindlimb representation can be predicted reliably based on stereotactic coordinates. Across the sample of rats, the hindlimb representation was found 1.25–3.75 mm posterior to Bregma, with an average center location ~ 2.6 mm posterior to Bregma. Likewise, the hindlimb representation was found 1–3.25 mm lateral to the midline, with an average center location ~ 2 mm lateral to midline. Conclusions The location of the cortical hindlimb motor representation in Fischer-344 rats can be reliably located based on its stereotactic position posterior to Bregma and lateral to the longitudinal skull suture at midline. The ability to accurately predict the cortical localization of functional hindlimb territories in a rodent model is important, as such animal models are being used increasingly in the development of brain-computer interfaces for restoration of function after spinal cord injury. PMID:23725395

Trunk robot rehabilitation training with active stepping reorganizes and enriches trunk motor cortex representations in spinal transected rats.

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Oza, Chintan S; Giszter, Simon F

2015-05-06

Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI. Copyright © 2015 the authors 0270-6474/15/357174-16$15.00/0.

Region-specificity of GABAA receptor mediated effects on orientation and direction selectivity in cat visual cortical area 18.

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Jirmann, Kay-Uwe; Pernberg, Joachim; Eysel, Ulf T

2009-01-01

The role of GABAergic inhibition in orientation and direction selectivity has been investigated with the GABA(A)-Blocker bicuculline in the cat visual cortex, and results indicated a region specific difference of functional contributions of GABAergic inhibition in areas 17 and 18. In area 17 inhibition appeared mainly involved in sculpturing orientation and direction tuning, while in area 18 inhibition seemed more closely associated with temporal receptive field properties. However, different types of stimuli were used to test areas 17 and 18 and further studies performed in area 17 suggested an important influence of the stimulus type (single light bars vs. moving gratings) on the evoked responses (transient vs. sustained) and inhibitory mechanisms (GABA(A) vs. GABA(B)) which in turn might be more decisive for the specific results than the cortical region. To insert the missing link in this chain of arguments it was necessary to study GABAergic inhibition in area 18 with moving light bars, which has not been done so far. Therefore, in the present study we investigated area 18 cells responding to oriented moving light bars with extracellular recordings and reversible microiontophoretic blockade of GABAergig inhibition with bicuculline methiodide. The majority of neurons was characterized by a pronounced orientation specificity and variable degrees of direction selectivity. GABA(A)ergic inhibition significantly influenced preferred orientation and preferred direction in area 18. During the action of bicuculline orientation tuning width increased and orientation and direction selectivity indices decreased. Our results obtained in area 18 with moving bar stimuli, although in the proportion of affected cells similar to those described in area 17, quantitatively matched the findings for direction and orientation specificity obtained with moving gratings in area 18. Accordingly, stimulus type is not decisive in area 18 and the GABA(A) dependent, inhibitory intracortical

Cleveland Clinic Rehabilitation Research Program

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2015-12-01

Study 1: The penicillin-induced seizure animal model has been generated by acute focal intracortical injection of penicillin in the motor cortex of rats ... motor cortex of rats . The effects of transcranial magnetic stimulation (TMS) on penicillin-induced seizure have been investigated using behavioral...electroencephalographic (EEG) recording. Study 2: The motor cortex (M1) and the corticospinal tracts (CST) will be directly modulated using brain stimulation

Cortical Reorganization in Dual Innervation by Single Peripheral Nerve.

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Zheng, Mou-Xiong; Shen, Yun-Dong; Hua, Xu-Yun; Hou, Ao-Lin; Zhu, Yi; Xu, Wen-Dong

2017-09-21

Functional recovery after peripheral nerve injury and repair is related with cortical reorganization. However, the mechanism of innervating dual targets by 1 donor nerve is largely unknown. To investigate the cortical reorganization when the phrenic nerve simultaneously innervates the diaphragm and biceps. Total brachial plexus (C5-T1) injury rats were repaired by phrenic nerve-musculocutaneous nerve transfer with end-to-side (n = 15) or end-to-end (n = 15) neurorrhaphy. Brachial plexus avulsion (n = 5) and sham surgery (n = 5) rats were included for control. Behavioral observation, electromyography, and histologic studies were used for confirming peripheral nerve reinnervation. Cortical representations of the diaphragm and reinnervated biceps were studied by intracortical microstimulation techniques before and at months 0.5, 3, 5, 7, and 10 after surgery. At month 0.5 after complete brachial plexus injury, the motor representation of the injured forelimb disappeared. The diaphragm representation was preserved in the "end-to-side" group but absent in the "end-to-end" group. Rhythmic contraction of biceps appeared in "end-to-end" and "end-to-side" groups, and the biceps representation reappeared in the original biceps and diaphragm areas at months 3 and 5. At month 10, it was completely located in the original biceps area in the "end-to-end" group. Part of the biceps representation remained in the original diaphragm area in the "end-to-side" group. Destroying the contralateral motor cortex did not eliminate respiration-related contraction of biceps. The brain tends to resume biceps representation from the original diaphragm area to the original biceps area following phrenic nerve transfer. The original diaphragm area partly preserves reinnervated biceps representation after end-to-side transfer. Copyright © 2017 by the Congress of Neurological Surgeons

Plasticity and alterations of trunk motor cortex following spinal cord injury and non-stepping robot and treadmill training.

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Oza, Chintan S; Giszter, Simon F

2014-06-01

Spinal cord injury (SCI) induces significant reorganization in the sensorimotor cortex. Trunk motor control is crucial for postural stability and propulsion after low thoracic SCI and several rehabilitative strategies are aimed at trunk stability and control. However little is known about the effect of SCI and rehabilitation training on trunk motor representations and their plasticity in the cortex. Here, we used intracortical microstimulation to examine the motor cortex representations of the trunk in relation to other representations in three groups of chronic adult complete low thoracic SCI rats: chronic untrained, treadmill trained (but 'non-stepping') and robot assisted treadmill trained (but 'non-stepping') and compared with a group of normal rats. Our results demonstrate extensive and significant reorganization of the trunk motor cortex after chronic adult SCI which includes (1) expansion and rostral displacement of trunk motor representations in the cortex, with the greatest significant increase observed for rostral (to injury) trunk, and slight but significant increase of motor representation for caudal (to injury) trunk at low thoracic levels in all spinalized rats; (2) significant changes in coactivation and the synergy representation (or map overlap) between different trunk muscles and between trunk and forelimb. No significant differences were observed between the groups of transected rats for the majority of the comparisons. However, (3) the treadmill and robot-treadmill trained groups of rats showed a further small but significant rostral migration of the trunk representations, beyond the shift caused by transection alone. We conclude that SCI induces a significant reorganization of the trunk motor cortex, which is not qualitatively altered by non-stepping treadmill training or non-stepping robot assisted treadmill training, but is shifted further from normal topography by the training. This shift may potentially make subsequent rehabilitation with

Adaptive changes in the motor cortex during and after longterm forelimb immobilization in adult rats.

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Viaro, Riccardo; Budri, Mirco; Parmiani, Pierantonio; Franchi, Gianfranco

2014-05-15

Experimental and clinical studies have attempted to evaluate the changes in cortical activity seen after immobilization-induced longterm sensorimotor restriction, although results remain controversial. We used intracortical microstimulation (ICMS), which provides topographic movement representations of the motor areas in both hemispheres with optimal spatial characterization, combined with behavioural testing to unravel the effects of limb immobilization on movement representations in the rat primary motor cortex (M1). Unilateral forelimb immobilization in rats was achieved by casting the entire limb and leaving the cast in place for 15 or 30 days. Changes in M1 were bilateral and specific for the forelimb area, but were stronger in the contralateral-to-cast hemisphere. The threshold current required to evoke forelimb movement increased progressively over the period in cast, whereas the forelimb area size decreased and the non-excitable area size increased. Casting resulted in a redistribution of proximal/distal movement representations: proximal forelimb representation increased, whereas distal representation decreased in size. ICMS after cast removal showed a reversal of changes, which remained partial at 15 days. Local application of the GABAA-antagonist bicuculline revealed the impairment of cortical synaptic connectivity in the forelimb area during the period of cast and for up to 15 days after cast removal. Six days of rehabilitation using a rotarod performance protocol after cast removal did not advance map size normalization in the contralateral-to-cast M1 and enabled the cortical output towards the distal forelimb only in sites that had maintained their excitability. These results are relevant to our understanding of adult M1 plasticity during and after sensorimotor deprivation, and to new approaches to conditions that require longterm limb immobilization. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Stimulation of the basal and central amygdala in the mustached bat triggers echolocation and agonistic vocalizations within multimodal output.

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Ma, Jie; Kanwal, Jagmeet S

2014-01-01

The neural substrate for the perception of vocalizations is relatively well described, but how their timing and specificity are tightly coupled with accompanying physiological changes and context-appropriate behaviors remains unresolved. We hypothesized that temporally integrated vocal and emotive responses, especially the expression of fear, vigilance and aggression, originate within the amygdala. To test this hypothesis, we performed electrical microstimulation at 461 highly restricted loci within the basal and central amygdala in awake mustached bats. At a subset of these sites, high frequency stimulation with weak constant current pulses presented at near-threshold levels triggered vocalization of either echolocation pulses or social calls. At the vast majority of locations, microstimulation produced a constellation of changes in autonomic and somatomotor outputs. These changes included widespread co-activation of significant tachycardia and hyperventilation and/or rhythmic ear pinna movements (PMs). In a few locations, responses were constrained to vocalization and/or PMs despite increases in the intensity of stimulation. The probability of eliciting echolocation pulses vs. social calls decreased in a medial-posterior to anterolateral direction within the centrobasal amygdala. Microinjections of kainic acid (KA) at stimulation sites confirmed the contribution of cellular activity rather than fibers-of-passage in the control of multimodal outputs. The results suggest that localized clusters of neurons may simultaneously modulate the activity of multiple central pattern generators (CPGs) present within the brainstem.

Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys.

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Fleuriet, Jérome; Walton, Mark M G; Ono, Seiji; Mustari, Michael J

2016-06-01

Visually guided saccades are disconjugate in human and nonhuman strabismic primates. The superior colliculus (SC) is a region of the brain topographically organized in visual and motor maps where the saccade goal is spatially coded. The present study was designed to investigate if a site of stimulation on the topographic motor map was evoking similar or different saccade vectors for each eye. We used microelectrical stimulation (MS) of the SC in two strabismic (one esotrope and one exotrope) and two control macaques under binocular and monocular viewing conditions. We compared the saccade amplitudes and directions for each SC site and each condition independently of the fixating eye and then between each fixating eye. A comparison with disconjugacies of visually guided saccades was also performed. We observed different saccade vectors for the two eyes in strabismic monkeys, but conjugate saccades in normal monkeys. Evoked saccade vectors for the left eye when that eye was fixating the target were different from those of the right eye when it was fixating. The disconjugacies evoked by the MS were not identical but similar to those observed for visually guided saccades especially for the dominant eye. Our results suggest that, in strabismus, the saccade generator does not interpret activation of a single location of the SC as the same desired displacement for each eye. This finding is important for advancing understanding of the development of neural circuits in strabismus. French Abstract.

Coordination of eye and head components of movements evoked by stimulation of the paramedian pontine reticular formation

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Barton, Ellen J.; Sparks, David L.

2013-01-01

Constant frequency microstimulation of the paramedian pontine reticular formation (PPRF) in head-restrained monkeys evokes a constant velocity eye movement. Since the PPRF receives significant projections from structures that control coordinated eye-head movements, we asked whether stimulation of the pontine reticular formation in the head-unrestrained animal generates a combined eye-head movement or only an eye movement. Microstimulation of most sites yielded a constant-velocity gaze shift executed as a coordinated eye-head movement, although eye-only movements were evoked from some sites. The eye and head contributions to the stimulation-evoked movements varied across stimulation sites and were drastically different from the lawful relationship observed for visually-guided gaze shifts. These results indicate that the microstimulation activated elements that issued movement commands to the extraocular and, for most sites, neck motoneurons. In addition, the stimulation-evoked changes in gaze were similar in the head-restrained and head-unrestrained conditions despite the assortment of eye and head contributions, suggesting that the vestibuloocular reflex (VOR) gain must be near unity during the coordinated eye-head movements evoked by stimulation of the PPRF. These findings contrast the attenuation of VOR gain associated with visually-guided gaze shifts and suggest that the vestibulo-ocular pathway processes volitional and PPRF stimulation-evoked gaze shifts differently. PMID:18458891

Use of functional near-infrared spectroscopy to evaluate the effects of anodal transcranial direct current stimulation on brain connectivity in motor-related cortex

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Yan, Jiaqing; Wei, Yun; Wang, Yinghua; Xu, Gang; Li, Zheng; Li, Xiaoli

2015-04-01

Transcranial direct current stimulation (tDCS) is a noninvasive, safe and convenient neuro-modulatory technique in neurological rehabilitation, treatment, and other aspects of brain disorders. However, evaluating the effects of tDCS is still difficult. We aimed to evaluate the effects of tDCS using hemodynamic changes using functional near-infrared spectroscopy (fNIRS). Five healthy participants were employed and anodal tDCS was applied to the left motor-related cortex, with cathodes positioned on the right dorsolateral supraorbital area. fNIRS data were collected from the right motor-related area at the same time. Functional connectivity (FC) between intracortical regions was calculated between fNIRS channels using a minimum variance distortion-less response magnitude squared coherence (MVDR-MSC) method. The levels of Oxy-HbO change and the FC between channels during the prestimulation, stimulation, and poststimulation stages were compared. Results showed no significant level difference, but the FC measured by MVDR-MSC significantly decreased during tDCS compared with pre-tDCS and post-tDCS, although the FC difference between pre-tDCS and post-tDCS was not significant. We conclude that coherence calculated from resting state fNIRS may be a useful tool for evaluating the effects of anodal tDCS and optimizing parameters for tDCS application.

Stimulation of the Basal and Central Amygdala in the Mustached Bat Triggers Echolocation and Agonistic Vocalizations within Multimodal Output

Directory of Open Access Journals (Sweden)

Jie eMa

2014-03-01

Full Text Available The neural substrate for the perception of vocalization is relatively well described, but we know much less about how the timing and specificity of vocalizations is tightly coupled with audiovocal communication behavior. In many vocal species, well-timed vocalizations accompany fear, vigilance and aggression. These emotive responses likely originate within the amygdala and other limbic structures, but the organization of motor outputs for triggering species-appropriate behaviors remains unclear. We performed electrical microstimulation at 461 highly restricted loci within the basal and central amygdala in awake mustached bats. At a subset of these sites, high frequency stimulation with weak constant current pulses presented at near-threshold levels triggered vocalization of either echolocation pulses or social calls. At the vast majority of locations, microstimulation produced a constellation of changes in autonomic and somatomotor outputs. These changes included widespread co-activation of significant tachycardia and hyperventilation and/or rhythmic ear pinna movements. In a few locations, responses were constrained to vocalization and/or pinna movements despite increases in the intensity of stimulation. The probability of eliciting echolocation pulses versus social calls decreased in a medial-posterior to anterolateral direction within the centrobasal amygdala. Microinjections of kainic acid at stimulation sites confirmed the contribution of cellular activity rather than fibers-of-passage in the control of multimodal outputs. The results suggest that multimodal clusters of neurons may simultaneously modulate the activity of multiple central pattern generators present within the brainstem.

Modulation of motor cortex excitability by paired peripheral and transcranial magnetic stimulation.

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Kumru, Hatice; Albu, Sergiu; Rothwell, John; Leon, Daniel; Flores, Cecilia; Opisso, Eloy; Tormos, Josep Maria; Valls-Sole, Josep

2017-10-01

Repetitive application of peripheral electrical stimuli paired with transcranial magnetic stimulation (rTMS) of M1 cortex at low frequency, known as paired associative stimulation (PAS), is an effective method to induce motor cortex plasticity in humans. Here we investigated the effects of repetitive peripheral magnetic stimulation (rPMS) combined with low frequency rTMS ('magnetic-PAS') on intracortical and corticospinal excitability and whether those changes were widespread or circumscribed to the cortical area controlling the stimulated muscle. Eleven healthy subjects underwent three 10min stimulation sessions: 10HzrPMS alone, applied in trains of 5 stimuli every 10s (60 trains) on the extensor carpi radialis (ECR) muscle; rTMS alone at an intensity 120% of ECR threshold, applied over motor cortex of ECR and at a frequency of 0.1Hz (60 stimuli) and magnetic PAS, i.e., paired rPMS and rTMS. We recorded motor evoked potentials (MEPs) from ECR and first dorsal interosseous (FDI) muscles. We measured resting motor threshold, motor evoked potentials (MEP) amplitude at 120% of RMT, short intracortical inhibition (SICI) at interstimulus interval (ISI) of 2ms and intracortical facilitation (ICF) at an ISI of 15ms before and immediately after each intervention. Magnetic-PAS , but not rTMS or rPMS applied separately, increased MEP amplitude and reduced short intracortical inhibition in ECR but not in FDI muscle. Magnetic-PAS can increase corticospinal excitability and reduce intracortical inhibition. The effects may be specific for the area of cortical representation of the stimulated muscle. Application of magnetic-PAS might be relevant for motor rehabilitation. Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.

Transcranial magnetic stimulation probes the excitability of the primary motor cortex: A framework to account for the facilitating effects of acute whole-body exercise on motor processes

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Karen Davranche

2015-03-01

Full Text Available The effects of exercise on decision-making performance have been studied using a wide variety of cognitive tasks and exercise interventions. Although the current literature supports a beneficial influence of acute exercise on cognitive performance, the mechanisms underlying this phenomenon have not yet been elucidated. We review studies that used single-pulse transcranial magnetic stimulation (TMS to probe the excitability of motor structures during whole-body exercise and present a framework to account for the facilitating effects of acute exercise on motor processes. Recent results suggest that, even in the absence of fatigue, the increase in corticospinal excitability classically reported during submaximal and exhausting exercises may be accompanied by a reduction in intracortical inhibition. We propose that reduced intracortical inhibition elicits an adaptive central mechanism that counteracts the progressive reduction in muscle responsiveness caused by peripheral fatigue. Such a reduction would render the motor cortex more sensitive to upstream influences, thus causing increased corticospinal excitability. Furthermore, reduction of intracortical inhibition may account for the more efficient descending drive and for the improvement of reaction time performance during exercise. The adaptive modulation in intracortical inhibition could be implemented through a general increase in reticular activation that would further account for enhanced sensory sensitivity.

Abnormal interhemispheric connectivity in male psychopathic offenders.

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Hoppenbrouwers, Sylco S; De Jesus, Danilo R; Sun, Yinming; Stirpe, Tania; Hofman, Dennis; McMaster, Jeff; Hughes, Ginny; Daskalakis, Zafiris J; Schutter, Dennis J L G

2014-01-01

Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking. We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity. We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere. The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders. To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders.

Differential behavioral and physiological effects of anodal transcranial direct current stimulation in healthy adults of younger and older age

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Heise, Kirstin-Friederike; Niehoff, Martina; Feldheim, J.-F.; Liuzzi, Gianpiero; Gerloff, Christian; Hummel, Friedhelm C.

2014-01-01

Changes in γ-aminobutyric acid (GABA) mediated synaptic transmission have been associated with age-related motor and cognitive functional decline. Since anodal transcranial direct current stimulation (atDCS) has been suggested to target cortical GABAergic inhibitory interneurons, its potential for the treatment of deficient inhibitory activity and functional decline is being increasingly discussed. Therefore, after-effects of a single session of atDCS on resting-state and event-related short-interval intracortical inhibition (SICI) as evaluated with double-pulse TMS and dexterous manual performance were examined using a sham-controlled cross-over design in a sample of older and younger participants. The atDCS effect on resting-state inhibition differed in direction, magnitude, and timing, i.e., late relative release of inhibition in the younger and early relative increase in inhibition in the older. More pronounced release of event-related inhibition after atDCS was exclusively seen in the older. Event-related modulation of inhibition prior to stimulation predicted the magnitude of atDCS-induced effects on resting-state inhibition. Specifically, older participants with high modulatory capacity showed a disinhibitory effect comparable to the younger. Beneficial effects on behavior were mainly seen in the older and in tasks requiring higher dexterity, no clear association with physiological changes was found. Differential effects of atDCS on SICI, discussed to reflect GABAergic inhibition at the level of the primary motor cortex, might be distinct in older and younger participants depending on the functional integrity of the underlying neural network. Older participants with preserved modulatory capacity, i.e., a physiologically “young” motor network, were more likely to show a disinhibitory effect of atDCS. These results favor individually tailored application of tDCS with respect to specific target groups. PMID:25071555

BDNF-Val66Met-Polymorphism Impact on Cortical Plasticity in Schizophrenia Patients: A Proof-of-Concept Study

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Nitsche, Michael A.; Wobrock, Thomas; Bunse, Tilmann; Rein, Bettina; Herrmann, Maximiliane; Schmitt, Andrea; Nieratschker, Vanessa; Witt, Stephanie H.; Rietschel, Marcella; Falkai, Peter; Hasan, Alkomiet

2015-01-01

Background: Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients. Methods: Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied. Results: Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS. Conclusions: These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory

Delta-9-tetrahydrocannabinol (THC) affects forelimb motor map expression but has little effect on skilled and unskilled behavior.

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Scullion, K; Guy, A R; Singleton, A; Spanswick, S C; Hill, M N; Teskey, G C

2016-04-05

It has previously been shown in rats that acute administration of delta-9-tetrahydrocannabinol (THC) exerts a dose-dependent effect on simple locomotor activity, with low doses of THC causing hyper-locomotion and high doses causing hypo-locomotion. However the effect of acute THC administration on cortical movement representations (motor maps) and skilled learned movements is completely unknown. It is important to determine the effects of THC on motor maps and skilled learned behaviors because behaviors like driving place people at a heightened risk. Three doses of THC were used in the current study: 0.2mg/kg, 1.0mg/kg and 2.5mg/kg representing the approximate range of the low to high levels of available THC one would consume from recreational use of cannabis. Acute peripheral administration of THC to drug naïve rats resulted in dose-dependent alterations in motor map expression using high resolution short duration intracortical microstimulation (SD-ICMS). THC at 0.2mg/kg decreased movement thresholds and increased motor map size, while 1.0mg/kg had the opposite effect, and 2.5mg/kg had an even more dramatic effect. Deriving complex movement maps using long duration (LD)-ICMS at 1.0mg/kg resulted in fewer complex movements. Dosages of 1.0mg/kg and 2.5mg/kg THC reduced the number of reach attempts but did not affect percentage of success or the kinetics of reaching on the single pellet skilled reaching task. Rats that received 2.5mg/kg THC did show an increase in latency of forelimb removal on the bar task, while dose-dependent effects of THC on unskilled locomotor activity using the rotorod and horizontal ladder tasks were not observed. Rats may be employing compensatory strategies after receiving THC, which may account for the robust changes in motor map expression but moderate effects on behavior. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Unilateral nasal obstruction affects motor representation development within the face primary motor cortex in growing rats.

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Abe, Yasunori; Kato, Chiho; Uchima Koecklin, Karin Harumi; Okihara, Hidemasa; Ishida, Takayoshi; Fujita, Koichi; Yabushita, Tadachika; Kokai, Satoshi; Ono, Takashi

2017-06-01

Postnatal growth is influenced by genetic and environmental factors. Nasal obstruction during growth alters the electromyographic activity of orofacial muscles. The facial primary motor area represents muscles of the tongue and jaw, which are essential in regulating orofacial motor functions, including chewing and jaw opening. This study aimed to evaluate the effect of chronic unilateral nasal obstruction during growth on the motor representations within the face primary motor cortex (M1). Seventy-two 6-day-old male Wistar rats were randomly divided into control ( n = 36) and experimental ( n = 36) groups. Rats in the experimental group underwent unilateral nasal obstruction after cauterization of the external nostril at 8 days of age. Intracortical microstimulation (ICMS) mapping was performed when the rats were 5, 7, 9, and 11 wk old in control and experimental groups ( n = 9 per group per time point). Repeated-measures multivariate ANOVA was used for intergroup and intragroup statistical comparisons. In the control and experimental groups, the total number of positive ICMS sites for the genioglossus and anterior digastric muscles was significantly higher at 5, 7, and 9 wk, but there was no significant difference between 9 and 11 wk of age. Moreover, the total number of positive ICMS sites was significantly smaller in the experimental group than in the control at each age. It is possible that nasal obstruction induced the initial changes in orofacial motor behavior in response to the altered respiratory pattern, which eventually contributed to face-M1 neuroplasticity. NEW & NOTEWORTHY Unilateral nasal obstruction in rats during growth periods induced changes in arterial oxygen saturation (SpO 2 ) and altered development of the motor representation within the face primary cortex. Unilateral nasal obstruction occurring during growth periods may greatly affect not only respiratory function but also craniofacial function in rats. Nasal obstruction should be treated

Transcranial magnetic stimulation distinguishes Alzheimer disease from frontotemporal dementia.

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Benussi, Alberto; Di Lorenzo, Francesco; Dell'Era, Valentina; Cosseddu, Maura; Alberici, Antonella; Caratozzolo, Salvatore; Cotelli, Maria Sofia; Micheli, Anna; Rozzini, Luca; Depari, Alessandro; Flammini, Alessandra; Ponzo, Viviana; Martorana, Alessandro; Caltagirone, Carlo; Padovani, Alessandro; Koch, Giacomo; Borroni, Barbara

2017-08-15

To determine whether a transcranial magnetic stimulation (TMS) multiparadigm approach can be used to distinguish Alzheimer disease (AD) from frontotemporal dementia (FTD). Paired-pulse TMS was used to investigate short-interval intracortical inhibition (SICI) and facilitation (ICF), long-interval intracortical inhibition, and short-latency afferent inhibition (SAI) to measure the activity of different intracortical circuits in patients with AD, patients with FTD, and healthy controls (HC). The primary outcome measures were sensitivity and specificity of TMS measures, derived from receiver operating curve analysis. A total of 175 participants met the inclusion criteria. We diagnosed 79 patients with AD, 64 patients with FTD, and 32 HC. We found that while patients with AD are characterized by a specific impairment of SAI, FTD shows a remarkable dysfunction of SICI-ICF intracortical circuits. With the use of the best indexes, TMS differentiated FTD from AD with a sensitivity of 91.8% and specificity of 88.6%, AD from HC with a sensitivity of 84.8% and specificity of 90.6%, and FTD from HC with a sensitivity of 90.2% and specificity of 78.1%. These results were confirmed in patients with mild disease. TMS is a noninvasive procedure that reliably distinguishes AD from FTD and HC and, if these findings are replicated in larger studies, could represent a useful additional diagnostic tool for clinical practice. This study provides Class III evidence that TMS measures can distinguish patients with AD from those with FTD. © 2017 American Academy of Neurology.

Effects of theta burst stimulation on motor cortex excitability in Parkinson's disease.

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Zamir, Orit; Gunraj, Carolyn; Ni, Zhen; Mazzella, Filomena; Chen, Robert

2012-04-01

Long-term potentiation (LTP)-like plasticity induced by paired associative stimulation (PAS) is impaired in Parkinson's disease (PD). Intermittent theta burst stimulation (iTBS) is another rTMS protocol that produces LTP-like effects and increases cortical excitability but its effects are independent of afferent input. The aim of the present study was to examine the effects of iTBS on cortical excitability in PD. iTBS was applied to the motor cortex in 10 healthy subjects and 12 PD patients ON and OFF dopaminergic medications. Motor evoked potential (MEP) before and for 60 min after iTBS were used to examine the changes in cortical excitability induced by iTBS. Paired-pulse TMS was used to test whether intracortical circuits, including short interval intracortical inhibition, intracortical facilitation, short and long latency afferent inhibition, were modulated by iTBS. After iTBS, the control, PD ON and OFF groups had similar increases in MEP amplitude compared to baseline over the course of 60 min. Changes in intracortical circuits induced by iTBS were also similar for the different groups. iTBS produced similar effects on cortical excitability for PD patients and controls. Spike-timing dependent heterosynaptic LTP-like plasticity induced by PAS may be more impaired in PD than frequency dependent homosynaptic LTP-like plasticity induced by iTBS. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Cortical influences drive amyotrophic lateral sclerosis.

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Eisen, Andrew; Braak, Heiko; Del Tredici, Kelly; Lemon, Roger; Ludolph, Albert C; Kiernan, Matthew C

2017-11-01

The early motor manifestations of sporadic amyotrophic lateral sclerosis (ALS), while rarely documented, reflect failure of adaptive complex motor skills. The development of these skills correlates with progressive evolution of a direct corticomotoneuronal system that is unique to primates and markedly enhanced in humans. The failure of this system in ALS may translate into the split hand presentation, gait disturbance, split leg syndrome and bulbar symptomatology related to vocalisation and breathing, and possibly diffuse fasciculation, characteristic of ALS. Clinical neurophysiology of the brain employing transcranial magnetic stimulation has convincingly demonstrated a presymptomatic reduction or absence of short interval intracortical inhibition, accompanied by increased intracortical facilitation, indicating cortical hyperexcitability. The hallmark of the TDP-43 pathological signature of sporadic ALS is restricted to cortical areas as well as to subcortical nuclei that are under the direct control of corticofugal projections. This provides anatomical support that the origins of the TDP-43 pathology reside in the cerebral cortex itself, secondarily in corticofugal fibres and the subcortical targets with which they make monosynaptic connections. The latter feature explains the multisystem degeneration that characterises ALS. Consideration of ALS as a primary neurodegenerative disorder of the human brain may incorporate concepts of prion-like spread at synaptic terminals of corticofugal axons. Further, such a concept could explain the recognised widespread imaging abnormalities of the ALS neocortex and the accepted relationship between ALS and frontotemporal dementia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Intracortical Interactions in Visual Processing

Science.gov (United States)

1986-05-01

demonstrated tolerance. End-tidal CO- was then brought below 3’S% and a craniotomy and durectomy performed over each nemisphere. Halothane was discontinued...Kanizsa, 1976) reported by von der Heydt, Peterhans £ Baumgartner (I98A) in awake monkey Area I8. The existence of such facilitation had been suggested

GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans.

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Nitsche, Michael A; Liebetanz, David; Schlitterlau, Anett; Henschke, Undine; Fricke, Kristina; Frommann, Kai; Lang, Nicolas; Henning, Stefan; Paulus, Walter; Tergau, Frithjof

2004-05-01

Weak transcranial DC stimulation (tDCS) of the human motor cortex results in excitability shifts during and after the end of stimulation, which are most probably localized intracortically. Anodal stimulation enhances excitability, whereas cathodal stimulation reduces it. Although the after-effects of tDCS are NMDA receptor-dependent, nothing is known about the involvement of additional receptors. Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after-effects elicited by anodal tDCS. Administration of the GABA(A) receptor agonist lorazepam resulted in a delayed, but then enhanced and prolonged anodal tDCS-induced excitability elevation. The initial absence of an excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS-generated intracortical diminution of inhibition and enhancement of facilitation, which occurs without pharmacological intervention. The reasons for the late-occurring excitability enhancement remain unclear. Because intracortical inhibition and facilitation are not changed in this phase compared with pre-tDCS values, excitability changes originating from remote cortical or subcortical areas could be involved.

An artificial arm/hand system with a haptic sensory function using electric stimulation of peripheral sensory nerve fibers.

Science.gov (United States)

Mabuchi, Kunihiko

2013-01-01

We are currently developing an artificial arm/hand system which is capable of sensing stimuli and then transferring these stimuli to users as somatic sensations. Presently, we are evoking the virtual somatic sensations by electrically stimulating a sensory nerve fiber which innervates a single mechanoreceptor unit at the target area; this is done using a tungsten microelectrode that was percutaneously inserted into the use's peripheral nerve (a microstimulation method). The artificial arm/hand system is composed of a robot hand equipped with a pressure sensor system on its fingers. The sensor system detects mechanical stimuli, which are transferred to the user by means of the microstimulation method so that the user experiences the stimuli as the corresponding somatic sensations. In trials, the system worked satisfactorily and there was a good correlation between the pressure applied to the pressure sensors on the robot fingers and the subjective intensities of the evoked pressure sensations.

Transcranial magnetic stimulation reveals cortical hyperexcitability in episodic cluster headache.

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Cosentino, Guiseppe; Brighina, Filippo; Brancato, Sara; Valentino, Francesca; Indovino, Serena; Fierro, Brigida

2015-01-01

Evidence shows involvement of the cerebral cortex in the pathophysiology of cluster headache (CH). Here we investigated cortical excitability in episodic CH patients by using transcranial magnetic stimulation. In 25 patients with episodic CH and 13 healthy subjects we evaluated the motor cortical response to single-pulse (ie, motor threshold, input-output curves, cortical silent period) and paired-pulse (ie, intracortical facilitation, short intracortical inhibition) transcranial magnetic stimulation in both hemispheres. Thirteen patients were evaluated outside bout and the remaining 12 patients inside bout. Our results showed increased slope of the input-output curves after stimulation of both hemispheres in patients outside bout and in the hemisphere contralateral to the headache side in patients inside bout. Increased intracortical facilitation was observed in the hemisphere ipsilateral to the headache side in patients evaluated both outside and inside bout; reduced short intracortical inhibition was observed in patients inside bout ipsilateral to the side of pain. In conclusion, we provide evidence of increased cortical excitability in episodic CH both outside and inside bout, especially in the hemisphere ipsilateral to the side of headache attacks. Our results suggest that an abnormal regulation of cortical excitability could be involved in the pathophysiology of CH. We investigated cortical excitability in episodic cluster headache by using transcranial magnetic stimulation, providing evidence of cortical hyperexcitability in patients both inside and outside bout. We suggest that an abnormal state of cortical excitability could be involved in the pathophysiology of the disease. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Lateral Spread of Orientation Selectivity in V1 is Controlled by Intracortical Cooperativity

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Chavane, Frédéric; Sharon, Dahlia; Jancke, Dirk; Marre, Olivier; Frégnac, Yves; Grinvald, Amiram

2011-01-01

Neurons in the primary visual cortex receive subliminal information originating from the periphery of their receptive fields (RF) through a variety of cortical connections. In the cat primary visual cortex, long-range horizontal axons have been reported to preferentially bind to distant columns of similar orientation preferences, whereas feedback connections from higher visual areas provide a more diverse functional input. To understand the role of these lateral interactions, it is crucial to characterize their effective functional connectivity and tuning properties. However, the overall functional impact of cortical lateral connections, whatever their anatomical origin, is unknown since it has never been directly characterized. Using direct measurements of postsynaptic integration in cat areas 17 and 18, we performed multi-scale assessments of the functional impact of visually driven lateral networks. Voltage-sensitive dye imaging showed that local oriented stimuli evoke an orientation-selective activity that remains confined to the cortical feedforward imprint of the stimulus. Beyond a distance of one hypercolumn, the lateral spread of cortical activity gradually lost its orientation preference approximated as an exponential with a space constant of about 1 mm. Intracellular recordings showed that this loss of orientation selectivity arises from the diversity of converging synaptic input patterns originating from outside the classical RF. In contrast, when the stimulus size was increased, we observed orientation-selective spread of activation beyond the feedforward imprint. We conclude that stimulus-induced cooperativity enhances the long-range orientation-selective spread. PMID:21629708

Huperzine A prophylaxis against pentylenetetrazole-induced seizures in rats is associated with increased cortical inhibition.

Science.gov (United States)

Gersner, R; Ekstein, D; Dhamne, S C; Schachter, S C; Rotenberg, A

2015-11-01

Huperzine A (HupA) is a naturally occurring compound found in the firmoss Huperzia serrata. While HupA is a potent acetylcholinesterase inhibitor, its full pharmacologic profile is incompletely described. Since previous works suggested a capacity for HupA to prophylax against seizures, we tested the HupA antiepileptic potential in pentylenetetrazole (PTZ) rat epilepsy model and explored its mechanism of action by spectral EEG analysis and by paired-pulse transcranial magnetic stimulation (ppTMS), a measure of GABA-mediated intracortical inhibition. We tested whether HupA suppresses seizures in the rat PTZ acute seizure model, and quantified latency to first myoclonus and to generalized tonic-clonic seizure, and spike frequency on EEG. Additionally, we measured power in the EEG gamma frequency band which is associated with GABAergic cortical interneuron activation. Then, as a step toward further examining the HupA antiepileptic mechanism of action, we tested long-interval intracortical inhibition (LICI) using ppTMS coupled with electromyography to assess whether HupA augments GABA-mediated paired-pulse inhibition of the motor evoked potential. We also tested whether the HupA effect on paired-pulse inhibition was central or peripheral by comparison of outcomes following administration of HupA or the peripheral acetylcholinesterase inhibitor pyridostigmine. We also tested whether the HupA effect was dependent on central muscarinic or GABAA receptors by co-administration of HupA and atropine or PTZ, respectively. In tests of antiepileptic potential, HupA suppressed seizures and epileptic spikes on EEG. Spectral EEG analysis also revealed enhanced gamma frequency band power with HupA treatment. By ppTMS we found that HupA increases intracortical inhibition and blocks PTZ-induced cortical excitation. Atropine co-administration with HupA did not alter HupA-induced intracortical inhibition suggesting independent of muscarinic acetylcholine receptors mechanism in this model

Area 5 influences excitability within the primary motor cortex in humans.

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Azra Premji

Full Text Available In non-human primates, Brodmann's area 5 (BA 5 has direct connectivity with primary motor cortex (M1, is largely dedicated to the representation of the hand and may have evolved with the ability to perform skilled hand movement. Less is known about human BA 5 and its interaction with M1 neural circuits related to hand control. The present study examines the influence of BA 5 on excitatory and inhibitory neural circuitry within M1 bilaterally before and after continuous (cTBS, intermittent (iTBS, and sham theta-burst stimulation (sham TBS over left hemisphere BA 5. Using single and paired-pulse TMS, measurements of motor evoked potentials (MEPs, short interval intracortical inhibition (SICI, and intracortical facilitation (ICF were quantified for the representation of the first dorsal interosseous muscle. Results indicate that cTBS over BA 5 influences M1 excitability such that MEP amplitudes are increased bilaterally for up to one hour. ITBS over BA 5 results in an increase in MEP amplitude contralateral to stimulation with a delayed onset that persists up to one hour. SICI and ICF were unaltered following TBS over BA 5. Similarly, F-wave amplitude and latency were unaltered following cTBS over BA 5. The data suggest that BA 5 alters M1 output directed to the hand by influencing corticospinal neurons and not interneurons that mediate SICI or ICF circuitry. Targeting BA 5 via cTBS and iTBS is a novel mechanism to powerfully modulate activity within M1 and may provide an avenue for investigating hand control in healthy populations and modifying impaired hand function in clinical populations.

Leg Regrowth in Blaberus discoidalis (Discoid Cockroach) following Limb Autotomy versus Limb Severance and Relevance to Neurophysiology Experiments

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Marzullo, Timothy C.

2016-01-01

Background Many insects can regenerate limbs, but less is known about the regrowth process with regard to limb injury type. As part of our neurophysiology education experiments involving the removal of a cockroach leg, 1) the ability of Blaberus discoidalis cockroaches to regenerate a metathoracic leg was examined following autotomy at the femur/trochanter joint versus severance via a transverse coxa-cut, and 2) the neurophysiology of the detached legs with regard to leg removal type was studied by measuring spike firing rate and microstimulation movement thresholds. Leg Regrowth Results First appearance of leg regrowth was after 5 weeks in the autotomy group and 12 weeks in the coxa-cut group. Moreover, regenerated legs in the autotomy group were 72% of full size on first appearance, significantly larger (pbarbs, and a 10% higher electrical microstimulation threshold for movement. Summary It is recommended that neurophysiology experiments on cockroach legs remove the limb at autotomy joints instead of coxa cuts, as the leg regenerates significantly faster when autotomized and does not detract from the neurophysiology educational content. PMID:26824931

Whole-body water flow stimulation to the lower limbs modulates excitability of primary motor cortical regions innervating the hands: a transcranial magnetic stimulation study.

Directory of Open Access Journals (Sweden)

Daisuke Sato

Full Text Available Whole-body water immersion (WI has been reported to change sensorimotor integration. However, primary motor cortical excitability is not affected by low-intensity afferent input. Here we explored the effects of whole-body WI and water flow stimulation (WF on corticospinal excitability and intracortical circuits. Eight healthy subjects participated in this study. We measured the amplitude of motor-evoked potentials (MEPs produced by single transcranial magnetic stimulation (TMS pulses and examined conditioned MEP amplitudes by paired-pulse TMS. We evaluated short-interval intracortical inhibition (SICI and intracortical facilitation (ICF using the paired-TMS technique before and after 15-min intervention periods. Two interventions used were whole-body WI with water flow to the lower limbs (whole-body WF and whole-body WI without water flow to the lower limbs (whole-body WI. The experimental sequence included a baseline TMS assessment (T0, intervention for 15 min, a second TMS assessment immediately after intervention (T1, a 10 min resting period, a third TMS assessment (T2, a 10 min resting period, a fourth TMS assessment (T3, a 10 min resting period, and the final TMS assessment (T4. SICI and ICF were evaluated using a conditioning stimulus of 90% active motor threshold and a test stimulus adjusted to produce MEPs of approximately 1-1.2 mV, and were tested at intrastimulus intervals of 3 and 10 ms, respectively. Whole-body WF significantly increased MEP amplitude by single-pulse TMS and led to a decrease in SICI in the contralateral motor cortex at T1, T2 and T3. Whole-body WF also induced increased corticospinal excitability and decreased SICI. In contrast, whole-body WI did not change corticospinal excitability or intracortical circuits.

Restoring cortical control of functional movement in a human with quadriplegia.

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Bouton, Chad E; Shaikhouni, Ammar; Annetta, Nicholas V; Bockbrader, Marcia A; Friedenberg, David A; Nielson, Dylan M; Sharma, Gaurav; Sederberg, Per B; Glenn, Bradley C; Mysiw, W Jerry; Morgan, Austin G; Deogaonkar, Milind; Rezai, Ali R

2016-05-12

Millions of people worldwide suffer from diseases that lead to paralysis through disruption of signal pathways between the brain and the muscles. Neuroprosthetic devices are designed to restore lost function and could be used to form an electronic 'neural bypass' to circumvent disconnected pathways in the nervous system. It has previously been shown that intracortically recorded signals can be decoded to extract information related to motion, allowing non-human primates and paralysed humans to control computers and robotic arms through imagined movements. In non-human primates, these types of signal have also been used to drive activation of chemically paralysed arm muscles. Here we show that intracortically recorded signals can be linked in real-time to muscle activation to restore movement in a paralysed human. We used a chronically implanted intracortical microelectrode array to record multiunit activity from the motor cortex in a study participant with quadriplegia from cervical spinal cord injury. We applied machine-learning algorithms to decode the neuronal activity and control activation of the participant's forearm muscles through a custom-built high-resolution neuromuscular electrical stimulation system. The system provided isolated finger movements and the participant achieved continuous cortical control of six different wrist and hand motions. Furthermore, he was able to use the system to complete functional tasks relevant to daily living. Clinical assessment showed that, when using the system, his motor impairment improved from the fifth to the sixth cervical (C5-C6) to the seventh cervical to first thoracic (C7-T1) level unilaterally, conferring on him the critical abilities to grasp, manipulate, and release objects. This is the first demonstration to our knowledge of successful control of muscle activation using intracortically recorded signals in a paralysed human. These results have significant implications in advancing neuroprosthetic technology

Whole-body water flow stimulation to the lower limbs modulates excitability of primary motor cortical regions innervating the hands: a transcranial magnetic stimulation study.

Science.gov (United States)

Sato, Daisuke; Yamashiro, Koya; Onishi, Hideaki; Baba, Yasuhiro; Nakazawa, Sho; Shimoyama, Yoshimitsu; Maruyama, Atsuo

2014-01-01

Whole-body water immersion (WI) has been reported to change sensorimotor integration. However, primary motor cortical excitability is not affected by low-intensity afferent input. Here we explored the effects of whole-body WI and water flow stimulation (WF) on corticospinal excitability and intracortical circuits. Eight healthy subjects participated in this study. We measured the amplitude of motor-evoked potentials (MEPs) produced by single transcranial magnetic stimulation (TMS) pulses and examined conditioned MEP amplitudes by paired-pulse TMS. We evaluated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) using the paired-TMS technique before and after 15-min intervention periods. Two interventions used were whole-body WI with water flow to the lower limbs (whole-body WF) and whole-body WI without water flow to the lower limbs (whole-body WI). The experimental sequence included a baseline TMS assessment (T0), intervention for 15 min, a second TMS assessment immediately after intervention (T1), a 10 min resting period, a third TMS assessment (T2), a 10 min resting period, a fourth TMS assessment (T3), a 10 min resting period, and the final TMS assessment (T4). SICI and ICF were evaluated using a conditioning stimulus of 90% active motor threshold and a test stimulus adjusted to produce MEPs of approximately 1-1.2 mV, and were tested at intrastimulus intervals of 3 and 10 ms, respectively. Whole-body WF significantly increased MEP amplitude by single-pulse TMS and led to a decrease in SICI in the contralateral motor cortex at T1, T2 and T3. Whole-body WF also induced increased corticospinal excitability and decreased SICI. In contrast, whole-body WI did not change corticospinal excitability or intracortical circuits.

Rapid Identification of Cortical Motor Areas in Rodents by High-Frequency Automatic Cortical Stimulation and Novel Motor Threshold Algorithm

Directory of Open Access Journals (Sweden)

Mitsuaki Takemi

2017-10-01

Full Text Available Cortical stimulation mapping is a valuable tool to test the functional organization of the motor cortex in both basic neurophysiology (e.g., elucidating the process of motor plasticity and clinical practice (e.g., before resecting brain tumors involving the motor cortex. However, compilation of motor maps based on the motor threshold (MT requires a large number of cortical stimulations and is therefore time consuming. Shortening the time for mapping may reduce stress on the subjects and unveil short-term plasticity mechanisms. In this study, we aimed to establish a cortical stimulation mapping procedure in which the time needed to identify a motor area is reduced to the order of minutes without compromising reliability. We developed an automatic motor mapping system that applies epidural cortical surface stimulations (CSSs through one-by-one of 32 micro-electrocorticographic electrodes while examining the muscles represented in a cortical region. The next stimulus intensity was selected according to previously evoked electromyographic responses in a closed-loop fashion. CSS was repeated at 4 Hz and electromyographic responses were submitted to a newly proposed algorithm estimating the MT with smaller number of stimuli with respect to traditional approaches. The results showed that in all tested rats (n = 12 the motor area maps identified by our novel mapping procedure (novel MT algorithm and 4-Hz CSS significantly correlated with the maps achieved by the conventional MT algorithm with 1-Hz CSS. The reliability of the both mapping methods was very high (intraclass correlation coefficients ≧0.8, while the time needed for the mapping was one-twelfth shorter with the novel method. Furthermore, the motor maps assessed by intracortical microstimulation and the novel CSS mapping procedure in two rats were compared and were also significantly correlated. Our novel mapping procedure that determined a cortical motor area within a few minutes could help

X-ray of osteopathies

International Nuclear Information System (INIS)

Freyschmidt, J.

1980-01-01

Osteoporosis, osteomalcia, fibro-osteoclasia and osteosclerosis are essential reactions to pathologicometabolic processes of the bone. The X-ray film shows precisely which changes have taken place in the bone structure, thus supplying the means for an analysis based on anatomic pathology. These phenomena are discussed in detail, special attention being paid to structural modifications. Attention is also focused on the problems connected with X-ray technology. The value of direct and indirect magnification of the skeleton of the hand for the identification and classification of esteopathies is explained. Phenomena observed in X-ray films, such as enosteal erosion, intracortical longitudinal stripes or tunnelisation, as well as subperiostal absorption, can be of pathognomonic importance for certain osteopathies. (orig.) [de

Silver-Coated Nylon Dressing Plus Active DC Microcurrent for Healing of Autogenous Skin Donor Sites

Science.gov (United States)

2013-08-01

harvested; (c) bloodstream infection, burn-wound infection, hemodynamic instability requiring the use of pressors, or critical illness such as one...or nursing ; (h) sensitivity to silver or nylon; and (i) patient unable to provide written informed consent. Study Device The active microstimulator...the microcurrent stimulator. A research nurse monitored patient compli- ance by recording the amount of time the microcurrent stimulator was

Level of action of cathodal DC polarisation induced inhibition of the human motor cortex.

Science.gov (United States)

Nitsche, Michael A; Nitsche, Maren S; Klein, Cornelia C; Tergau, Frithjof; Rothwell, John C; Paulus, Walter

2003-04-01

To induce prolonged motor cortical excitability reductions by transcranial direct current stimulation in the human. Cathodal direct current stimulation was applied transcranially to the hand area of the human primary motor cortex from 5 to 9 min in separate sessions in twelve healthy subjects. Cortico-spinal excitability was tested by single pulse transcranial magnetic stimulation. Transcranial electrical stimulation and H-reflexes were used to learn about the origin of the excitability changes. Neurone specific enolase was measured before and after the stimulation to prove the safety of the stimulation protocol. Five and 7 min direct current stimulation resulted in motor cortical excitability reductions, which lasted for minutes after the end of stimulation, 9 min stimulation induced after-effects for up to an hour after the end of stimulation, as revealed by transcranial magnetic stimulation. Muscle evoked potentials elicited by transcranial electric stimulation and H-reflexes did not change. Neurone specific enolase concentrations remained stable throughout the experiments. Cathodal transcranial direct current stimulation is capable of inducing prolonged excitability reductions in the human motor cortex non-invasively. These changes are most probably localised intracortically.

Bio-robots automatic navigation with electrical reward stimulation.

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Sun, Chao; Zhang, Xinlu; Zheng, Nenggan; Chen, Weidong; Zheng, Xiaoxiang

2012-01-01

Bio-robots that controlled by outer stimulation through brain computer interface (BCI) suffer from the dependence on realtime guidance of human operators. Current automatic navigation methods for bio-robots focus on the controlling rules to force animals to obey man-made commands, with animals' intelligence ignored. This paper proposes a new method to realize the automatic navigation for bio-robots with electrical micro-stimulation as real-time rewards. Due to the reward-seeking instinct and trial-and-error capability, bio-robot can be steered to keep walking along the right route with rewards and correct its direction spontaneously when rewards are deprived. In navigation experiments, rat-robots learn the controlling methods in short time. The results show that our method simplifies the controlling logic and realizes the automatic navigation for rat-robots successfully. Our work might have significant implication for the further development of bio-robots with hybrid intelligence.

The clinical impact of cerebellar grey matter pathology in multiple sclerosis.

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Alfredo Damasceno

Full Text Available BACKGROUND: The cerebellum is an important site for cortical demyelination in multiple sclerosis, but the functional significance of this finding is not fully understood. OBJECTIVE: To evaluate the clinical and cognitive impact of cerebellar grey-matter pathology in multiple sclerosis patients. METHODS: Forty-two relapsing-remitting multiple sclerosis patients and 30 controls underwent clinical assessment including the Multiple Sclerosis Functional Composite, Expanded Disability Status Scale (EDSS and cerebellar functional system (FS score, and cognitive evaluation, including the Paced Auditory Serial Addition Test (PASAT and the Symbol-Digit Modalities Test (SDMT. Magnetic resonance imaging was performed with a 3T scanner and variables of interest were: brain white-matter and cortical lesion load, cerebellar intracortical and leukocortical lesion volumes, and brain cortical and cerebellar white-matter and grey-matter volumes. RESULTS: After multivariate analysis high burden of cerebellar intracortical lesions was the only predictor for the EDSS (p<0.001, cerebellar FS (p = 0.002, arm function (p = 0.049, and for leg function (p<0.001. Patients with high burden of cerebellar leukocortical lesions had lower PASAT scores (p = 0.013, while patients with greater volumes of cerebellar intracortical lesions had worse SDMT scores (p = 0.015. CONCLUSIONS: Cerebellar grey-matter pathology is widely present and contributes to clinical dysfunction in relapsing-remitting multiple sclerosis patients, independently of brain grey-matter damage.

Signal processing methods for reducing artifacts in microelectrode brain recordings caused by functional electrical stimulation

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Young, D.; Willett, F.; Memberg, W. D.; Murphy, B.; Walter, B.; Sweet, J.; Miller, J.; Hochberg, L. R.; Kirsch, R. F.; Ajiboye, A. B.

2018-04-01

Objective. Functional electrical stimulation (FES) is a promising technology for restoring movement to paralyzed limbs. Intracortical brain-computer interfaces (iBCIs) have enabled intuitive control over virtual and robotic movements, and more recently over upper extremity FES neuroprostheses. However, electrical stimulation of muscles creates artifacts in intracortical microelectrode recordings that could degrade iBCI performance. Here, we investigate methods for reducing the cortically recorded artifacts that result from peripheral electrical stimulation. Approach. One participant in the BrainGate2 pilot clinical trial had two intracortical microelectrode arrays placed in the motor cortex, and thirty-six stimulating intramuscular electrodes placed in the muscles of the contralateral limb. We characterized intracortically recorded electrical artifacts during both intramuscular and surface stimulation. We compared the performance of three artifact reduction methods: blanking, common average reference (CAR) and linear regression reference (LRR), which creates channel-specific reference signals, composed of weighted sums of other channels. Main results. Electrical artifacts resulting from surface stimulation were 175  ×  larger than baseline neural recordings (which were 110 µV peak-to-peak), while intramuscular stimulation artifacts were only 4  ×  larger. The artifact waveforms were highly consistent across electrodes within each array. Application of LRR reduced artifact magnitudes to less than 10 µV and largely preserved the original neural feature values used for decoding. Unmitigated stimulation artifacts decreased iBCI decoding performance, but performance was almost completely recovered using LRR, which outperformed CAR and blanking and extracted useful neural information during stimulation artifact periods. Significance. The LRR method was effective at reducing electrical artifacts resulting from both intramuscular and surface FES, and

A bimodal neurophysiological study of motor control in attention-deficit hyperactivity disorder: a step towards core mechanisms?

Science.gov (United States)

Heinrich, Hartmut; Hoegl, Thomas; Moll, Gunther H; Kratz, Oliver

2014-04-01

Knowledge about the core neural mechanisms of attention-deficit hyperactivity disorder, a pathophysiologically heterogeneous psychiatric disorder starting in childhood, is still limited. Progress may be achieved by combining different methods and levels of investigation. In the present study, we investigated neural mechanisms of motor control in 19 children with attention-deficit hyperactivity disorder (aged 9-14 years) and 21 age-matched typically developing children by relating neural markers of attention and response control (using event-related potentials) and measures of motor excitability/inhibition (evoked by transcranial magnetic stimulation). Thus, an interplay of processes at a subsecond scale could be studied. Using a monetary incentives-based cued Go/No-Go task, parameters that are well-known to be reduced in attention-deficit hyperactivity disorder were analysed: event-related potential components P3 (following cue stimuli; in Go and No-Go trials) and contingent negative variation as well as the transcranial magnetic stimulation-based short-interval intracortical inhibition measured at different latencies in Go and No-Go trials. For patient and control groups, different associations were obtained between performance, event-related potential and transcranial magnetic stimulation measures. In children with attention-deficit hyperactivity disorder, the P3 amplitude in Go trials was not correlated with reaction time measures but with short-interval intracortical inhibition at rest (r=0.56, P=0.01). In No-Go trials, P3 and short-interval intracortical inhibition after inhibiting the response (at 500 ms post-stimulus) were correlated in these children only (r=0.62; P=0.008). A classification rate of 90% was achieved when using short-interval intracortical inhibition (measured shortly before the occurrence of a Go or No-Go stimulus) and the amplitude of the P3 in cue trials as input features in a linear discriminant analysis. Findings indicate deviant neural

Using Arrays of Microelectrodes Implanted in Residual Peripheral Nerves to Provide Dexterous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis

Science.gov (United States)

2017-10-01

systems integration) and the software for offline analysis and real- time decoding and stimulation . They have had experience performing...microstimulation sessions). All experimental sessions were recorded with a video camera, which was time -stamped to the neural recording or stimulation data. 2.5...evoked an ‘electric shock’ like quality, and lower frequencies (1–25 Hz) and longer stimulation times (up to 60 s) could evoke more physiological

Increased use-dependent plasticity in chronic insomnia.

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Salas, Rachel E; Galea, Joseph M; Gamaldo, Alyssa A; Gamaldo, Charlene E; Allen, Richard P; Smith, Michael T; Cantarero, Gabriela; Lam, Barbara D; Celnik, Pablo A

2014-03-01

During normal sleep several neuroplasticity changes occur, some of which are considered to be fundamental to strengthen memories. Given the evidence linking sleep to neuroplasticity, it is conceivable that individuals with chronic sleep disruption, such as patients with chronic insomnia (CI), would experience abnormalities in neuroplastic processes during daytime. Protocols testing use-dependent plasticity (UDP), one of the mechanisms underlying formation of motor memories traces, provide a sensitive measure to assess neuroplasticity in the context of motor training. A well-established transcranial magnetic stimulation (TMS) paradigm was used to evaluate the ability of patients with CI and age-matched good sleeper controls to undergo UDP. We also investigated the effect of insomnia on intracortical motor excitability measures reflecting GABAergic and glutamatergic mechanisms. Human Brain Physiology Laboratory, Johns Hopkins Medical Institutions. We found that patients with CI experienced increased UDP changes relative to controls. This effect was not due to differences in motor training. In addition, patients with CI showed enhanced intracortical facilitation relative to controls, in the absence of changes in intracortical inhibitory measures. This study provides the first evidence that patients with chronic insomnia have an increased plasticity response to physical exercise, possibly due to larger activation of glutamatergic mechanisms. This suggests a heightened state of neuroplasticity, which may reflect a form of maladaptive plasticity, similar to what has been described in dystonia patients and chronic phantom pain after amputation. These results could lead to development of novel treatments for chronic insomnia.

Short-term immobilization influences use-dependent cortical plasticity and fine motor performance.

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Opie, George M; Evans, Alexandra; Ridding, Michael C; Semmler, John G

2016-08-25

Short-term immobilization that reduces muscle use for 8-10h is known to influence cortical excitability and motor performance. However, the mechanisms through which this is achieved, and whether these changes can be used to modify cortical plasticity and motor skill learning, are not known. The purpose of this study was to investigate the influence of short-term immobilization on use-dependent cortical plasticity, motor learning and retention. Twenty-one adults were divided into control and immobilized groups, both of which underwent two experimental sessions on consecutive days. Within each session, transcranial magnetic stimulation (TMS) was used to assess motor-evoked potential (MEP) amplitudes, short- (SICI) and long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF) before and after a grooved pegboard task. Prior to the second training session, the immobilized group underwent 8h of left hand immobilization targeting the index finger, while control subjects were allowed normal limb use. Immobilization produced a reduction in MEP amplitudes, but no change in SICI, LICI or ICF. While motor performance improved for both groups in each session, the level of performance was greater 24-h later in control, but not immobilized subjects. Furthermore, training-related MEP facilitation was greater after, compared with before, immobilization. These results indicate that immobilization can modulate use-dependent plasticity and the retention of motor skills. They also suggest that changes in intracortical excitability are unlikely to contribute to the immobilization-induced modification of cortical excitability. Copyright © 2016. Published by Elsevier Ltd.

A single bout of high-intensity interval training improves motor skill retention in individuals with stroke

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Nepveu, Jean-Francois; Thiel, Alexander; Tang, Ada

2017-01-01

imbalances in GABAA-mediated short-interval intracortical inhibition but changes in other markers of excitability were not statistically significant. The group that performed high-intensity interval training showed a better retention of the motor skill. CONCLUSIONS: The performance of a maximal graded...

Multiple sessions of low-frequency repetitive transcranial magnetic stimulation in focal hand dystonia

DEFF Research Database (Denmark)

Kimberley, Teresa Jacobson; Borich, Michael R; Arora, Sanjeev

2013-01-01

, respectively. Behavioral measures included pen force and velocity during handwriting and subjective report. Results: Multiple-session rTMS strengthened intracortical inhibition causing a prolongation of CSP after 3 days of intervention and pen force was reduced at day 1 and 5, leaving other measures unchanged...

Corticospinal excitability as a biomarker of myofascial pain syndrome

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Aurore Thibaut

2017-06-01

Conclusion:. Intracortical disinhibition seems to be a marker that has been consistently observed in MPS. Future prospective cohort studies could provide new insights in the development of neoplastic and maladaptive changes occurring in chronic pain syndromes and help the development of new therapeutic options.

Directed polymers versus directed percolation

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Halpin-Healy, Timothy

1998-10-01

Universality plays a central role within the rubric of modern statistical mechanics, wherein an insightful continuum formulation rises above irrelevant microscopic details, capturing essential scaling behaviors. Nevertheless, occasions do arise where the lattice or another discrete aspect can constitute a formidable legacy. Directed polymers in random media, along with its close sibling, directed percolation, provide an intriguing case in point. Indeed, the deep blood relation between these two models may have sabotaged past efforts to fully characterize the Kardar-Parisi-Zhang universality class, to which the directed polymer belongs.

Second time around: Corticospinal responses following repeated sports-related concussions within the same season. A transcranial magnetic stimulation study

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Alan J Pearce

2014-01-01

Conclusions: This multiple-case study has demonstrated that concussion result in increased intracortical inhibition and reduction in cognitive and motor performance. Further, TMS, in conjunction with tests of cognitive and motor performance, can be useful as a prognostic technique in assessing recovery from acute concussion injury.

Salmonella osteomyelitis by sickle cell anemia

International Nuclear Information System (INIS)

Rausch, H.; Tran, V.T.; Boeckmann, U.; Duesseldorf Univ.

1985-01-01

Case report of a 28 year old black sickle cell anemia patient with salmonella osteomyelitis of the radius. Aside from sickle cell anemia patients this skeletal complication of enteric salmonellosis is an extreme rarity. Description of the typical roentgenological features includes intracortical fissures and sequestration. (orig.) [de

Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

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Li, Guangye; Zhang, Dingguo

2016-01-01

An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

On the role of emerging voluntary control of vocalization in language evolution. Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib

Science.gov (United States)

Coudé, Gino

2016-03-01

This comment will be focused on the role of monkey vocal control in the evolution of language. I will essentially reiterate the observations expressed in a commentary [1] about the book ;How the brain got language: the mirror system hypothesis;, written by Arbib [2]. I will hopefully clarify our suggestion that non-human primates vocal communication, in conjunction with gestures, could have had an active role in the emergence of the first voluntary forms of utterances that will later shape protospeech. This suggestion is mainly rooted in neurophysiological data about vocal control in monkey. I will very briefly summarize how neurophysiological data allowed us to suggest a possible role for monkey vocalization in language evolution. We conducted a study [3] in which we recorded from ventral premotor cortex (PMv) of macaques trained to emit vocalizations (i.e. coo-calls). The results showed that the rostro-lateral part of PMv contains neurons that fire during conditioned vocalization. The involvement of PMv in vocalization production was further supported by electrical microstimulation of the cortical sector where some of the vocalization neurons were found. Microstimulation elicited in some cases a combination of jaw, tongue and larynx movements. To us, the evolutionary implications of those results were obvious: a partial voluntary vocal control was already taking place in the primate PMv cortex some 25 million years ago.

Wireless link and microelectronics design for retinal prostheses

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Liu, Wentai [Univ. of California, Santa Cruz, CA (United States)

2012-02-29

This project focuses on delivering power and data to the artificial retinal implant inside the eye and the implant microstimulator electronics which delivers the current pulses to stimulate the retinal layer to elicit visual perception. Since the use of invasive means such as tethering wires to transmit power and data results in discomfort to the patients which could eventually cause infection due to the abrasion caused by the wire and contact of the internals of the eye to the external environment, a completely wireless approach is used to transfer both power and data. Power is required inside the eye for the microelectronic implant which uses a dual voltage supply scheme (positive and negative) to deliver biphasic (anodic and cathodic) current pulses. Data in the form of digital bits from the data transmitter external to the eye, carries information about the amplitude, phase width, interphase delay, stimulation sequence for each implant electrode. The data receiver unit decodes the digital stream and the microstimulator unit generates the appropriate current stimuli. Since the external unit consisting of the power transmitter can experience coupling a variation with the power receiver due to the patient’s movements, a closed loop approach is used which varies the transmitted power dynamically to automatically compensate for such movements. This report presents the salient features of this research activities and results.

Brain-derived neurotrophic factor enhances conditioned taste aversion retention.

Science.gov (United States)

Castillo, Diana V; Figueroa-Guzmán, Yazmín; Escobar, Martha L

2006-01-05

Brain-derived neurotrophic factor (BDNF) has recently emerged as one of the most potent molecular mediators of not only central synaptic plasticity, but also behavioral interactions between an organism and its environment. Our previous studies on the insular cortex (IC), a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that induction of long-term potentiation (LTP) in the projection from the basolateral nucleus of the amygdala (Bla) to the IC, previous to CTA training, enhances the retention of this task. Recently, we found that intracortical microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the Bla-IC projection of adult rats in vivo. In this work, we present experimental data showing that intracortical microinfusion of BDNF previous to CTA training enhances the retention of this task. These findings support the concept that BDNF may contribute to memory-related functions performed by a neocortical area, playing a critical role in long-term synaptic plasticity.

The logic of single-cell projections from visual cortex.

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Han, Yunyun; Kebschull, Justus M; Campbell, Robert A A; Cowan, Devon; Imhof, Fabia; Zador, Anthony M; Mrsic-Flogel, Thomas D

2018-04-05

Neocortical areas communicate through extensive axonal projections, but the logic of information transfer remains poorly understood, because the projections of individual neurons have not been systematically characterized. It is not known whether individual neurons send projections only to single cortical areas or distribute signals across multiple targets. Here we determine the projection patterns of 591 individual neurons in the mouse primary visual cortex using whole-brain fluorescence-based axonal tracing and high-throughput DNA sequencing of genetically barcoded neurons (MAPseq). Projections were highly diverse and divergent, collectively targeting at least 18 cortical and subcortical areas. Most neurons targeted multiple cortical areas, often in non-random combinations, suggesting that sub-classes of intracortical projection neurons exist. Our results indicate that the dominant mode of intracortical information transfer is not based on 'one neuron-one target area' mapping. Instead, signals carried by individual cortical neurons are shared across subsets of target areas, and thus concurrently contribute to multiple functional pathways.

Therapeutic intraspinal stimulation to generate activity and promote long-term recovery

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Sarah E. Mondello

2014-02-01

Full Text Available Neuroprosthetic approaches have tremendous potential for the treatment of injuries to the brain and spinal cord by inducing appropriate neural activity in otherwise disordered circuits. Substantial work has demonstrated that stimulation applied to both the central and peripheral nervous system leads to immediate and in some cases sustained benefits after injury. Here we focus on cervical intraspinal microstimulation (ISMS as a promising method of activating the spinal cord distal to an injury site, either to directly produce movements or more intriguingly to improve subsequent volitional control of the paretic extremities. Incomplete injuries to the spinal cord are the most commonly observed in human patients, and these injuries spare neural tissue bypassing the lesion that could be influenced by neural devices to promote recovery of function. In fact, recent results have demonstrated that therapeutic ISMS leads to modest but sustained improvements in forelimb function after an incomplete spinal cord injury. This therapeutic spinal stimulation may promote long-term recovery of function by providing the necessary electrical activity needed for neuron survival, axon growth, and synaptic stability.

Integrated circuit amplifiers for multi-electrode intracortical recording.

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Jochum, Thomas; Denison, Timothy; Wolf, Patrick

2009-02-01

Significant progress has been made in systems that interpret the electrical signals of the brain in order to control an actuator. One version of these systems senses neuronal extracellular action potentials with an array of up to 100 miniature probes inserted into the cortex. The impedance of each probe is high, so environmental electrical noise is readily coupled to the neuronal signal. To minimize this noise, an amplifier is placed close to each probe. Thus, the need has arisen for many amplifiers to be placed near the cortex. Commercially available integrated circuits do not satisfy the area, power and noise requirements of this application, so researchers have designed custom integrated-circuit amplifiers. This paper presents a comprehensive survey of the neural amplifiers described in publications prior to 2008. Methods to achieve high input impedance, low noise and a large time-constant high-pass filter are reviewed. A tutorial on the biological, electrochemical, mechanical and electromagnetic phenomena that influence amplifier design is provided. Areas for additional research, including sub-nanoampere electrolysis and chronic cortical heating, are discussed. Unresolved design concerns, including teraohm circuitry, electrical overstress and component failure, are identified.

Weaker Seniors Exhibit Motor Cortex Hypoexcitability and Impairments in Voluntary Activation.

Science.gov (United States)

Clark, Brian C; Taylor, Janet L; Hong, S Lee; Law, Timothy D; Russ, David W

2015-09-01

Weakness predisposes seniors to a fourfold increase in functional limitations. The potential for age-related degradation in nervous system function to contribute to weakness and physical disability has garnered much interest of late. In this study, we tested the hypothesis that weaker seniors have impairments in voluntary (neural) activation and increased indices of GABAergic inhibition of the motor cortex, assessed using transcranial magnetic stimulation. Young adults (N = 46; 21.2±0.5 years) and seniors (N = 42; 70.7±0.9 years) had their wrist flexion strength quantified along with voluntary activation capacity (by comparing voluntary and electrically evoked forces). Single-pulse transcranial magnetic stimulation was used to measure motor-evoked potential amplitude and silent period duration during isometric contractions at 15% and 30% of maximum strength. Paired-pulse transcranial magnetic stimulation was used to measure intracortical facilitation and short-interval and long-interval intracortical inhibition. The primary analysis compared seniors to young adults. The secondary analysis compared stronger seniors (top two tertiles) to weaker seniors (bottom tertile) based on strength relative to body weight. The most novel findings were that weaker seniors exhibited: (i) a 20% deficit in voluntary activation; (ii) ~20% smaller motor-evoked potentials during the 30% contraction task; and (iii) nearly twofold higher levels of long-interval intracortical inhibition under resting conditions. These findings indicate that weaker seniors exhibit significant impairments in voluntary activation, and that this impairment may be mechanistically associated with increased GABAergic inhibition of the motor cortex. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Neurophysiologic Correlates of Post-Stroke Mood and Emotional Control

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Deniz Doruk

2016-08-01

Full Text Available Objective: Emotional disturbance is a common complication of stroke significantly affecting functional recovery and quality of life. Identifying relevant neurophysiologic markers associated with post-stroke emotional disturbance may lead to a better understanding of this disabling condition, guiding the diagnosis, development of new interventions and the assessments of treatment response. Methods: Thirty-five subjects with chronic stroke were enrolled in this study. The emotion sub-domain of Stroke Impact Scale (SIS-Emotion was used to assess post-stroke mood and emotional control. The relation between SIS-Emotion and neurophysiologic measures was assessed by using covariance mapping and univariate linear regression. Multivariate analyses were conducted to identify and adjust for potential confounders. Neurophysiologic measures included power asymmetry and coherence assessed by electroencephalography (EEG; and motor threshold, intracortical inhibition (ICI and intracortical facilitation (ICF measured by transcranial magnetic stimulation (TMS. Results: Lower scores on SIS-Emotion was associated with 1 frontal EEG power asymmetry in alpha and beta bands, 2 central EEG power asymmetry in alpha and theta bands, and 3 lower inter-hemispheric coherence over frontal and central areas in alpha band. SIS-Emotion also correlated with higher ICF and MT in the unlesioned hemisphere as measured by TMS. Conclusions: To our knowledge, this is the first study using EEG and TMS to index neurophysiologic changes associated with post-stroke mood and emotional control. Our results suggest that inter-hemispheric imbalance measured by EEG power and coherence, as well as an increased intracortical facilitation in the unlesioned hemisphere measured by TMS might be relevant markers associated with post-stroke mood and emotional control which can guide future studies investigating new diagnostic and treatment modalities in stroke rehabilitation.

Stab injury and device implantation within the brain results in inversely multiphasic neuroinflammatory and neurodegenerative responses

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Potter, Kelsey A.; Buck, Amy C.; Self, Wade K.; Capadona, Jeffrey R.

2012-08-01

An estimated 25 million people in the US alone rely on implanted medical devices, ˜2.5 million implanted within the nervous system. Even though many devices perform adequately for years, the host response to medical devices often severely limits tissue integration and long-term performance. This host response is believed to be particularly limiting in the case of intracortical microelectrodes, where it has been shown that glial cell encapsulation and localized neuronal cell loss accompany intracortical microelectrode implantation. Since neuronal ensembles must be within ˜50 µm of the electrode to obtain neuronal spikes and local field potentials, developing a better understanding of the molecular and cellular environment at the device-tissue interface has been the subject of significant research. Unfortunately, immunohistochemical studies of scar maturation in correlation to device function have been inconclusive. Therefore, here we present a detailed quantitative study of the cellular events and the stability of the blood-brain barrier (BBB) following intracortical microelectrode implantation and cortical stab injury in a chronic survival model. We found two distinctly inverse multiphasic profiles for neuronal survival in device-implanted tissue compared to stab-injured animals. For chronically implanted animals, we observed a biphasic paradigm between blood-derived/trauma-induced and CNS-derived inflammatory markers driving neurodegeneration at the interface. In contrast, stab injured animals demonstrated a CNS-mediated neurodegenerative environment. Collectively these data provide valuable insight to the possibility of multiple roles of chronic neuroinflammatory events on BBB disruption and localized neurodegeneration, while also suggesting the importance to consider multiphasic neuroinflammatory kinetics in the design of therapeutic strategies for stabilizing neural interfaces.

75 FR 76630 - Direct Investment Surveys: BE-577, Quarterly Survey of U.S. Direct Investment Abroad-Direct...

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2010-12-09

....S. Direct Investment Abroad--Direct Transactions of U.S. Reporter With Foreign Affiliate.'' The..., Quarterly Survey of U.S. Direct Investment Abroad--Direct Transactions of U.S. Reporter With Foreign...] RIN 0691--AA75 Direct Investment Surveys: BE-577, Quarterly Survey of U.S. Direct Investment Abroad...

Reproducibility of Single-Pulse, Paired-Pulse, and Intermittent Theta-Burst TMS Measures in Healthy Aging, Type-2 Diabetes, and Alzheimer’s Disease

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Peter J. Fried

2017-08-01

Full Text Available Background: Transcranial magnetic stimulation (TMS can be used to assess neurophysiology and the mechanisms of cortical brain plasticity in humans in vivo. As the use of these measures in specific populations (e.g., Alzheimer’s disease; AD increases, it is critical to understand their reproducibility (i.e., test–retest reliability in the populations of interest.Objective: Reproducibility of TMS measures was evaluated in older adults, including healthy, AD, and Type-2 diabetes mellitus (T2DM groups.Methods: Participants received two identical neurophysiological assessments within a year including motor thresholds, baseline motor evoked potentials (MEPs, short- and long-interval intracortical inhibition (SICI, LICI and intracortical facilitation (ICF, and MEP changes following intermittent theta-burst stimulation (iTBS. Cronbach’s α coefficients were calculated to assess reproducibility. Multiple linear regression analyses were used to investigate factors related to intraindividual variability.Results: Reproducibility was highest for motor thresholds, followed by baseline MEPs, SICI and LICI, and was lowest for ICF and iTBS aftereffects. The AD group tended to show higher reproducibility than T2DM or controls. Intraindividual variability of baseline MEPs was related to age and variability of RMT, while the intraindividual variability in post-iTBS measures was related to baseline MEP variability, intervisit duration, and Brain-derived neurotrophic factor (BDNF polymorphism.Conclusion: Increased reproducibility in AD may reflect pathophysiological declines in the efficacy of neuroplastic mechanisms. Reproducibility of iTBS aftereffects can be improved by keeping baseline MEPs consistent, controlling for BDNF genotype, and waiting at least a week between visits.Significance: These findings provide the first direct assessment of reproducibility of TMS measures in older clinical populations. Reproducibility coefficients may be used to adjust

Altered cortical processing of motor inhibition in schizophrenia.

Science.gov (United States)

Lindberg, Påvel G; Térémetz, Maxime; Charron, Sylvain; Kebir, Oussama; Saby, Agathe; Bendjemaa, Narjes; Lion, Stéphanie; Crépon, Benoît; Gaillard, Raphaël; Oppenheim, Catherine; Krebs, Marie-Odile; Amado, Isabelle

2016-12-01

Inhibition is considered a key mechanism in schizophrenia. Short-latency intracortical inhibition (SICI) in the motor cortex is reduced in schizophrenia and is considered to reflect locally deficient γ-aminobutyric acid (GABA)-ergic modulation. However, it remains unclear how SICI is modulated during motor inhibition and how it relates to neural processing in other cortical areas. Here we studied motor inhibition Stop signal task (SST) in stabilized patients with schizophrenia (N = 28), healthy siblings (N = 21) and healthy controls (n = 31) matched in general cognitive status and educational level. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) were used to investigate neural correlates of motor inhibition. SST performance was similar in patients and controls. SICI was modulated by the task as expected in healthy controls and siblings but was reduced in patients with schizophrenia during inhibition despite equivalent motor inhibition performance. fMRI showed greater prefrontal and premotor activation during motor inhibition in schizophrenia. Task-related modulation of SICI was higher in subjects who showed less inhibition-related activity in pre-supplementary motor area (SMA) and cingulate motor area. An exploratory genetic analysis of selected markers of inhibition (GABRB2, GAD1, GRM1, and GRM3) did not explain task-related differences in SICI or cortical activation. In conclusion, this multimodal study provides direct evidence of a task-related deficiency in SICI modulation in schizophrenia likely reflecting deficient GABA-A related processing in motor cortex. Compensatory activation of premotor areas may explain similar motor inhibition in patients despite local deficits in intracortical processing. Task-related modulation of SICI may serve as a useful non-invasive GABAergic marker in development of therapeutic strategies in schizophrenia. Copyright © 2016 Elsevier Ltd. All rights reserved.

High serotonin levels during brain development alter the structural input-output connectivity of neural networks in the rat somatosensory layer IV

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Stéphanie eMiceli

2013-06-01

Full Text Available Homeostatic regulation of serotonin (5-HT concentration is critical for normal topographical organization and development of thalamocortical (TC afferent circuits. Down-regulation of the serotonin transporter (SERT and the consequent impaired reuptake of 5-HT at the synapse, results in a reduced terminal branching of developing TC afferents within the primary somatosensory cortex (S1. Despite the presence of multiple genetic models, the effect of high extracellular 5-HT levels on the structure and function of developing intracortical neural networks is far from being understood. Here, using juvenile SERT knockout (SERT-/- rats we investigated, in vitro, the effect of increased 5-HT levels on the structural organization of (i the thalamocortical projections of the ventroposteromedial thalamic nucleus towards S1, (ii the general barrel-field pattern and (iii the electrophysiological and morphological properties of the excitatory cell population in layer IV of S1 (spiny stellate and pyramidal cells. Our results confirmed previous findings that high levels of 5-HT during development lead to a reduction of the topographical precision of TCA projections towards the barrel cortex. Also, the barrel pattern was altered but not abolished in SERT-/- rats. In layer IV, both excitatory spiny stellate and pyramidal cells showed a significantly reduced intracolumnar organization of their axonal projections. In addition, the layer IV spiny stellate cells gave rise to a prominent projection towards the infragranular layer Vb. Our findings point to a structural and functional reorganization, of TCAs, as well as early stage intracortical microcircuitry, following the disruption of 5-HT reuptake during critical developmental periods. The increased projection pattern of the layer IV neurons suggests that the intracortical network changes are not limited to the main entry layer IV but may also affect the subsequent stages of the canonical circuits of the barrel

75 FR 53611 - Direct Investment Surveys: BE-577, Quarterly Survey of U.S. Direct Investment Abroad-Direct...

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2010-09-01

...] RIN 0691-AA75 Direct Investment Surveys: BE-577, Quarterly Survey of U.S. Direct Investment Abroad--Direct Transactions of U.S. Reporter With Foreign Affiliate AGENCY: Bureau of Economic Analysis, Commerce...-577 quarterly survey of U.S. direct investment abroad. The survey is conducted quarterly and obtains...

Direct Heat

Energy Technology Data Exchange (ETDEWEB)

Lienau, P J

1990-01-01

Potential resources and applications of earth heat in the form of geothermal energy are large. United States direct uses amount to 2,100 MWt thermal and worldwide 8,850 MWt above a reference temperature of 35 degrees Celsius. Space and district heating are the major direct uses of geothermal energy. Equipment employed in direct use projects is of standard manufacture and includes downhole and circulation pumps, transmission and distribution pipelines, heat exchangers and convectors, heat pumps and chillers. Direct uses of earth heat discussed are space and district heating, greenhouse heating and fish farming, process and industrial applications. The economic feasibility of direct use projects is governed by site specific factors such as location of user and resource, resource quality, system load factor and load density, as well as financing. Examples are presented of district heating in Klamath Falls, and Elko. Further developments of direct uses of geothermal energy will depend on matching user needs to the resource, and improving load factors and load density.

Direct Democracy

DEFF Research Database (Denmark)

Beramendi, Virginia; Ellis, Andrew; Kaufman, Bruno

While many books on direct democracy have a regional or national approach, or simply focus on one of the many mechanisms associated with direct democracy, this Handbook delves into a global comparison of direct democracy mechanisms, including referendums, citizens' initiatives, agenda initiatives...... learned. In addition, the uniquely comprehensive world survey outlines direct democracy provisions in 214 countries and territories and indicates which, if any, of these provisions are used by each country or territory at both the national and sub-national levels. Furthermore, the world survey includes...

Direct UV-written broadband directional broadband planar waveguide couplers

DEFF Research Database (Denmark)

Olivero, Massimo; Svalgaard, Mikael

2005-01-01

We report the fabrication of broadband directional couplers by direct UV-writing. The fabrication process is shown to be beneficial, robust and flexible. The components are compact and show superior performance in terms of loss and broadband operation.......We report the fabrication of broadband directional couplers by direct UV-writing. The fabrication process is shown to be beneficial, robust and flexible. The components are compact and show superior performance in terms of loss and broadband operation....

Preventing Ischial Pressure Ulcers: III. Clinical Pilot Study of Chronic Neuromuscular Electrical Stimulation

Directory of Open Access Journals (Sweden)

Hilton M. Kaplan

2011-01-01

Full Text Available Objective: BIONs™ (BIOnic Neurons are injectable, wireless microstimulators that make chronic BION Active Seating (BAS possible for pressure ulcer prevention (PUP. Neuromuscular electrical stimulation (NMES produces skeletal motion and activates trophic factors, counteracting three major etiological mechanisms leading to pressure ulcers (PUs: immobility, soft-tissue atrophy, and ischemia. Companion papers I and II reviewed prior experience with NMES for PUP, and analyzed the biomechanical considerations, respectively. This paper presents a treatment strategy derived from this analysis, and the clinical results of the first three cases.

Getting signals into the brain: visual prosthetics through thalamic microstimulation.

Science.gov (United States)

Pezaris, John S; Eskandar, Emad N

2009-07-01

Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface.

Verification of the directivity index and other measures of directivity in predicting directional benefit

Science.gov (United States)

Dittberner, Andrew; Bentler, Ruth

2005-09-01

The relationship between various directivity measures and subject performance with directional microphone hearing aids was determined. Test devices included first- and second-order directional microphones. Recordings of sentences and noise (Hearing in Noise Test, HINT) were made through each test device in simple, complex, and anisotropic background noise conditions. Twenty-six subjects, with normal hearing, were administered the HINT test recordings, and directional benefit was computed. These measures were correlated to theoretical, free-field, and KEMAR DI values, as well as front-to-back ratios, in situ SNRs, and a newly proposed Db-SNR, wherein a predictive value of the SNR improvement is calculated as a function of the noise source incidence. The different predictive scores showed high correlation to the measured directional benefit scores in the complex (diffuse-like) background noise condition (r=0.89-0.97, pThe Db-SNR approach and the in situ SNR measures provided excellent prediction of subject performance in all background noise conditions (0.85-0.97, pthe predictive measures could account for the effects of reverberation on the speech signal (r=0.35-0.40, p<0.05).

Extracting weights from edge directions to find communities in directed networks

International Nuclear Information System (INIS)

Lai, Darong; Lu, Hongtao; Nardini, Christine

2010-01-01

Community structures are found to exist ubiquitously in real-world complex networks. We address here the problem of community detection in directed networks. Most of the previous literature ignores edge directions and applies methods designed for community detection in undirected networks, which discards valuable information and often fails when different communities are defined on the basis of incoming and outgoing edges. We suggest extracting information about edge directions using a PageRank random walk and translating such information into edge weights. After extraction we obtain a new weighted directed network in which edge directions can then be safely ignored. We thus transform community detection in directed networks into community detection in reweighted undirected networks. Such an approach can benefit directly from the large volume of algorithms for the detection of communities in undirected networks already developed, since it is not obvious how to extend these algorithms to account for directed networks and the procedure is often difficult. Validations on synthetic and real-world networks demonstrate that the proposed framework can effectively detect communities in directed networks

Directing Creativity

DEFF Research Database (Denmark)

Darsø, Lotte; Ibbotson, Piers

2008-01-01

In this article we argue that leaders facing complex challenges can learn from the arts, specifically that leaders can learn by examining how theatre directors direct creativity through creative constraints. We suggest that perceiving creativity as a boundary phenomenon is helpful for directing it....... Like leaders, who are caught in paradoxical situations where they have to manage production and logistics simultaneously with making space for creativity and innovation, theatre directors need to find the delicate balance between on one hand renewal of perceptions, acting and interaction...... and on the other hand getting ready for the opening night. We conclude that the art of directing creativity is linked to developing competencies of conscious presence, attention and vigilance, whereas the craft of directing creativity concerns communication, framing and choice....

Playing the electric light orchestra--how electrical stimulation of visual cortex elucidates the neural basis of perception.

Science.gov (United States)

Cicmil, Nela; Krug, Kristine

2015-09-19

Vision research has the potential to reveal fundamental mechanisms underlying sensory experience. Causal experimental approaches, such as electrical microstimulation, provide a unique opportunity to test the direct contributions of visual cortical neurons to perception and behaviour. But in spite of their importance, causal methods constitute a minority of the experiments used to investigate the visual cortex to date. We reconsider the function and organization of visual cortex according to results obtained from stimulation techniques, with a special emphasis on electrical stimulation of small groups of cells in awake subjects who can report their visual experience. We compare findings from humans and monkeys, striate and extrastriate cortex, and superficial versus deep cortical layers, and identify a number of revealing gaps in the 'causal map' of visual cortex. Integrating results from different methods and species, we provide a critical overview of the ways in which causal approaches have been used to further our understanding of circuitry, plasticity and information integration in visual cortex. Electrical stimulation not only elucidates the contributions of different visual areas to perception, but also contributes to our understanding of neuronal mechanisms underlying memory, attention and decision-making.

Playing the electric light orchestra—how electrical stimulation of visual cortex elucidates the neural basis of perception

Science.gov (United States)

Cicmil, Nela; Krug, Kristine

2015-01-01

Vision research has the potential to reveal fundamental mechanisms underlying sensory experience. Causal experimental approaches, such as electrical microstimulation, provide a unique opportunity to test the direct contributions of visual cortical neurons to perception and behaviour. But in spite of their importance, causal methods constitute a minority of the experiments used to investigate the visual cortex to date. We reconsider the function and organization of visual cortex according to results obtained from stimulation techniques, with a special emphasis on electrical stimulation of small groups of cells in awake subjects who can report their visual experience. We compare findings from humans and monkeys, striate and extrastriate cortex, and superficial versus deep cortical layers, and identify a number of revealing gaps in the ‘causal map′ of visual cortex. Integrating results from different methods and species, we provide a critical overview of the ways in which causal approaches have been used to further our understanding of circuitry, plasticity and information integration in visual cortex. Electrical stimulation not only elucidates the contributions of different visual areas to perception, but also contributes to our understanding of neuronal mechanisms underlying memory, attention and decision-making. PMID:26240421

Co-clustering directed graphs to discover asymmetries and directional communities.

Science.gov (United States)

Rohe, Karl; Qin, Tai; Yu, Bin

2016-10-21

In directed graphs, relationships are asymmetric and these asymmetries contain essential structural information about the graph. Directed relationships lead to a new type of clustering that is not feasible in undirected graphs. We propose a spectral co-clustering algorithm called di-sim for asymmetry discovery and directional clustering. A Stochastic co-Blockmodel is introduced to show favorable properties of di-sim To account for the sparse and highly heterogeneous nature of directed networks, di-sim uses the regularized graph Laplacian and projects the rows of the eigenvector matrix onto the sphere. A nodewise asymmetry score and di-sim are used to analyze the clustering asymmetries in the networks of Enron emails, political blogs, and the Caenorhabditis elegans chemical connectome. In each example, a subset of nodes have clustering asymmetries; these nodes send edges to one cluster, but receive edges from another cluster. Such nodes yield insightful information (e.g., communication bottlenecks) about directed networks, but are missed if the analysis ignores edge direction.

Modulation of the spike activity of neocortex neurons during a conditioned reflex.

Science.gov (United States)

Storozhuk, V M; Sanzharovskii, A V; Sachenko, V V; Busel, B I

2000-01-01

Experiments were conducted on cats to study the effects of iontophoretic application of glutamate and a number of modulators on the spike activity of neurons in the sensorimotor cortex during a conditioned reflex. These studies showed that glutamate, as well as exerting a direct influence on neuron spike activity, also had a delayed facilitatory action lasting 10-20 min after iontophoresis was finished. Adrenomimetics were found to have a double modulatory effect on intracortical glutamate connections: inhibitory and facilitatory effects were mediated by beta1 and beta2 adrenoceptors respectively. Although dopamine, like glutamate, facilitated neuron spike activity during the period of application, the simultaneous facilitatory actions of glutamate and L-DOPA were accompanied by occlusion of spike activity, and simultaneous application of glutamate and haloperidol suppressed spike activity associated with the conditioned reflex response. Facilitation thus appears to show a significant level of dependence on metabotropic glutamate receptors which, like dopamine receptors, are linked to the intracellular medium via Gi proteins.

Leg Regrowth in Blaberus discoidalis (Discoid Cockroach following Limb Autotomy versus Limb Severance and Relevance to Neurophysiology Experiments.

Directory of Open Access Journals (Sweden)

Timothy C Marzullo

Full Text Available Many insects can regenerate limbs, but less is known about the regrowth process with regard to limb injury type. As part of our neurophysiology education experiments involving the removal of a cockroach leg, 1 the ability of Blaberus discoidalis cockroaches to regenerate a metathoracic leg was examined following autotomy at the femur/trochanter joint versus severance via a transverse coxa-cut, and 2 the neurophysiology of the detached legs with regard to leg removal type was studied by measuring spike firing rate and microstimulation movement thresholds.First appearance of leg regrowth was after 5 weeks in the autotomy group and 12 weeks in the coxa-cut group. Moreover, regenerated legs in the autotomy group were 72% of full size on first appearance, significantly larger (p<0.05 than coxa-cut legs (29% of full size at first appearance. Regenerated legs in both groups grew in size with each subsequent molt; the autotomy-removed legs grew to full size within 18 weeks, whereas coxa-cut legs took longer than 28 weeks to regrow. Removal of the metathoracic leg in both conditions did not have an effect on mortality compared to matched controls with unmolested legs.Autotomy-removed legs had lower spontaneous firing rates, similar marked increased firing rates upon tactile manipulation of tibial barbs, and a 10% higher electrical microstimulation threshold for movement.It is recommended that neurophysiology experiments on cockroach legs remove the limb at autotomy joints instead of coxa cuts, as the leg regenerates significantly faster when autotomized and does not detract from the neurophysiology educational content.

A normalization model suggests that attention changes the weighting of inputs between visual areas.

Science.gov (United States)

Ruff, Douglas A; Cohen, Marlene R

2017-05-16

Models of divisive normalization can explain the trial-averaged responses of neurons in sensory, association, and motor areas under a wide range of conditions, including how visual attention changes the gains of neurons in visual cortex. Attention, like other modulatory processes, is also associated with changes in the extent to which pairs of neurons share trial-to-trial variability. We showed recently that in addition to decreasing correlations between similarly tuned neurons within the same visual area, attention increases correlations between neurons in primary visual cortex (V1) and the middle temporal area (MT) and that an extension of a classic normalization model can account for this correlation increase. One of the benefits of having a descriptive model that can account for many physiological observations is that it can be used to probe the mechanisms underlying processes such as attention. Here, we use electrical microstimulation in V1 paired with recording in MT to provide causal evidence that the relationship between V1 and MT activity is nonlinear and is well described by divisive normalization. We then use the normalization model and recording and microstimulation experiments to show that the attention dependence of V1-MT correlations is better explained by a mechanism in which attention changes the weights of connections between V1 and MT than by a mechanism that modulates responses in either area. Our study shows that normalization can explain interactions between neurons in different areas and provides a framework for using multiarea recording and stimulation to probe the neural mechanisms underlying neuronal computations.

Direct selling particularities

OpenAIRE

Greifová, Daniela

2009-01-01

Bachelor thesis is focused on the parcularities of direct selling, self regulation of this industry, multi-level marketing which is the most used sales method in the field of direct selling. The part of the thesis is dedicated to the issue of customer psychology that is very important for achieving success in direct selling. Main goals are to provide readers with the general view of direct selling and analysis of growing possibilities of the industry in the future.

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

Science.gov (United States)

Silas, Jonathan; Brandt, Karen R

2016-03-11

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

Inner-Directed and Other-Directed Values of Professional Journalists.

Science.gov (United States)

Schwartz, Stuart H.

1978-01-01

Reports that an analysis of the responses of 35 journalists to 50 value items revealed two types of journalists: the inner-directed high professional and the other-directed low professional. Discusses attitudes and values of the two types. (GT)

Incomplete oblique sagittal fractures of the dorsal cortex of the third metacarpal bone in six horses

International Nuclear Information System (INIS)

Watt, B.C.; Foerner, J.J.; Haines, G.R.

1998-01-01

To describe incomplete oblique sagittal dorsal cortical fractures of the equine third metacarpal bone, their surgical repair, and subsequent performance of the horses. Retrospective examination of medical records and racing performance. Six Thoroughbred race horses, 2 to 4 years of age. Radiographic confirmation of all fractures preceded general anesthesia and surgical correction. Three fractures were treated by intracortical compression using screws placed in lag fashion, and five fractures were treated by osteostixis. Race records were reviewed for each horse to determine performance after surgery. Fractures were best observed on palmarodorsal radiographic projections. Three horses treated by intracortical compression returned to racing, but fracture recurred in one horse and was treated by osteostixis. This horse and the other three horses treated by osteostixis raced after surgery. Horses with incomplete oblique sagittal fractures of the dorsal cortex of the third metacarpal bone can race after surgical management of the fracture by screws placed in lag fashion or osteostixis. The authors' preferred surgical procedure for managing this fracture is osteostixis. Palmarodorsal radiographic projections of the third metacarpal bone are recommended in young Thoroughbred race horses suspected of having dorsal metacarpal stress fractures

Simultaneous surface and depth neural activity recording with graphene transistor-based dual-modality probes.

Science.gov (United States)

Du, Mingde; Xu, Xianchen; Yang, Long; Guo, Yichuan; Guan, Shouliang; Shi, Jidong; Wang, Jinfen; Fang, Ying

2018-05-15

Subdural surface and penetrating depth probes are widely applied to record neural activities from the cortical surface and intracortical locations of the brain, respectively. Simultaneous surface and depth neural activity recording is essential to understand the linkage between the two modalities. Here, we develop flexible dual-modality neural probes based on graphene transistors. The neural probes exhibit stable electrical performance even under 90° bending because of the excellent mechanical properties of graphene, and thus allow multi-site recording from the subdural surface of rat cortex. In addition, finite element analysis was carried out to investigate the mechanical interactions between probe and cortex tissue during intracortical implantation. Based on the simulation results, a sharp tip angle of π/6 was chosen to facilitate tissue penetration of the neural probes. Accordingly, the graphene transistor-based dual-modality neural probes have been successfully applied for simultaneous surface and depth recording of epileptiform activity of rat brain in vivo. Our results show that graphene transistor-based dual-modality neural probes can serve as a facile and versatile tool to study tempo-spatial patterns of neural activities. Copyright © 2018 Elsevier B.V. All rights reserved.

Directional output distance functions: endogenous directions based on exogenous normalization constraints

Science.gov (United States)

In this paper we develop a model for computing directional output distance functions with endogenously determined direction vectors. We show how this model is related to the slacks-based directional distance function introduced by Fare and Grosskopf and show how to use the slacks-based function to e...

Crosstalk between intracellular and extracellular signals regulating interneuron production, migration and integration into the cortex

OpenAIRE

Peyre, Elise; Silva, Carla G.; Nguyen, Laurent

2015-01-01

During embryogenesis, cortical interneurons are generated by ventral progenitors located in the ganglionic eminences of the telencephalon. They travel along multiple tangential paths to populate the cortical wall. As they reach this structure they undergo intracortical dispersion to settle in their final destination. At the cellular level, migrating interneurons are highly polarized cells that extend and retract processes using dynamic remodeling of microtubule and actin cytoskeleton. Differe...

MR features of multiple enchondromas with associated chondrosarcoma in the lower extremities

Energy Technology Data Exchange (ETDEWEB)

Yang, Kyung Yoon; Sung, Mi Sook; Lee, Hee Jeong; Park, Il Joong; Lee, Jae Young; Yu, Won Jong; Lee, Gook Jin; Jeon, Sang Hoon; Yu, Mi Na; Yoon, Se Cheol [College of Medicine, The Catholic University of Korea, Bucheon St. Mary' s Hospital, Bucheon (Korea, Republic of)

2016-02-15

Multiple enchondromas are well described in the literature, however, the associated spectrum of MR imaging findings remains unclear. Secondary chondrosarcoma of the hand and feet associated with multiple enchondromas is extremely rare. Herein, we reported a case of multiple enchondromas of intramedullary, intracortical, and periosteal location with associated low-grade chondrosarcomas in the lower extremities on MR imaging in a 57 year old woman.

The double cortical line: a sign of osteopenia

International Nuclear Information System (INIS)

Lamb, C.R.

1990-01-01

The double cortical line is a radiographic sign of osteopenia which results from intracortical resorption of bone. This sign is frequently seen in humans with osteopenia but has received minimal attention in the veterinary literature. This report describes the double cortical line in cases of senile osteopenia, nutritional secondary hyperparathyroidism, suspected renal secondary hyperparathyroidism and in the acetabulum following triple pelvic osteotomy for hip dysplasia

Transcranial alternating current stimulation at beta frequency: lack of immediate effects on excitation and interhemispheric inhibition of the human motor cortex

Directory of Open Access Journals (Sweden)

Viola Rjosk

2016-11-01

Full Text Available Transcranial alternating current stimulation (tACS is a form of noninvasive brain stimulation and is capable of influencing brain oscillations and cortical networks. In humans, the endogenous oscillation frequency in sensorimotor areas peaks at 20 Hz. This beta-band typically occurs during maintenance of tonic motor output and seems to play a role in interhemispheric coordination of movements. Previous studies showed that tACS applied in specific frequency bands over primary motor cortex (M1 or the visual cortex modulates cortical excitability within the stimulated hemisphere. However, the particular impact remains controversial because effects of tACS were shown to be frequency, duration and location specific. Furthermore, the potential of tACS to modulate cortical interhemispheric processing, like interhemispheric inhibition (IHI, remains elusive. Transcranial magnetic stimulation (TMS is a noninvasive and well-tolerated method of directly activating neurons in superficial areas of the human brain and thereby a useful tool for evaluating the functional state of motor pathways. The aim of the present study was to elucidate the immediate effect of 10 min tACS in the β-frequency band (20 Hz over left M1 on IHI between M1s in 19 young, healthy, right-handed participants. A series of TMS measurements (MEP size, RMT, IHI from left to right M1 and vice versa was performed before and immediately after tACS or sham using a double-blinded, cross-over design. We did not find any significant tACS-induced modulations of intracortical excitation (as assessed by MEP size and RMT and/or interhemispheric inhibition (IHI. These results indicate that 10 min of 20 Hz tACS over left M1 seems incapable of modulating immediate brain activity or inhibition. Further studies are needed to elucidate potential aftereffects of 20 Hz tACS as well as frequency-specific effects of tACS on intracortical excitation and interhemispheric inhibition.

The effects of anodal-tDCS on corticospinal excitability enhancement and its after-effects: conventional versus unihemispheric concurrent dual-site stimulation

Directory of Open Access Journals (Sweden)

Bita eVaseghi

2015-09-01

Full Text Available Previous researchers have approved the ability of anodal transcranial direct current stimulation (a-tDCS of the primary motor cortex (M1 to enhance corticospinal excitability (CSE. The primary aim of the current study was to investigate the effect of concurrent stimulation of M1 and a functionally connected cortical site of M1 on CSE modulation. This new technique is called unihemispheric concurrent dual-site a-tDCS (a-tDCSUHCDS. The secondary aim was to investigate the mechanisms underlying the efficacy of this new approach in healthy individuals. In a randomized crossover study, 12 healthy right-handed volunteers received a-tDCS under five conditions: a-tDCS of M1, a-tDCSUHCDS of M1– dorsolateral prefrontal cortex (DLPFC, a-tDCSUHCDS of M1– primary sensory cortex (S1, a-tDCSUHCDS of M1– primary visual cortex (V1, and sham a-tDCSUHCDS. Peak-to-peak amplitude of transcranial magnetic stimulation (TMS induced MEPs, short-interval intracortical inhibition and intracortical facilitation were assessed before and four times after each condition. A-tDCSUHCDS conditions induced larger MEPs than conventional a-tDCS. The level of M1 CSE was significantly higher following a-tDCSUHCDS of M1-DLPFC than other a-tDCSUHCDS conditions (P < 0.001, and lasted for over 24 hours. The paired-pulse TMS results after a-tDCS of M1-DLPFC showed significant facilitatory increase and inhibitory change. A-tDCSUHCDS of M1-DLPFC increases M1 CSE twofold that of conventional a-tDCS. A-tDCSUHCDS of M1-DLPFC enhances the activity of glutamergic mechanisms for at least 24 hours. Such long-lasting M1 CSE enhancement induced by a-tDCSUHCDS of M1-DLPFC could be a valuable finding in clinical scenarios such as learning, motor performance, or pain management.The present study has been registered on the Australian New Zealand Clinical Trial at http://www.anzctr.org.au/ with registry number of ACTRN12614000817640.

Future direction of direct writing

Science.gov (United States)

Kim, Nam-Soo; Han, Kenneth N.

2010-11-01

Direct write technology using special inks consisting of finely dispersed metal nanoparticles in liquid is receiving an undivided attention in recent years for its wide range of applicability in modern electronic industry. The application of this technology covers radio frequency identification-tag (RFID-tag), flexible-electronics, organic light emitting diodes (OLED) display, e-paper, antenna, bumpers used in flip-chip, underfilling, frit, miniresistance applications and biological uses, artificial dental applications and many more. In this paper, the authors have reviewed various direct write technologies on the market and discussed their advantages and shortfalls. Emphasis has given on microdispensing deposition write (MDDW), maskless mesoscale materials deposition (M3D), and ink-jet technologies. All of these technologies allow printing various patterns without employing a mask or a resist with an enhanced speed with the aid of computer. MDDW and M3D are capable of drawing patterns in three-dimension and MDDW, in particular, is capable of writing nanoinks with high viscosity. However, it is still far away for direct write to be fully implemented in the commercial arena. One of the hurdles to overcome is in manufacturing conductive inks which are chemically and physically stable, capable of drawing patterns with acceptable conductivity, and also capable of drawing patterns with acceptable adhesiveness with the substrates. The authors have briefly discussed problems involved in manufacturing nanometal inks to be used in various writing devices. There are numerous factors to be considered in manufacturing such inks. They are reducing agents, concentrations, oxidation, compact ability allowing good conductivity, and stability in suspension.

Matlab Source Code for Species Transport through Nafion Membranes in Direct Ethanol, Direct Methanol, and Direct Glucose Fuel Cells

OpenAIRE

JH, Summerfield; MW, Manley

2016-01-01

A simple simulation of chemical species movement is presented. The species traverse a Nafion membrane in a fuel cell. Three cells are examined: direct methanol, direct ethanol, and direct glucose. The species are tracked using excess proton concentration, electric field strength, and voltage. The Matlab computer code is provided.

Directing 101.

Science.gov (United States)

Pintoff, Ernest

Providing an introduction to anyone considering directing as a field of study or career, this book takes a broad look at the process of directing and encourages students and professionals alike to look outside of the movie industry for inspiration. Chapters in the book discuss selecting and acquiring material; budgeting and financing; casting and…

Directed Energy Weapons

Science.gov (United States)

2007-12-01

future business . In defense systems, the key to future business is the existence of funded programs. Military commanders understand the lethality and...directed energp capabilities that can provide visibiliy into the likey futur business case for sustaining directed energy industry capabilities...the USD (I) staff to be afocalpointfor advocating improvement in all dimensions of directed energy intelligence. - The Director, Defense Inteligence

Directed network modules

International Nuclear Information System (INIS)

Palla, Gergely; Farkas, Illes J; Pollner, Peter; Derenyi, Imre; Vicsek, Tamas

2007-01-01

A search technique locating network modules, i.e. internally densely connected groups of nodes in directed networks is introduced by extending the clique percolation method originally proposed for undirected networks. After giving a suitable definition for directed modules we investigate their percolation transition in the Erdos-Renyi graph both analytically and numerically. We also analyse four real-world directed networks, including Google's own web-pages, an email network, a word association graph and the transcriptional regulatory network of the yeast Saccharomyces cerevisiae. The obtained directed modules are validated by additional information available for the nodes. We find that directed modules of real-world graphs inherently overlap and the investigated networks can be classified into two major groups in terms of the overlaps between the modules. Accordingly, in the word-association network and Google's web-pages, overlaps are likely to contain in-hubs, whereas the modules in the email and transcriptional regulatory network tend to overlap via out-hubs

Spatial integration in mouse primary visual cortex

OpenAIRE

Vaiceliunaite, Agne; Erisken, Sinem; Franzen, Florian; Katzner, Steffen; Busse, Laura

2013-01-01

Responses of many neurons in primary visual cortex (V1) are suppressed by stimuli exceeding the classical receptive field (RF), an important property that might underlie the computation of visual saliency. Traditionally, it has proven difficult to disentangle the underlying neural circuits, including feedforward, horizontal intracortical, and feedback connectivity. Since circuit-level analysis is particularly feasible in the mouse, we asked whether neural signatures of spatial integration in ...

Protein synthesis underlies post-retrieval memory consolidation to a restricted degree only when updated information is obtained

OpenAIRE

Rodriguez-Ortiz, Carlos J.; De la Cruz, Vanesa; Gutiérrez, Ranier; Bermudez-Rattoni, Federico

2005-01-01

Consolidation theory proposes that through the synthesis of new proteins recently acquired memories are strengthened over time into a stable long-term memory trace. However, evidence has accumulated suggesting that retrieved memory is susceptible to disruption, seeming to consolidate again (reconsolidate) to be retained in long-term storage. Here we show that intracortical blockade of protein synthesis in the gustatory cortex after retrieval of taste-recognition memory disrupts previously con...

Rapid reorganization of adult rat motor cortex somatic representation patterns after motor nerve injury.

OpenAIRE

Sanes, J N; Suner, S; Lando, J F; Donoghue, J P

1988-01-01

The potential for peripheral nerve injury to reorganize motor cortical representations was investigated in adult rats. Maps reflecting functional connections between the motor cortex and somatic musculature were generated with intracortical electrical stimulation techniques. Comparison of cortical somatotopic maps obtained in normal rats with maps generated from rats with a facial nerve lesion indicated that the forelimb and eye/eyelid representations expanded into the normal vibrissa area. R...

Directivity of singers

Science.gov (United States)

Jers, Harald

2005-09-01

Studies of acoustical balance between singers within a choir by means of room acoustical measurements have shown that the directional sound propagation of the source is important. For this reason the directivity of female and male singers for different vowels has been measured in this investigation. Measurements of a pilot study and some first measurements in 1998 have been supplemented with new measurements and an enhanced setup. A special measurement setup with reference and recording microphones was used to collect the directivity data. A resolution of 10 deg for azimuth and elevation angle was obtained. The results will be shown in 3D spherical plots with frequency adjustments in semitones from 80 to 8000 Hz. The measurements are compared to an artificial singer's directivity, and the influence of a sheet music binder in front of a singer will be shown. The results give information on the directivity of singers and are relevant for the prediction of self-to-other-ratios that result from placement and formation aspects within a choir.

Directed line liquids

International Nuclear Information System (INIS)

Kamien, R.D.

1992-01-01

This thesis is devoted to the study of ensembles of dense directed lines. These lines are principally to be thought of as polymers, though they also have the morphology of flux lines in high temperature superconductors, strings of colloidal spheres in electrorheological fluids and the world lines of quantum mechanical bosons. The authors discuss how directed polymer melts, string-like formations in electrorheological and ferro-fluids, flux lines in high temperature superconductors and the world lines of quantum mechanical bosons all share similar descriptions. They study a continuous transition in all of these systems, and then study the critical mixing properties of binary mixtures of directed polymers through the renormalization group. They predict the exponents for a directed polymer blend consolute point and a novel two-phase superfluid liquid-gas critical point

Transcranial magnetic stimulation: language function.

Science.gov (United States)

Epstein, C M

1998-07-01

Studies of language using transcranial magnetic stimulation (TMS) have focused both on identification of language areas and on elucidation of function. TMS may result in either inhibition or facilitation of language processes and may operate directly at a presumptive site of language cortex or indirectly through intracortical networks. TMS has been used to create reversible "temporary lesions," similar to those produced by Wada tests and direct cortical electrical stimulation, in cerebral cortical areas subserving language function. Rapid-rate TMS over the left inferior frontal region blocks speech output in most subjects. However, the results are not those predicted from classic models of language organization. Speech arrest is obtained most easily over facial motor cortex, and true aphasia is rare, whereas right hemisphere or bilateral lateralization is unexpectedly prominent. A clinical role for these techniques is not yet fully established. Interfering with language comprehension and verbal memory is currently more difficult than blocking speech output, but numerous TMS studies have demonstrated facilitation of language-related tasks, including oral word association, story recall, digit span, and picture naming. Conversely, speech output also facilitates motor responses to TMS in the dominant hemisphere. Such new and often-unexpected findings may provide important insights into the organization of language.

Estimating directional epistasis

Science.gov (United States)

Le Rouzic, Arnaud

2014-01-01

Epistasis, i.e., the fact that gene effects depend on the genetic background, is a direct consequence of the complexity of genetic architectures. Despite this, most of the models used in evolutionary and quantitative genetics pay scant attention to genetic interactions. For instance, the traditional decomposition of genetic effects models epistasis as noise around the evolutionarily-relevant additive effects. Such an approach is only valid if it is assumed that there is no general pattern among interactions—a highly speculative scenario. Systematic interactions generate directional epistasis, which has major evolutionary consequences. In spite of its importance, directional epistasis is rarely measured or reported by quantitative geneticists, not only because its relevance is generally ignored, but also due to the lack of simple, operational, and accessible methods for its estimation. This paper describes conceptual and statistical tools that can be used to estimate directional epistasis from various kinds of data, including QTL mapping results, phenotype measurements in mutants, and artificial selection responses. As an illustration, I measured directional epistasis from a real-life example. I then discuss the interpretation of the estimates, showing how they can be used to draw meaningful biological inferences. PMID:25071828

Direction-Dependence Analysis: A Confirmatory Approach for Testing Directional Theories

Science.gov (United States)

Wiedermann, Wolfgang; von Eye, Alexander

2015-01-01

The concept of direction dependence has attracted growing attention due to its potential to help decide which of two competing linear regression models (X ? Y or Y ? X) is more likely to reflect the correct causal flow. Several tests have been proposed to evaluate hypotheses compatible with direction dependence. In this issue, Thoemmes (2015)…

Neurophysiological Correlates of Central Fatigue in Healthy Subjects and Multiple Sclerosis Patients before and after Treatment with Amantadine

Directory of Open Access Journals (Sweden)

Emiliano Santarnecchi

2015-01-01

Full Text Available In ten healthy subjects and in ten patients suffering from Multiple Sclerosis (MS, we investigated the cortical functional changes induced by a standard fatiguing repetitive tapping task. The Cortical Silent Period (CSP, an intracortical, mainly GABAB-mediated inhibitory phenomenon, was recorded by two different hand muscles, one acting as prime mover of the fatiguing index-thumb tapping task (First Dorsal Interosseous, FDI and the other one not involved in the task but sharing largely overlapping central, spinal, and peripheral innervation (Abductor Digiti Minimi, ADM. At baseline, the CSP was shorter in patients than in controls. As fatigue developed, CSP changes involved both the “fatigued” FDI and the “unfatigued” ADM muscles, suggesting a cortical spread of central fatigue mechanisms. Chronic therapy with amantadine annulled differences in CSP duration between controls and patients, possibly through restoration of more physiological levels of intracortical inhibition in the motor cortex. These inhibitory changes correlated with the improvement of fatigue scales. The CSP may represent a suitable marker of neurophysiological mechanisms accounting for central fatigue generation either in controls or in MS patients, involving corticospinal neural pools supplying not only the fatigued muscle but also adjacent muscles sharing an overlapping cortical representation.

The reliability of repeated TMS measures in older adults and in patients with subacute and chronic stroke

Directory of Open Access Journals (Sweden)

Heidi M. Schambra

2015-09-01

Full Text Available The reliability of transcranial magnetic stimulation (TMS measures in healthy older adults and stroke patients has been insufficiently characterized. We determined whether common TMS measures could reliably evaluate change in individuals and in groups using the smallest detectable change (SDC, or could tell subjects apart using the intraclass correlation coefficient (ICC. We used a single-rater test-retest design in older healthy, subacute stroke, and chronic stroke subjects. At twice daily sessions on two consecutive days, we recorded resting motor threshold, test stimulus intensity, recruitment curves, short-interval intracortical inhibition and facilitation, and long-interval intracortical inhibition. Using variances estimated from a random effects model, we calculated the SDC and ICC for each TMS measure. For all TMS measures in all groups, SDCs for single subjects were large; only with modest group sizes did the SDCs become low. Thus, while these TMS measures cannot be reliably used as a biomarker to detect individual change, they can reliably detect change exceeding measurement noise in moderate-sized groups. For several of the TMS measures, ICCs were universally high, suggesting that they can reliably discriminate between subjects. Though most TMS measures have sufficient reliability in particular contexts, work establishing their validity, responsiveness, and clinical relevance is still needed.

Generator localization by current source density (CSD): Implications of volume conduction and field closure at intracranial and scalp resolutions

Science.gov (United States)

Tenke, Craig E.; Kayser, Jürgen

2012-01-01

The topographic ambiguity and reference-dependency that has plagued EEG/ERP research throughout its history are largely attributable to volume conduction, which may be concisely described by a vector form of Ohm’s Law. This biophysical relationship is common to popular algorithms that infer neuronal generators via inverse solutions. It may be further simplified as Poisson’s source equation, which identifies underlying current generators from estimates of the second spatial derivative of the field potential (Laplacian transformation). Intracranial current source density (CSD) studies have dissected the “cortical dipole” into intracortical sources and sinks, corresponding to physiologically-meaningful patterns of neuronal activity at a sublaminar resolution, much of which is locally cancelled (i.e., closed field). By virtue of the macroscopic scale of the scalp-recorded EEG, a surface Laplacian reflects the radial projections of these underlying currents, representing a unique, unambiguous measure of neuronal activity at scalp. Although the surface Laplacian requires minimal assumptions compared to complex, model-sensitive inverses, the resulting waveform topographies faithfully summarize and simplify essential constraints that must be placed on putative generators of a scalp potential topography, even if they arise from deep or partially-closed fields. CSD methods thereby provide a global empirical and biophysical context for generator localization, spanning scales from intracortical to scalp recordings. PMID:22796039

A Tensor-Product-Kernel Framework for Multiscale Neural Activity Decoding and Control

Science.gov (United States)

Li, Lin; Brockmeier, Austin J.; Choi, John S.; Francis, Joseph T.; Sanchez, Justin C.; Príncipe, José C.

2014-01-01

Brain machine interfaces (BMIs) have attracted intense attention as a promising technology for directly interfacing computers or prostheses with the brain's motor and sensory areas, thereby bypassing the body. The availability of multiscale neural recordings including spike trains and local field potentials (LFPs) brings potential opportunities to enhance computational modeling by enriching the characterization of the neural system state. However, heterogeneity on data type (spike timing versus continuous amplitude signals) and spatiotemporal scale complicates the model integration of multiscale neural activity. In this paper, we propose a tensor-product-kernel-based framework to integrate the multiscale activity and exploit the complementary information available in multiscale neural activity. This provides a common mathematical framework for incorporating signals from different domains. The approach is applied to the problem of neural decoding and control. For neural decoding, the framework is able to identify the nonlinear functional relationship between the multiscale neural responses and the stimuli using general purpose kernel adaptive filtering. In a sensory stimulation experiment, the tensor-product-kernel decoder outperforms decoders that use only a single neural data type. In addition, an adaptive inverse controller for delivering electrical microstimulation patterns that utilizes the tensor-product kernel achieves promising results in emulating the responses to natural stimulation. PMID:24829569

Protecting me from my Directive: Ensuring Appropriate Safeguards for Advance Directives in Dementia.

Science.gov (United States)

Auckland, Cressida

2018-02-01

With one in six people over 80 now suffering from dementia, advance directives provide an important means of empowerment. Upholding directives in the context of dementia, however, raises extra challenges, given the potential for the directive to conflict with an assessment of what is in the person's current best interests. Given the profound harm that tying a person with dementia to their previous wishes can do, it is essential that we have sufficient safeguards in place to ensure that we only uphold such directives where we can be sure they are truly autonomous and are intended to apply to the situation at hand-safeguards which are at present, severely lacking. This article will consider various mechanisms by which safeguards can be built into the legal regime to ensure that the original decision is autonomous, including making it mandatory for the person to undergo a consultation with a healthcare professional, which would involve a contemporaneous capacity assessment. Clinicians must also be confident that the directive applies to the situation at hand. Introducing formalities, including a standardised (though not mandatory) proforma, may help to enhance specificity about when the directive is triggered, and to what treatments it relates, to enable clinicians to better assess the directive's applicability. A national registry for advance directives might also be beneficial. It will be argued that health care professionals will have to play a much greater role in the drafting and registering of advance directives, if we are to feel comfortable in upholding them.

Directional Scanning as a Function of Stimulus Characteristics, Reading Habits, and Directional Set

Science.gov (United States)

Nachshon, Israel; And Others

1977-01-01

"32 English readers and 32 Hebrew readers were shown stimuli with directional characteristics (English and Hebrew letters) and stimuli with no directional characteristics (arrays of different circles, bars, colors, and geometric figures) for scanning. The results showed that, while directional stimulus characteristics affected the direction…

Directional velocity estimation using focusing along the flow direction - I: Theory and simulation

DEFF Research Database (Denmark)

Jensen, Jørgen Arendt

2003-01-01

A new method for directional velocity estimation is presented. The method uses beamformation along the flow direction to generate data in which the correct velocity magnitude can be directly estimated from the shift in position of the received consecutive signals. The shift is found by cross-corr...

Direct conversion of nuclear energy into radiation: New direction in thermonuclear laser fusion

International Nuclear Information System (INIS)

Babaev, Yu.N.; Vedenov, A.A.; Filyukov, A.A.

1995-01-01

In investigations dealing with thermonuclear fusion, a radical new direction appeared some time ago, namely the direct conversion of nuclear and thermonuclear energy into radiation energy. This paper reviews early work on this topic in Russia and the United States and discusses some recent new directions

Direct and semi-direct radiative forcing of smoke aerosols over clouds

Directory of Open Access Journals (Sweden)

E. M. Wilcox

2012-01-01

Full Text Available Observations from Earth observing satellites indicate that dark carbonaceous aerosols that absorb solar radiation are widespread in the tropics and subtropics. When these aerosols mix with clouds, there is generally a reduction of cloudiness owing to absorption of solar energy in the aerosol layer. Over the subtropical South Atlantic Ocean, where smoke from savannah burning in southern Africa resides above a persistent deck of marine stratocumulus clouds, radiative heating of the smoke layer leads to a thickening of the cloud layer. Here, satellite observations of the albedo of overcast scenes of 25 km² size or larger are combined with additional satellite observations of clouds and aerosols to estimate the top-of-atmosphere direct radiative forcing attributable to presence of dark aerosol above bright cloud, and the negative semi-direct forcing attributable to the thickening of the cloud layer. The average positive direct radiative forcing by smoke over an overcast scene is 9.2±6.6 W m⁻² for cases with an unambiguous signal of absorbing aerosol over cloud in passive ultraviolet remote sensing observations. However, cloud liquid water path is enhanced by 16.3±7.7 g m⁻² across the range of values for sea surface temperature for cases of smoke over cloud. The negative radiative forcing associated with this semi-direct effect of smoke over clouds is estimated to be −5.9±3.5 W m⁻². Therefore, the cooling associated with the semi-direct cloud thickening effect compensates for greater than 60 % of the direct radiative effect. Accounting for the frequency of occurrence of significant absorbing aerosol above overcast scenes leads to an estimate of the average direct forcing of 1.0±0.7 W m⁻² contributed by these scenes averaged over the subtropical southeast Atlantic Ocean during austral winter. The regional average of the negative semi-direct forcing is −0.7±0.4 W m⁻²

Direct contamination - seasonality

International Nuclear Information System (INIS)

Aarkrog, A.

1994-01-01

Direct contamination is the primary pathway to terrestrial vegetation in the first period after an activity release to the atmosphere. All radionuclides are able to be transferred via this pathway. Deposition, interception and retention are the three processes involved in direct contamination of crops. Wet deposition is more important than dry deposition in temperature regions. Resuspension and rainsplash both belong to secondary direct deposition and became evident for e.g. radiocaesium after the Chernobyl accident. Seasonality is the varying response to radioactive contamination of crops according to the time of the year when the contamination occurs. Shortlived radionuclides (as 131 I) and those that mainly enter the foodchain by direct contamination (e.g. 137 Cs) are especially important in this connection. In particular, the contamination of cereal crops is influenced by seasonality. As a result of seasonality the impact of the Chernobyl accident on the radioactive contamination of human diet was for the same deposition density higher in southern than in northern Europe. (orig.)

Tactile pavement for guiding walking direction: An assessment of heading direction and gait stability.

Science.gov (United States)

Pluijter, Nanda; de Wit, Lieke P W; Bruijn, Sjoerd M; Plaisier, Myrthe A

2015-10-01

For maintaining heading direction while walking we heavily rely on vision. Therefore, walking in the absence of vision or with visual attention directed elsewhere potentially leads to dangerous situations. Here we investigated whether tactile information from the feet can be used as a (partial) substitute for vision in maintaining a stable heading direction. If so, participants should be better able to keep a constant heading direction on tactile pavement that indicates directionality than on regular flat pavement. However, such a pavement may also be destabilizing. Thus we asked participants to walk straight ahead on regular pavement, and on tactile pavement (tiles with ridges along the walking direction) while varying the amount of vision. We assessed the effects of the type of pavement as well as the amount of vision on the variability of the heading direction as well as gait stability. Both of these measures were calculated from accelerations and angular velocities recorded from a smartphone attached to the participants trunk. Results showed that on tactile pavement participants had a less variations in their heading direction than on regular pavement. The drawback, however, was that the tactile pavement used in this study decreased gait stability. In sum, tactile pavement can be used as a partial substitute for vision in maintaining heading direction, but it can also decrease gait stability. Future work should focus on designing tactile pavement that does provided directional clues, but is less destabilizing. Copyright © 2015 Elsevier B.V. All rights reserved.

Thalamocortical control of feed-forward inhibition in awake somatosensory 'barrel' cortex.

OpenAIRE

Swadlow, Harvey A

2002-01-01

Intracortical inhibition plays a role in shaping sensory cortical receptive fields and is mediated by both feed-forward and feedback mechanisms. Feed-forward inhibition is the faster of the two processes, being generated by inhibitory interneurons driven by monosynaptic thalamocortical (TC) input. In principle, feed-forward inhibition can prevent targeted cortical neurons from ever reaching threshold when TC input is weak. To do so, however, inhibitory interneurons must respond to TC input at...

Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

Science.gov (United States)

Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

2009-01-01

This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

DIRECTIONS OF USING DIRECT PAYMENTS BY THE INDIVIDUAL FARMS LOCATED IN CHOSEN REGIONS

Directory of Open Access Journals (Sweden)

Arkadiusz Sadowski

2012-01-01

Full Text Available This paper assesses the diversity of directions for use of direct payments in different types of individual farms. The questionnaire surveys were performed on 295 farms located in dif-ferent parts of the country. Analysed farms were divided into groups according to the amount direct support received. Based on the survey concluded that in all analysed groups the largest share of direct payments is spent on the purchase of means of production. The smallest farms also spend to a high extent, the money on household purposes (20.5% and the largest ones to finance the investment (17.7%.

Direct reading dosimeter

International Nuclear Information System (INIS)

Thomson, I.

1985-01-01

This invention is a direct reading dosimeter which is light, small enough to be worn on a person, and measures both dose rates and total dose. It is based on a semiconductor sensor. The gate threshold voltage change rather than absolute value is measured and displayed as a direct reading of the dose rate. This is effected by continuously switching the gate of an MOS transistor from positive to negative bias. The output can directly drive a digital readout or trigger an audible alarm. The sensor device can be a MOSFET, bipolar transistor, or MOSFET capacitor which has its electrical characteristics change due to the trapped charge in the insulating layer of the device

Dark matter spin determination with directional direct detection experiments

Science.gov (United States)

Catena, Riccardo; Conrad, Jan; Döring, Christian; Ferella, Alfredo Davide; Krauss, Martin B.

2018-01-01

If dark matter has spin 0, only two WIMP-nucleon interaction operators can arise as leading operators from the nonrelativistic reduction of renormalizable single-mediator models for dark matter-quark interactions. Based on this crucial observation, we show that about 100 signal events at next generation directional detection experiments can be enough to enable a 2 σ rejection of the spin 0 dark matter hypothesis in favor of alternative hypotheses where the dark matter particle has spin 1 /2 or 1. In this context, directional sensitivity is crucial since anisotropy patterns in the sphere of nuclear recoil directions depend on the spin of the dark matter particle. For comparison, about 100 signal events are expected in a CF4 detector operating at a pressure of 30 torr with an exposure of approximately 26,000 cubic-meter-detector days for WIMPs of 100 GeV mass and a WIMP-fluorine scattering cross section of 0.25 pb. Comparable exposures require an array of cubic meter time projection chamber detectors.

Dynamic behaviors in directed networks

International Nuclear Information System (INIS)

Park, Sung Min; Kim, Beom Jun

2006-01-01

Motivated by the abundance of directed synaptic couplings in a real biological neuronal network, we investigate the synchronization behavior of the Hodgkin-Huxley model in a directed network. We start from the standard model of the Watts-Strogatz undirected network and then change undirected edges to directed arcs with a given probability, still preserving the connectivity of the network. A generalized clustering coefficient for directed networks is defined and used to investigate the interplay between the synchronization behavior and underlying structural properties of directed networks. We observe that the directedness of complex networks plays an important role in emerging dynamical behaviors, which is also confirmed by a numerical study of the sociological game theoretic voter model on directed networks

Seveso directive: the leading innovations

International Nuclear Information System (INIS)

Cozzani, V.; Zanelli, S.

1998-01-01

Directive 96/82/EC on the control of major accident hazards caused by dangerous substances, also known as 'Seveso-II' Directive, was adopted by the European Council on December 1996. The member states of the European Community shall bring into force the Directive not later than February 1999. Some innovative aspects of the Directive are discussed. In particular, this paper focuses on the effects of the new criteria for the identification of establishments to which the Directive obligations will apply and for land use planning in the vicinity of the establishments [it

Poly(3,4-ethylene dioxythiophene (PEDOT as a micro-neural interface material for electrostimulation

Directory of Open Access Journals (Sweden)

Seth J Wilks

2009-06-01

Full Text Available Chronic microstimulation-based devices are being investigated to treat conditions such as blindness, deafness, pain, paralysis and epilepsy. Small area electrodes are desired to achieve high selectivity. However, a major trade-off with electrode miniaturization is an increase in impedance and charge density requirements. Thus, the development of novel materials with lower interfacial impedance and enhanced charge storage capacity is essential for the development of micro-neural interface-based neuroprostheses. In this report, we study the use of conducting polymer poly(3,4-ethylene dioxythiophene (PEDOT as a neural interface material for microstimulation of small area iridium electrodes on silicon-substrate arrays. Characterized by electrochemical impedance spectroscopy, electrodeposition of PEDOT results in lower interfacial impedance at physiologically-relevant frequencies, with the 1kHz impedance magnitude being 23.3 ± 0.7 kΩ compared to 113.6 ± 3.5 kΩ for iridium oxide (IrOx on 177μm2 sites. Further, PEDOT exhibits enhanced charge storage capacity at 75.6 ± 5.4 mC/cm2 compared to 28.8 ± 0.3 mC/cm2 for IrOx, characterized by cyclic voltammetry (50 mV/s. These improvements at the electrode interface were corroborated by observation of the voltage excursions that result from constant current pulsing. The PEDOT coatings provide both a lower amplitude voltage and a more ohmic representation of the applied current compared to IrOx. During repetitive pulsing, PEDOT-coated electrodes show stable performance and little change in electrical properties, even at relatively high current densities which cause IrOx instability. These findings support the potential of PEDOT coatings as a micro-neural interface material for electrostimulation.

Intra-articular chondroma of the knee

Energy Technology Data Exchange (ETDEWEB)

Talwalkar, S.C.; Kambhampati, S.B.S.; Lang Stevenson, A.I. [Oldchurch Hospital, Romford, Essex (United Kingdom); Whitehouse, R. [Manchester University, Department of Radiology, Manchester (United Kingdom); Freemont, A. [University of Manchester, Department of Osteoarticular Pathology, Manchester (United Kingdom)

2005-06-01

Chondromas are tumours that develop in relation to the periosteum and, although they are common around the knee, most reports deal with soft tissue chondromas in para-articular locations or intracortical tumours in extra-articular regions. We report a rare case of an intra-articular chondroma in a 16-year-old boy of Asian origin developing in the region of the medial femoral condyle of the femur and extending into the femoral sulcus and the patellofemoral joint. (orig.)

Intra-articular chondroma of the knee

International Nuclear Information System (INIS)

Talwalkar, S.C.; Kambhampati, S.B.S.; Lang Stevenson, A.I.; Whitehouse, R.; Freemont, A.

2005-01-01

Chondromas are tumours that develop in relation to the periosteum and, although they are common around the knee, most reports deal with soft tissue chondromas in para-articular locations or intracortical tumours in extra-articular regions. We report a rare case of an intra-articular chondroma in a 16-year-old boy of Asian origin developing in the region of the medial femoral condyle of the femur and extending into the femoral sulcus and the patellofemoral joint. (orig.)

Neurostimulation for bladder evacuation: is sacral root stimulation a substitute for microstimulation?

Science.gov (United States)

Probst, M; Piechota, H J; Hohenfellner, M; Gleason, C A; Tanagho, E A

1997-04-01

To determine by anatomical and functional studies whether stimulation of sacral rootlets might permit selective stimulation of autonomic fibres, thus avoiding the detrusor/sphincter dyssynergia characteristic of current techniques of neurostimulation for bladder evacuation. In 10 male mongrel dogs, the S2 root was isolated and its constituent rootlets followed from their origin in the spinal cord to the point of exit from the dura. The entire root and the individual rootlets were then stimulated, including intra- and extra-dural stimulation and at proximal, mid and distal levels. Neuroanatomical and histological findings showed that rootlets of ventral S2 maintain their identity throughout their intradural course; some carry predominantly autonomic fibres, some predominantly somatic and some a mixture of the two. It appears surgically feasible to identify, isolate and sever the predominantly somatic rootlets intradurally, sparing the predominantly autonomic rootlets for inclusion in extradural electrode placement around the entire sacral root, thus eliminating sphincteric interference with detrusor contraction for voiding at low pressure.

How directional change in reading/writing habits relates to directional change in displayed pictures.

Science.gov (United States)

Lee, Hachoung; Oh, Songjoo

2016-01-01

It has been suggested that reading/writing habits may influence the appreciation of pictures. For example, people who read and write in a rightward direction have an aesthetic preference for pictures that face rightward over pictures that face leftward, and vice versa. However, correlations for this phenomenon have only been found in cross-cultural studies. Will a directional change in reading/writing habits within a culture relate to changes in picture preference? Korea is a good place to research this question because the country underwent gradual changes in reading/writing direction habits, from leftward to rightward, during the 20th century. In this study, we analyzed the direction of drawings and photos published in the two oldest newspapers in Korea from 1920-2013. The results show that the direction of the drawings underwent a clear shift from the left to the right, but the direction of the photos did not change. This finding suggests a close psychological link between the habits of reading/writing and drawing that cannot be accounted for simply by an accidental correspondence across different cultures.

A Randomized Controlled Trial Comparing the Letter Project Advance Directive to Traditional Advance Directive.

Science.gov (United States)

Periyakoil, Vyjeyanthi S; Neri, Eric; Kraemer, Helena

2017-09-01

Simpler alternatives to traditional advance directives that are easy to understand and available in multiple formats and can be initiated by patients and families will help facilitate advance care planning. The goal of this study was to compare the acceptability of the letter advance directive (LAD) to the traditional advance directive (TAD) of the state of California. A web-based, randomized controlled trial was conducted, in which the participants were randomized to one of two types of advance directives (ADs): the LAD (intervention) or the TAD (control). Primary outcomes were participant ratings of the ease, value, and their level of comfort in the AD document they completed. A total of 400 participants completed the study, with 216 randomized to the LAD and 184 to the TAD by a computerized algorithm. Overall, participants preferred the LAD to the TAD (success rate difference [SRD] = 0.46, 95th percentile confidence interval [CI]: 0.36-0.56, p advance directive to be a better alternative to the traditional advance directive form.

Directed GF-spaces

Directory of Open Access Journals (Sweden)

F.G. Arenas

2001-10-01

Full Text Available In this paper we introduce the concept of directed fractal structure, which is a generalization of the concept of fractal structure (introduced by the authors. We study the relation with transitive quasiuniformities and inverse limits of posets. We define the concept of GF-compactification and apply it to prove that the Stone-Cech compactification can be obtained as the GF-compactification of the directed fractal structure associated to the Pervin quasi-uniformity.

Epidemic threshold in directed networks

Science.gov (United States)

Li, Cong; Wang, Huijuan; Van Mieghem, Piet

2013-12-01

Epidemics have so far been mostly studied in undirected networks. However, many real-world networks, such as the online social network Twitter and the world wide web, on which information, emotion, or malware spreads, are directed networks, composed of both unidirectional links and bidirectional links. We define the directionality ξ as the percentage of unidirectional links. The epidemic threshold τc for the susceptible-infected-susceptible (SIS) epidemic is lower bounded by 1/λ1 in directed networks, where λ1, also called the spectral radius, is the largest eigenvalue of the adjacency matrix. In this work, we propose two algorithms to generate directed networks with a given directionality ξ. The effect of ξ on the spectral radius λ1, principal eigenvector x1, spectral gap (λ1-λ2), and algebraic connectivity μN-1 is studied. Important findings are that the spectral radius λ1 decreases with the directionality ξ, whereas the spectral gap and the algebraic connectivity increase with the directionality ξ. The extent of the decrease of the spectral radius depends on both the degree distribution and the degree-degree correlation ρD. Hence, in directed networks, the epidemic threshold is larger and a random walk converges to its steady state faster than that in undirected networks with the same degree distribution.

The Water Framework Directive and the Strategic Environmental Assessment Directive: Exploring the linkages

International Nuclear Information System (INIS)

Carter, Jeremy; Howe, Joe

2006-01-01

This paper highlights, explores and reflects on the linkages between the Water Framework Directive (WFD) and the Strategic Environmental Assessment (SEA) Directive. The assessment of river basin management plans (RBMPs), the key procedural linkage between the two Directives, is addressed. The assessment of other actions affecting the water environment, particularly land use plans, could also aid the achievement of the aims of the Water Framework Directive. As water quality is related intimately to the development and use of land, this significant issue is considered. There are numerous potential benefits that could arise from exploring the linkages between these two pieces of EU environmental legislation. These are highlighted, and include encouraging resource savings, generating a holistic approach to water resource management and ultimately the promotion of more sustainable forms of development

Direction-dependent exponential biassing

International Nuclear Information System (INIS)

Bending, R.C.

1974-01-01

When Monte Carlo methods are applied to penetration problems, the use of variance reduction techniques is essential if realistic computing times are to be achieved. A technique known as direction-dependent exponential biassing is described which is simple to apply and therefore suitable for problems with difficult geometry. The material cross section in any region is multiplied by a factor which depends on the particle direction, so that particles travelling in a preferred direction ''see'' a smaller cross section than those travelling in the opposite direction. A theoretical study shows that substantial gains may be obtained, and that the choice of biassing parameter is not critical. The method has been implemented alongside other importance sampling techniques in the general Monte Carlo code SPARTAN, and results obtained for simple problems using this code are included. 4 references. (U.S.)

Potential theory for directed networks.

Directory of Open Access Journals (Sweden)

Qian-Ming Zhang

Full Text Available Uncovering factors underlying the network formation is a long-standing challenge for data mining and network analysis. In particular, the microscopic organizing principles of directed networks are less understood than those of undirected networks. This article proposes a hypothesis named potential theory, which assumes that every directed link corresponds to a decrease of a unit potential and subgraphs with definable potential values for all nodes are preferred. Combining the potential theory with the clustering and homophily mechanisms, it is deduced that the Bi-fan structure consisting of 4 nodes and 4 directed links is the most favored local structure in directed networks. Our hypothesis receives strongly positive supports from extensive experiments on 15 directed networks drawn from disparate fields, as indicated by the most accurate and robust performance of Bi-fan predictor within the link prediction framework. In summary, our main contribution is twofold: (i We propose a new mechanism for the local organization of directed networks; (ii We design the corresponding link prediction algorithm, which can not only testify our hypothesis, but also find out direct applications in missing link prediction and friendship recommendation.

Potential Theory for Directed Networks

Science.gov (United States)

Zhang, Qian-Ming; Lü, Linyuan; Wang, Wen-Qiang; Zhou, Tao

2013-01-01

Uncovering factors underlying the network formation is a long-standing challenge for data mining and network analysis. In particular, the microscopic organizing principles of directed networks are less understood than those of undirected networks. This article proposes a hypothesis named potential theory, which assumes that every directed link corresponds to a decrease of a unit potential and subgraphs with definable potential values for all nodes are preferred. Combining the potential theory with the clustering and homophily mechanisms, it is deduced that the Bi-fan structure consisting of 4 nodes and 4 directed links is the most favored local structure in directed networks. Our hypothesis receives strongly positive supports from extensive experiments on 15 directed networks drawn from disparate fields, as indicated by the most accurate and robust performance of Bi-fan predictor within the link prediction framework. In summary, our main contribution is twofold: (i) We propose a new mechanism for the local organization of directed networks; (ii) We design the corresponding link prediction algorithm, which can not only testify our hypothesis, but also find out direct applications in missing link prediction and friendship recommendation. PMID:23408979

75 FR 57217 - Direct Investment Surveys: BE-11, Annual Survey of U.S. Direct Investment Abroad

Science.gov (United States)

2010-09-20

... both U.S. and international definitions for foreign direct investment and must be represented in the...] RIN 0691-AA74 Direct Investment Surveys: BE-11, Annual Survey of U.S. Direct Investment Abroad AGENCY... the reporting requirements for the BE-11, Annual Survey of U.S. Direct Investment Abroad. The survey...

Decrease of motor cortex excitability following exposure to a 20 Hz magnetic field as generated by a rotating permanent magnet.

Science.gov (United States)

Gallasch, Eugen; Rafolt, Dietmar; Postruznik, Magdalena; Fresnoza, Shane; Christova, Monica

2018-04-19

Rotation of a static magnet over the motor cortex (MC) generates a transcranial alternating magnetic field (tAMF), and a linked alternating electrical field. The aim of this transcranial magnetic stimulation (TMS) study is to investigate whether such fields are able to influence MC excitability, and whether there are parallels to tACS induced effects. Fourteen healthy volunteers received 20 Hz tAMF stimulation over the MC, over the vertex, and 20 Hz tACS over the MC, each with a duration of 15 min. TMS assessments were performed before and after the interventions. Changes in motor evoked potentials (MEP), short interval intra-cortical inhibition (SICI) and intra-cortical facilitation (ICF) were evaluated. The tACS and the tAMF stimulation over the MC affected cortical excitability in a different way. After tAMF stimulation MEP amplitudes and ICF decreased and the effect of SICI increased. After tACS MEP amplitudes increased and there were no effects on SICI and ICF. The recorded single and paired pulse MEPs indicate a general decrease of MC excitability following 15 min of tAMF stimulation. The effects demonstrate that devices based on rotating magnets are potentially suited to become a novel brain stimulation tool in clinical neurophysiology. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography

Science.gov (United States)

Kerckhofs, G.; Durand, M.; Vangoitsenhoven, R.; Marin, C.; van der Schueren, B.; Carmeliet, G.; Luyten, F. P.; Geris, L.; Vandamme, K.

2016-10-01

High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging.

[Transcranial magnetic stimulation (TMS), inhibition processes and attention deficit/hyperactivity disorder (ADHD) - an overview].

Science.gov (United States)

Hoegl, Thomas; Bender, Stephan; Buchmann, Johannes; Kratz, Oliver; Moll, Gunther H; Heinrich, Hartmut

2014-11-01

Motor system excitability can be tested by transcranial magnetic stimulation CFMS). In this article, an overview of recent methodological developments and research findings related to attention deficit/hyperactivity disorder (ADHD) is provided. Different TMS parameters that reflect the function of interneurons in the motor cortex may represent neurophysiological markers of inhibition in ADHD, particularly the so-called intracortical inhibition. In children with a high level of hyperactivity and impulsivity, intracortical inhibition was comparably low at rest as shortly before the execution of a movement. TMS-evoked potentials can also be measured in the EEG so that investigating processes of excitability is not restricted to motor areas in future studies. The effects of methylphenidate on motor system excitability may be interpreted in the sense of a 'fine-tuning' with these mainly dopaminergic effects also depending on genetic parameters (DAT1 transporter). A differentiated view on the organization of motor control can be achieved by a combined analysis of TMS parameters and event-related potentials. Applying this bimodal approach, strong evidence for a deviant implementation of motor control in children with ADHD and probably compensatory mechanisms (with involvement of the prefrontal cortex) was obtained. These findings, which contribute to a better understanding of hyperactivity/impulsivity, inhibitory processes and motor control in ADHD as well as the mechanisms of medication, underline the relevance of TMS as a neurophysiological method in ADHD research.

Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography

Science.gov (United States)

Kerckhofs, G.; Durand, M.; Vangoitsenhoven, R.; Marin, C.; Van der Schueren, B.; Carmeliet, G.; Luyten, F. P.; Geris, L.; Vandamme, K.

2016-01-01

High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging. PMID:27759061

Type-Directed Partial Evaluation

DEFF Research Database (Denmark)

Danvy, Olivier

1998-01-01

Type-directed partial evaluation uses a normalization function to achieve partial evaluation. These lecture notes review its background, foundations, practice, and applications. Of specific interest is the modular technique of offline and online type-directed partial evaluation in Standard ML...

Type-Directed Partial Evaluation

DEFF Research Database (Denmark)

Danvy, Olivier

1998-01-01

Type-directed partial evaluation uses a normalization function to achieve partial evaluation. These lecture notes review its background, foundations, practice, and applications. Of specific interest is the modular technique of offline and online type-directed partial evaluation in Standard ML of ...

Efficient Placement of Directional Antennas

Energy Technology Data Exchange (ETDEWEB)

Pan, Feng [Los Alamos National Laboratory; Kasiviswanathan, Shiva [Los Alamos National Laboratory

2010-09-20

Directional antenna is an technology for the proliferation of wireless networks. In centralized wireless network, wireless devices communicate through base stations. Directed antennas are placed on base stations and form a backbone of communication. The communication between base stations and wireless devices can be interfered due to a large number of wireless device. Methodically positioning and orienting directed antennas can help to reduce the interference while saving energy. An integer linear programming is developed for siting and directing antennas on multiple base stations, and this formulation can be extended to model non-overlapping channels. Through the integer programming formulation, optimal antenna positions can be used to analyze the performance of directed antennas with different parameters like the number base stations and the number of non-overlapping channels.

Directional Tuning Curves, Elementary Movement Detectors, and the Estimation of the Direction of Visual Movement

NARCIS (Netherlands)

Hateren, J.H. van

1990-01-01

Both the insect brain and the vertebrate retina detect visual movement with neurons having broad, cosine-shaped directional tuning curves oriented in either of two perpendicular directions. This article shows that this arrangement can lead to isotropic estimates of the direction of movement: for any

Direct Manipulation in Virtual Reality

Science.gov (United States)

Bryson, Steve

2003-01-01

Virtual Reality interfaces offer several advantages for scientific visualization such as the ability to perceive three-dimensional data structures in a natural way. The focus of this chapter is direct manipulation, the ability for a user in virtual reality to control objects in the virtual environment in a direct and natural way, much as objects are manipulated in the real world. Direct manipulation provides many advantages for the exploration of complex, multi-dimensional data sets, by allowing the investigator the ability to intuitively explore the data environment. Because direct manipulation is essentially a control interface, it is better suited for the exploration and analysis of a data set than for the publishing or communication of features found in that data set. Thus direct manipulation is most relevant to the analysis of complex data that fills a volume of three-dimensional space, such as a fluid flow data set. Direct manipulation allows the intuitive exploration of that data, which facilitates the discovery of data features that would be difficult to find using more conventional visualization methods. Using a direct manipulation interface in virtual reality, an investigator can, for example, move a data probe about in space, watching the results and getting a sense of how the data varies within its spatial volume.

Directionality of dog vocalizations

Science.gov (United States)

Frommolt, Karl-Heinz; Gebler, Alban

2004-07-01

The directionality patterns of sound emission in domestic dogs were measured in an anechoic environment using a microphone array. Mainly long-distance signals from four dogs were investigated. The radiation pattern of the signals differed clearly from an omnidirectional one with average differences in sound-pressure level between the frontal and rear position of 3-7 dB depending from the individual. Frequency dependence of directionality was shown for the range from 250 to 3200 Hz. The results indicate that when studying acoustic communication in mammals, more attention should be paid to the directionality pattern of sound emission.

Invariance of directed spaces and persistence

DEFF Research Database (Denmark)

2006-01-01

With motivations arising from concurrency theory within Computer Science, a new field of research, directed algebraic topology, has emerged. The main characteristic is, that it involves spaces of "directed paths'' (or timed paths, executions) in a "directed space''; these directed paths can be co...

PROTOTIPE VIDEO EDITOR DENGAN MENGGUNAKAN DIRECT X DAN DIRECT SHOW

Directory of Open Access Journals (Sweden)

Djoni Haryadi Setiabudi

2004-01-01

Full Text Available Technology development had given people the chance to capture their memorable moments in video format. A high quality digital video is a result of a good editing process. Which in turn, arise the new need of an editor application. In accordance to the problem, here the process of making a simple application for video editing needs. The application development use the programming techniques often applied in multimedia applications, especially video. First part of the application will begin with the video file compression and decompression, then we'll step into the editing part of the digital video file. Furthermore, the application also equipped with the facilities needed for the editing processes. The application made with Microsoft Visual C++ with DirectX technology, particularly DirectShow. The application provides basic facilities that will help the editing process of a digital video file. The application will produce an AVI format file after the editing process is finished. Through the testing process of this application shows the ability of this application to do the 'cut' and 'insert' of video files in AVI, MPEG, MPG and DAT formats. The 'cut' and 'insert' process only can be done in static order. Further, the aplication also provide the effects facility for transition process in each clip. Lastly, the process of saving the new edited video file in AVI format from the application. Abstract in Bahasa Indonesia : Perkembangan teknologi memberi kesempatan masyarakat untuk mengabadikan saat - saat yang penting menggunakan video. Pembentukan video digital yang baik membutuhkan proses editing yang baik pula. Untuk melakukan proses editing video digital dibutuhkan program editor. Berdasarkan permasalahan diatas maka pada penelitian ini dibuat prototipe editor sederhana untuk video digital. Pembuatan aplikasi memakai teknik pemrograman di bidang multimedia, khususnya video. Perencanaan dalam pembuatan aplikasi tersebut dimulai dengan pembentukan

Thalamocortical NMDA conductances and intracortical inhibition can explain cortical temporal tuning

Science.gov (United States)

Krukowski, A. E.; Miller, K. D.

2001-01-01

Cells in cerebral cortex fail to respond to fast-moving stimuli that evoke strong responses in the thalamic nuclei innervating the cortex. The reason for this behavior has remained a mystery. We study an experimentally motivated model of the thalamic input-recipient layer of cat primary visual cortex that accounts for many aspects of cortical orientation tuning. In this circuit, inhibition dominates over excitation, but temporal modulations of excitation and inhibition occur out of phase with one another, allowing excitation to transiently drive cells. We show that this circuit provides a natural explanation of cortical low-pass temporal frequency tuning, provided N-methyl-D-aspartate (NMDA) receptors are present in thalamocortical synapses in proportions measured experimentally. This suggests a new and unanticipated role for NMDA conductances in shaping the temporal response properties of cortical cells, and suggests that common cortical circuit mechanisms underlie both spatial and temporal response tuning.

Direct Sulfation of Limestone

DEFF Research Database (Denmark)

Hu, Guilin; Dam-Johansen, Kim; Wedel, Stig

2007-01-01

The direct sulfation of limestone was studied in a laboratory fixed-bed reactor. It is found that the direct sulfation of limestone involves nucleation and crystal grain growth of the solid product (anhydrite). At 823 K and at low-conversions (less than about 0.5 %), the influences of SO2, O-2...... and CO2 on the direct sulfation of limestone corresponds to apparent reaction orders of about 0.2, 0.2 and -0.5, respectively. Water is observed to promote the sulfation reaction and increase the apparent reaction orders of SO2 and O-2. The influence of O-2 at high O-2 concentrations (> about 15...... %) becomes negligible. In the temperature interval from 723 K to 973 K, an apparent activation energy of about 104 kJ/mol is observed for the direct sulfation of limestone. At low temperatures and low conversions, the sulfation process is most likely under mixed control by chemical reaction and solid...

Directive and Non-Directive Movement in Child Therapy.

Science.gov (United States)

Krason, Katarzyna; Szafraniec, Grazyna

1999-01-01

Presents a new authorship method of child therapy based on visualization through motion. Maintains that this method stimulates motor development and musical receptiveness, and promotes personality development. Suggests that improvised movement to music facilitates the projection mechanism and that directed movement starts the channeling phase.…

40 CFR 73.72 - Direct sales.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Direct sales. 73.72 Section 73.72... ALLOWANCE SYSTEM Auctions, Direct Sales, and Independent Power Producers Written Guarantee § 73.72 Direct sales. Allowances that were formerly part of the direct sale program, which has been terminated under...

Direct Conversion of Energy.

Science.gov (United States)

Corliss, William R.

This publication is one of a series of information booklets for the general public published by the United States Atomic Energy Commission. Direct energy conversion involves energy transformation without moving parts. The concepts of direct and dynamic energy conversion plus the laws governing energy conversion are investigated. Among the topics…

Decisions Concerning Directional Dependence

Science.gov (United States)

von Eye, Alexander; DeShon, Richard P.

2012-01-01

In this rejoinder, von Eye and DeShon discuss the decision strategies proposed in their original article ("Directional Dependence in Developmental Research," this issue), as well as the ones proposed by the authors of the commentary (Pornprasertmanit and Little, "Determining Directional Dependency in Causal Associations," this issue). In addition,…

Direct oral anticoagulants: An update.

Science.gov (United States)

Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

2017-12-30

Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

NASA directives: Master list and index

Science.gov (United States)

1994-01-01

This Handbook sets forth in two parts the following information for the guidance of users of the NASA Management Directives System. Chapter 1 contains introductory information material on how to use this Handbook. Chapter 2 is a complete master list of Agency-wide management directives, describing each directive by type, number, effective date, expiration date, title, and organization code of the office responsible for the directive. Chapter 3 includes a consolidated numerical list of all delegations of authority and a breakdown of such delegation by the office of Installation to which special authority is assigned. Chapter 4 sets forth a consolidated list of all NASA Handbooks (NHB's) and important footnotes covering the control and ordering of such documents. Chapter 5 is a consolidated list of NASA management directives applicable to the Jet Propulsion Laboratory. Chapter 6 is a consolidated list of NASA management directives published in the code of Federal Regulations. Complementary manuals to the NASA Management Directives System are described in Chapter 7. Part B contains an in-depth alphabetical index to all NASA management directives other than Handbooks.

A wide-range direction neutron spectrometer

International Nuclear Information System (INIS)

Luszik-Bhadra, M.; D'Errico, F.; Hecker, O.; Matzke, M.

2002-01-01

A new device is presented which has been developed for measuring the energy and direction of distribution of neutron fluence in fields of broad energy spectra (thermal to 100 MeV) and with a high background of photon, electron and muon radiation. The device was tested in reference fields with different energy and direction distributions of neutron fluence. The direction-integrated fluence spectra agree fairly well with reference spectra. In all cases, the ambient and personal dose equivalent values calculated from measured direction-differential spectra are within 35% of the reference values. Independent measurements of the directional dose equivalent were performed with a directional dose equivalent monitor based on superheated drop detectors

Direct cooled power electronics substrate

Science.gov (United States)

Wiles, Randy H [Powell, TN; Wereszczak, Andrew A [Oak Ridge, TN; Ayers, Curtis W [Kingston, TN; Lowe, Kirk T [Knoxville, TN

2010-09-14

The disclosure describes directly cooling a three-dimensional, direct metallization (DM) layer in a power electronics device. To enable sufficient cooling, coolant flow channels are formed within the ceramic substrate. The direct metallization layer (typically copper) may be bonded to the ceramic substrate, and semiconductor chips (such as IGBT and diodes) may be soldered or sintered onto the direct metallization layer to form a power electronics module. Multiple modules may be attached to cooling headers that provide in-flow and out-flow of coolant through the channels in the ceramic substrate. The modules and cooling header assembly are preferably sized to fit inside the core of a toroidal shaped capacitor.

Direct and semi-direct approaches to lepton mixing with a massless neutrino

International Nuclear Information System (INIS)

King, Stephen F.; Ludl, Patrick Otto

2016-01-01

We discuss the possibility of enforcing a massless Majorana neutrino in the direct and semi-direct approaches to lepton mixing, in which the PMNS matrix is partly predicted by subgroups of a discrete family symmetry, extending previous group searches up to order 1535. We find a phenomenologically viable scheme for the semi-direct approach based on Q(648) which contains Δ(27) and the quaternion group as subgroups. This leads to novel predictions for the first column of the PMNS matrix corresponding to a normal neutrino mass hierarchy with m_1=0, and sum rules for the mixing angles and phase which are characterised by the solar angle being on the low side θ_1_2∼31"∘ and the Dirac (oscillation) CP phase δ being either about ±45"∘ or ±π.

Brain machine interface and limb reanimation technologies: restoring function after spinal cord injury through development of a bypass system.

Science.gov (United States)

Lobel, Darlene A; Lee, Kendall H

2014-05-01

Functional restoration of limb movement after traumatic spinal cord injury (SCI) remains the ultimate goal in SCI treatment and directs the focus of current research strategies. To date, most investigations in the treatment of SCI focus on repairing the injury site. Although offering some promise, these efforts have met with significant roadblocks because treatment measures that are successful in animal trials do not yield similar results in human trials. In contrast to biologic therapies, there are now emerging neural interface technologies, such as brain machine interface (BMI) and limb reanimation through electrical stimulators, to create a bypass around the site of the SCI. The BMI systems analyze brain signals to allow control of devices that are used to assist SCI patients. Such devices may include a computer, robotic arm, or exoskeleton. Limb reanimation technologies, which include functional electrical stimulation, epidural stimulation, and intraspinal microstimulation systems, activate neuronal pathways below the level of the SCI. We present a concise review of recent advances in the BMI and limb reanimation technologies that provides the foundation for the development of a bypass system to improve functional outcome after traumatic SCI. We also discuss challenges to the practical implementation of such a bypass system in both these developing fields. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

State-Dependent Decoding Algorithms Improve the Performance of a Bidirectional BMI in Anesthetized Rats

Directory of Open Access Journals (Sweden)

Vito De Feo

2017-05-01

Full Text Available Brain-machine interfaces (BMIs promise to improve the quality of life of patients suffering from sensory and motor disabilities by creating a direct communication channel between the brain and the external world. Yet, their performance is currently limited by the relatively small amount of information that can be decoded from neural activity recorded form the brain. We have recently proposed that such decoding performance may be improved when using state-dependent decoding algorithms that predict and discount the large component of the trial-to-trial variability of neural activity which is due to the dependence of neural responses on the network's current internal state. Here we tested this idea by using a bidirectional BMI to investigate the gain in performance arising from using a state-dependent decoding algorithm. This BMI, implemented in anesthetized rats, controlled the movement of a dynamical system using neural activity decoded from motor cortex and fed back to the brain the dynamical system's position by electrically microstimulating somatosensory cortex. We found that using state-dependent algorithms that tracked the dynamics of ongoing activity led to an increase in the amount of information extracted form neural activity by 22%, with a consequently increase in all of the indices measuring the BMI's performance in controlling the dynamical system. This suggests that state-dependent decoding algorithms may be used to enhance BMIs at moderate computational cost.

State-Dependent Decoding Algorithms Improve the Performance of a Bidirectional BMI in Anesthetized Rats.

Science.gov (United States)

De Feo, Vito; Boi, Fabio; Safaai, Houman; Onken, Arno; Panzeri, Stefano; Vato, Alessandro

2017-01-01

Brain-machine interfaces (BMIs) promise to improve the quality of life of patients suffering from sensory and motor disabilities by creating a direct communication channel between the brain and the external world. Yet, their performance is currently limited by the relatively small amount of information that can be decoded from neural activity recorded form the brain. We have recently proposed that such decoding performance may be improved when using state-dependent decoding algorithms that predict and discount the large component of the trial-to-trial variability of neural activity which is due to the dependence of neural responses on the network's current internal state. Here we tested this idea by using a bidirectional BMI to investigate the gain in performance arising from using a state-dependent decoding algorithm. This BMI, implemented in anesthetized rats, controlled the movement of a dynamical system using neural activity decoded from motor cortex and fed back to the brain the dynamical system's position by electrically microstimulating somatosensory cortex. We found that using state-dependent algorithms that tracked the dynamics of ongoing activity led to an increase in the amount of information extracted form neural activity by 22%, with a consequently increase in all of the indices measuring the BMI's performance in controlling the dynamical system. This suggests that state-dependent decoding algorithms may be used to enhance BMIs at moderate computational cost.

Algorithm for counting large directed loops

Energy Technology Data Exchange (ETDEWEB)

Bianconi, Ginestra [Abdus Salam International Center for Theoretical Physics, Strada Costiera 11, 34014 Trieste (Italy); Gulbahce, Natali [Theoretical Division and Center for Nonlinear Studies, Los Alamos National Laboratory, NM 87545 (United States)

2008-06-06

We derive a Belief-Propagation algorithm for counting large loops in a directed network. We evaluate the distribution of the number of small loops in a directed random network with given degree sequence. We apply the algorithm to a few characteristic directed networks of various network sizes and loop structures and compare the algorithm with exhaustive counting results when possible. The algorithm is adequate in estimating loop counts for large directed networks and can be used to compare the loop structure of directed networks and their randomized counterparts.

Advanced directives: open issues

Directory of Open Access Journals (Sweden)

Gabriella Negrini

2013-05-01

Full Text Available BACKGROUND In Italy Advanced directives have not been regulated by law yet. Moreover, there is a confusion of concepts: advanced directives, refusal of treatment, medical futility and euthanasia are not synonymous.DISCUSSION The following aspects are then discussed: object of directives; elapse of time between their expression and their application; knowledge of the directives and their obligatory nature. The refusal of a treatment that can save a person’s life is a critical subject. There are different ethical points of view: according to lay ethics, the patient’s self-determination prevails; the religious viewpoint, instead, says that life is a gift which we cannot dispose of. In any case, the patient will be confronted with the professional autonomy of the doctor. Should the doctor save a patient’s life in any case or should he achieve best clinical practice, in respect of his will? The doctor should interpret the patient’s will but with caution and judgment. An exemption from responsibility should be provided by law for doctors who respect patient’s living will.

Multi-Directional Environmental Sensors

Science.gov (United States)

Manohara, Harish (Inventor); Del Castillo, Linda Y. (Inventor); Mojarradi, Mohammed M. (Inventor)

2016-01-01

Systems and methods in accordance with embodiments of the invention implement multi-directional environmental sensors. In one embodiment, a multi-directional environmental sensor includes: an inner conductive element that is substantially symmetrical about three orthogonal planes; an outer conductive element that is substantially symmetrical about three orthogonal planes; and a device that measures the electrical characteristics of the multi-directional environmental sensor, the device having a first terminal and a second terminal; where the inner conductive element is substantially enclosed within the outer conductive element; where the inner conductive element is electrically coupled to the first terminal of the device; and where the outer conductive element is electrically coupled to the second terminal of the device.

Direct catastrophic injury in sports.

Science.gov (United States)

Boden, Barry P

2005-11-01

Catastrophic sports injuries are rare but tragic events. Direct (traumatic) catastrophic injury results from participating in the skills of a sport, such as a collision in football. Football is associated with the greatest number of direct catastrophic injuries for all major team sports in the United States. Pole vaulting, gymnastics, ice hockey, and football have the highest incidence of direct catastrophic injuries for sports in which males participate. In most sports, the rate of catastrophic injury is higher at the collegiate than at the high school level. Cheerleading is associated with the highest number of direct catastrophic injuries for all sports in which females participate. Indirect (nontraumatic) injury is caused by systemic failure as a result of exertion while participating in a sport. Cardiovascular conditions, heat illness, exertional hyponatremia, and dehydration can cause indirect catastrophic injury. Understanding the common mechanisms of injury and prevention strategies for direct catastrophic injuries is critical in caring for athletes.

Direct photons in WA98

CERN Document Server

Aggarwal, M M; Ahammed, Z; Angelis, Aris L S; Antonenko, V G; Arefev, V; Astakhov, V A; Avdeichikov, V; Awes, T C; Baba, P V K S; Badyal, S K; Barlag, C; Bathe, S; Batyunya, B; Bernier, T; Bhalla, K B; Bhatia, V S; Blume, C; Bock, R; Bohne, E M; Böröcz, Z K; Bucher, D; Buijs, A; Büsching, H; Carlén, L; Chalyshev, V; Chattopadhyay, S; Cherbachev, R; Chujo, T; Claussen, A; Das, A C; Decowski, M P; Delagrange, H; Dzhordzhadze, V; Dönni, P; Dubovik, I; Dutt, S; Dutta-Majumdar, M R; El-Chenawi, K F; Eliseev, S; Enosawa, K; Foka, P Y; Fokin, S L; Ganti, M S; Garpman, S; Gavrishchuk, O P; Geurts, F J M; Ghosh, T K; Glasow, R; Gupta, S K; Guskov, B; Gustafsson, Hans Åke; Gutbrod, H H; Higuchi, R; Hrivnacova, I; Ippolitov, M S; Kalechofsky, H; Kamermans, R; Kampert, K H; Karadzhev, K; Karpio, K; Kato, S; Kees, S; Klein-Bösing, C; Knoche, S; Kolb, B W; Kosarev, I G; Kucheryaev, I; Krümpel, T; Kugler, A; Kulinich, P A; Kurata, M; Kurita, K; Kuzmin, N A; Langbein, I; Lee, Y Y; Löhner, H; Luquin, Lionel; Mahapatra, D P; Man'ko, V I; Martin, M; Martínez, G; Maksimov, A; Mgebrishvili, G; Miake, Y; Mir, M F; Mishra, G C; Miyamoto, Y; Mohanty, B; Morrison, D; Mukhopadhyay, D S; Naef, H; Nandi, B K; Nayak, S K; Nayak, T K; Neumaier, S; Nyanin, A; Nikitin, V A; Nikolaev, S; Nilsson, P O; Nishimura, S; Nomokonov, V P; Nystrand, J; Obenshain, F E; Oskarsson, A; Otterlund, I; Pachr, M; Pavlyuk, S; Peitzmann, Thomas; Petracek, V; Pinganaud, W; Plasil, F; Von Poblotzki, U; Purschke, M L; Rak, J; Raniwala, R; Raniwala, S; Ramamurthy, V S; Rao, N K; Retière, F; Reygers, K; Roland, G; Rosselet, L; Rufanov, I A; Roy, C; Rubio, J M; Sako, H; Sambyal, S S; Santo, R; Sato, S; Schlagheck, H; Schmidt, H R; Schutz, Y; Shabratova, G; Shah, T H; Sibiryak, Yu; Siemiarczuk, T; Silvermyr, D; Sinha, B C; Slavin, N V; Söderström, K; Solomey, Nickolas; Sood, G; Sørensen, S P; Stankus, P; Stefanek, G; Steinberg, P; Stenlund, E; Stüken, D; Sumbera, M; Svensson, S; Trivedi, M D; Tsvetkov, A A; Tykarski, L; Urbahn, J; Van den Pijll, E C; van Eijndhoven, N; van Nieuwenhuizen, G J; Vinogradov, A; Viyogi, Y P; Vodopyanov, A S; Vörös, S; Wyslouch, B; Yagi, K; Yokota, Y; Young, G R

2002-01-01

A measurement of direct photon production in /sup 208/Pb+/sup 208/Pb collisions at 158 A GeV has been carried out in the CERN WA98 experiment. The invariant yield of direct photons was extracted as a function of transverse momentum in the interval 0.51.5 GeV/c. the result constitutes the first observation of direct photons in ultrarelativistic heavy-ion collisions. (19 refs).

NASA directives master list and index

Science.gov (United States)

1995-01-01

This handbook sets forth in two parts, Master List of Management Directives and Index to NASA Management Directives, the following information for the guidance of users of the NASA Management Directives System. Chapter 1 contains introductory information material on how to use this handbook. Chapter 2 is a complete master list of agencywide management directives, describing each directive by type, number, effective date, expiration date, title, and organization code of the office responsible for the directive. Chapter 3 includes a consolidated numerical list of all delegations of authority and a breakdown of such delegation by the office or center to which special authority is assigned. Chapter 4 sets forth a consolidated list of all NASA handbooks (NHB's) and important footnotes covering the control and ordering of such documents. Chapter 5 is a consolidated list of NASA management directives applicable to the Jet Propulsion Laboratory. Chapter 6 is a consolidated list of NASA regulations published in the Code of Federal Regulations. Chapter 7 is a consolidated list of NASA regulations published in Title 14 of the Code of Federal Regulations. Complementary manuals to the NASA Management Directives System are described in Chapter 8. The second part contains an in depth alphabetical index to all NASA management directives other than handbooks, most of which are indexed by titles only.

Direct Problem-Based Learning (DPBL): A Framework for Integrating Direct Instruction and Problem-Based Learning Approach

Science.gov (United States)

Winarno, Sri; Muthu, Kalaiarasi Sonai; Ling, Lew Sook

2018-01-01

Direct instruction approach has been widely used in higher education. Many studies revealed that direct instruction improved students' knowledge. The characteristics of direct instruction include the subject delivered through face-to-face interaction with the lecturers and materials that sequenced deliberately and taught explicitly. However,…

Asynchronous machines. Direct torque control; Machines asynchrones. Commande par controle direct de couple

Energy Technology Data Exchange (ETDEWEB)

Fornel, B. de [Institut National Polytechnique, 31 - Toulouse (France)

2006-05-15

The asynchronous machine, with its low cost and robustness, is today the most widely used motor to make speed variators. However, its main drawback is that the same current generates both the magnetic flux and the torque, and thus any torque variation creates a flux variation. Such a coupling gives to the asynchronous machine a nonlinear behaviour which makes its control much more complex. The direct self control (DSC) method has been developed to improve the low efficiency of the scalar control method and for the specific railway drive application. The direct torque control (DTC) method is derived from the DSC method but corresponds to other type of applications. The DSC and DTC algorithms for asynchronous motors are presented in this article: 1 - direct control of the stator flux (DSC): principle, flux control, torque control, switching frequency of the inverter, speed estimation; 2 - direct torque control (DTC): principle, electromagnetic torque derivative, signals shape and switching frequency, some results, DTC speed variator without speed sensor, DTC application to multi-machine multi-converter systems; 3 - conclusion. (J.S.)

Preparation of directly iodinated steroid hormones and related directly halogenated compounds

International Nuclear Information System (INIS)

Sahadevan, V.

1981-01-01

The preparation of directly iodinated radioactive steroid hormones is described for use in radioimmunoassays or radiolocalization and treatment of human breast tumours. The radioactive iodinated steroid hormone is prepared by reacting a parent steroid hormone with an alkali metal iodide containing radioactive 123 I, 125 I, 130 I or 131 I in the presence of hydrogen peroxide or chloramine-T. The parent steroid hormones include the adrenal corticosteroids, the estrogens, the progestogens, the progestins and the diuretic and antidiuretic agents. The radioactive iodinated steroid hormone is prepared by iodinating the parent steroid hormone directly on the cyclopentanophenanthrene nucleus. The radioactive iodinated steroid hormones have the same antigenicity and receptor site specificity as the parent steroid hormone. The invention is illustrated by 1) the method of iodination of estradiol-17β, 2) results for the percentage labelling of several steroids and steroid hormones, 3) results for the radioimmunoassay of 125 I-estradiol and 4) results for the binding of directly iodinated estradiol-17β in an estrogen receptor assay of human breast cancer. (U.K.)

Stimulus driver for epilepsy seizure suppression with adaptive loading impedance

Science.gov (United States)

Ker, Ming-Dou; Lin, Chun-Yu; Chen, Wei-Ling

2011-10-01

A stimulus driver circuit for a micro-stimulator used in an implantable device is presented in this paper. For epileptic seizure control, the target of the driver was to output 30 µA stimulus currents when the electrode impedance varied between 20 and 200 kΩ. The driver, which consisted of the output stage, control block and adaptor, was integrated in a single chip. The averaged power consumption of the stimulus driver was 0.24-0.56 mW at 800 Hz stimulation rate. Fabricated in a 0.35 µm 3.3 V/24 V CMOS process and applied to a closed-loop epileptic seizure monitoring and controlling system, the proposed design has been successfully verified in the experimental results of Long-Evans rats with epileptic seizures.

Law, autonomy and advance directives.

Science.gov (United States)

Willmott, Lindy; White, Ben; Mathews, Ben

2010-12-01

The principle of autonomy underpins legal regulation of advance directives that refuse life-sustaining medical treatment. The primacy of autonomy in this domain is recognised expressly in the case law, through judicial pronouncement, and implicitly in most Australian jurisdictions, through enactment into statute of the right to make an advance directive. This article seeks to justify autonomy as an appropriate principle for regulating advance directives and relies on three arguments: the necessity of autonomy in a liberal democracy; the primacy of autonomy in medical ethics discourse; and the uncontested importance of autonomy in the law on contemporaneous refusal of medical treatment. This article also responds to key criticisms that autonomy is not an appropriate organising principle to underpin legal regulation of advance directives.

76 FR 58420 - Direct Investment Surveys: BE-12, Benchmark Survey of Foreign Direct Investment in the United States

Science.gov (United States)

2011-09-21

...] RIN 0691-AA80 Direct Investment Surveys: BE-12, Benchmark Survey of Foreign Direct Investment in the... of Foreign Direct Investment in the United States. Benchmark surveys are conducted every five years; the prior survey covered 2007. The benchmark survey covers the universe of foreign direct investment...

Tactile pavement for guiding walking direction: An assessment of heading direction and gait stability.

NARCIS (Netherlands)

Pluyter, N.; de Wit, L.P.; Bruijn, S.M.; Plaisier, M.A.

2015-01-01

For maintaining heading direction while walking we heavily rely on vision. Therefore, walking in the absence of vision or with visual attention directed elsewhere potentially leads to dangerous situations. Here we investigated whether tactile information from the feet can be used as a (partial)

Direct channel problems and phenomena

International Nuclear Information System (INIS)

Cutkosky, R.E.

1975-01-01

Direct channel problems and phenomena are considered covering the need for precision hadron spectroscopy, the data base for precision hadron spectroscopy, some relations between direct-channel and cross-channel effects, and spin rotation phenomena

Psychiatric Advance Directives: Getting Started

Science.gov (United States)

... News Legal Issues Search for: About PADs A psychiatric advance directive (PAD) is a legal document that ... decisions during a mental health crisis. Getting Started Psychiatric advance directives (PADs) are relatively new legal instruments ...

Entrance Counseling Guide for Direct Loan Borrowers

Science.gov (United States)

Federal Student Aid, US Department of Education, 2010

2010-01-01

This guide describes the four types of loans offered by the Direct Loan Program[SM]: (1) Direct Subsidized Loans; (2) Direct Unsubsidized Loans; (3) Direct PLUS Loans; and (4) Direct Consolidation Loans. Among the topics covered in the guide are: Use of Your Loan Money, The Master Promissory Note, How Your Loans Will Be Disbursed (Paid Out),…

Direct ophthalmoscopy on YouTube

DEFF Research Database (Denmark)

Borgersen, Nanna Jo; Henriksen, Mikael Johannes Vuokko; Konge, Lars

2016-01-01

BACKGROUND: Direct ophthalmoscopy is well-suited for video-based instruction, particularly if the videos enable the student to see what the examiner sees when performing direct ophthalmoscopy. We evaluated the pedagogical effectiveness of instructional YouTube videos on direct ophthalmoscopy...... in general. We then systematically searched YouTube. Two authors reviewed eligible videos to assess eligibility and extract data on video statistics, content, and approach to visualization. Correlations between video statistics and contents were investigated using two-tailed Spearman's correlation. RESULTS...... the patient and how to examine the fundus. Time spent on fundus examination correlated with the number of views per week (Spearman's ρ=0.53; P=0.029). CONCLUSION: Videos may help overcome the pedagogical issues in teaching direct ophthalmoscopy; however, the few available videos on YouTube fail to address...

Directed Innovation of Business Models

Directory of Open Access Journals (Sweden)

Stelian Brad

2016-06-01

Full Text Available Business model innovation is an important issue to keep business competitive and increase company’s profits. Due to many market attractors, identification of appropriate paths of business model evolution is a painful and risky process. To improve decision’s effectiveness in this process, an architectural construct of analysis and conceptualization for business model innovation that combines directed evolution and blue ocean concepts is proposed in this paper under the name of directed innovation. It displays the key points where innovations would happen to direct adaptation of the business model towards sustainable competitiveness. Formulation of mature solutions is supported by inventive problem solving tools. The significance of the directed innovation approach is demonstrated in a case study dealing with business model innovation of a software company.

Innovative tool of direct marketing

OpenAIRE

T.S. Maksymova

2010-01-01

The aspects of direct marketing activation on the basis of interactive applications introduction are examined. Basic advantages, linked with the use of the integrated marketing communications during formation of direct marketing strategies are open up.

Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex.

Science.gov (United States)

Yang, Jinfang; Wang, Qian; He, Fenfen; Ding, Yanxia; Sun, Qingyan; Hua, Tianmiao; Xi, Minmin

2016-01-01

Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability.

EXiO-A Brain-Controlled Lower Limb Exoskeleton for Rhesus Macaques.

Science.gov (United States)

Vouga, Tristan; Zhuang, Katie Z; Olivier, Jeremy; Lebedev, Mikhail A; Nicolelis, Miguel A L; Bouri, Mohamed; Bleuler, Hannes

2017-02-01

Recent advances in the field of brain-machine interfaces (BMIs) have demonstrated enormous potential to shape the future of rehabilitation and prosthetic devices. Here, a lower-limb exoskeleton controlled by the intracortical activity of an awake behaving rhesus macaque is presented as a proof-of-concept for a locomotorBMI. A detailed description of the mechanical device, including its innovative features and first experimental results, is provided. During operation, BMI-decoded position and velocity are directly mapped onto the bipedal exoskeleton's motions, which then move the monkey's legs as the monkey remains physicallypassive. To meet the unique requirements of such an application, the exoskeleton's features include: high output torque with backdrivable actuation, size adjustability, and safe user-robot interface. In addition, a novel rope transmission is introduced and implemented. To test the performance of the exoskeleton, a mechanical assessment was conducted, which yielded quantifiable results for transparency, efficiency, stiffness, and tracking performance. Usage under both brain control and automated actuation demonstrates the device's capability to fulfill the demanding needs of this application. These results lay the groundwork for further advancement in BMI-controlled devices for primates including humans.

Direct RF modulation transmitter, sampling clock frequency setting method for direct RF modulation transmitter

NARCIS (Netherlands)

Fukuda, Shuichi; Nauta, Bram

2013-01-01

PROBLEM TO BE SOLVED: To provide a direct RF modulation transmitter capable of satisfying a radiation level regulation even without providing a SAW filter. SOLUTION: A direct RF modulation transmitter includes: digital/RF converters 105, 106 to which an I digital baseband signal, a Q digital

Direct RF modulation transmitter, sampling clock frequency setting method for direct RF modulation transmitter

NARCIS (Netherlands)

Fukuda, Shuichi; Nauta, Bram

2014-01-01

PROBLEM TO BE SOLVED: To provide a direct RF modulation transmitter capable of satisfying a radiation level regulation even without providing a SAW filter. SOLUTION: A direct RF modulation transmitter includes: digital/RF converters 105, 106 to which an I digital baseband signal, a Q digital

76 FR 79054 - Direct Investment Surveys: BE-12, Benchmark Survey of Foreign Direct Investment in the United States

Science.gov (United States)

2011-12-21

...] RIN 0691-AA80 Direct Investment Surveys: BE-12, Benchmark Survey of Foreign Direct Investment in the... reporting requirements for the 2012 BE-12, Benchmark Survey of Foreign Direct Investment in the United... survey covers the universe of foreign direct investment in the United States, and is BEA's most detailed...

Directe en indirecte werknemersparticipatie in Europa

NARCIS (Netherlands)

van Houten, Gijs; Akkerman, Agnes; Sluiter, Roderick; Jansen, Giedo; Vermeylen, Greet

2016-01-01

This study looks at different forms of direct and indirect employee participation in the EU. The research questions are: (1) which forms of direct and indirect employee participation can we distinguish?; (2) to what extent do forms of direct and indirect employee participation coincide within

Rejuvenating direct modulation and direct detection for modern optical communications

Science.gov (United States)

Che, Di; Li, An; Chen, Xi; Hu, Qian; Shieh, William

2018-02-01

High-speed transoceanic optical fiber transmission using direct modulation (DM) and direct detection (DD) was one of the most stirring breakthroughs for telecommunication in 1990s, which drove the internet as a global phenomenon. However, the later evolution of optical coherent communications in 2000s gradually took over the long-haul applications, due to its superior optical spectral efficiency. Nowadays, DM-DD systems are dominant mainly in cost- and power-sensitive short-reach applications, because of its natural characteristics-the simplicity. This paper reviews the recent advances of DM-DD transceivers from both hardware and signal processing perspectives. It introduces a variety of modified DM and/or DD systems for 3 application scenarios: very-short-reach interconnect with little fiber channel impact; single or a few spans of fiber transmission up to several hundred km; and distance beyond the 2nd scenario. Besides the DM-DD and multi-dimension DM-DD with polarization diversity, this paper focuses on how to rejuvenate traditional DM and DD technologies in order to bridge the transmission application gap between DM-DD and coherent transceivers, using technologies such as dispersion compensation, signal field recovery from the intensity-only DD receiver, and complex direct modulation with coherent detection. More than 30 years since the birth, DM and DD still hold indispensable roles in modern optical communications.

Tracking Positioning Algorithm for Direction of Arrival Based on Direction Lock Loop

Directory of Open Access Journals (Sweden)

Xiu-Zhi Cheng

2015-06-01

Full Text Available In order to solve the problem of poor real-time performance, low accuracy and high computational complexity in the traditional process of locating and tracking of Direction of Arrival (DOA of moving targets, this paper proposes a DOA algorithm based on the Direction Lock Loop (DILL which adopts Lock Loop structure to realize the estimation and location of DOA and can adjust the direction automatically along with the changes of a signal’s angular variation to track the position of the signal. Meanwhile, to reduce the influence of nonlinearity and noise on its performance, the UKF filter is designed for eliminating interference of the estimated target signal to improve accuracy of the signal tracking and stability of the system. Simulation results prove that the algorithm can not only get a high resolution DOA estimate signal, but can also locate and track multiple mobile targets effectively with enhanced accuracy, efficiency and stability.

Estimation of directional wave spreading

Digital Repository Service at National Institute of Oceanography (India)

Mandal, S.; Bhat, S.S.; Anand, N.M.; Nayak, B.U.

Directional properties of ocean waves are of great economic interest. The knowledge of wave directionality is important for the design of maritime structures and offshore operations. Two main aspects are considered for this study for the data...

Estimation of wave directional spreading

Digital Repository Service at National Institute of Oceanography (India)

Deo, M.C.; Gondane, D.S.; SanilKumar, V.

One of the useful measures of waves directional spreading at a given location is the directional spreading parameter. This paper presents a new approach to arrive at its characteristic value using the computational technique of Artificial Neural...

Direct conversion of fusion energy

International Nuclear Information System (INIS)

Johansson, Markus

2003-03-01

Deuterium and tritium are expected to be used as fuel in the first fusion reactors. Energy is released as kinetic energy of ions and neutrons, when deuterium reacts with tritium. One way to convert the kinetic energy to electrical energy, is to let the ions and neutrons hit the reactor wall and convert the heat that is caused by the particle bombardment to electrical energy with ordinary thermal conversion. If the kinetic energy of the ions instead is converted directly to electrical energy, a higher efficiency of the energy conversion is possible. The majority of the fusion energy is released as kinetic energy of neutrons, when deuterium reacts with tritium. Fusion reactions such as the D-D reactions, the D- 3 He reaction and the p- 11 B reaction, where a larger part of the fusion energy becomes kinetic energy of charged particles, appears therefore more suitable for direct conversion. Since they have lower reactivity than the D-T reaction, they need a larger βB 2 0 to give sufficiently high fusion power density. Because of this, the fusion configurations spherical torus (ST) and field-reversed configuration (FRC), where high β values are possible, appear interesting. Rosenbluth and Hinton come to the conclusion that efficient direct conversion isn't possible in closed field line systems and that open geometries, which facilitate direct conversion, provide inadequate confinement for D- 3 He. It is confirmed in this study that it doesn't seem possible to achieve as high direct conversion efficiency in closed systems as in open systems. ST and FRC fusion power plants that utilize direct conversion seem however interesting. Calculations with the help of Maple indicate that the reactor parameters needed for a D-D ST and a D 3 He ST hopefully are possible to achieve. The best energy conversion option for a D-D or D 3 He ST appears to be direct electrodynamic conversion (DEC) together with ordinary thermal conversion or liquid metal MHD conversion (LMMHD). For a D

Direct conversion of fusion energy

Energy Technology Data Exchange (ETDEWEB)

Johansson, Markus

2003-03-01

Deuterium and tritium are expected to be used as fuel in the first fusion reactors. Energy is released as kinetic energy of ions and neutrons, when deuterium reacts with tritium. One way to convert the kinetic energy to electrical energy, is to let the ions and neutrons hit the reactor wall and convert the heat that is caused by the particle bombardment to electrical energy with ordinary thermal conversion. If the kinetic energy of the ions instead is converted directly to electrical energy, a higher efficiency of the energy conversion is possible. The majority of the fusion energy is released as kinetic energy of neutrons, when deuterium reacts with tritium. Fusion reactions such as the D-D reactions, the D-{sup 3}He reaction and the p-{sup 11}B reaction, where a larger part of the fusion energy becomes kinetic energy of charged particles, appears therefore more suitable for direct conversion. Since they have lower reactivity than the D-T reaction, they need a larger {beta}B{sup 2}{sub 0} to give sufficiently high fusion power density. Because of this, the fusion configurations spherical torus (ST) and field-reversed configuration (FRC), where high {beta} values are possible, appear interesting. Rosenbluth and Hinton come to the conclusion that efficient direct conversion isn't possible in closed field line systems and that open geometries, which facilitate direct conversion, provide inadequate confinement for D-{sup 3}He. It is confirmed in this study that it doesn't seem possible to achieve as high direct conversion efficiency in closed systems as in open systems. ST and FRC fusion power plants that utilize direct conversion seem however interesting. Calculations with the help of Maple indicate that the reactor parameters needed for a D-D ST and a D{sub 3} He ST hopefully are possible to achieve. The best energy conversion option for a D-D or D{sub 3} He ST appears to be direct electrodynamic conversion (DEC) together with ordinary thermal conversion

Geothermal Technologies Program: Direct Use

Energy Technology Data Exchange (ETDEWEB)

2004-08-01

This general publication describes geothermal direct use systems, and how they have been effectively used throughout the country. It also describes the DOE program R&D efforts in this area, and summarizes several projects using direct use technology.

Model-Based Design of Stimulus Trains for Selective Microstimulation of Targeted Neuronal Populations

National Research Council Canada - National Science Library

McIntyre, Cameron

2001-01-01

... that accurately reproduced the dynamic firing properties of mammalian neurons, The neuron models were coupled to a three-dimensional finite element model of the spinal cord that solved for the potentials...

31 CFR 357.26 - Direct Deposit.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Direct Deposit. 357.26 Section 357.26 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE... AND BILLS HELD IN LEGACY TREASURY DIRECT Legacy Treasury Direct Book-Entry Securities System (Legacy...

19 CFR 351.509 - Direct taxes.

Science.gov (United States)

2010-04-01

... Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE ANTIDUMPING AND COUNTERVAILING DUTIES Identification and Measurement of Countervailable Subsidies § 351.509 Direct taxes. (a) Benefit—(1) Exemption or... direct tax (e.g., an income tax), or a reduction in the base used to calculate a direct tax, a benefit...

Polymer Directed Protein Assemblies

Directory of Open Access Journals (Sweden)

Patrick van Rijn

2013-05-01

Full Text Available Protein aggregation and protein self-assembly is an important occurrence in natural systems, and is in some form or other dictated by biopolymers. Very obvious influences of biopolymers on protein assemblies are, e.g., virus particles. Viruses are a multi-protein assembly of which the morphology is dictated by poly-nucleotides namely RNA or DNA. This “biopolymer” directs the proteins and imposes limitations on the structure like the length or diameter of the particle. Not only do these bionanoparticles use polymer-directed self-assembly, also processes like amyloid formation are in a way a result of directed protein assembly by partial unfolded/misfolded biopolymers namely, polypeptides. The combination of proteins and synthetic polymers, inspired by the natural processes, are therefore regarded as a highly promising area of research. Directed protein assembly is versatile with respect to the possible interactions which brings together the protein and polymer, e.g., electrostatic, v.d. Waals forces or covalent conjugation, and possible combinations are numerous due to the large amounts of different polymers and proteins available. The protein-polymer interacting behavior and overall morphology is envisioned to aid in clarifying protein-protein interactions and are thought to entail some interesting new functions and properties which will ultimately lead to novel bio-hybrid materials.

Neurofeedback Control of the Human GABAergic System Using Non-invasive Brain Stimulation.

Science.gov (United States)

Koganemaru, Satoko; Mikami, Yusuke; Maezawa, Hitoshi; Ikeda, Satoshi; Ikoma, Katsunori; Mima, Tatsuya

2018-06-01

Neurofeedback has been a powerful method for self-regulating brain activities to elicit potential ability of human mind. GABA is a major inhibitory neurotransmitter in the central nervous system. Transcranial magnetic stimulation (TMS) is a tool that can evaluate the GABAergic system within the primary motor cortex (M1) using paired-pulse stimuli, short intracortical inhibition (SICI). Herein we investigated whether neurofeedback learning using SICI enabled us to control the GABAergic system within the M1 area. Forty-five healthy subjects were randomly divided into two groups: those receiving SICI neurofeedback learning or those receiving no neurofeedback (control) learning. During both learning periods, subjects made attempts to change the size of a circle, which was altered according to the degree of SICI in the SICI neurofeedback learning group, and which was altered independent of the degree of SICI in the control learning group. Results demonstrated that the SICI neurofeedback learning group showed a significant enhancement in SICI. Moreover, this group showed a significant reduction in choice reaction time compared to the control group. Our findings indicate that humans can intrinsically control the intracortical GABAergic system within M1 and can thus improve motor behaviors by SICI neurofeedback learning. SICI neurofeedback learning is a novel and promising approach to control our neural system and potentially represents a new therapy for patients with abnormal motor symptoms caused by CNS disorders. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Renal hemodynamics in uranyl acetate-induced acute renal failure of rabbits

International Nuclear Information System (INIS)

Sudo, M.; Honda, N.; Hishida, A.; Nagase, M.

1977-01-01

The role of renal hemodynamic alterations in the curtailment of renal function was studied in rabbits with uranyl acetate-induced acute renal failure. The day following the i.v. injection of uranyl acetate (2 mg/kg of body wt), renal blood flow (RBF) and clearance of creatinine (Ccr) decreased to approximately 60 and 20% of controls, respectively. Intracortical fractional flow distribution, estimated by radioactive microsphere method, did not change. The extraction ratio of para-aminohippurate (EPAH) decreased and the renal extraction of sodium (CNa/Ccr) increased, with minimal structural change in the kidney. Urine output increased two to three times that of the control. After three days oliguria appeared despite complete recovery of RBF. The zonal flow redistributed toward the deep cortex. CCr and EPAH reached their minimums, concomitantly with tubular necrosis and intratubular casts. After seven days animals could be divided into the oliguric and diuretic groups. CCr and EPAH were higher in the diuretic group, while there was no significant difference in RBF and the flow distribution between groups. Regeneration of damaged tubular cells was found in the diuretic group but not in the oliguric group. The findings suggest the minor roles of RBF and the intracortical flow distribution, and a fundamental role of back leakage of filtrate across damaged tubular epithelium in the maintenance of reduced CCR and urine output during the oliguric stage in rabbits with uranyl acetate-induced renal failure

Theta Burst Stimulation of the Cerebellum Modifies the TMS-Evoked N100 Potential, a Marker of GABA Inhibition.

Directory of Open Access Journals (Sweden)

Allanah Harrington

Full Text Available Theta burst stimulation (TBS of the cerebellum, a potential therapy for neurological disease, can modulate corticospinal excitability via the dentato-thalamo-cortical pathway, but it is uncertain whether its effects are mediated via inhibitory or facilitatory networks. The aim of this study was to investigate the effects of 30Hz cerebellar TBS on the N100 waveform of the TMS-evoked potential (TEP, a marker of intracortical GABAB-mediated inhibition. 16 healthy participants (aged 18-30 years; 13 right handed and 3 left handed received 30Hz intermittent TBS (iTBS, continuous TBS (cTBS or sham stimulation over the right cerebellum, in three separate sessions. The first 8 participants received TBS at a stimulus intensity of 80% of active motor threshold (AMT, while the remainder received 90% of AMT. Motor evoked potentials (MEP and TEP were recorded before and after each treatment, by stimulating the first dorsal interosseus area of the left motor cortex. Analysis of the 13 right handed participants showed that iTBS at 90% of AMT increased the N100 amplitude compared to sham and cTBS, without significantly altering MEP amplitude. cTBS at 80% of active motor threshold decreased the N100 amplitude and cTBS overall reduced resting MEP amplitude. The study demonstrates effects of 30Hz cerebellar TBS on inhibitory cortical networks that may be useful for treatment of neurological conditions associated with dysfunctional intracortical inhibition.

Abnormal cortical synaptic plasticity in primary motor area in progressive supranuclear palsy.

Science.gov (United States)

Conte, Antonella; Belvisi, Daniele; Bologna, Matteo; Ottaviani, Donatella; Fabbrini, Giovanni; Colosimo, Carlo; Williams, David R; Berardelli, Alfredo

2012-03-01

No study has yet investigated whether cortical plasticity in primary motor area (M1) is abnormal in patients with progressive supranuclear palsy (PSP). We studied M1 plasticity in 15 PSP patients and 15 age-matched healthy subjects. We used intermittent theta-burst stimulation (iTBS) to investigate long-term potentiation (LTP) and continuous TBS (cTBS) to investigate long-term depression (LTD)-like cortical plasticity in M1. Ten patients underwent iTBS again 1 year later. We also investigated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in M1 with paired-pulse transcranial magnetic stimulation, tested H reflex from upper limb flexor muscles before and after iTBS, and measured motor evoked potential (MEP) input-output (I/O) curves before and after iTBS. iTBS elicited a significantly larger MEP facilitation after iTBS in patients than in healthy subjects. Whereas in healthy subjects, cTBS inhibited MEP, in patients it significantly facilitated MEPs. In patients, SICI was reduced, whereas ICF was normal. H reflex size remained unchanged after iTBS. Patients had steeper MEP I/O slopes than healthy subjects at baseline and became even more steeper after iTBS only in patients. The iTBS-induced abnormal MEP facilitation in PSP persisted at 1-year follow-up. In conclusion, patients with PSP have abnormal M1 LTP/LTD-like plasticity. The enhanced LTP-like cortical synaptic plasticity parallels disease progression.

New directions in information organization

CERN Document Server

Park, Jung-ran; Spink, Amanda

2013-01-01

New Directions in Information Organization, co-edited by Dr. Jung-ran Park and Dr. Lynne Howarth seeks to provide an overview and understanding of the future directions, leading edge theories and models for research and practice in information organization.

Potential Dimension Yields From Direct Processing

Science.gov (United States)

Wenjie Lin; D. Earl Kline; Philip A. Araman

1994-01-01

As the price of timber increases and environmental leigslation limits harvestable log volumes, the process of converting logs directly into dimension parts needs further exploration. Direct processing converts logs directly into rough green dimension parts without the intermediate steps of lumber manufacturing, grading, trading, shipping and drying. A major attraction...

Direct e-mail marketing: Case of Serbia

OpenAIRE

Končar Jelena A.; Vukmirović Goran; Katai Žita

2005-01-01

Direct e-mail marketing refers to approaching customers directly, without employing intermediaries. It represents a direct mode of communication with the target population, which affects the creation of stronger and more loyal relationships with prospective customers, compared to traditional direct marketing resources (TV, radio, print and advertising panels, etc). The main goal of direct e-mail marketing is building long-term "one to one" relationships with current and prospective customers....

Directional wave measurements and modelling

Digital Repository Service at National Institute of Oceanography (India)

Anand, N.M.; Nayak, B.U.; Bhat, S.S.; SanilKumar, V.

Some of the results obtained from analysis of the monsoon directional wave data measured over 4 years in shallow waters off the west coast of India are presented. The directional spectrum computed from the time series data seems to indicate...

Direct marketing

Directory of Open Access Journals (Sweden)

Čičić Muris

2002-01-01

Full Text Available Direct Marketing (DM is usually treated as unworthy activity, with actions at the edge of legality and activities minded cheating. Despite obvious problems regarding ethics and privacy threat, DM with its size, importance and role in a concept of integrated marketing communication deserves respect and sufficient analysis and review

Regional impacts of abolishing direct payments

DEFF Research Database (Denmark)

Uthes, Sandra; Priorr, Annette; Zander, Peter

2011-01-01

The direct payment system of the Common Agricultural Policy (CAP) provides income transfers to European farmers. Recently, several countries including England and Sweden have advocated the elimination of direct payments after 2013. The extent to which an elimination of direct payments would affect...... with different production orientations and land management types was modeled under the presence and absence of direct payments using a combination of agent-based and bio-economic modeling. We found that the initial characteristics of the regions, such as the historical farm structure and regional site conditions...

Direct e-mail marketing: Case of Serbia

Directory of Open Access Journals (Sweden)

Končar Jelena A.

2005-01-01

Full Text Available Direct e-mail marketing refers to approaching customers directly, without employing intermediaries. It represents a direct mode of communication with the target population, which affects the creation of stronger and more loyal relationships with prospective customers, compared to traditional direct marketing resources (TV, radio, print and advertising panels, etc. The main goal of direct e-mail marketing is building long-term "one to one" relationships with current and prospective customers. Direct e-mail marketing is not aimed at momentary sale, but at boosting certain product preferences due to the engagement of numerous electronic media.

Records Management Directive

Data.gov (United States)

Office of Personnel Management — The Office of Personnel Management (OPM) Records Management Directive provides guidelines for the management of OPM records, and identifies the records management...

Personalized direct marketing using digital publishing

Science.gov (United States)

Kutty, Cheeniyil L.; Prabhakaran, Jayasree K.

2006-02-01

In today's cost-conscious business climate, marketing and customer service decision makers are increasingly concerned with how to increase customer response and retention rates. Companies spend large amounts of money on Customer Relationship Management (CRM) solutions and data acquisition but they don't know how to use the information stored in these systems to improve the effectiveness of their direct marketing campaigns. By leveraging the customer information they already have, companies can create personalized, printed direct mail programs that generate high response rates, greater returns, and stronger customer loyalty, while gaining a significant edge over their competitors. To reach the promised land of one-to-one direct marketing (personalized direct marketing - PDM), companies need an end-to-end solution for creating, managing, printing, and distributing personalized direct mail "on demand." Having access to digital printing is just one piece of the solution. A more complete approach includes leveraging personalization technology into a useful direct marketing tool that provides true one-to-one marketing, allowing variable images and text in a personalized direct mail. This paper discusses integration of CRM with a Print-on-Demand solution so as to create truly personalized printed marketing campaigns for one or many individuals based on the profile information, preferences and purchase history stored in the CRM.

Empirical Evaluation of Directional-Dependence Tests

Science.gov (United States)

Thoemmes, Felix

2015-01-01

Testing of directional dependence is a method to infer causal direction that recently has attracted some attention. Previous examples by e.g. von Eye and DeShon (2012a) and extensive simulation studies by Pornprasertmanit and Little (2012) have demonstrated that under specific assumptions, directional-dependence tests can recover the true causal…

14 CFR 212.7 - Direct sales.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Direct sales. 212.7 Section 212.7... REGULATIONS CHARTER RULES FOR U.S. AND FOREIGN DIRECT AIR CARRIERS § 212.7 Direct sales. (a) Certificated and foreign air carriers may sell or offer for sale, and operate, as principal, Public Charter flights under...

Feasibility of self-directed learning in clerkships

DEFF Research Database (Denmark)

Tolsgaard, M G; Arendrup, H; Pedersen, P

2013-01-01

Self-directed learning has been well described in preclinical settings. However, studies report conflicting results when self-directed initiatives are implemented in clinical clerkships.......Self-directed learning has been well described in preclinical settings. However, studies report conflicting results when self-directed initiatives are implemented in clinical clerkships....

[Advance directives in clinical practice : Living will, healthcare power of attorney and care directive].

Science.gov (United States)

Hack, J; Buecking, B; Lopez, C L; Ruchholtz, S; Kühne, C A

2017-06-01

In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

Seeking coherence among environmental directives

NARCIS (Netherlands)

Beijen, Barbara

2014-01-01

European environmental law consists of a large number of directives and regulations dealing with environmental domains such as air, water, or waste, or with issues such as greenhouse gases, chemicals or industrial emissions. These directives and regulations do not form a comprehensive system of

Object Detection: Current and Future Directions

Directory of Open Access Journals (Sweden)

Rodrigo eVerschae

2015-11-01

Full Text Available Object detection is a key ability required by most computer and robot vision systems. The latest research on this area has been making great progress in many directions. In the current manuscript we give an overview of past research on object detection, outline the current main research directions, and discuss open problems and possible future directions.

Determining Directional Dependency in Causal Associations

Science.gov (United States)

Pornprasertmanit, Sunthud; Little, Todd D.

2012-01-01

Directional dependency is a method to determine the likely causal direction of effect between two variables. This article aims to critique and improve upon the use of directional dependency as a technique to infer causal associations. We comment on several issues raised by von Eye and DeShon (2012), including: encouraging the use of the signs of…

The dynamic regulation of cortical excitability is altered in episodic ataxia type 2

DEFF Research Database (Denmark)

Helmich, Rick C; Siebner, Hartwig R; Giffin, Nicola

2010-01-01

-pulse transcranial magnetic stimulation at an interstimulus interval of 2 and 10 ms to assess intracortical inhibition and facilitation, respectively. The time course of burst-induced excitability changes differed between groups. Healthy controls showed a short-lived increase in excitability that was only present 50...... different from either controls or patients with episodic ataxia type 2. Together, these findings indicate that patients with episodic ataxia type 2 have an excessive increase in motor cortex excitability following a strong facilitatory input. We argue that this deficient control of cortical excitability may...

The mode of progression of subperiosteal resorption in the hyperparathyroidism of chronic renal future

International Nuclear Information System (INIS)

Meema, H.E.; Oreopoulos, D.G.; Toronto Univ., Ontario

1983-01-01

Subperiosteal resorption in finger phalanges is usually thought to be the result of osteoclastic bone resorption on the periosteal surface of bone, progressive centripetally with creation of the serrated appearances and ''lace-like'' patterns in periosteal cortical bone. Our longitudinal microradioscopic observations in patients with secondary hyperparathyroidism of chronic renal failure have revealed evidence of another pathogenetic mechanism: by the enlargement of intracortical juxtaperiosteal resorption spaces, the remaining thin layer of bone is broken down from inside the bone, i.e., a centrifugal rather then centripetal process. (orig.)

Direct activation of microcrystalline zeolites

NARCIS (Netherlands)

Ortiz-Iniesta, Maria Jesus; Heeres, Hero Jan; Melian-Cabrera, Ignacio

2013-01-01

In this work a direct activation route of zeolites is assessed. It consists of NH4-exchanging the as-synthesized solids before removing the organic template. Calcination afterwards serves to combust the organic template and creates the Bronsted sites directly; thus applying merely a single thermal

Isomorphisms and traversability of directed path graphs

NARCIS (Netherlands)

Broersma, Haitze J.; Li, Xueliang; Li, X.

1998-01-01

The concept of a line digraph is generalized to that of a directed path graph. The directed path graph $\\forw P_k(D)$ of a digraph $D$ is obtained by representing the directed paths on $k$ vertices of $D$ by vertices. Two vertices are joined by an arc whenever the corresponding directed paths in $D$

Effect of Direction Type, Emotional Valence of Words And Gender on Directed Forgetting

OpenAIRE

Sayar, Filiz

2018-01-01

In the present study, the effects of emotional valence of words and gender on directed forgettingwere investigated. The directed forgetting effect was investigated by requiring from participants toforget the words that they have to recall and at the same time, to recall the words that they have toforget. The study was composed of two experiments. In the first experiment, the participants werepresented with a list of words consisting of neutral and emotional words once, while the participantsw...

78 FR 11141 - BE-577: Quarterly Survey of U.S. Direct Investment Abroad- Direct Transactions of U.S. Reporter...

Science.gov (United States)

2013-02-15

... BE-577: Quarterly Survey of U.S. Direct Investment Abroad-- Direct Transactions of U.S. Reporter With... that it is conducting the mandatory surveys titled BE-577, Quarterly Survey of U.S. Direct Investment Abroad--Direct Transactions of U.S. Reporter with Foreign Affiliate. This survey is authorized by the...

Eldercare at Home: Advanced Directives

Science.gov (United States)

... permanently? Helping the person fill out a living will (advance directive) A living will states a person's wishes about medical care if ... never be in a situation where another person will have to make decisions ... it is to have an advance directive. However, don't assume that your loved ...

Target selection for direct marketing.

NARCIS (Netherlands)

Bult, Jan Roelf

1993-01-01

In this thesis we concentrated on the use ol direct mail for targeting potential buyers. The major characteristics that influences the success of a plomotional direct mail campaign are the of-fbr,the communication elements, the timing or sequence of these communication elements, and the list of

Direct convertor based upon space charge effects

International Nuclear Information System (INIS)

Gitomer, S.J.

1977-01-01

A device capable of converting directly the kinetic energy of charged particles into electrical energy is considered. The device differs from earlier ones (such as Post's periodic focus electrostatic direct convertor) in that it makes use of the space charge repulsion in a high density charged particle beam. The beam is directed into a monotonic decelerating electrostatic field of a several-stage planar-finned structure. The collector fins coincide with vacuum equipotential surfaces. Space charge blowup of the beam directs particles onto various collector fins. The energy efficiency of a 4-stage device has been determined using a numberical simulation approach. We find that efficiencies approaching 75 percent are possible. An approximate scaling law is derived for the space charge based direct converter and a comparison is made to the periodic focus direct convertor. We find the space charge based direct convertor to be superior to a number of ways

Direct filtration of Biesbosch water and Algae and water treatment in the Netherlands : 3rd Direct Filtration Seminar

NARCIS (Netherlands)

Petrusevski, B.; Vlaski, A.; Van Breemen, A.N.; Alaerts, G.J.

1993-01-01

This presentation summarises basic information on direct filtration, and demonstrates the main research findings, related to the performance of simple in-line direct filtration. The results reported are part of a comprehensive ongoing research programm "Direct filtration of Biesbosch water"

Direct-to-consumer advertising of pharmaceuticals.

Science.gov (United States)

Gellad, Ziad F; Lyles, Kenneth W

2007-06-01

Since the US Food and Drug Administration (FDA) released new guidelines on broadcast direct-to-consumer advertising in 1997, the prevalence of direct-to-consumer advertising of prescription drugs has increased exponentially. The impact on providers, patients, and the health care system is varied and dynamic, and the rapid changes in the last several years have markedly altered the health care landscape. To continue providing optimal medical care, physicians and other health care providers must be able to manage this influence on their practice, and a more thorough understanding of this phenomenon is an integral step toward this goal. This review will summarize the history of direct-to-consumer drug advertisements and the current regulations governing them. It will summarize the evidence concerning the impact of direct-to-consumer advertising on the public, providers, and the health care system, and conclude with observations regarding the future of direct-to-consumer advertising.

Case study: Comparison of motivation for achieving higher performance between self-directed and manager-directed aerospace engineering teams

Science.gov (United States)

Erlick, Katherine

"The stereotype of engineers is that they are not people oriented; the stereotype implies that engineers would not work well in teams---that their task emphasis is a solo venture and does not encourage social aspects of collaboration" (Miner & Beyerlein, 1999, p. 16). The problem is determining the best method of providing a motivating environment where design engineers may contribute within a team in order to achieve higher performance in the organization. Theoretically, self-directed work teams perform at higher levels. But, allowing a design engineer to contribute to the team while still maintaining his or her anonymity is the key to success. Therefore, a motivating environment must be established to encourage greater self-actualization in design engineers. The purpose of this study is to determine the favorable motivational environment for design engineers and describe the comparison between two aerospace design-engineering teams: one self-directed and the other manager directed. Following the comparison, this study identified whether self-direction or manager-direction provides the favorable motivational environment for operating as a team in pursuit of achieving higher performance. The methodology used in this research was the case study focusing on the team's levels of job satisfaction and potential for higher performance. The collection of data came from three sources, (a) surveys, (b) researcher observer journal and (c) collection of artifacts. The surveys provided information regarding personal behavior characteristics, potentiality for higher performance and motivational attributes. The researcher journal provided information regarding team dynamics, individual interaction, conflict and conflict resolution. The milestone for performance was based on the collection of artifacts from the two teams. The findings from this study illustrated that whether the team was manager-directed or self-directed does not appear to influence the needs and wants of the

Reasoning about cardinal directions between extended objects

OpenAIRE

Liu, Weiming; Zhang, Xiaotong; Li, Sanjiang; Ying, Mingsheng

2010-01-01

Direction relations between extended spatial objects are important commonsense knowledge. Recently, Goyal and Egenhofer proposed a formal model, known as Cardinal Direction Calculus (CDC), for representing direction relations between connected plane regions. CDC is perhaps the most expressive qualitative calculus for directional information, and has attracted increasing interest from areas such as artificial intelligence, geographical information science, and image retrieval. Given a network ...

Hydrothermal industrialization: direct heat development. Final report

Energy Technology Data Exchange (ETDEWEB)

1982-05-01

A description of hydrothermal resources suitable for direct applications, their associated temperatures, geographic distribution and developable capacity are given. An overview of the hydrothermal direct-heat development infrastructure is presented. Development activity is highlighted by examining known and planned geothermal direct-use applications. Underlying assumptions and results for three studies conducted to determine direct-use market penetration of geothermal energy are discussed.

Focal Electrically Administered Therapy (FEAT): Device parameter effects on stimulus perception in humans

Science.gov (United States)

Borckardt, Jeffrey J.; Linder, Katie; Ricci, Raffaella; Li, Xingbao; Anderson, Berry; Arana, Ashley; Nahas, Ziad; Amassian, Vahe; Long, James; George, Mark S.; Sackeim, Harold A.

2010-01-01

Background Focal Electrically-Administered Therapy (FEAT) is a new method of transcranial electrical stimulation capable of focal modulation of cerebral activity. Other than invasive studies in animals and examination of motor output in humans, there are limited possibilities for establishing basic principles about how variation in stimulus parameters impact on patterns of intracortical stimulation. This study used a simpler paradigm, and evaluated the effects of different stimulation parameters on subjective perception of the quality and location of scalp pain. Methods In two studies, 19 subjects were randomly stimulated over the left forehead, varying the anode-cathode arrangement, the intensity of stimulation, the electrode size and placement, and whether the current flow was unidirectional or bidirectional. Subjects rated the location of the sensation, and its quality. Results The perceived center of stimulation moved toward the cathode, regardless of placement. This shift in subjective sensation was more prominent when the electricity was unidirectional. Additionally, more intense stimulation, as well as stimulation with a smaller electrode, caused greater perceived pain. Unidirectional stimulation was rated more painful when traveling from a large anode to a small cathode and less painful when traveling from a small anode to a large cathode. Finally, participants were more likely to perceive the electrical stimulation as moving towards a specific direction when the intensity was high than when it was low. Conclusions The intensity and location of sensations can be manipulated by varying the intensity, current direction, or geometry of electrodes. PMID:19092677

FOREIGN DIRECT INVESTMENTS DURING FINANCIAL CRISES

Directory of Open Access Journals (Sweden)

VINTILA DENISIA MARIANA

2011-12-01

Full Text Available The fundamental idea of International capital flows is that short-term flows can be easily reversed, while flows on a longer time horizon are more stable. Crises are associated with withdrawals of short-term capital flows and growth of the foreign direct investment flows. The current crisis has meant a major decline of international capital flows, also of the foreign direct investment. The analysis in this article tries to establish if and under which conditions foreign direct investments can bring greater stability during the crisis, comparing the evolution of foreign direct investments in the current crisis with their response in previous crises. We show that during previous crises foreign direct investments were stable, behaving differently from other types of capital. Yet, during the current crisis, foreign direct investments have proven to be not so stable and all the components declined, raising questions about the resumption of the positive trend. The stability of foreign direct investments in the past was given by the increase of mergers and acquisitions during the crisis, reflecting fire-sale FDI. This feature is not found in the current crisis as mergers and acquisitions were severe affected by the crises and recorded a major decline. The current paper is realized in the doctoral program entitled PhD in economics at the standards of European knowledge- DoEsEc, scientific coordinator Prof. PhD Rodica Zaharia, institution The Academy of Economic Studies Bucharest, Faculty of International Business, period of research 2009-2012.

Exchange effects in direct reactions

International Nuclear Information System (INIS)

LeMere, M.; Kanellopoulos, E.J.; Suenkel, W.; Tang, Y.C.

1979-01-01

The effect of antisymmetrization in direct reactions is examined by studying the properties of the coupling-normalization kernel function occurring in a resonating-group formulation. From this study, one obtains useful information concerning the general behavior of direct-reactiion processes and some justification for the use of three-body models in phenomenological analyses

From Nonradiating Sources to Directionally Invisible Objects

Science.gov (United States)

Hurwitz, Elisa

The goal of this dissertation is to extend the understanding of invisible objects, in particular nonradiating sources and directional nonscattering scatterers. First, variations of null-field nonradiating sources are derived from Maxwell's equations. Next, it is shown how to design a nonscattering scatterer by applying the boundary conditions for nonradiating sources to the scalar wave equation, referred to here as the "field cloak method". This technique is used to demonstrate directionally invisible scatterers for an incident field with one direction of incidence, and the influence of symmetry on the directionality is explored. This technique, when applied to the scalar wave equation, is extended to show that a directionally invisible object may be invisible for multiple directions of incidence simultaneously. This opens the door to the creation of optically switchable, directionally invisible objects which could be implemented in couplers and other novel optical devices. Next, a version of the "field cloak method" is extended to the Maxwell's electro-magnetic vector equations, allowing more flexibility in the variety of directionally invisible objects that can be designed. This thesis concludes with examples of such objects and future applications.

Apparent directional selection by biased pleiotropic mutation.

Science.gov (United States)

Tanaka, Yoshinari

2010-07-01

Pleiotropic effects of deleterious mutations are considered to be among the factors responsible for genetic constraints on evolution by long-term directional selection acting on a quantitative trait. If pleiotropic phenotypic effects are biased in a particular direction, mutations generate apparent directional selection, which refers to the covariance between fitness and the trait owing to a linear association between the number of mutations possessed by individuals and the genotypic values of the trait. The present analysis has shown how the equilibrium mean value of the trait is determined by a balance between directional selection and biased pleiotropic mutations. Assuming that genes act additively both on the trait and on fitness, the total variance-standardized directional selection gradient was decomposed into apparent and true components. Experimental data on mutation bias from the bristle traits of Drosophila and life history traits of Daphnia suggest that apparent selection explains a small but significant fraction of directional selection pressure that is observed in nature; the data suggest that changes induced in a trait by biased pleiotropic mutation (i.e., by apparent directional selection) are easily compensated for by (true) directional selection.

Progress toward ignition with direct-drive

International Nuclear Information System (INIS)

McCrory, R.L. Jr.

1993-01-01

The goal of the direct-drive laser fusion program is to validate high-performance, direct-drive targets. A decision to construct a direct-drive capability on the proposed 1-to-2-MJ National Ignition Facility (NIF) in the USA will be based on target physics experiments conducted on the OMEGA Upgrade laser system now under construction at the LLE. The OMEGA Upgrade will provide up to 30 kJ of UV laser energy in precisely shaped pulses with irradiation nonuniformities in the range of 1 pc. to 2 pc. An understanding and predictive capability for direct-drive targets are required to assure reliable estimates of ignition and gain with 1-2 MJ of incident laser energy. This paper reviews the target physics efforts currently underway to assess the critical physics issues of direct-drive ICF; plans for the experimental program to be carried out on the OMEGA Upgrade laser are also presented. 14 figs., 15 refs

FAA Directives System

Science.gov (United States)

1992-08-26

Consistent with the Federal Aviation Administration's mission to foster a safe, : secure, and efficient aviation system is the need for an effective and efficient : process for communitcating policy and procedures. The FAA Directives System : provide...

Supplementary income. Direct selling in Germany

International Nuclear Information System (INIS)

Roesner, Sven

2014-01-01

This document treats, first, of the evolution of the German support mechanisms to renewable energy sources. Then, it presents the legal framework of direct electricity selling (goal, evolution, facilities in concern and eligibility criteria). Next, the operation of direct selling since August 2014 in Germany is presented (producers eligibility, over- and under-production, reference values, income, tariffs). Finally, the perspectives and conditions of direct selling success are summarized in the conclusion

Incretin secretion: direct mechanisms

DEFF Research Database (Denmark)

Balk-Møller, Emilie; Holst, Jens Juul; Kuhre, Rune Ehrenreich

2014-01-01

The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from gastro-intestinal K- and L-cells, respectively, and play an important role in post-prandial blood glucose regulation. They do this by direct stimulation of the pancreatic β...... enzyme responsible for incretin degradation (dipeptidyl peptidase-4) is inhibited (drugs are already on the market) while the secretion of endogenous GLP-1 secretion is stimulated at the same time may prove particularly rewarding. In this section we review current knowledge on the mechanisms for direct...

The direction of time

CERN Document Server

Reichenbach, Hans

1999-01-01

Ever a source of philosophical conjecture and debate, the concept of time represents the beating heart of physics. This final work by the distinguished physicist Hans Reichenbach represents the culmination and integration of a lifetime's philosophical contributions and inquiries into the analysis of time. The result is an outstanding overview of such qualitative, or topological, attributes of time as order and direction.Beginning with a discussion of the emotive significance of time, Reichenbach turns to an examination of the time order of mechanics, the time direction of thermodynamics and m

Directional outlyingness for multivariate functional data

KAUST Repository

Dai, Wenlin

2018-04-07

The direction of outlyingness is crucial to describing the centrality of multivariate functional data. Motivated by this idea, classical depth is generalized to directional outlyingness for functional data. Theoretical properties of functional directional outlyingness are investigated and the total outlyingness can be naturally decomposed into two parts: magnitude outlyingness and shape outlyingness which represent the centrality of a curve for magnitude and shape, respectively. This decomposition serves as a visualization tool for the centrality of curves. Furthermore, an outlier detection procedure is proposed based on functional directional outlyingness. This criterion applies to both univariate and multivariate curves and simulation studies show that it outperforms competing methods. Weather and electrocardiogram data demonstrate the practical application of our proposed framework.

Bistability breaks-off deterministic responses to intracortical stimulation during non-REM sleep

Directory of Open Access Journals (Sweden)

Andrea Pigorini

2015-04-01

These results point to bistability as the underlying critical mechanism that prevents the emergence of complex interactions in human thalamocortical networks during NREM sleep. Besides sleep, the same basic neurophysiological dynamics may play a role in pathological conditions(Casali et al., 2013; Rosanova et al., 2012 where cortico-cortical communication and consciousness are impaired in spite of preserved neuronal activity.

Preparation for the Implantation of an Intracortical Visual Prosthesis in a Human

Science.gov (United States)

2015-12-01

which angular distortions are 0.016°±7.0°; we expect to obtain similar accuracies in ICVP recipients. In her most recent work, Ms. Kaskhedikar has... Java , Labview and VGA/NTSC output," IEEE International Conference on Electro/Information Technology, pp. 521-526, May 2007. Link 22 38. Suh, S

Empirical validation of directed functional connectivity.

Science.gov (United States)

Mill, Ravi D; Bagic, Anto; Bostan, Andreea; Schneider, Walter; Cole, Michael W

2017-02-01

Mapping directions of influence in the human brain connectome represents the next phase in understanding its functional architecture. However, a host of methodological uncertainties have impeded the application of directed connectivity methods, which have primarily been validated via "ground truth" connectivity patterns embedded in simulated functional MRI (fMRI) and magneto-/electro-encephalography (MEG/EEG) datasets. Such simulations rely on many generative assumptions, and we hence utilized a different strategy involving empirical data in which a ground truth directed connectivity pattern could be anticipated with confidence. Specifically, we exploited the established "sensory reactivation" effect in episodic memory, in which retrieval of sensory information reactivates regions involved in perceiving that sensory modality. Subjects performed a paired associate task in separate fMRI and MEG sessions, in which a ground truth reversal in directed connectivity between auditory and visual sensory regions was instantiated across task conditions. This directed connectivity reversal was successfully recovered across different algorithms, including Granger causality and Bayes network (IMAGES) approaches, and across fMRI ("raw" and deconvolved) and source-modeled MEG. These results extend simulation studies of directed connectivity, and offer practical guidelines for the use of such methods in clarifying causal mechanisms of neural processing. Copyright © 2016 Elsevier Inc. All rights reserved.

Bio-Inspired Micromechanical Directional Acoustic Sensor

Science.gov (United States)

Swan, William; Alves, Fabio; Karunasiri, Gamani

Conventional directional sound sensors employ an array of spatially separated microphones and the direction is determined using arrival times and amplitudes. In nature, insects such as the Ormia ochracea fly can determine the direction of sound using a hearing organ much smaller than the wavelength of sound it detects. The fly's eardrums are mechanically coupled, only separated by about 1 mm, and have remarkable directional sensitivity. A micromechanical sensor based on the fly's hearing system was designed and fabricated on a silicon on insulator (SOI) substrate using MEMS technology. The sensor consists of two 1 mm2 wings connected using a bridge and to the substrate using two torsional legs. The dimensions of the sensor and material stiffness determine the frequency response of the sensor. The vibration of the wings in response to incident sound at the bending resonance was measured using a laser vibrometer and found to be about 1 μm/Pa. The electronic response of the sensor to sound was measured using integrated comb finger capacitors and found to be about 25 V/Pa. The fabricated sensors showed good directional sensitivity. In this talk, the design, fabrication and characteristics of the directional sound sensor will be described. Supported by ONR and TDSI.

A robo-pigeon based on an innovative multi-mode telestimulation system.

Science.gov (United States)

Yang, Junqing; Huai, Ruituo; Wang, Hui; Lv, Changzhi; Su, Xuecheng

2015-01-01

In this paper, we describe a new multi-mode telestimulation system for brain-microstimulation for the navigation of a robo-pigeon, a new type of bio-robot based on Brain-Computer Interface (BCI) techniques. The multi-mode telestimulation system overcomes neuron adaptation that was a key shortcoming of the previous single-mode stimulation by the use of non-steady TTL biphasic pulses accomplished by randomly alternating pulse modes. To improve efficiency, a new behavior model ("virtual fear") is proposed and applied to the robo-pigeon. Unlike the previous "virtual reward" model, the "virtual fear" behavior model does not require special training. The performance and effectiveness of the system to alleviate the adaptation of neurons was verified by a robo-pigeon navigation test, simultaneously confirming the practicality of the "virtual fear" behavioral model.

Cantonese versus Canadian Evaluation of Directive and Non-Directive Therapy.

Science.gov (United States)

Waxer, Peter H.

1989-01-01

Examined differences between Canadian and Cantonese university students who read transcripts of Carl Rogers and Albert Ellis counseling sessions and rated these counselors on directiveness, forcefulness, repetitiveness, sensitivity, politeness, and willingness to see either Ellis or Rogers. Found Canadians more willing to see Rogers than Chinese…

Direct photons in heavy-ion collisions

Energy Technology Data Exchange (ETDEWEB)

Baeuchle, Bjoern

2010-12-13

Direct photon emission from heavy-ion collisions has been calculated and compared to available experimental data. Three different models have been combined to extract direct photons from different environments in a heavy-ion collision: Thermal photons from partonic and hadronic matter have been extracted from relativistic, non-viscous 3+1-dimensional hydrodynamic calculations. Thermal and non-thermal photons from hadronic interactions have been calculated from relativistic transport theory. The impact of different physics assumptions about the thermalized matter has been studied. The models used for the determination of photons from both hydrodynamic and transport calculations have been elucidated and their numerical properties tested. The origin of direct photons, itemised by emission stage, emission time, channel and baryon number density, has been investigated for various systems, as have the transverse momentum spectra and elliptic flow patterns of direct photons. Taking into account the full (vacuum) spectral function of the rho-meson decreases the direct photon emission by approximately 10% at low photon transverse momentum. In all systems that have been considered -- heavy-ion collisions at E{sub lab}=35 AGeV and 158 AGeV, (s{sub NN}){sup 1/2}=62.4 GeV, 130 GeV and 200 GeV -- thermal emission from a system with partonic degrees of freedom is greatly enhanced over that from hadronic systems, while the difference between the direct photon yields from a viscous and a non-viscous hadronic system (transport vs. hydrodynamics) is found to be very small. Predictions for direct photon emission in central U+U-collisions at 35 AGeV have been made. (orig.)

Direct photons in heavy-ion collisions

International Nuclear Information System (INIS)

Baeuchle, Bjoern

2010-01-01

Direct photon emission from heavy-ion collisions has been calculated and compared to available experimental data. Three different models have been combined to extract direct photons from different environments in a heavy-ion collision: Thermal photons from partonic and hadronic matter have been extracted from relativistic, non-viscous 3+1-dimensional hydrodynamic calculations. Thermal and non-thermal photons from hadronic interactions have been calculated from relativistic transport theory. The impact of different physics assumptions about the thermalized matter has been studied. The models used for the determination of photons from both hydrodynamic and transport calculations have been elucidated and their numerical properties tested. The origin of direct photons, itemised by emission stage, emission time, channel and baryon number density, has been investigated for various systems, as have the transverse momentum spectra and elliptic flow patterns of direct photons. Taking into account the full (vacuum) spectral function of the rho-meson decreases the direct photon emission by approximately 10% at low photon transverse momentum. In all systems that have been considered -- heavy-ion collisions at E lab =35 AGeV and 158 AGeV, (s NN ) 1/2 =62.4 GeV, 130 GeV and 200 GeV -- thermal emission from a system with partonic degrees of freedom is greatly enhanced over that from hadronic systems, while the difference between the direct photon yields from a viscous and a non-viscous hadronic system (transport vs. hydrodynamics) is found to be very small. Predictions for direct photon emission in central U+U-collisions at 35 AGeV have been made. (orig.)

Boosters and barriers for direct cardiac reprogramming.

Science.gov (United States)

Talkhabi, Mahmood; Zonooz, Elmira Rezaei; Baharvand, Hossein

2017-06-01

Heart disease is currently the most significant cause of morbidity and mortality worldwide, which accounts for approximately 33% of all deaths. Recently, a promising and alchemy-like strategy has been developed called direct cardiac reprogramming, which directly converts somatic cells such as fibroblasts to cardiac lineage cells such as cardiomyocytes (CMs), termed induced CMs or iCMs. The first in vitro cardiac reprogramming study, mediated by cardiac transcription factors (TFs)-Gata4, Tbx5 and Mef2C-, was not enough efficient to produce an adequate number of fully reprogrammed, functional iCMs. As a result, numerous combinations of cardiac TFs exist for direct cardiac reprogramming of mouse and human fibroblasts. However, the efficiency of direct cardiac reprogramming remains low. Recently, a number of cellular and molecular mechanisms have been identified to increase the efficiency of direct cardiac reprogramming and the quality of iCMs. For example, microgrooved substrate, cardiogenic growth factors [VEGF, FGF, BMP4 and Activin A], and an appropriate stoichiometry of TFs boost the direct cardiac reprogramming. On the other hand, serum, TGFβ signaling, activators of epithelial to mesenchymal transition, and some epigenetic factors (Bmi1 and Ezh2) are barriers for direct cardiac reprogramming. Manipulating these mechanisms by the application of boosters and removing barriers can increase the efficiency of direct cardiac reprogramming and possibly make iCMs reliable for cell-based therapy or other potential applications. In this review, we summarize the latest trends in cardiac TF- or miRNA-based direct cardiac reprogramming and comprehensively discuses all molecular and cellular boosters and barriers affecting direct cardiac reprogramming. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of teacher-directed versus student-directed instruction and cues versus no cues for improving spelling performance

OpenAIRE

Gettinger, Maribeth

1985-01-01

The purpose of this study was twofold: to examine the effects of imitating children's spelling errors alone and in combination with visual and verbal cues on spelling accuracy and retention among poor spellers and to compare the effectiveness of student-directed versus teacher-directed spelling instruction on children's spelling accuracy and retention. Nine children received four alternating experimental treatments during a 16-week spelling program. Results indicated that student-directed ins...

Verbal directionality and argument alternation in Dinka

DEFF Research Database (Denmark)

Andersen, Torben

2012-01-01

The derivational morphology of verbs in Dinka includes a distinction between direction towards the deictic center (centripetal) and a direction not towards the deictic center (centrifugal). A goal adverbial requires a directional verb, and an object of such a verb refers to something that moves t...... of a simple verb may correspond to, respectively, a goal adverbial and an object of the directional verb. Another type of argument alternation results from the possibility of expressing a goal as an object of an applicative verb with an intransitive or transitive base.......(wards) an explicit or implicit goal. The object of a directional verb may play another role in the event described by the sentence than the object of the corresponding simple (and non-directional) verb. This gives rise to so-called argument alternation, in that, for instance, an object and an instrumental adverbial...

Head direction cell activity in mice: robust directional signal depends on intact otolith organs

Science.gov (United States)

Yoder, Ryan M.; Taube, Jeffrey S.

2009-01-01

The head direction (HD) cell signal is a representation of an animal's perceived directional heading with respect to its environment. This signal appears to originate in the vestibular system, which includes the semicircular canals and otolith organs. Preliminary studies indicate the semicircular canals provide a necessary component of the HD signal, but involvement of otolithic information in the HD signal has not been tested. The present study was designed to determine the otolithic contribution to the HD signal, as well as to compare HD cell activity of mice to that of rats. HD cell activity in the anterodorsal thalamus was assessed in wild-type C57BL/6J and otoconia-deficient tilted mice during locomotion within a cylinder containing a prominent visual landmark. HD cell firing properties in C57BL/6J mice were generally similar to those in rats. However, in C57BL/6J mice, landmark rotation failed to demonstrate dominant control of the HD signal in 36% of the sessions. In darkness, directional firing became unstable during 42% of the sessions, but landmark control was not associated with HD signal stability in darkness. HD cells were identified in tilted mice, but directional firing properties were not as robust as those of C57BL/6J mice. Most HD cells in tilted mice were controlled by landmark rotation, but showed substantial signal degradation across trials. These results support current models that suggest otolithic information is involved in the perception of directional heading. Furthermore, compared to rats, the HD signal in mice appears to be less reliably anchored to prominent environmental cues. PMID:19176815

Search Directions for Direct H2O2 Synthesis Catalysts Starting from Au-12 Nanoclusters

DEFF Research Database (Denmark)

Grabow, Lars; Larsen, Britt Hvolbæk; Falsig, Hanne

2012-01-01

that the rate of H2O2 and H2O formation can be determined from a single descriptor, namely, the binding energy of oxygen (E-O). Our model predicts the search direction starting from an Au-12 nanocluster for an optimal catalyst in terms of activity and selectivity for direct H2O2 synthesis. Taking also stability......We present density functional theory calculations on the direct synthesis of H2O2 from H-2 and O-2 over an Au-12 corner model of a gold nanoparticle. We first show a simple route for the direct formation of H2O2 over a gold nanocatalyst, by studying the energetics of 20 possible elementary...... reactions involved in the oxidation of H-2 by O-2. The unwanted side reaction to H2O is also considered. Next we evaluate the degree of catalyst control and address the factors controlling the activity and the selectivity. By combining well-known energy scaling relations with microkinetic modeling, we show...

Developing Self-Directed Executive Functioning: Recent Findings and Future Directions

Science.gov (United States)

Barker, Jane E.; Munakata, Yuko

2015-01-01

How do children become increasingly self-directed across development, achieving their goals without help from others? How might such developments be impacted by societal changes in how children spend their time? Children's abilities to achieve their goals are supported by developing executive functions (EFs), cognitive processes that predict…

Directional connectivity in hydrology and ecology

Science.gov (United States)

Larsen, Laurel G.; Choi, Jungyill; Nungesser, Martha K.; Harvey, Judson W.

2012-01-01

Quantifying hydrologic and ecological connectivity has contributed to understanding transport and dispersal processes and assessing ecosystem degradation or restoration potential. However, there has been little synthesis across disciplines. The growing field of ecohydrology and recent recognition that loss of hydrologic connectivity is leading to a global decline in biodiversity underscore the need for a unified connectivity concept. One outstanding need is a way to quantify directional connectivity that is consistent, robust to variations in sampling, and transferable across scales or environmental settings. Understanding connectivity in a particular direction (e.g., streamwise, along or across gradient, between sources and sinks, along cardinal directions) provides critical information for predicting contaminant transport, planning conservation corridor design, and understanding how landscapes or hydroscapes respond to directional forces like wind or water flow. Here we synthesize progress on quantifying connectivity and develop a new strategy for evaluating directional connectivity that benefits from use of graph theory in ecology and percolation theory in hydrology. The directional connectivity index (DCI) is a graph-theory based, multiscale metric that is generalizable to a range of different structural and functional connectivity applications. It exhibits minimal sensitivity to image rotation or resolution within a given range and responds intuitively to progressive, unidirectional change. Further, it is linearly related to the integral connectivity scale length—a metric common in hydrology that correlates well with actual fluxes—but is less computationally challenging and more readily comparable across different landscapes. Connectivity-orientation curves (i.e., directional connectivity computed over a range of headings) provide a quantitative, information-dense representation of environmental structure that can be used for comparison or detection of

Directional connectivity in hydrology and ecology.

Science.gov (United States)

Larsen, Laurel G; Choi, Jungyill; Nungesser, Martha K; Harvey, Judson W

2012-12-01

Quantifying hydrologic and ecological connectivity has contributed to understanding transport and dispersal processes and assessing ecosystem degradation or restoration potential. However, there has been little synthesis across disciplines. The growing field of ecohydrology and recent recognition that loss of hydrologic connectivity is leading to a global decline in biodiversity underscore the need for a unified connectivity concept. One outstanding need is a way to quantify directional connectivity that is consistent, robust to variations in sampling, and transferable across scales or environmental settings. Understanding connectivity in a particular direction (e.g., streamwise, along or across gradient, between sources and sinks, along cardinal directions) provides critical information for predicting contaminant transport, planning conservation corridor design, and understanding how landscapes or hydroscapes respond to directional forces like wind or water flow. Here we synthesize progress on quantifying connectivity and develop a new strategy for evaluating directional connectivity that benefits from use of graph theory in ecology and percolation theory in hydrology. The directional connectivity index (DCI) is a graph-theory based, multiscale metric that is generalizable to a range of different structural and functional connectivity applications. It exhibits minimal sensitivity to image rotation or resolution within a given range and responds intuitively to progressive, unidirectional change. Further, it is linearly related to the integral connectivity scale length--a metric common in hydrology that correlates well with actual fluxes--but is less computationally challenging and more readily comparable across different landscapes. Connectivity-orientation curves (i.e., directional connectivity computed over a range of headings) provide a quantitative, information-dense representation of environmental structure that can be used for comparison or detection of

Developing a Strong Direct Care Workforce.

Science.gov (United States)

Stear, Lynda A

The aging population of the United States has led to a need for more direct care workers to provide personal care to older adults and disabled people in their homes. The U.S. Bureau of Labor Statistics predicts employment of paraprofessionals in home care will grow 49% between 2012 and 2022 as the baby boomer generation ages and requires more assistance in activities of daily living. The typical direct care worker is a female aged 25 to 54 years old, a demographic that is projected to remain flat in the coming years. Direct care workers typically are poorly paid for work that is labor-intensive and often work in less than optimal working conditions. It is important that agencies hiring direct care workers understand the challenges these workers face and institute sound hiring practices and provide proper training and ongoing supervision. It is possible to have a quality direct care team. Proper training, role modeling, and supervision will improve employee satisfaction, decrease turnover, and improve care outcomes for patients.

Directional outlyingness for multivariate functional data

KAUST Repository

Dai, Wenlin; Genton, Marc G.

2018-01-01

The direction of outlyingness is crucial to describing the centrality of multivariate functional data. Motivated by this idea, classical depth is generalized to directional outlyingness for functional data. Theoretical properties of functional

Towards host-directed therapies for tuberculosis.

Science.gov (United States)

Zumla, Alimuddin; Maeurer, Markus; Chakaya, Jeremiah; Hoelscher, Michael; Ntoumi, Francine; Rustomjee, Roxana; Vilaplana, Cristina; Yeboah-Manu, Dorothy; Rasolof, Voahangy; Munderi, Paula; Singh, Nalini; Aklillu, Eleni; Padayatchi, Nesri; Macete, Eusebio; Kapata, Nathan; Mulenga, Modest; Kibiki, Gibson; Mfinanga, Sayoki; Nyirenda, Thomas; Maboko, Leonard; Garcia-Basteiro, Alberto; Rakotosamimanana, Niaina; Bates, Matthew; Mwaba, Peter; Reither, Klaus; Gagneux, Sebastien; Edwards, Sarah; Mfinanga, Elirehema; Abdulla, Salim; Cardona, Pere-Joan; Russell, James B W; Gant, Vanya; Noursadeghi, Mahdad; Elkington, Paul; Bonnet, Maryline; Menendez, Clara; Dieye, Tandakha N; Diarra, Bassirou; Maiga, Almoustapha; Aseffa, Abraham; Parida, Shreemanta; Wejse, Christian; Petersen, Eskild; Kaleebu, Pontiano; Oliver, Matt; Craig, Gill; Corrah, Tumena; Tientcheu, Leopold; Antonio, Martin; Rao, Martin; McHugh, Timothy D; Sheikh, Aziz; Ippolito, Giuseppe; Ramjee, Gita; Kaufmann, Stefan H E; Churchyard, Gavin; Steyn, Andrie; Grobusch, Martin; Sanne, Ian; Martinson, Neil; Madansein, Rajhmun; Wilkinson, Robert J; Mayosi, Bongani; Schito, Marco; Wallis, Robert S

2015-08-01

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies.

Directional interstitial brachytherapy from simulation to application

Science.gov (United States)

Lin, Liyong

Organs at risk (OAR) are sometimes adjacent to or embedded in or overlap with the clinical target volume (CTV) to be treated. The purpose of this PhD study is to develop directionally low energy gamma-emitting interstitial brachytherapy sources. These sources can be applied between OAR to selectively reduce hot spots in the OARs and normal tissues. The reduction of dose over undesired regions can expand patient eligibility or reduce toxicities for the treatment by conventional interstitial brachytherapy. This study covers the development of a directional source from design optimization to construction of the first prototype source. The Monte Carlo code MCNP was used to simulate the radiation transport for the designs of directional sources. We have made a special construction kit to assemble radioactive and gold-shield components precisely into D-shaped titanium containers of the first directional source. Directional sources have a similar dose distribution as conventional sources on the treated side but greatly reduced dose on the shielded side, with a sharp dose gradient between them. A three-dimensional dose deposition kernel for the 125I directional source has been calculated. Treatment plans can use both directional and conventional 125I sources at the same source strength for low-dose-rate (LDR) implants to optimize the dose distributions. For prostate tumors, directional 125I LDR brachytherapy can potentially reduce genitourinary and gastrointestinal toxicities and improve potency preservation for low risk patients. The combination of better dose distribution of directional implants and better therapeutic ratio between tumor response and late reactions enables a novel temporary LDR treatment, as opposed to permanent or high-dose-rate (HDR) brachytherapy for the intermediate risk T2b and high risk T2c tumors. Supplemental external-beam treatments can be shortened with a better brachytherapy boost for T3 tumors. In conclusion, we have successfully finished the

Experimental investigation of a directionally enhanced DHX concept for high temperature Direct Reactor Auxiliary Cooling Systems

International Nuclear Information System (INIS)

Hughes, Joel T.; Blandford, Edward D.

2016-01-01

Highlights: • A novel directional heat exchanger design has been developed. • Hydrodynamic tests have been performed on the proposed design. • Heat transfer performance is inferred by hydrodynamic results. • Results are discussed and future work is suggested. - Abstract: The use of Direct Reactor Auxiliary Cooling Systems (DRACSs) as a safety-related decay heat removal system for advanced reactors has developed historically through the Sodium Fast Reactor (SFR) community. Beginning with the EBR-II, DRACSs have been utilized in a large number of past and current SFR designs. More recently, the DRACS has been adopted for Fluoride Salt-Cooled High-Temperature Reactors (FHRs) for similar decay heat removal functions. In this paper we introduce a novel directionally enhanced DRACS Heat Exchanger (DHX) concept. We present design options for optimizing such a heat exchanger so that shell-side heat transfer is enhanced in one primary coolant flow direction and degraded in the opposite coolant flow direction. A reduced-scale experiment investigating the hydrodynamics of a directionally enhanced DHX was built and the data collected is presented. The concept of thermal diodicity is expanded to heat exchanger technologies and used as performance criteria for evaluating design options. A heat exchanger that can perform as such would be advantageous for use in advanced reactor concepts where primary coolant flow reversal is expected during Loss-of-Forced-Circulation (LOFC) accidents where the ability to circulate coolant is compromised. The design could also find potential use in certain advanced Sodium Fast Reactor (SFR) designs utilizing fluidic diode concepts.

Experimental investigation of a directionally enhanced DHX concept for high temperature Direct Reactor Auxiliary Cooling Systems

Energy Technology Data Exchange (ETDEWEB)

Hughes, Joel T.; Blandford, Edward D., E-mail: edb@unm.edu

2016-07-15

Highlights: • A novel directional heat exchanger design has been developed. • Hydrodynamic tests have been performed on the proposed design. • Heat transfer performance is inferred by hydrodynamic results. • Results are discussed and future work is suggested. - Abstract: The use of Direct Reactor Auxiliary Cooling Systems (DRACSs) as a safety-related decay heat removal system for advanced reactors has developed historically through the Sodium Fast Reactor (SFR) community. Beginning with the EBR-II, DRACSs have been utilized in a large number of past and current SFR designs. More recently, the DRACS has been adopted for Fluoride Salt-Cooled High-Temperature Reactors (FHRs) for similar decay heat removal functions. In this paper we introduce a novel directionally enhanced DRACS Heat Exchanger (DHX) concept. We present design options for optimizing such a heat exchanger so that shell-side heat transfer is enhanced in one primary coolant flow direction and degraded in the opposite coolant flow direction. A reduced-scale experiment investigating the hydrodynamics of a directionally enhanced DHX was built and the data collected is presented. The concept of thermal diodicity is expanded to heat exchanger technologies and used as performance criteria for evaluating design options. A heat exchanger that can perform as such would be advantageous for use in advanced reactor concepts where primary coolant flow reversal is expected during Loss-of-Forced-Circulation (LOFC) accidents where the ability to circulate coolant is compromised. The design could also find potential use in certain advanced Sodium Fast Reactor (SFR) designs utilizing fluidic diode concepts.

Advance directives: survey of primary care patients.

Science.gov (United States)

O'Sullivan, Rory; Mailo, Kevin; Angeles, Ricardo; Agarwal, Gina

2015-04-01

To establish the prevalence of patients with advance directives in a family practice, and to describe patients' perspectives on a family doctor's role in initiating discussions about advance directives. A self-administered patient questionnaire. A busy urban family medicine teaching clinic in Hamilton, Ont. A convenience sample of adult patients attending the clinic over the course of a typical business week. The prevalence of advance directives in the patient population was determined, and the patients' expectations regarding the role of their family doctors were elucidated. The survey population consisted of 800 participants (a response rate of 72.5%) well distributed across age groups; 19.7% had written advance directives and 43.8% had previously discussed the topic of advance directives, but only 4.3% of these discussions had occurred with family doctors. In 5.7% of cases, a family physician had raised the issue; 72.3% of respondents believed patients should initiate the discussion. Patients who considered advance directives extremely important were significantly more likely to want their family doctors to start the conversation (odds ratio 3.98; P < .05). Advance directives were not routinely addressed in the family practice. Most patients preferred to initiate the discussion of advance directives. However, patients who considered the subject extremely important wanted their family doctors to initiate the discussion. Copyright© the College of Family Physicians of Canada.

Early Studies of Binocular and Binaural Directions

Directory of Open Access Journals (Sweden)

Nicholas J. Wade

2018-03-01

Full Text Available Understanding how the eyes work together to determine the direction of objects provided the impetus for examining integration of signals from the ears to locate sounds. However, the advantages of having two eyes were recorded long before those for two ears were appreciated. In part, this reflects the marked differences in how we can compare perception with one or two organs. It is easier to close one eye and examine monocular vision than to “close” one ear and study monaural hearing. Moreover, we can move our eyes either in the same or in opposite directions, but humans have no equivalent means of moving the ears in unison. Studies of binocular single vision can be traced back over two thousand years and they were implicitly concerned with visual directions from each eye. The location of any point in visual or auditory space can be described by specifying its direction and distance, from the vantage point of an observer. From the late 18th century experiments indicated that binocular direction involved an eye movement component and experimental studies of binaural direction commenced slightly later. However, these early binocular and binaural experiments were not incorporated into theoretical accounts until almost a century later. The early history of research on visual direction with two eyes is contrasted to that on auditory direction with two ears.

Configuring NIF for direct drive experiments

International Nuclear Information System (INIS)

Eimerl, D.; Rothenberg, J.; Key, M.

1995-01-01

The National Ignition Facility (NIF) is a proposed 1.8 MJ laser facility for carrying out experiments in inertial confinement fusion, currently designed for indirect drive experiments. The direct drive approach is being pursued at the 30 kJ Omega facility at the University of Rochester. In this paper we discuss the modifications to the NIF laser that would be required for both indirect and direct drive experiments. A primary concern is the additional cost of adding direct drive capability to the facility

Directional Wide-Angle Range Finder (DWARF)

Data.gov (United States)

National Aeronautics and Space Administration — The proposed innovation, the Directional Wide-Angle Range Finder (DWARF) is the creation of a laser range-finder with a wide field-of-view (FOV) and a directional...

Microsoft DirectAccess best practices and troubleshooting

CERN Document Server

Krause, Jordan

2013-01-01

This book covers best practices and acts as a complete guide to DirectAccess and automatic remote access.Microsoft DirectAccess Best Practices and Troubleshooting is an ideal guide for any existing or future DirectAccess administrator and system administrators who are working on Windows Server 2012. This book will also be beneficial for someone with a basic knowledge of networking and deployment of Microsoft operating systems and software who wants to learn the intricacies of DirectAccess and its interfaces.

Direct Optimal Control of Duffing Dynamics

Science.gov (United States)

Oz, Hayrani; Ramsey, John K.

2002-01-01

The "direct control method" is a novel concept that is an attractive alternative and competitor to the differential-equation-based methods. The direct method is equally well applicable to nonlinear, linear, time-varying, and time-invariant systems. For all such systems, the method yields explicit closed-form control laws based on minimization of a quadratic control performance measure. We present an application of the direct method to the dynamics and optimal control of the Duffing system where the control performance measure is not restricted to a quadratic form and hence may include a quartic energy term. The results we present in this report also constitute further generalizations of our earlier work in "direct optimal control methodology." The approach is demonstrated for the optimal control of the Duffing equation with a softening nonlinear stiffness.

Breakdown of interdependent directed networks.

Science.gov (United States)

Liu, Xueming; Stanley, H Eugene; Gao, Jianxi

2016-02-02

Increasing evidence shows that real-world systems interact with one another via dependency connectivities. Failing connectivities are the mechanism behind the breakdown of interacting complex systems, e.g., blackouts caused by the interdependence of power grids and communication networks. Previous research analyzing the robustness of interdependent networks has been limited to undirected networks. However, most real-world networks are directed, their in-degrees and out-degrees may be correlated, and they are often coupled to one another as interdependent directed networks. To understand the breakdown and robustness of interdependent directed networks, we develop a theoretical framework based on generating functions and percolation theory. We find that for interdependent Erdős-Rényi networks the directionality within each network increases their vulnerability and exhibits hybrid phase transitions. We also find that the percolation behavior of interdependent directed scale-free networks with and without degree correlations is so complex that two criteria are needed to quantify and compare their robustness: the percolation threshold and the integrated size of the giant component during an entire attack process. Interestingly, we find that the in-degree and out-degree correlations in each network layer increase the robustness of interdependent degree heterogeneous networks that most real networks are, but decrease the robustness of interdependent networks with homogeneous degree distribution and with strong coupling strengths. Moreover, by applying our theoretical analysis to real interdependent international trade networks, we find that the robustness of these real-world systems increases with the in-degree and out-degree correlations, confirming our theoretical analysis.

78 FR 53635 - Airworthiness Directives; Airbus Airplanes

Science.gov (United States)

2013-08-30

... Airworthiness Directives; Airbus Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: We are adopting a new airworthiness directive (AD) for certain Airbus Model A330-200 and... Sec. 39.13 by adding the following new airworthiness directive (AD): 2013-17-03 Airbus: Amendment 39...

Directed Forgetting of Recently Recalled Autobiographical Memories

Science.gov (United States)

Barnier, Amanda J.; Conway, Martin A.; Mayoh, Lyndel; Speyer, Joanne; Avizmil, Orit; Harris, Celia B.

2007-01-01

In 6 experiments, the authors investigated list-method directed forgetting of recently recalled autobiographical memories. Reliable directed forgetting effects were observed across all experiments. In 4 experiments, the authors examined the impact of memory valence on directed forgetting. The forget instruction impaired recall of negative,…

The Direct Satellite Connection: Definitions and Prospects.

Science.gov (United States)

Wigand, Rolf T.

1980-01-01

Defines direct satellite broadcasting as the transmission of broadcast signals via high-powered satellites that permit direct reception of television or radio programs by means of small antennas. Outlines American, European, and Japanese plans for direct-to-home television reception and implications for the broadcasting industry. (JMF)

A method for estimating the orientation of a directional sound source from source directivity and multi-microphone recordings: principles and application

DEFF Research Database (Denmark)

Guarato, Francesco; Jakobsen, Lasse; Vanderelst, Dieter

2011-01-01

Taking into account directivity of real sound sources makes it possible to try solving an interesting and biologically relevant problem: estimating the orientation in three-dimensional space of a directional sound source. The source, of known directivity, produces a broadband signal (in the ultra......Taking into account directivity of real sound sources makes it possible to try solving an interesting and biologically relevant problem: estimating the orientation in three-dimensional space of a directional sound source. The source, of known directivity, produces a broadband signal (in...

Intravascular ultrasound guided directional atherectomy versus directional atherectomy guided by angiography for the treatment of femoropopliteal in-stent restenosis

Science.gov (United States)

Krishnan, Prakash; Tarricone, Arthur; K-Raman, Purushothaman; Majeed, Farhan; Kapur, Vishal; Gujja, Karthik; Wiley, Jose; Vasquez, Miguel; Lascano, Rheoneil A.; Quiles, Katherine G.; Distin, Tashanne; Fontenelle, Ran; Atallah-Lajam, Farah; Kini, Annapoorna; Sharma, Samin

2017-01-01

Background: The aim of this study was to compare 1-year outcomes for patients with femoropopliteal in-stent restenosis using directional atherectomy guided by intravascular ultrasound (IVUS) versus directional atherectomy guided by angiography. Methods and results: This was a retrospective analysis for patients with femoropopliteal in-stent restenosis treated with IVUS-guided directional atherectomy versus directional atherectomy guided by angiography from a single center between March 2012 and February 2016. Clinically driven target lesion revascularization was the primary endpoint and was evaluated through medical chart review as well as phone call follow up. Conclusions: Directional atherectomy guided by IVUS reduces clinically driven target lesion revascularization for patients with femoropopliteal in-stent restenosis. PMID:29265002

The New EU Public Procurement Directives

DEFF Research Database (Denmark)

, transparency requirements, competitive dialogue, framework agreements, use of social and environmental criteria, Partnering and Public Private Partnerships and concessions. This book contains contributions based on presentations given by a number of the international and Danish speakers at the conference.......31 March 2004 the EU adopted two new public procurement directives: one for the public sector (2004/18/EC) and one for utilities (2004/17/EC). The new directives aim at simplification and modernisation of the previously existing directives including adaptation to electronic purchasing techniques...

48 CFR 1552.237-71 - Technical direction.

Science.gov (United States)

2010-10-01

.... (d) Technical direction will be issued in writing or confirmed in writing within five (5) days after... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Technical direction. 1552... Technical direction. As prescribed in 1537.110, insert a clause substantially the same as the following...

On the Retrieval of the Directional Scattering Matrix from Directional Noise

NARCIS (Netherlands)

Wapenaar, C.P.A.; Thorbecke, J.W.

2013-01-01

The crosscorrelation of ambient acoustic noise observed at two receivers yields the impulse response between these receivers, assuming that the noise field is diffuse. In practical situations the noise field exhibits directionality, which imprints the angle-dependent correlation function. For the

Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis.

Directory of Open Access Journals (Sweden)

Peter Jonas Grahn

2014-09-01

Full Text Available Movement is planned and coordinated by the brain and carried out by contracting muscles acting on specific joints. Motor commands initiated in the brain travel through descending pathways in the spinal cord to effector motor neurons before reaching target muscles. Damage to these pathways by spinal cord injury (SCI can result in paralysis below the injury level. However, the planning and coordination centers of the brain, as well as peripheral nerves and the muscles that they act upon, remain functional. Neuroprosthetic devices can restore motor function following SCI by direct electrical stimulation of the neuromuscular system. Unfortunately, conventional neuroprosthetic techniques are limited by a myriad of factors that include, but are not limited to, a lack of characterization of non-linear input/output system dynamics, mechanical coupling, limited number of degrees of freedom, high power consumption, large device size, and rapid onset of muscle fatigue. Wireless multi-channel closed-loop neuroprostheses that integrate command signals from the brain with sensor-based feedback from the environment and the system’s state offer the possibility of increasing device performance, ultimately improving quality of life for people with SCI. In this manuscript, we review neuroprosthetic technology for improving functional restoration following SCI and describe brain-machine interfaces suitable for control of neuroprosthetic systems with multiple degrees of freedom. Additionally, we discuss novel stimulation paradigms that can improve synergy with higher planning centers and improve fatigue-resistant activation of paralyzed muscles. In the near future, integration of these technologies will provide SCI survivors with versatile closed-loop neuroprosthetic systems for restoring function to paralyzed muscles.

Wave directional spectrum from array measurements

Digital Repository Service at National Institute of Oceanography (India)

Fernandes, A.A; Sarma, Y; Menon, H.B.

Using the method of Esteva (1976, 1977), whcih assumes that at the frequency band the waves approach from just a single "mean" wave direction, wave direction has been consistently, accurately and unambiguously evaluated as a function of frequency...

Learning to trade via direct reinforcement.

Science.gov (United States)

Moody, J; Saffell, M

2001-01-01

We present methods for optimizing portfolios, asset allocations, and trading systems based on direct reinforcement (DR). In this approach, investment decision-making is viewed as a stochastic control problem, and strategies are discovered directly. We present an adaptive algorithm called recurrent reinforcement learning (RRL) for discovering investment policies. The need to build forecasting models is eliminated, and better trading performance is obtained. The direct reinforcement approach differs from dynamic programming and reinforcement algorithms such as TD-learning and Q-learning, which attempt to estimate a value function for the control problem. We find that the RRL direct reinforcement framework enables a simpler problem representation, avoids Bellman's curse of dimensionality and offers compelling advantages in efficiency. We demonstrate how direct reinforcement can be used to optimize risk-adjusted investment returns (including the differential Sharpe ratio), while accounting for the effects of transaction costs. In extensive simulation work using real financial data, we find that our approach based on RRL produces better trading strategies than systems utilizing Q-learning (a value function method). Real-world applications include an intra-daily currency trader and a monthly asset allocation system for the S&P 500 Stock Index and T-Bills.

Integrating and interpreting the Habitats- and Birds Directives

NARCIS (Netherlands)

Kistenkas, F.H.

2005-01-01

The Birds Directive of 1979 and the Habitats Directive of 1992 might be seen as the two major EU nature conservation directives, both protecting a habitats network throughout Europe and species. The transposition of both the Habitats and Birds Directive (HBD) into domestic national or subnational

A three-port direct current converter

DEFF Research Database (Denmark)

2016-01-01

circuit comprises a connection between the at least one input direct current source and the at least one storage battery, the primary side circuit configured for operating as a buck converter; a second magnetic component serially coupled to the first single magnetic component, wherein the first and second...... magnetic components are configured to perform a voltage step-up, wherein the secondary side circuit comprises a connection between the at least one storage battery and at least one load, the secondary side configured for operating as a tapped boost converter; wherein the three-port direct current converter......The three-port direct current converter comprising: at least one input direct current source; at least one storage battery; a primary side circuit; a secondary side circuit; a first single magnetic component shared by the primary side circuit and the secondary side circuit, wherein the primary side...

Directional Transverse Oscillation Vector Flow Estimation

DEFF Research Database (Denmark)

Jensen, Jørgen Arendt

2017-01-01

A method for estimating vector velocities using transverse oscillation (TO) combined with directional beamforming is presented. In Directional Transverse Oscillation (DTO) a normal focused field is emitted and the received signals are beamformed in the lateral direction transverse to the ultrasound...... beam to increase the amount of data for vector velocity estimation. The approach is self-calibrating as the lateral oscillation period is estimated from the directional signal through a Fourier transform to yield quantitative velocity results over a large range of depths. The approach was extensively...... simulated using Field IIpro and implemented on the experimental SARUS scanner in connection with a BK Medical 8820e convex array transducer. Velocity estimates for DTO are found for beam-to-flow angles of 60, 75, and 90, and vessel depths from 24 to 156 mm. Using 16 emissions the Standard Deviation (SD...

Spontaneous direct and reverse osmosis

International Nuclear Information System (INIS)

Valitov, N.Kh.

1996-01-01

It has been ascertained experimentally that in the course of separation of CsCl, KCl, NaCl aqueous solutions by semi-permeable membrane from distilled water the direct and then reverse osmosis are observed. The same sequence is observed in case of separation of CsCl aqueous solutions from NaCl of different concentrations. The reason for the direct and reverse osmosis has been explained. 5 refs.; 3 figs. 1 tab

Direct Bandgap Group IV Materials

Science.gov (United States)

2016-01-21

AFRL-AFOSR-JP-TR-2017-0049 Direct Bandgap group IV Materials Hung Hsiang Cheng NATIONAL TAIWAN UNIVERSITY Final Report 01/21/2016 DISTRIBUTION A...NAME(S) AND ADDRESS(ES) NATIONAL TAIWAN UNIVERSITY 1 ROOSEVELT RD. SEC. 4 TAIPEI CITY, 10617 TW 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING...14. ABSTRACT Direct bandgap group IV materials have been long sought for in both academia and industry for the implementation of photonic devices

Direct use in Hawaii

International Nuclear Information System (INIS)

Beck, A.G.

1990-01-01

This paper reports on a public laboratory, Noi'i O Puna, that was established in Hawaii to support direct use research in 1985, tapping the previously unutilized heat in brines from the HGP-A well. Two rounds of small grants were offered to entrepreneurs. With the closure of the HGP-A power plant in late 1989, Noi'i O Puna is expanding its facilities. When the HGP-A well is back in service, Noi'i O Puna will be able to support additional research and development projects, as well as pre-commercial ventures. Direct use industries, which support existing agricultural activities in the region have good potential

Enhancing Scalability of Sparse Direct Methods

International Nuclear Information System (INIS)

Li, Xiaoye S.; Demmel, James; Grigori, Laura; Gu, Ming; Xia, Jianlin; Jardin, Steve; Sovinec, Carl; Lee, Lie-Quan

2007-01-01

TOPS is providing high-performance, scalable sparse direct solvers, which have had significant impacts on the SciDAC applications, including fusion simulation (CEMM), accelerator modeling (COMPASS), as well as many other mission-critical applications in DOE and elsewhere. Our recent developments have been focusing on new techniques to overcome scalability bottleneck of direct methods, in both time and memory. These include parallelizing symbolic analysis phase and developing linear-complexity sparse factorization methods. The new techniques will make sparse direct methods more widely usable in large 3D simulations on highly-parallel petascale computers

Direct marketing and market communication process

Directory of Open Access Journals (Sweden)

Jovović Sanja

2007-01-01

Full Text Available Direct marketing is marketing which demands immediate reply. That reply can be an order, a request for an additional information, a registration, a telephone call or a visit. This work presents direct marketing as the most contemporary method of company communications with environs. A concept of direct marketing is made and aimed for complete identification of existing customers and for finding out potential customers. Mail, printed documents e-mail and new medias are used as modern communications channels. It is especially emphasizes the Internet as an important media.

Design and validation of a real-time spiking-neural-network decoder for brain-machine interfaces

Science.gov (United States)

Dethier, Julie; Nuyujukian, Paul; Ryu, Stephen I.; Shenoy, Krishna V.; Boahen, Kwabena

2013-06-01

Objective. Cortically-controlled motor prostheses aim to restore functions lost to neurological disease and injury. Several proof of concept demonstrations have shown encouraging results, but barriers to clinical translation still remain. In particular, intracortical prostheses must satisfy stringent power dissipation constraints so as not to damage cortex. Approach. One possible solution is to use ultra-low power neuromorphic chips to decode neural signals for these intracortical implants. The first step is to explore in simulation the feasibility of translating decoding algorithms for brain-machine interface (BMI) applications into spiking neural networks (SNNs). Main results. Here we demonstrate the validity of the approach by implementing an existing Kalman-filter-based decoder in a simulated SNN using the Neural Engineering Framework (NEF), a general method for mapping control algorithms onto SNNs. To measure this system’s robustness and generalization, we tested it online in closed-loop BMI experiments with two rhesus monkeys. Across both monkeys, a Kalman filter implemented using a 2000-neuron SNN has comparable performance to that of a Kalman filter implemented using standard floating point techniques. Significance. These results demonstrate the tractability of SNN implementations of statistical signal processing algorithms on different monkeys and for several tasks, suggesting that a SNN decoder, implemented on a neuromorphic chip, may be a feasible computational platform for low-power fully-implanted prostheses. The validation of this closed-loop decoder system and the demonstration of its robustness and generalization hold promise for SNN implementations on an ultra-low power neuromorphic chip using the NEF.

Seeing fearful body language rapidly freezes the observer's motor cortex.

Science.gov (United States)

Borgomaneri, Sara; Vitale, Francesca; Gazzola, Valeria; Avenanti, Alessio

2015-04-01

Fearful body language is a salient signal alerting the observer to the presence of a potential threat in the surrounding environment. Although detecting potential threats may trigger an immediate reduction of motor output in animals (i.e., freezing behavior), it is unclear at what point in time similar reductions occur in the human motor cortex and whether they originate from excitatory or inhibitory processes. Using single-pulse and paired-pulse transcranial magnetic stimulation (TMS), here we tested the hypothesis that the observer's motor cortex implements extremely fast suppression of motor readiness when seeing emotional bodies - and fearful body expressions in particular. Participants observed pictures of body postures and categorized them as happy, fearful or neutral while receiving TMS over the right or left motor cortex at 100-125 msec after picture onset. In three different sessions, we assessed corticospinal excitability, short intracortical inhibition (SICI) and intracortical facilitation (ICF). Independently of the stimulated hemisphere and the time of the stimulation, watching fearful bodies suppressed ICF relative to happy and neutral body expressions. Moreover, happy expressions reduced ICF relative to neutral actions. No changes in corticospinal excitability or SICI were found during the task. These findings show extremely rapid bilateral modulation of the motor cortices when seeing emotional bodies, with stronger suppression of motor readiness when seeing fearful bodies. Our results provide neurophysiological support for the evolutionary notions that emotion perception is inherently linked to action systems and that fear-related cues induce an urgent mobilization of motor reactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simulation of a Real-Time Brain Computer Interface for Detecting a Self-Paced Hitting Task.

Science.gov (United States)

Hammad, Sofyan H; Kamavuako, Ernest N; Farina, Dario; Jensen, Winnie

2016-12-01

An invasive brain-computer interface (BCI) is a promising neurorehabilitation device for severely disabled patients. Although some systems have been shown to work well in restricted laboratory settings, their utility must be tested in less controlled, real-time environments. Our objective was to investigate whether a specific motor task could be reliably detected from multiunit intracortical signals from freely moving animals in a simulated, real-time setting. Intracortical signals were first obtained from electrodes placed in the primary motor cortex of four rats that were trained to hit a retractable paddle (defined as a "Hit"). In the simulated real-time setting, the signal-to-noise-ratio was first increased by wavelet denoising. Action potentials were detected, and features were extracted (spike count, mean absolute values, entropy, and combination of these features) within pre-defined time windows (200 ms, 300 ms, and 400 ms) to classify the occurrence of a "Hit." We found higher detection accuracy of a "Hit" (73.1%, 73.4%, and 67.9% for the three window sizes, respectively) when the decision was made based on a combination of features rather than on a single feature. However, the duration of the window length was not statistically significant (p = 0.5). Our results showed the feasibility of detecting a motor task in real time in a less restricted environment compared to environments commonly applied within invasive BCI research, and they showed the feasibility of using information extracted from multiunit recordings, thereby avoiding the time-consuming and complex task of extracting and sorting single units. © 2016 International Neuromodulation Society.

The effects of individualized theta burst stimulation on the excitability of the human motor system.

Science.gov (United States)

Brownjohn, Philip W; Reynolds, John N J; Matheson, Natalie; Fox, Jonathan; Shemmell, Jonathan B H

2014-01-01

Theta burst stimulation (TBS) is a pattern of repetitive transcranial magnetic stimulation that has been demonstrated to facilitate or suppress human corticospinal excitability when applied intermittently (iTBS) or continuously (cTBS), respectively. While the fundamental pattern of TBS, consisting of bursts of 50 Hz stimulation repeated at a 5 Hz theta frequency, induces synaptic plasticity in animals and in vitro preparations, the relationship between TBS and underlying cortical firing patterns in the human cortex has not been elucidated. To compare the effects of 5 Hz iTBS and cTBS with individualized TBS paradigms on corticospinal excitability and intracortical inhibitory circuits. Participants received standard and individualized iTBS (iTBS 5; iTBS I) and cTBS (cTBS 5; cTBS I), and sham TBS, in a randomised design. For individualized paradigms, the 5 Hz theta component of the TBS pattern was replaced by the dominant cortical frequency (4-16 Hz; upper frequency restricted by technical limitations) for each individual. We report that iTBS 5 and iTBS I both significantly facilitated motor evoked potential (MEP) amplitude to a similar extent. Unexpectedly, cTBS 5 and cTBS I failed to suppress MEP amplitude. None of the active TBS protocols had any significant effects on intracortical circuits when compared with sham TBS. In summary, iTBS facilitated MEP amplitude, an effect that was not improved by individualizing the theta component of the TBS pattern, while cTBS, a reportedly inhibitory paradigm, produced no change, or facilitation of MEP amplitude in our hands. Copyright © 2014 Elsevier Inc. All rights reserved.

Electroencephalographic precursors of spike-wave discharges in a genetic rat model of absence epilepsy: Power spectrum and coherence EEG analyses.

Science.gov (United States)

Sitnikova, Evgenia; van Luijtelaar, Gilles

2009-04-01

Periods in the electroencephalogram (EEG) that immediately precede the onset of spontaneous spike-wave discharges (SWD) were examined in WAG/Rij rat model of absence epilepsy. Precursors of SWD (preSWD) were classified based on the distribution of EEG power in delta-theta-alpha frequency bands as measured in the frontal cortex. In 95% of preSWD, an elevation of EEG power was detected in delta band (1-4Hz). 73% of preSWD showed high power in theta frequencies (4.5-8Hz); these preSWD might correspond to 5-9Hz oscillations that were found in GAERS before SWD onset [Pinault, D., Vergnes, M., Marescaux, C., 2001. Medium-voltage 5-9Hz oscillations give rise to spike-and-wave discharges in a genetic model of absence epilepsy: in vivo dual extracellular recording of thalamic relay and reticular neurons. Neuroscience 105, 181-201], however, theta component of preSWD in our WAG/Rij rats was not shaped into a single rhythm. It is concluded that a coalescence of delta and theta in the cortex is favorable for the occurrence of SWD. The onset of SWD was associated with strengthening of intracortical and thalamo-cortical coherence in 9.5-14Hz and in double beta frequencies. No features of EEG coherence can be considered as unique for any of preSWD subtype. Reticular and ventroposteromedial thalamic nuclei were strongly coupled even before the onset of SWD. All this suggests that SWD derive from an intermixed delta-theta EEG background; seizure onset associates with reinforcement of intracortical and cortico-thalamic associations.

Ontwerpen van onderwijs om ‘self-directed learning’ te stimuleren [Desiging instruction to foster self-directed learning

NARCIS (Netherlands)

Brand-Gruwel, Saskia

2010-01-01

Brand-Gruwel, S. (2010, March). Ontwerpen van onderwijs om ‘self-directed learning’ te stimuleren [Desiging instruction to foster self-directed learning]. Key-note presented at the 3th 4C/ID-conference, Utrecht, The Netherlands.

Direct Interval Forecasting of Wind Power

DEFF Research Database (Denmark)

Wan, Can; Xu, Zhao; Pinson, Pierre

2013-01-01

This letter proposes a novel approach to directly formulate the prediction intervals of wind power generation based on extreme learning machine and particle swarm optimization, where prediction intervals are generated through direct optimization of both the coverage probability and sharpness...

12 CFR 619.9135 - Direct lender.

Science.gov (United States)

2010-01-01

... and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM DEFINITIONS § 619.9135 Direct lender. The term direct lender refers to Farm Credit banks and associations (production credit associations, agricultural credit associations, and Federal land credit associations) authorized to lend to eligible...

Novel Random Mutagenesis Method for Directed Evolution.

Science.gov (United States)

Feng, Hong; Wang, Hai-Yan; Zhao, Hong-Yan

2017-01-01

Directed evolution is a powerful strategy for gene mutagenesis, and has been used for protein engineering both in scientific research and in the biotechnology industry. The routine method for directed evolution was developed by Stemmer in 1994 (Stemmer, Proc Natl Acad Sci USA 91, 10747-10751, 1994; Stemmer, Nature 370, 389-391, 1994). Since then, various methods have been introduced, each of which has advantages and limitations depending upon the targeted genes and procedure. In this chapter, a novel alternative directed evolution method which combines mutagenesis PCR with dITP and fragmentation by endonuclease V is described. The kanamycin resistance gene is used as a reporter gene to verify the novel method for directed evolution. This method for directed evolution has been demonstrated to be efficient, reproducible, and easy to manipulate in practice.

Directional loudness perception

DEFF Research Database (Denmark)

Sivonen, Ville Pekka

developed. The research and modeling of loudness have mainly been concerned with the temporal and spectral aspects of sounds, while the spatial aspects have mostly been overlooked. This PhD thesis investigates the spatial aspects of loudness perception, namely, how does the direction from which a sound...

Patterns of postural deformity in non-ambulant people with cerebral palsy: what is the relationship between the direction of scoliosis, direction of pelvic obliquity, direction of windswept hip deformity and side of hip dislocation?

Science.gov (United States)

Porter, David; Michael, Shona; Kirkwood, Craig

2007-12-01

To investigate: (a) associations between the direction of scoliosis, direction of pelvic obliquity, direction of windswept deformity and side of hip subluxation/ dislocation in non-ambulant people with cerebral palsy; and (b) the lateral distribution of these postural asymmetries. Cross-sectional observational study. Posture management services in three centres in the UK. Non-ambulant people at level five on the gross motor function classification system for cerebral palsy. Direction of pelvic obliquity and lateral spinal curvature determined from physical examination, direction of windswept hip deformity derived from range of hip abduction/adduction, and presence/side of unilateral hip subluxation defined by hip migration percentage. A total of 747 participants were included in the study, aged 6-80 years (median 18 years 10 months). Associations between the direction of scoliosis and direction of pelvic obliquity, and between the direction of windswept hip deformity and side hip subluxation/dislocation were confirmed. A significant association was also seen between the direction of scoliosis and the direction of the windswept hip deformity (P<0.001) such that the convexity of the lateral spinal curve was more likely to be opposite to the direction of windsweeping. Furthermore, significantly more windswept deformities to the right (P=0.007), hips subluxed on the left (P=0.002) and lateral lumbar/lower thoracic spinal curves convex to the left (P=0.03) were observed. The individual asymmetrical postural deformities are not unrelated in terms of direction and not equally distributed to the left/right. A pattern of postural deformity was observed.

5 CFR 330.402 - Direct recruitment.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Direct recruitment. 330.402 Section 330.402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS RECRUITMENT, SELECTION, AND PLACEMENT (GENERAL) Positions Restricted to Preference Eligibles § 330.402 Direct recruitment...

Spillovers from Foreign Direct Investment

DEFF Research Database (Denmark)

Meyer, Klaus E.; Sinani, Evis

2005-01-01

The extensive empirical literature analyzing productivity spillovers from foreign direct investment to local firms provides inconclusive results. Some studies find that foreign presence has a positive impact on the productivity of domestic firms, while others find no evidence or a negative effect...... for industrialized countries in the 1990s. Transition economies may experience spillovers, but these have been declining in recent years. Keywords: developing countries, transition economies, spillovers, foreign direct investment, technology transfer, meta-analysis...

Directed forgetting: Comparing pictures and words.

Science.gov (United States)

Quinlan, Chelsea K; Taylor, Tracy L; Fawcett, Jonathan M

2010-03-01

The authors investigated directed forgetting as a function of the stimulus type (picture, word) presented at study and test. In an item-method directed forgetting task, study items were presented 1 at a time, each followed with equal probability by an instruction to remember or forget. Participants exhibited greater yes-no recognition of remember than forget items for each of the 4 study-test conditions (picture-picture, picture-word, word-word, word-picture). However, this difference was significantly smaller when pictures were studied than when words were studied. This finding demonstrates that the magnitude of the directed forgetting effect can be reduced by high item memorability, such as when the picture superiority effect is operating. This suggests caution in using pictures at study when the goal of an experiment is to examine potential group differences in the magnitude of the directed forgetting effect. 2010 APA, all rights reserved.

Directed Energy Anechoic Chamber

Data.gov (United States)

Federal Laboratory Consortium — The Directed Energy Anechoic Chamber comprises a power anechoic chamber and one transverse electromagnetic cell for characterizing radiofrequency (RF) responses of...

Directional sound radiation from substation transformers

International Nuclear Information System (INIS)

Maybee, N.

2009-01-01

This paper presented the results of a study in which acoustical measurements at two substations were analyzed to investigate the directional behaviour of typical arrays having 2 or 3 transformers. Substation transformers produce a characteristic humming sound that is caused primarily by vibration of the core at twice the frequency of the power supply. The humming noise radiates predominantly from the tank enclosing the core. The main components of the sound are harmonics of 120 Hz. Sound pressure level data were obtained for various directions and distances from the arrays, ranging from 0.5 m to over 100 m. The measured sound pressure levels of the transformer tones displayed substantial positive and negative excursions from the calculated average values for many distances and directions. The results support the concept that the directional effects are associated with constructive and destructive interference of tonal sound waves emanating from different parts of the array. Significant variations in the directional sound pattern can occur in the near field of a single transformer or an array, and the extent of the near field is significantly larger than the scale of the array. Based on typical dimensions for substation sites, the distance to the far field may be much beyond the substation boundary and beyond typical setbacks to the closest dwellings. As such, the directional sound radiation produced by transformer arrays introduces additional uncertainty in the prediction of substation sound levels at dwellings within a few hundred meters of a substation site. 4 refs., 4 figs.

Laser direct writing using submicron-diameter fibers.

Science.gov (United States)

Tian, Feng; Yang, Guoguang; Bai, Jian; Xu, Jianfeng; Hou, Changlun; Liang, Yiyong; Wang, Kaiwei

2009-10-26

In this paper, a novel direct writing technique using submicron-diameter fibers is presented. The submicron-diameter fiber probe serves as a tightly confined point source and it adopts micro touch mode in the process of writing. The energy distribution of direct writing model is analyzed by Three-Dimension Finite-Difference Time-Domain method. Experiments demonstrate that submicron-diameter fiber direct writing has some advantages: simple process, 350-nm-resolution (lower than 442-nm-wavelength), large writing area, and controllable width of lines. In addition, by altering writing direction of lines, complex submicron patterns can be fabricated.

DIRECTIVE SPEECH ACTS REALIZATION OF INDONESIAN EFL TEACHER

Directory of Open Access Journals (Sweden)

Cucu Suhartini

2015-06-01

Full Text Available This research examines the types and functions of directive speech act performed by an Indonesian EFL teacher in one senior high school in Kuningan, Indonesia. This study uses qualitative method. The data of this research were taken from the video transcription which contains directives spoken by the EFL teacher and analyzed based on Kreidler’s (1998 theory. The findings show that there are three types of directives used by the teacher. They are commands, requests, and suggestions. The most frequent type of directives performed is commands with 233 occurrences (94.8%. It was also found that there are five functions seized by the directives, they are elicitation, instruction, advice, threat, and attention-getter. The most frequent function of directives used is elicitation with 108 occurrences (44%. From the findings, it is concluded that the using of commands shows teacher’s dominance. Yet, this type of directives is not easily understood by the students. Therefore, it is suggested that the teacher should use other types of directives more, such as requests and suggestions, to encourage students’ participation.

Comparison of NGA-West2 directivity models

Science.gov (United States)

Spudich, Paul A.; Rowshandel, Badie; Shahi, Shrey; Baker, Jack W.; Chiou, Brian S-J

2014-01-01

Five directivity models have been developed based on data from the NGA-West2 database and based on numerical simulations of large strike-slip and reverse-slip earthquakes. All models avoid the use of normalized rupture dimension, enabling them to scale up to the largest earthquakes in a physically reasonable way. Four of the five models are explicitly “narrow-band” (in which the effect of directivity is maximum at a specific period that is a function of earthquake magnitude). Several strategies for determining the zero-level for directivity have been developed. We show comparisons of maps of the directivity amplification. This comparison suggests that the predicted geographic distributions of directivity amplification are dominated by effects of the models' assumptions, and more than one model should be used for ruptures dipping less than about 65 degrees.

Directional borehole antenna - Theory

International Nuclear Information System (INIS)

Falk, L.

1992-02-01

A directional antenna has been developed for the borehole radar constructed during phase 2 of the Stripa project. The new antenna can determine the azimuth of a strong reflector with an accuracy of about 3 degrees as confirmed during experiments in Stripa, although the ratio of borehole diameter to wavelength is small, about 0.03. The antenna synthesizes the effect of a loop antenna rotating in the borehole from four signals measured in turn by a stationary antenna. These signals are also used to calculate an electric dipole signal and a check sum which is used to examine the function of the system. The theory of directional antennas is reviewed and used to design an antenna consisting of four parallel wires. The radiation pattern of this antenna is calculated using transmission line theory with due regard to polarization, which is of fundamental importance for the analysis of directional data. In particular the multipole expansion of the field is calculated to describe the antenna radiation pattern. Various sources of error, e.g. the effect of the borehole, are discussed and the methods of calibrating the antenna are reviewed. The ambiguity inherent in a loop antenna can be removed by taking the phase of the signal into account. Typical reflectors in rock, e.g. fracture zones an tunnels, may be modelled as simple geometrical structures. The corresponding analysis is described and exemplified on measurements from Stripa. Radar data is nowadays usually analyzed directly on the computer screen using the program RADINTER developed within the Stripa project. An algorithm for automatic estimation of the parameters of a reflector have been tested with some success. The relation between measured radar data and external coordinates as determined by rotational indicators is finally expressed in terms of Euler angles. (au)

Study on the combustion and hydrocarbon emission characteristics of direct injection spark-ignition engines during the direct-start process

International Nuclear Information System (INIS)

Shi, Lei; Xiao, Maoyu; Deng, Kangyao

2015-01-01

Highlights: • Mixture concentration in first-combustion cylinder of direct start is measured. • Factors that affect direct start performances are investigated. • Combustion characteristics of first-combustion cylinder are analyzed. • Hydrocarbon emission is considered to determined control strategies of direct start. - Abstract: This study was conducted to investigate the combustion and emissions characteristics of the first-combustion cylinder in a direct-start process. The explosive energy of the first combustion is important for the success of a direct start, but this combustion was rarely addressed in recent research. For a 2.0 L direct-injection spark-ignition engine, the in-cylinder mixture concentration, cylinder pressure, engine speed and exhaust hydrocarbon concentration were detected to analyze the fuel evaporation, combustion, engine movement and engine emissions, respectively. In the first-combustion cylinder of the direct-start process, the injected fuel was often enriched to ensure that an appropriate mixture concentration was obtained for ignition without misfiring. Approximately one-third of the injected fuel would not participate in the combustion process and would therefore reduce the exhaust hydrocarbon emissions. The start position determined the amount of the total explosive energy in the first-combustion cylinder, and an optimal start position for a direct start was found to be at a 70–80° crank angle before the top dead center to obtain a better combustion performance and lower emissions. A lower coolant temperature increased the maximum explosion energy of the first combustion, but additional hydrocarbon emissions were generated. Because there was almost no problem in the direct-start capability with different coolant temperatures after an idling stop, it was necessary to maintain the coolant temperature when the engine was stopped

12 CFR 567.4 - Capital directives.

Science.gov (United States)

2010-01-01

... requirement, the leverage ratio requirement, the tangible capital requirement, or individual minimum capital... capital directive, it may become effective immediately. A capital directive shall remain in effect and... plan shall continue in full force and effect. (b) Relation to other administrative actions. The Office...

Thermal imitators with single directional invisibility

Science.gov (United States)

Wang, Ruizhe; Xu, Liujun; Huang, Jiping

2017-12-01

Thermal metamaterials have been intensively studied during the past years to achieve the long-standing dream of invisibility, illusion, and other inconceivable thermal phenomena. However, many thermal metamaterials can only exhibit omnidirectional thermal response, which take on the distinct feature of geometrical isotropy. In this work, we theoretically design and experimentally fabricate a pair of thermal imitators by applying geometrical anisotropy provided by elliptical/ellipsoidal particles and layered structures. This pair of thermal imitators possesses thermal invisibility in one direction, while having thermal opacity in other directions. This work may open a gate in designing direction-dependent thermal metamaterials.

High precision studies of directional correlations

International Nuclear Information System (INIS)

El-khosht, M.

1980-01-01

Two applications of the method of directional correlations are described. The first part deals with gamma-gamma directional correlations measurements. A total of 27 cascades have been studied in 97 Tc, 206 Pb and 206 Bi. Information is obtained on the angular momenta of levels, multipolarities of electromagnetic transitions and further, reduced transition probabilities. The later part of this thesis describes a determination of anisotropic directional correlation between gamma-rays and LX-rays in 160 Dy. To the authors' knowledge this is the first observation of an anisotropic correlation between gamma rays and X-rays following internal conversion. (Auth.)

Direct energy recovery from helium ion beams by a beam direct converter with secondary electron suppressors

International Nuclear Information System (INIS)

Yoshikawa, K.; Yamamoto, Y.; Toku, H.; Kobayashi, A.; Okazaki, T.

1989-01-01

A 5-yr study of beam direct energy conversion was performed at the Kyoto University Institute of Atomic Energy to clarify the essential features of direct energy recovery from monoenergetic ion beams so that the performance characteristics of energy recovery can be predicted reasonably well by numerical calculations. The study used an improved version of an electrostatically electron-suppressed beam direct converter. Secondary electron suppressor grids were added, and a helium ion beam was used with typical parameters of 15.4 keV, 90 mA, and 100 ms. This paper presents a comparison of experimental results with numerical results by the two-dimensional Kyoto University Advanced Dart (KUAD) code, including evaluation of atomic processes

Direct electromechanical driving systems: diversity, constraints and solutions; Les entrainements electromecaniques directs: diversite, contraintes et solutions

Energy Technology Data Exchange (ETDEWEB)

Multon, B. [Ecole Normale Superieure, 94 - Cachan (France); Bonal, J. [Promethee Groupe Schneider Electric S.A., 92 - Boulogne-Billancourt (France)

1999-11-01

Direct electromechanical drives are the simplest possible transmission systems requiring no additional mechanical components such as gearboxes or rotary to linear converters. This simplicity leads a number of advantages including greater reliability, less maintenance, improved dynamic characteristics and reduced weight and volume. However, the performance specification of direct drives is usually high, with a correspondingly high cost, and often this cannot be justified in complete systems where the other components limit the overall performance. This factor alone has been sufficient to restrict the market penetration of direct drives. The majority of applications are in linear actuators, and in motors operating at very high or very low speeds. New developments are constantly being introduced, especially in relation to structures.

Radiation-induced focal cortical necrosis of the femur presenting as a lytic lesion

Energy Technology Data Exchange (ETDEWEB)

Ilaslan, Hakan; Schils, Jean [Cleveland Clinic, Musculoskeletal Radiology, Cleveland, OH (United States); Joyce, Michael [Cleveland Clinic, Orthopedic Oncology, Cleveland, OH (United States); Shah, Chirag [Cleveland Clinic, Radiation Oncology, Cleveland, OH (United States); Zhang, Yaxia [Cleveland Clinic, Pathology, Cleveland, OH (United States)

2017-11-15

Management of soft tissue sarcomas is often complicated, requiring radiation before and in some cases after limb-sparing surgery. Radiation necrosis is a severe complication after radiation treatment and is typically dose related and involves medullary bone. We report on two cases of hitherto unreported focal circumscribed intra-cortical lytic lesions within the radiation portal, which appeared 19 months and 31 months, respectively, after the conclusion of radiation treatment. Both patients had a history of soft tissue sarcoma treated with radiation (66 Gy) and surgical resection. Biopsy of these lesions showed necrotic bone attributed to radiation. (orig.)

Direct Lending Works.

Science.gov (United States)

Riley, Richard W.

1997-01-01

In its third year, direct lending is working well for college students and administration. It is a simpler, faster, more efficient way of getting loan funds to students that cuts out financial middlemen. It helps students manage their finances better when repaying loans, promotes competition, stimulates program innovation, leads to greater…

Geothermal Direct Heat Application Potential

Energy Technology Data Exchange (ETDEWEB)

Lienau, Paul J

1989-01-01

The geothermal direct-use industry growth trends, potential, needs, and how they can be met, are addressed. Recent investigations about the current status of the industry and the identification of institutional and technical needs provide the basis on which this paper is presented. Initial drilling risk is the major obstacle to direct-use development. The applications presented include space and district heating projects, heat pumps (heating and cooling), industrial processes, resorts and pools, aquaculture and agriculture.

Memoization in Type-Directed Partial Evaluation

DEFF Research Database (Denmark)

Balat, Vincent; Danvy, Olivier

2002-01-01

the functions and type-directed partial evaluation provides a convenient setting to obtain the normal form of their composition. However, off-the-shelf type-directed partial evaluation turns out to yield gigantic normal forms. We identify that this gigantism is due to redundancies, and that these redundancies...

48 CFR 31.202 - Direct costs.

Science.gov (United States)

2010-10-01

... REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 31.202 Direct... amount as an indirect cost if the accounting treatment— (1) Is consistently applied to all final cost... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Direct costs. 31.202...

Direct-heating solar-collector dump valve

Science.gov (United States)

Howikman, T. C.

1977-01-01

Five-port ganged valve isolates collector from primary load system pressure and drains collectors, allowing use of direct heating with all its advantages. Valve is opened and closed by same switch that controls pump or by temperature sensor set at O C, while providing direct dump option.

Predicting Market Direction from Direct Speech by Business Leaders

OpenAIRE

Drury, Brett M.; Almeida, José João

2012-01-01

Direct quotations from business leaders can communicate to the wider public the latent state of their organization as well as the beliefs of the organization's leaders. Candid quotes from business leaders can have dramatic effects upon the share price of their organization. For example, Gerald Ratner in 1991 stated that his company's products were crap and consequently his company (Ratners) lost in excess of 500 million pounds in market value. Information in quotes from business leaders can b...

Direct radiological magnification in experimental medicine

International Nuclear Information System (INIS)

Poulsen Nautrup, C.; Berens von Rautenfeld, D.

1991-01-01

Some aspects of direct radiological magnification in experimental medicine are shown by teratological investigations of the fetal rat skeleton and by indirect lymphadenography in rabbits. A combination of microfocal radiography and high-resolution non-screen films or digital image processing allows the evaluation of structures with a minimum size of 5 μm. Pseudo-3D images correlate directly with scanning electron micrographs of equivalent casts. Therefore radiography with direct magnification can make difficult preparations and time-consuming staining processes unnecessary. Besides saving time, the main advantage of this method is the amount of new information it yields. For the first time, for example, the filling mechanism becomes visible even in minute vessels, such as the intranodal sinuses, which measure about 10 μm. Hitherto, we have only been able to infer this mechanism from histological specimens. A further benefit of direct radiological magnification over the conventional microscopical method is the smaller number of experimental animals needed. (orig.) [de

Mutation direction by irradiation in rice

International Nuclear Information System (INIS)

Wang Cailian; Chen Qiufang; Jin Wei; Lu Yimei

2001-01-01

The mutation directions of rice were studied. The results indicated that the mutation directions of rice induced by 14 C were invert correlation to their genetic backgrounds of tested rice varieties, i.e. early mature and short stem varieties produced later mature and higher stem mutation; late mature and high stem varieties produced earlier mature and shorter stem mutation; the varieties of middle maturity and height produced both direction mutations of earlier and later maturity or shorter and higher stem. The mutation directions induced by 14 C were also related to treated doses and stages. Frequency of earlier maturity mutation by protons treatment were higher than those induced by other mutagens. Frequency of later maturity by γ-rays were higher than those induced by other mutagens. Frequency of short stem mutation by synchronous irradiation (soft X-rays) were higher than those induced by other mutagens. Frequency of beneficial mutation induced by proton treatment were higher than those induced by γ-rays

Maximizing Lumen Gain With Directional Atherectomy.

Science.gov (United States)

Stanley, Gregory A; Winscott, John G

2016-08-01

To describe the use of a low-pressure balloon inflation (LPBI) technique to delineate intraluminal plaque and guide directional atherectomy in order to maximize lumen gain and achieve procedure success. The technique is illustrated in a 77-year-old man with claudication who underwent superficial femoral artery revascularization using a HawkOne directional atherectomy catheter. A standard angioplasty balloon was inflated to 1 to 2 atm during live fluoroscopy to create a 3-dimensional "lumenogram" of the target lesion. Directional atherectomy was performed only where plaque impinged on the balloon at a specific fluoroscopic orientation. The results of the LPBI technique were corroborated with multimodality diagnostic imaging, including digital subtraction angiography, intravascular ultrasound, and intra-arterial pressure measurements. With the LPBI technique, directional atherectomy can routinely achieve <10% residual stenosis, as illustrated in this case, thereby broadly supporting a no-stent approach to lower extremity endovascular revascularization. © The Author(s) 2016.

Determination of backbone chain direction of PDA using FFM

Science.gov (United States)

Jo, Sadaharu; Okamoto, Kentaro; Takenaga, Mitsuru

2010-01-01

The effect of backbone chains on friction force was investigated on both Langmuir-Blodgett (LB) films of 10,12-heptacosadiynoic acid and the (0 1 0) surfaces of single crystals of 2,4-hexadiene-1,6-diol using friction force microscopy (FFM). It was observed that friction force decreased when the scanning direction was parallel to the [0 0 1] direction in both samples. Moreover, friction force decreased when the scanning direction was parallel to the crystallographic [1 0 2], [1 0 1], [1 0 0] and [1 0 1¯] directions in only the single crystals. For the LB films, the [0 0 1] direction corresponds to the backbone chain direction of 10,12-heptacosadiynoic acid. For the single crystals, both the [0 0 1] and [1 0 1] directions correspond to the backbone chain direction, and the [1 0 2], [1 0 0] and [1 0 1¯] directions correspond to the low-index crystallographic direction. In both the LB films and single crystals, the friction force was minimized when the directions of scanning and the backbone chain were parallel.

A novel Direct Small World network model

Directory of Open Access Journals (Sweden)

LIN Tao

2016-10-01

Full Text Available There is a certain degree of redundancy and low efficiency of existing computer networks.This paper presents a novel Direct Small World network model in order to optimize networks.In this model,several nodes construct a regular network.Then,randomly choose and replot some nodes to generate Direct Small World network iteratively.There is no change in average distance and clustering coefficient.However,the network performance,such as hops,is improved.The experiments prove that compared to traditional small world network,the degree,average of degree centrality and average of closeness centrality are lower in Direct Small World network.This illustrates that the nodes in Direct Small World networks are closer than Watts-Strogatz small world network model.The Direct Small World can be used not only in the communication of the community information,but also in the research of epidemics.

Finding Direction in the Search for Selection.

Science.gov (United States)

Thiltgen, Grant; Dos Reis, Mario; Goldstein, Richard A

2017-01-01

Tests for positive selection have mostly been developed to look for diversifying selection where change away from the current amino acid is often favorable. However, in many cases we are interested in directional selection where there is a shift toward specific amino acids, resulting in increased fitness in the species. Recently, a few methods have been developed to detect and characterize directional selection on a molecular level. Using the results of evolutionary simulations as well as HIV drug resistance data as models of directional selection, we compare two such methods with each other, as well as against a standard method for detecting diversifying selection. We find that the method to detect diversifying selection also detects directional selection under certain conditions. One method developed for detecting directional selection is powerful and accurate for a wide range of conditions, while the other can generate an excessive number of false positives.

Quantum computation via local control theory: Direct sum vs. direct product Hilbert spaces

International Nuclear Information System (INIS)

Sklarz, Shlomo E.; Tannor, David J.

2006-01-01

The central objective in any quantum computation is the creation of a desired unitary transformation; the mapping that this unitary transformation produces between the input and output states is identified with the computation. In [S.E. Sklarz, D.J. Tannor, arXiv:quant-ph/0404081 (submitted to PRA) (2004)] it was shown that local control theory can be used to calculate fields that will produce such a desired unitary transformation. In contrast with previous strategies for quantum computing based on optimal control theory, the local control scheme maintains the system within the computational subspace at intermediate times, thereby avoiding unwanted decay processes. In [S.E. Sklarz et al.], the structure of the Hilbert space had a direct sum structure with respect to the computational register and the mediating states. In this paper, we extend the formalism to the important case of a direct product Hilbert space. The final equations for the control algorithm for the two cases are remarkably similar in structure, despite the fact that the derivations are completely different and that in one case the dynamics is in a Hilbert space and in the other case the dynamics is in a Liouville space. As shown in [S.E. Sklarz et al.], the direct sum implementation leads to a computational mechanism based on virtual transitions, and can be viewed as an extension of the principles of Stimulated Raman Adiabatic Passage from state manipulation to evolution operator manipulation. The direct product implementation developed here leads to the intriguing concept of virtual entanglement - computation that exploits second-order transitions that pass through entangled states but that leaves the subsystems nearly separable at all intermediate times. Finally, we speculate on a connection between the algorithm developed here and the concept of decoherence free subspaces

Direct marketing a automobilový trh

OpenAIRE

Humaj, Matúš

2011-01-01

Bachelor's thesis focuses on direct marketing in close links with car market in Czech republic. Theoretical part points to direct marketing like event of marketing communication, it mentions about advantages and disadvantages, functions, tools and about adjustmen. In practical part I try to find the weak site of the market by the help of market's analysis and questionnaire and I propose the concept of direct marketing utilization.

Direct Spanish Investments in Latin America

Directory of Open Access Journals (Sweden)

Alfredo Arahuetes García

1995-11-01

Full Text Available In the period 1981-1992, the international flow of direct investments witnessed significant changes which affected their magnitude, geographical orientation, sectorial distribution, forms of investment and sources of financing. This happened in such a way that traditional distribution among industrialized and developing countries was modified as was the capacity for attraction of the different areas in development. In this sense, the main contrast could be seen in the growing importance of East and South East Asia and the decline of Latin American countries which traditionally have been the largest receivers of direct investments within the group of developing countries. The expansive phase of direct investments begun in 1986 threatened to exclude Latin American countries but the establishment of a new framework for the treatment of the problem of external debt -the Brady Plan-, the change in the context of theinternational economy in 1990 and the stability and economic growth of the countries of the region favoured, without a doubt, the recovery of the capacity for attraction for new flows of direct investments regarding Latin American countries.In this way, Latin America registered once again a growing participation in the international flow of direct investments. The evolution of direct Spanish investment in Latin America followed a path similar to that of wider international flows and, after the intense absorption of the first years of the Eighties, the rest of the decade registered a discreet attraction for investors which only began to change course from 1989 onwards with the reestablishment of the new phase of the economic cycle in the countries of the region.

Multi-Directional Experimental Facility

Data.gov (United States)

Federal Laboratory Consortium — The ATLSS Multi-directional Experimental Laboratory was constructed in 1987 under funding from the National Science Foundation to be a major facility for large-scale...

Quantum direct communication with authentication

International Nuclear Information System (INIS)

Lee, Hwayean; Lim, Jongin; Yang, HyungJin

2006-01-01

We propose two quantum direct communication (QDC) protocols with user authentication. Users can identify each other by checking the correlation of Greenberger-Horne-Zeilinger (GHZ) states. Alice can directly send a secret message to Bob without any previously shared secret using the remaining GHZ states after authentication. Our second QDC protocol can be used even though there is no quantum link between Alice and Bob. The security of the transmitted message is guaranteed by properties of entanglement of GHZ states

Ecodesign Directive version 2.0

DEFF Research Database (Denmark)

This present report reports on the main findings of the project Ecodesign Directive version 2.0 - from Energy Efficiency to Resource Efficiency. The project is financed by the Danish Environmental Protection Agency and ran from December 2012 to June 2014.......This present report reports on the main findings of the project Ecodesign Directive version 2.0 - from Energy Efficiency to Resource Efficiency. The project is financed by the Danish Environmental Protection Agency and ran from December 2012 to June 2014....

Use of direct marketing in nonprofit organizations

Directory of Open Access Journals (Sweden)

Popović Ana

2010-01-01

Full Text Available Non profit organizations represent very heterogenus group of organizations which can be determined by the fact that they are being used as forums for creation and distribution of new ideas. Their aim is to raise public awareness on the purpose they promote and get the reply for their initiatives for gaining support in form of monetary sources for charities, vote for political candidate or achieving a communicational goal. Non governmental organizations, as the dominant form of non profit organizations, are being founded with mission to raise public awareness on some issue or provide help to certain marginalized group. The direct marketing instruments and techniques are considered to be very useful for achieving mission formulated that way. They are, by their nature, precisely targeted and objective-oriented and require direct reply. Apart from that, direct marketing activities are cost-efficient, costs that they generate can be shown in financial reports, and results of undertaken initiatives are directly measurable. All the mentioned lead to conclusion that direct marketing is, for additional reasons, even more appropriate for NPOs having in mind that they usually have limited available resources. In the relevant literature two main roles of direct marketing in non profit organizations are mentioned - managing relations with representatives of stakeholder groups and fundraising. In this paper, therefore, after the facts referring functioning of NPOs, direct marketing strategies used for mentioned purposes will be presented consequently.

TOOL ASSEMBLY WITH BI-DIRECTIONAL BEARING

Science.gov (United States)

Longhurst, G.E.

1961-07-11

A two-direction motion bearing which is incorporated in a refueling nuclear fuel element trsnsfer tool assembly is described. A plurality of bi- directional bearing assembliesare fixed equi-distantly about the circumference of the transfer tool assembly to provide the tool assembly with a bearing surface- for both axial and rotational motion. Each bi-directional bearing assembly contains a plurality of circumferentially bulged rollers mounted in a unique arrangement which will provide a bearing surface for rotational movement of the tool assembly within a bore. The bi-direc tional bearing assembly itself is capable of rational motion and thus provides for longitudinal movement of the tool assembly.

Direct magnification radiography of the hand

International Nuclear Information System (INIS)

Presacco, D.; Pellegrini, A.; Di Maggio, C.

1987-01-01

The value of direct magnification radiography of the hand and the wrist has been studied in 128 patients affected by rheumatic diseases. Only in a small group (3.17%) magnification determined a higher percentage of correct diagnosis; in the 17.06% of cases direct magnification radiography provided useful increase in information but did not change the diagnisis correctly reached by conventional techniques. In most cases (79.76%) magnification provided only a better image quality but no more information helpful for the diagnosis, because of the high level achieved by convetional techniques. Therefore direct magnification radiography must be used only in selected cases and not as routine radiographyc technique

30 CFR 256.71 - Directional drilling.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Directional drilling. 256.71 Section 256.71... drilling. In accordance with an approved exploration plan or development and production plan, a lease may be maintained in force by directional wells drilled under the leased area from surface locations on...

Directed-energy process technology efforts

Science.gov (United States)

Alexander, P.

1985-01-01

A summary of directed-energy process technology for solar cells was presented. This technology is defined as directing energy or mass to specific areas on solar cells to produce a desired effect in contrast to exposing a cell to a thermal or mass flow environment. Some of these second generation processing techniques are: ion implantation; microwave-enhanced chemical vapor deposition; rapid thermal processing; and the use of lasers for cutting, assisting in metallization, assisting in deposition, and drive-in of liquid dopants. Advantages of directed energy techniques are: surface heating resulting in the bulk of the cell material being cooler and unchanged; better process control yields; better junction profiles, junction depths, and metal sintering; lower energy consumption during processing and smaller factory space requirements. These advantages should result in higher-efficiency cells at lower costs. The results of the numerous contracted efforts were presented as well as the application potentials of these new technologies.

BNL Direct Wind Superconducting Magnets

Energy Technology Data Exchange (ETDEWEB)

Parker, B.; Anerella, M.; Escallier, J.; Ghosh, A.; Jain, A.; Marone, A.; Muratore, A.; Wanderer, P.

2011-09-12

BNL developed Direct Wind magnet technology is used to create a variety of complex multi-functional multi-layer superconducting coil structures without the need for creating custom production tooling and fixturing for each new project. Our Direct Wind process naturally integrates prestress into the coil structure so external coil collars and yokes are not needed; the final coil package transverse size can then be very compact. Direct Wind magnets are produced with very good field quality via corrections applied during the course of coil winding. The HERA-II and BEPC-II Interaction Region (IR) magnet, J-PARC corrector and Alpha antihydrogen magnetic trap magnets and our BTeV corrector magnet design are discussed here along with a full length ILC IR prototype magnet presently in production and the coils that were wound for an ATF2 upgrade at KEK. A new IR septum magnet design concept for a 6.2 T combined-function IR magnet for eRHIC, a future RHIC upgrade, is introduced here.

Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex.

Directory of Open Access Journals (Sweden)

Jinfang Yang

Full Text Available Previous studies have reported inconsistent effects of dietary restriction (DR on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1 of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability.

The effects of working memory training on functional brain network efficiency.

Science.gov (United States)

Langer, Nicolas; von Bastian, Claudia C; Wirz, Helen; Oberauer, Klaus; Jäncke, Lutz

2013-10-01

The human brain is a highly interconnected network. Recent studies have shown that the functional and anatomical features of this network are organized in an efficient small-world manner that confers high efficiency of information processing at relatively low connection cost. However, it has been unclear how the architecture of functional brain networks is related to performance in working memory (WM) tasks and if these networks can be modified by WM training. Therefore, we conducted a double-blind training study enrolling 66 young adults. Half of the subjects practiced three WM tasks and were compared to an active control group practicing three tasks with low WM demand. High-density resting-state electroencephalography (EEG) was recorded before and after training to analyze graph-theoretical functional network characteristics at an intracortical level. WM performance was uniquely correlated with power in the theta frequency, and theta power was increased by WM training. Moreover, the better a person's WM performance, the more their network exhibited small-world topology. WM training shifted network characteristics in the direction of high performers, showing increased small-worldness within a distributed fronto-parietal network. Taken together, this is the first longitudinal study that provides evidence for the plasticity of the functional brain network underlying WM. Copyright © 2013 Elsevier Ltd. All rights reserved.

Direct Energy Marketing Ltd. 1998 annual report

International Nuclear Information System (INIS)

1999-01-01

A corporate profile of Direct Energy Marketing Ltd. was presented for the benefit of shareholders. Direct Energy is responsible for marketing and distributing natural gas to residential, commercial and industrial customers. The company owns physical natural gas reserves that serve as a supply hedge to its growing customer base. The highlights for the natural gas distribution income fund (OPTUS) for 1998 were described. OPTUS acquired WestCastle Energy, adding 38 mmcf/d of natural gas supply. It also amalgamated Channel Lake Petroleum and WestCastle Energy into Direct Energy and created the production division, Direct Energy Resources. It also formed Energy America with Sempra Energy, adding over 160,000 retail customers in Michigan and Ohio. Direct Energy's consolidated financial statements were presented for the benefit of shareholders. These included statements of earnings and deficit, balance sheets, and statements of changes in financial position. Notes to the consolidated financial statements included highlights of significant accounting policies, changes in accounting policies, acquisitions, discontinued operations, and capital assets. tabs., figs

Danish directional adverbs:

DEFF Research Database (Denmark)

Hovmark, Henrik

2013-01-01

Danish directional adverbs (DDA) (for instance op ’up’, ned ’down’, and ud ’out’) are characterized by an important special feature as satellites – they have different forms: a zero-form (ud-Ø), a form with a derivative e-suffix (ud-e), and a third form with a prepositional ad-suffix (‘ wards’). ...

Alternative approach for Article 5. Energie Efficiency Directive; Alternatieve aanpak artikel 5. Energy Efficiency Directive

Energy Technology Data Exchange (ETDEWEB)

Menkveld, M.; Jablonska, B. [ECN Beleidsstudies, Petten (Netherlands)

2013-05-15

Article 5 of the Energy Efficiency Directive (EED) is an annual obligation to renovate 3% of the building stock of central government. After renovation the buildings will meet the minimum energy performance requirements laid down in Article 4 of the EPBD. The Directive gives room to an alternative approach to achieve the same savings. The Ministry of Interior Affairs has asked ECN to assist with this alternative approach. ECN calculated what saving are achieved with the 3% renovation obligation under the directive. Then ECN looked for the possibilities for an alternative approach to achieve the same savings [Dutch] In artikel 5 van de Energie Efficiency Directive (EED) staat een verplichting om jaarlijks 3% van de gebouwvoorraad van de centrale overheid te renoveren. Die 3% van de gebouwvoorraad moet na renovatie voldoen aan de minimum eisen inzake energieprestatie die door het betreffende lidstaat zijn vastgelegd op grond van artikel 4 in de EPBD. De verplichting betreft gebouwen die in bezit en in gebruik zijn van de rijksoverheid met een gebruiksoppervlakte groter dan 500 m{sup 2}, vanaf juli 2015 groter dan 250 m{sup 2}. De gebouwen die eigendom zijn van de Rijksgebouwendienst betreft kantoren van rijksdiensten, gerechtsgebouwen, gebouwen van douane en politie en gevangenissen. Van de gebouwen van Defensie hoeven alleen kantoren en legeringsgebouwen aan de verplichting te voldoen.

24 CFR 9.131 - Direct threat.

Science.gov (United States)

2010-04-01

... health or safety of others. (b) “Direct threat” means a significant risk to the health or safety of... provision of auxiliary aids or services. (c) In determining whether an individual poses a direct threat to the health or safety of others, the agency must make an individualized assessment, based on reasonable...

Controlling selective stimulations below a spinal cord hemisection using brain recordings with a neural interface system approach

Science.gov (United States)

Panetsos, Fivos; Sanchez-Jimenez, Abel; Torets, Carlos; Largo, Carla; Micera, Silvestro

2011-08-01

In this work we address the use of realtime cortical recordings for the generation of coherent, reliable and robust motor activity in spinal-lesioned animals through selective intraspinal microstimulation (ISMS). The spinal cord of adult rats was hemisectioned and groups of multielectrodes were implanted in both the central nervous system (CNS) and the spinal cord below the lesion level to establish a neural system interface (NSI). To test the reliability of this new NSI connection, highly repeatable neural responses recorded from the CNS were used as a pattern generator of an open-loop control strategy for selective ISMS of the spinal motoneurons. Our experimental procedure avoided the spontaneous non-controlled and non-repeatable neural activity that could have generated spurious ISMS and the consequent undesired muscle contractions. Combinations of complex CNS patterns generated precisely coordinated, reliable and robust motor actions.

Direct Reactions

Energy Technology Data Exchange (ETDEWEB)

Austern, N. [University of Pittsburgh, Pittsburgh, PA (United States)

1963-01-15

In order to give a unified presentation of one point of view, these lectures are devoted only to a detailed development of the standard theories of direct reactions, starting from basic principles. Discussion is given of the present status of the theories, of the techniques used for practical calculation, and of possible future developments. The direct interaction (DI) aspects of a reaction are those which involve only a few of the many degrees of freedom of a nucleus. In fact the minimum number of degrees of freedom which must be involved in a reaction are those required to describe the initial and final channels, and DI studies typically consider these degrees of freedom and no others. Because of this simplicity DI theories may be worked out in painstaking detail. DI processes concern only part of the wave function for a problem. The other part involves complicated excitations of many degrees of freedom, and gives the compound nucleus (CN) effects. While it is extremely interesting to learn how to separate DI and CN effects in an orderly manner, if they are both present in a reaction, no suitable method has yet been found. Instead, current work stresses the kinds of reactions and the kinds of final states in which DI effects dominate and in which CN effects may almost be forgotten. The DI cross-sections which are studied are often extremely large, comparable to elastic scattering cross-sections. (author)

Delphi's new direct acting common rail injection system; Das neue Direct Acting Common Rail System von Delphi

Energy Technology Data Exchange (ETDEWEB)

Schoeppe, Detlev; Zuelch, Stefan; Geurts, Derk; Gris, Christian; Jorach, Rainer W. [Delphi Diesel Systems, Europe (United Kingdom)

2009-07-01

With the serial start of the Direct Acting Common Rail injection system with 2.000 bar Delphi Diesel Systems could supplement its product portfolio with a valuable component. In Delphi's directly propelled Common Rail injector, the Injection needle directly is set in operation with the help of a piezo-ceramic actuator instead of only controlling this with a conventional servo-hydraulic circuit indirectly. This enables a fast opening and closing of the nozzle needle possible independently from the rail pressure. The process of injection is controllable accurately at any time with the again developed two-stage needle movement amplifier. The additionally in the injector integrated fuel storage works as a 'Rail in the Injector' and improves the quality particularly during multiple injection. The injector completely works leakage-free and thereby helps to reach the future CO{sub 2} targets. The use of piezo-actuators as driving force behind the directly working injector leads to a set of requirements to the electronics. A control electronics was developed in order to head optimally the Direct Acting Injector. The sum of all advantages of the Direct Acting of CR systems enables lowest emissions with simultaneously small fuel consumption while new dimensions are reached with power density and engine torque. The authors of the contribution under consideration report on the construction, on the work principle of the Direct Acting CR system and on its performance characteristics as a basis for the premium diesel engine.

Directional Validation of Wave Predictions

Science.gov (United States)

2007-03-01

motivators: I) the desire to make the problem more solution is simply to use only variables directly Cx- manageable via frequency-wise integration of direc...ViaW()2 + bi(f), where . = j F(f) d. The calculation in reverse is a, = in, cosO , and b, = ni, sinf0 . Note that if we choose f, andf2 as values close...34). The use of a broader band of frequencies makes the metric more stable, but CALCULATION OF MEAN WAVE DIRECTION AND increases the risk that two

Directions for improved fusion reactors

International Nuclear Information System (INIS)

Krakowski, R.A.; Miller, R.L.; Delene, J.G.

1986-01-01

Conceptual fusion reactor studies over the past 10 to 15 years have projected systems that may be too large, complex, and costly to be of commercial interest. One main direction for improved fusion reactors points towards smaller, higher-power-density approaches. First-order economic issues (i.e., unit direct cost and cost of electricity) are used to support the need for more compact fusion reactors. A generic fusion physics/engineering/costing model is used to provide a quantiative basis for these arguments for specific fusion concepts

Directional sensitivity of MuSTAnG muon telescope

Directory of Open Access Journals (Sweden)

Ganeva Marina

2013-04-01

Full Text Available We investigate directional sensitivity of MuSTAnG muon telescope by deriving the distribution of secondary muons, which create the counting rate of telescope, by asymptotic directions of primary protons. This distribution, defined as “directivity function”, allows us to clarify protons appearing from which direction essentially contribute to counting rate of detector. Directivity function has different behavior for the muons falling on the telescope at different zenith and polar angles. Vertical, West, and East fluxes exhibit strong maximums near the asymptotic longitude about 61°, whereas North and South fluxes have larger spread distributions. About 65% of muons, which create the Vertical counting rate of MuSTAnG, are produced by the primary protons, coming in the interval of asymptotic longitudes about (50°, 80°. Using directivity function will allow one to more correctly determine the location of interplanetary disturbances. Analogous analysis, made for other muon detectors, will clarify their directional sensitivities, improving by this the forecasting capability of network of ground-based muon detectors.

Does climate directly influence NPP globally?

Science.gov (United States)

Chu, Chengjin; Bartlett, Megan; Wang, Youshi; He, Fangliang; Weiner, Jacob; Chave, Jérôme; Sack, Lawren

2016-01-01

The need for rigorous analyses of climate impacts has never been more crucial. Current textbooks state that climate directly influences ecosystem annual net primary productivity (NPP), emphasizing the urgent need to monitor the impacts of climate change. A recent paper challenged this consensus, arguing, based on an analysis of NPP for 1247 woody plant communities across global climate gradients, that temperature and precipitation have negligible direct effects on NPP and only perhaps have indirect effects by constraining total stand biomass (Mtot ) and stand age (a). The authors of that study concluded that the length of the growing season (lgs ) might have a minor influence on NPP, an effect they considered not to be directly related to climate. In this article, we describe flaws that affected that study's conclusions and present novel analyses to disentangle the effects of stand variables and climate in determining NPP. We re-analyzed the same database to partition the direct and indirect effects of climate on NPP, using three approaches: maximum-likelihood model selection, independent-effects analysis, and structural equation modeling. These new analyses showed that about half of the global variation in NPP could be explained by Mtot combined with climate variables and supported strong and direct influences of climate independently of Mtot , both for NPP and for net biomass change averaged across the known lifetime of the stands (ABC = average biomass change). We show that lgs is an important climate variable, intrinsically correlated with, and contributing to mean annual temperature and precipitation (Tann and Pann ), all important climatic drivers of NPP. Our analyses provide guidance for statistical and mechanistic analyses of climate drivers of ecosystem processes for predictive modeling and provide novel evidence supporting the strong, direct role of climate in determining vegetation productivity at the global scale. © 2015 John Wiley & Sons Ltd.

Direct access: how is it working?

Science.gov (United States)

Turner, S; Ross, M

2017-02-10

Aim The aim of this study was to identify and survey dental hygienists and therapists working in direct access practices in the UK, obtain their views on its benefits and disadvantages, establish which treatments they provided, and what barriers they had encountered.Method The study used a purposive sample of GDC-registered hygienists and therapists working in practices offering direct access, identified through a 'Google' search. An online survey was set up through the University of Edinburgh, and non-responses followed up by post.Results The initial search identified 243 individuals working in direct access practices. Where a practice listed more than one hygienist/therapist, one was randomly selected. This gave a total of 179 potential respondents. Eighty-six responses were received, representing a response rate of 48%. A large majority of respondents (58, 73%) were favourable in their view of the GDC decision to allow direct access, and most thought advantages outnumbered disadvantages for patients, hygienists, therapists and dentists. There were no statistically significant differences in views between hygienists and therapists. Although direct access patients formed a small minority of their caseload for most respondents, it is estimated that on average respondents saw approximately 13 per month. Treatment was mainly restricted to periodontal work, irrespective of whether the respondent was singly or dually qualified. One third of respondents reported encountering barriers to successful practice, including issues relating to teamwork and dentists' unfavourable attitudes. However, almost two thirds (64%) felt that direct access had enhanced their job satisfaction, and 45% felt their clinical skills had increased.Discussion Comments were mainly positive, but sometimes raised worrying issues, for example in respect to training, lack of dental nurse support and the limited availability of periodontal treatment under NHS regulations.

Direct Marketing Communication at SEAL Communication Company

OpenAIRE

Wachtler, Kamilla Dóra

2010-01-01

The appearance of the Internet and new, rapidly changing emerging online technologies have led to some fundamental changes in marketing -- especially direct marketing. Besides the growing popularity of the Internet, the appearance of databases and one-to-one marketing are challenging traditional marketing methods. This thesis attempts to illustrate how direct marketing techniques can be implemented in an IT company. It starts with an overview of the concepts of direct marketing and its techni...

Directional control-response compatibility of joystick steered shuttle cars.

Science.gov (United States)

Burgess-Limerick, Robin; Zupanc, Christine M; Wallis, Guy

2012-01-01

Shuttle cars are an unusual class of vehicle operated in underground coal mines, sometimes in close proximity to pedestrians and steering errors may have very serious consequences. A directional control-response incompatibility has previously been described in shuttle cars which are controlled using a steering wheel oriented perpendicular to the direction of travel. Some other shuttle car operators are seated perpendicular to the direction of travel and steer the car via a seat mounted joystick. A virtual simulation was utilised to determine whether the steering arrangement in these vehicles maintains directional control-response compatibility. Twenty-four participants were randomly assigned to either a condition corresponding to this design (consistent direction), or a condition in which the directional steering response was reversed while driving in-bye (visual field compatible). Significantly less accurate steering performance was exhibited by the consistent direction group during the in-bye trials only. Shuttle cars which provide the joystick steering mechanism described here require operators to accommodate alternating compatible and incompatible directional control-response relationships with each change of car direction. A virtual simulation of an underground coal shuttle car demonstrates that the design incorporates a directional control-response incompatibility when driving the vehicle in one direction. This design increases the probability of operator error, with potential adverse safety and productivity consequences.

Substrate-Directed Catalytic Selective Chemical Reactions.

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Sawano, Takahiro; Yamamoto, Hisashi

2018-05-04

The development of highly efficient reactions at only the desired position is one of the most important subjects in organic chemistry. Most of the reactions in current organic chemistry are reagent- or catalyst-controlled reactions, and the regio- and stereoselectivity of the reactions are determined by the inherent nature of the reagent or catalyst. In sharp contrast, substrate-directed reaction determines the selectivity of the reactions by the functional group on the substrate and can strictly distinguish sterically and electronically similar multiple reaction sites in the substrate. In this Perspective, three topics of substrate-directed reaction are mainly reviewed: (1) directing group-assisted epoxidation of alkenes, (2) ring-opening reactions of epoxides by various nucleophiles, and (3) catalytic peptide synthesis. Our newly developed synthetic methods with new ligands including hydroxamic acid derived ligands realized not only highly efficient reactions but also pinpointed reactions at the expected position, demonstrating the substrate-directed reaction as a powerful method to achieve the desired regio- and stereoselective functionalization of molecules from different viewpoints of reagent- or catalyst-controlled reactions.

A centrifugal direct recombinase polymerase amplification (direct-RPA) microdevice for multiplex and real-time identification of food poisoning bacteria.

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Choi, Goro; Jung, Jae Hwan; Park, Byung Hyun; Oh, Seung Jun; Seo, Ji Hyun; Choi, Jong Seob; Kim, Do Hyun; Seo, Tae Seok

2016-06-21

In this study, we developed a centrifugal direct recombinase polymerase amplification (direct-RPA) microdevice for multiplex and real-time identification of food poisoning bacteria contaminated milk samples. The microdevice was designed to contain identical triplicate functional units and each unit has four reaction chambers, thereby making it possible to perform twelve direct-RPA reactions simultaneously. The integrated microdevice consisted of two layers: RPA reagents were injected in the top layer, while spiked milk samples with food poisoning bacteria were loaded into sample reservoirs in the bottom layer. For multiplex bacterial detection, the target gene-specific primers and probes were dried in each reaction chamber. The introduced samples and reagents could be equally aliquoted and dispensed into each reaction chamber by centrifugal force, and then the multiplex direct-RPA reaction was executed. The target genes of bacteria spiked in milk could be amplified at 39 °C without a DNA extraction step by using the direct-RPA cocktails, which were a combination of a direct PCR buffer and RPA enzymes. As the target gene amplification proceeded, the increased fluorescence signals coming from the reaction chambers were recorded in real-time at an interval of 2 min. The entire process, including the sample distribution, the direct-RPA reaction, and the real-time analysis, was accomplished with a custom-made portable genetic analyzer and a miniaturized optical detector. Monoplex, duplex, and triplex food poisoning bacteria (Salmonella enterica, Escherichia coli O157:H7, and Vibrio parahaemolyticus) detection was successfully performed with a detection sensitivity of 4 cells per 3.2 μL of milk samples within 30 min. By implementing the direct-PRA on the miniaturized centrifugal microsystem, the on-site food poisoning bacteria analysis would be feasible with high speed, sensitivity, and multiplicity.

Construction of a Direct Water-Injected Two-Stroke Engine for Phased Direct Fuel Injection-High Pressure Charging Investigations

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Somsel, James P.

1998-01-01

The development of a water injected Orbital Combustion Process (OCP) engine was conducted to assess the viability of using the powerplant for high altitude NASA aircraft and General Aviation (GA) applications. An OCP direct fuel injected, 1.2 liter, three cylinder, two-stroke engine has been enhanced to independently inject water directly into the combustion chamber. The engine currently demonstrates low brake specific fuel consumption capability and an excellent power to weight ratio. With direct water injection, significant improvements can be made to engine power, to knock limits/ignition advance timing, and to engine NO(x) emissions. The principal aim of the testing was to validate a cyclic model developed by the Systems Analysis Branch at NASA Ames Research Center. The work is a continuation of Ames' investigations into a Phased Direct Fuel Injection Engine with High Pressure Charging (PDFI-ITPC).

On the Strong Direct Summand Conjecture

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McCullough, Jason

2009-01-01

In this thesis, our aim is the study the Vanishing of Maps of Tor Conjecture of Hochster and Huneke. We mainly focus on an equivalent characterization called the Strong Direct Summand Conjecture, due to N. Ranganathan. Our results are separated into three chapters. In Chapter 3, we prove special cases of the Strong Direct Summand Conjecture in…

What Is Direct-to-Consumer Genetic Testing?

Science.gov (United States)

... consumer genetic testing? What kinds of direct-to-consumer genetic tests are available? What is genetic ancestry testing? What are the benefits and risks of direct-to-consumer genetic testing? ...