Advances in selective activation of muscles for non-invasive motor neuroprostheses.

PubMed

Koutsou, Aikaterini D; Moreno, Juan C; Del Ama, Antonio J; Rocon, Eduardo; Pons, José L

2016-06-13

Non-invasive neuroprosthetic (NP) technologies for movement compensation and rehabilitation remain with challenges for their clinical application. Two of those major challenges are selective activation of muscles and fatigue management. This review discusses how electrode arrays improve the efficiency and selectivity of functional electrical stimulation (FES) applied via transcutaneous electrodes. In this paper we review the principles and achievements during the last decade on techniques for artificial motor unit recruitment to improve the selective activation of muscles. We review the key factors affecting the outcome of muscle force production via multi-pad transcutaneous electrical stimulation and discuss how stimulation parameters can be set to optimize external activation of body segments. A detailed review of existing electrode array systems proposed by different research teams is also provided. Furthermore, a review of the targeted applications of existing electrode arrays for control of upper and lower limb NPs is provided. Eventually, last section demonstrates the potential of electrode arrays to overcome the major challenges of NPs for compensation and rehabilitation of patient-specific impairments.

Apparatus for measurements of thermal and optical stimulated exo-electron emission and luminescence

NASA Astrophysics Data System (ADS)

Pokorný, P.; Novotný, M.; Fitl, P.; Zuklín, J.; Vlček, J.; Nikl, J.; Marešová, E.; Hruška, P.; Bulíř, J.; Drahokoupil, J.; Čerňanský, M.; Lančok, J.

2018-06-01

The purpose of the design, construction and implementation of vacuum apparatus for measuring simultaneously three or more stimulated phenomena in dielectrics and eventually semiconductors is to investigate those phenomena as a function of temperature and wavelength. The test of equipment and its functionality were carried out step by step (apparatus, components and control sample) and associated with the calculation of the main physical parameters. The tests of individual parts of the apparatus clearly confirmed that the design, construction and selected components fulfil or even exceed the required properties. On the basis of the measurement of selected sample, it was shown that even weak signals from the material can be detected from both thermally stimulated luminescence and thermally stimulated exo-electron emission moreover transmission and desorption can be measured. NaCl:Ni (0.2%) was chosen as the test material. The activation energies and frequency factor were calculated using the methods of different authors.

Novel targets and stimulation paradigms for deep brain stimulation.

PubMed

De Jesus, Sol; Almeida, Leonardo; Peng-Chen, Zhongxing; Okun, Michael S; Hess, Christopher W

2015-01-01

Deep brain stimulation (DBS) is an accepted therapy for appropriately selected patients with movement disorders and psychiatric disease. The recent advances in lead technology and the advent of novel stimulation parameters have spurred a number of improvements that will likely be implemented in the clinical setting. Although the mechanisms and biology of DBS remain poorly understood, the progress in our understanding of network level dysfunction has driven the introduction of a variety of new targets and approaches to the treatment of human disease. Here we summarize the recent advances in novel stimulation patterns and customized field shaping. We also review new targets, novel applications of DBS and the immediate and long-term horizon for this therapy.

Effect of shorter pulse duration in cochlear neural activation with an 810-nm near-infrared laser.

PubMed

Wang, Jingxuan; Tian, Lan; Lu, Jianren; Xia, Ming; Wei, Ying

2017-02-01

Optical neural stimulation in the cochlea has been presented as an alternative technique to the electrical stimulation due to its potential in spatially selectivity enhancement. So far, few studies have selected the near-infrared (NIR) laser in cochlear neural stimulation and limited optical parameter space has been examined. This paper focused on investigating the optical parameter effect on NIR stimulation of auditory neurons, especially under shorter pulse durations. The spiral ganglion neurons in the cochlea of deafened guinea pigs were stimulated with a pulsed 810-nm NIR laser in vivo. The laser radiation was delivered by an optical fiber and irradiated towards the modiolus. Optically evoked auditory brainstem responses (OABRs) with various optical parameters were recorded and investigated. The OABRs could be elicited with the cochlear deafened animals by using the 810-nm laser in a wide pulse duration ranged from 20 to 1000 μs. Results showed that the OABR intensity increased along with the increasing laser radiant exposure of limited range at each specific pulse duration. In addition, for the pulse durations from 20 to 300 μs, the OABR intensity increased monotonically along with the pulse duration broadening. While for pulse durations above 300 μs, the OABR intensity basically kept stable with the increasing pulse duration. The 810-nm NIR laser could be an effective stimulus in evoking the cochlear neuron response. Our experimental data provided evidence to optimize the pulse duration range, and the results suggested that the pulse durations from 20 to 300 μs could be the optimized range in cochlear neural activation with the 810-nm-wavelength laser.

Effect of selective vagal nerve stimulation on blood pressure, heart rate and respiratory rate in rats under metoprolol medication.

PubMed

Gierthmuehlen, Mortimer; Plachta, Dennis T T

2016-02-01

Selective vagal nerve stimulation (sVNS) has been shown to reduce blood pressure without major side effects in rats. This technology might be the key to non-medical antihypertensive treatment in patients with therapy-resistant hypertension. β-blockers are the first-line therapy of hypertension and have in general a bradycardic effect. As VNS itself can also promote bradycardia, it was the aim of this study to investigate the influence of the β1-selective blocker Metoprolol on the effect of sVNS especially with respect to the heart rate. In 10 male Wistar rats, a polyimide multichannel-cuff electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibers. The stimulation parameters were adapted to the thresholds of individual animals and were in the following ranges: frequency 30-50 Hz, amplitude 0.3-1.8 mA and pulse width 0.3-1.3 ms. Blood pressure responses were detected with a microtip transducer in the carotid artery, and electrocardiography was recorded with s.c. chest electrodes. After IV administration of Metoprolol (2 mg kg(-1) body weight), the animals' mean arterial blood pressure (MAP) and heart rate (HR) decreased significantly. Although the selective electrical stimulation of the baroreceptive fibers reduced MAP and HR, both effects were significantly alleviated by Metoprolol. As a side effect, the rate of stimulation-induced apnea significantly increased after Metoprolol administration. sVNS can lower the MAP under Metoprolol without causing severe bradycardia.

Double-blind optimization of subcallosal cingulate deep brain stimulation for treatment-resistant depression: a pilot study.

PubMed

Ramasubbu, Rajamannar; Anderson, Susan; Haffenden, Angela; Chavda, Swati; Kiss, Zelma H T

2013-09-01

Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is reported to be a safe and effective new treatment for treatment-resistant depression (TRD). However, the optimal electrical stimulation parameters are unknown and generally selected by trial and error. This pilot study investigated the relationship between stimulus parameters and clinical effects in SCC-DBS treatment for TRD. Four patients with TRD underwent SCC-DBS surgery. In a double-blind stimulus optimization phase, frequency and pulse widths were randomly altered weekly, and corresponding changes in mood and depression were evaluated using a visual analogue scale (VAS) and the 17-item Hamilton Rating Scale for Depression (HAM-D-17). In the open-label postoptimization phase, depressive symptoms were evaluated biweekly for 6 months to determine long-term clinical outcomes. Longer pulse widths (270-450 μs) were associated with reductions in HAM-D-17 scores in 3 patients and maximal happy mood VAS responses in all 4 patients. Only 1 patient showed acute clinical or mood effects from changing the stimulation frequency. After 6 months of open-label therapy, 2 patients responded and 1 patient partially responded. Limitations include small sample size, weekly changes in stimulus parameters, and fixed-order and carry-forward effects. Longer pulse width stimulation may have a role in stimulus optimization for SCC-DBS in TRD. Longer pulse durations produce larger apparent current spread, suggesting that we do not yet know the optimal target or stimulus parameters for this therapy. Investigations using different stimulus parameters are required before embarking on large-scale randomized sham-controlled trials.

Transcranial Electric Stimulation for Precision Medicine: A Spatiomechanistic Framework

PubMed Central

Yavari, Fatemeh; Nitsche, Michael A.; Ekhtiari, Hamed

2017-01-01

During recent years, non-invasive brain stimulation, including transcranial electrical stimulation (tES) in general, and transcranial direct current stimulation (tDCS) in particular, have created new hopes for treatment of neurological and psychiatric diseases. Despite promising primary results in some brain disorders, a more widespread application of tES is hindered by the unsolved question of determining optimum stimulation protocols to receive meaningful therapeutic effects. tES has a large parameter space including various montages and stimulation parameters. Moreover, inter- and intra-individual differences in responding to stimulation protocols have to be taken into account. These factors contribute to the complexity of selecting potentially effective protocols for each disorder, different clusters of each disorder, and even each single patient. Expanding knowledge in different dimensions of basic and clinical neuroscience could help researchers and clinicians to select potentially effective protocols based on tES modulatory mechanisms for future clinical studies. In this article, we propose a heuristic spatiomechanistic framework which contains nine levels to address tES effects on brain functions. Three levels refer to the spatial resolution (local, small-scale networks and large-scale networks) and three levels of tES modulatory effects based on its mechanisms of action (neurochemical, neuroelectrical and oscillatory modulations). At the group level, this framework could be helpful to enable an informed and systematic exploration of various possible protocols for targeting a brain disorder or its neuroscience-based clusters. Considering recent advances in exploration of neurodiversity at the individual level with different brain mapping technologies, the proposed framework might also be used in combination with personal data to design individualized protocols for tES in the context of precision medicine in the future. PMID:28450832

Recording evoked potentials during deep brain stimulation: development and validation of instrumentation to suppress the stimulus artefact.

PubMed

Kent, A R; Grill, W M

2012-06-01

The clinical efficacy of deep brain stimulation (DBS) for the treatment of movement disorders depends on the identification of appropriate stimulation parameters. Since the mechanisms of action of DBS remain unclear, programming sessions can be time consuming, costly and result in sub-optimal outcomes. Measurement of electrically evoked compound action potentials (ECAPs) during DBS, generated by activated neurons in the vicinity of the stimulating electrode, could offer insight into the type and spatial extent of neural element activation and provide a potential feedback signal for the rational selection of stimulation parameters and closed-loop DBS. However, recording ECAPs presents a significant technical challenge due to the large stimulus artefact, which can saturate recording amplifiers and distort short latency ECAP signals. We developed DBS-ECAP recording instrumentation combining commercial amplifiers and circuit elements in a serial configuration to reduce the stimulus artefact and enable high fidelity recording. We used an electrical circuit equivalent model of the instrumentation to understand better the sources of the stimulus artefact and the mechanisms of artefact reduction by the circuit elements. In vitro testing validated the capability of the instrumentation to suppress the stimulus artefact and increase gain by a factor of 1000 to 5000 compared to a conventional biopotential amplifier. The distortion of mock ECAP (mECAP) signals was measured across stimulation parameters, and the instrumentation enabled high fidelity recording of mECAPs with latencies of only 0.5 ms for DBS pulse widths of 50 to 100 µs/phase. Subsequently, the instrumentation was used to record in vivo ECAPs, without contamination by the stimulus artefact, during thalamic DBS in an anesthetized cat. The characteristics of the physiological ECAP were dependent on stimulation parameters. The novel instrumentation enables high fidelity ECAP recording and advances the potential use of the ECAP as a feedback signal for the tuning of DBS parameters.

Temporal and Spatial Variability of Surface Motor Activation Zones in Hemiplegic Patients During Functional Electrical Stimulation Therapy Sessions.

PubMed

Malešević, Jovana; Štrbac, Matija; Isaković, Milica; Kojić, Vladimir; Konstantinović, Ljubica; Vidaković, Aleksandra; Dedijer Dujović, Suzana; Kostić, Miloš; Keller, Thierry

2017-11-01

The goal of this study was to investigate surface motor activation zones and their temporal variability using an advanced multi-pad functional electrical stimulation system. With this system motor responses are elicited through concurrent activation of electrode matrix pads collectively termed "virtual electrodes" (VEs) with appropriate stimulation parameters. We observed VEs used to produce selective wrist, finger, and thumb extension movements in 20 therapy sessions of 12 hemiplegic stroke patients. The VEs which produce these three selective movements were created manually on the ergonomic multi-pad electrode by experienced clinicians based on visual inspection of the muscle responses. Individual results indicated that changes in VE configuration were required each session for all patients and that overlap in joint movements was evident between some VEs. However, by analyzing group data, we defined the probability distribution over the electrode surface for the three VEs of interest. Furthermore, through Bayesian logic we obtained preferred stimulation zones that are in accordance with our previously reported heuristically obtained results. We have also analyzed the number of active pads and stimulation amplitudes for these three VEs. Presented results provide a basis for an automated electrode calibration algorithm built on a priori knowledge or the starting point for manual selection of stimulation points. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Analysis of compound action potentials elicited with specific current stimulating pulses in an isolated rat sciatic nerve.

PubMed

Žužek, Monika C; Rozman, Janez; Pečlin, Polona; Vrecl, Milka; Frangež, Robert

2017-02-01

The ability to selectively stimulate Aα, Aβ-fibers and Aδ-fibers in an isolated rat sciatic nerve (SNR) was assessed. The stimulus used was a current, biphasic pulse with a quasitrapezoidal cathodic phase and rectangular anodic phase where parameters were systematically varied: intensity of the cathodic phase (ic); width of the cathodic phase (tc); width of the cathodic exponential decay (texp) and time constant of the exponential decay (τexp). A SNR was stimulated using a pair of hook electrodes while conduction velocity (CV) and compound action potentials (CAP) were measured at two sites along the SNR using another two pairs of electrodes. Results showed that the highest CAP1 (8.5-9 mV), shall be expected when parameters of the stimulus were within the following range: ic=3.8-4 mA, tc=350-400 μs and texp=330-440 μs. Results also showed that with ascending tc and texp, CV of the corresponding superficial region of the SNR was reduced in both, conduction velocity of CAP1 and conduction velocity of CAP2. It was concluded that action potentials (APs) were activated in the Aβ-fibers and Aδ-fibers along with a slight AP inhibition in the Aβ-fibers. The obtained results, could serve as a tool for developing multi-electrode systems that potentially enable fiber-type selective stimulation of nerve fibers.

Analysis of Oscillatory Neural Activity in Series Network Models of Parkinson's Disease During Deep Brain Stimulation.

PubMed

Davidson, Clare M; de Paor, Annraoi M; Cagnan, Hayriye; Lowery, Madeleine M

2016-01-01

Parkinson's disease is a progressive, neurodegenerative disorder, characterized by hallmark motor symptoms. It is associated with pathological, oscillatory neural activity in the basal ganglia. Deep brain stimulation (DBS) is often successfully used to treat medically refractive Parkinson's disease. However, the selection of stimulation parameters is based on qualitative assessment of the patient, which can result in a lengthy tuning period and a suboptimal choice of parameters. This study explores fourth-order, control theory-based models of oscillatory activity in the basal ganglia. Describing function analysis is applied to examine possible mechanisms for the generation of oscillations in interacting nuclei and to investigate the suppression of oscillations with high-frequency stimulation. The theoretical results for the suppression of the oscillatory activity obtained using both the fourth-order model, and a previously described second-order model, are optimized to fit clinically recorded local field potential data obtained from Parkinsonian patients with implanted DBS. Close agreement between the power of oscillations recorded for a range of stimulation amplitudes is observed ( R(2)=0.69-0.99 ). The results suggest that the behavior of the system and the suppression of pathological neural oscillations with DBS is well described by the macroscopic models presented. The results also demonstrate that in this instance, a second-order model is sufficient to model the clinical data, without the need for added complexity. Describing the system behavior with computationally efficient models could aid in the identification of optimal stimulation parameters for patients in a clinical environment.

Dose-specific effects of transcutaneous electrical nerve stimulation (TENS) on experimental pain: a systematic review.

PubMed

Claydon, Leica S; Chesterton, Linda S; Barlas, Panos; Sim, Julius

2011-09-01

To determine the hypoalgesic effects of transcutaneous electrical nerve stimulation (TENS) parameter combinations on experimental models in healthy humans. Searches were performed using the electronic databases Ovid MEDLINE, CINAHL, AMED, and Web of Science (from inception to December 2009). Manual searches of journals and reference lists of retrieved trials were also performed. Randomized controlled trials (RCTs) were included in the review if they compared the hypoalgesic effect of TENS relative with placebo and control, using an experimental pain model in healthy human participants. Two reviewers independently selected the trials, assessed their methodologic quality and extracted data. Forty-three RCTs were eligible for inclusion. A best evidence synthesis revealed: Overall "conflicting" (inconsistent findings in multiple RCTs) evidence of TENS efficacy on experimental pain irrespective of TENS parameters used. Overall intense TENS has "moderate" evidence of efficacy (1 high-quality and 2 low-quality trials). Conventional TENS has overall conflicting evidence of efficacy, this is derived from "strong" evidence of efficacy (generally consistent findings in multiple high-quality RCTs) on pressure pain but strong evidence of inefficacy on other pain models. "Limited" evidence (positive findings from 1 RCT) of hypoalgesia exists for some novel parameters. Low-intensity, low-frequency, local TENS has strong evidence of inefficacy. Inappropriate TENS (using "barely perceptible" intensities) has moderate evidence of inefficacy. The level of hypoalgesic efficacy of TENS is clearly dependent on TENS parameter combination selection (defined in terms of intensity, frequency, and stimulation site) and experimental pain model. Future clinical RCTs may consider these TENS dose responses.

Effect of rhythmic auditory stimulation on gait kinematic parameters of patients with multiple sclerosis.

PubMed

Shahraki, M; Sohrabi, M; Taheri Torbati, H R; Nikkhah, K; NaeimiKia, M

2017-01-01

Purpose: This study aimed to examine the effect of rhythmic auditory stimulation on gait kinematic parameters of patients with multiple sclerosis. Subjects and Methods: In this study, 18 subjects, comprising 4 males and 14 females with Multiple Sclerosis with expanded disability status scale of 3 to 6 were chosen. Subjects were selected by available and targeted sampling and were randomly divided into two experimental (n = 9) and control (n = 9) groups. Exercises were gait with rhythmic auditory stimulation by a metronome device, in addition to gait without stimulation for the experimental and control groups, respectively. Training was carried out for 3 weeks, with 30 min duration for each session 3 times a week. Stride length, stride time, double support time, cadence and gait speed were measured by motion analysis device. Results: There was a significant difference between stride length, stride time, double support time, cadence and gait speed in the experimental group, before and after the training. Furthermore, there was a significant difference between the experimental and control groups in the enhancement of stride length, stride time, cadence and gait speed in favor of the experimental group. While this difference was not significant for double support time. Conclusion: The results of this study showed that rhythmic auditory stimulation is an effective rehabilitation method to improve gait kinematic parameters in patients with multiple sclerosis.

Assessing effects of BL67 points stimulation on fetal heart rate parameters and fetal movements during nonstress test.

PubMed

Pirhadi, Masume; Valiani, Mahboube

2017-01-01

One of the main goals of antenatal testing is to identify fetuses at the risk of neurologic injury or death so that these adverse outcomes can be prevented. We want to assess the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements during nonstress test (NST). We did a quasi-experimental design in Shahid Beheshti Hospital in Isfahan in 2011. This study aims to assessment of the effects of BL67 points' stimulation on fetal heart rate parameters and fetal movements. We did a randomized controlled clinical trial in Shahid Beheshti Hospital in Isfahan in 2011. This study is a quasi-experimental design that was conducted in one group and the two steps (before-after study). Participants were pregnant women (primigravida) who were 35-18 years that refer to Shahid Beheshti Hospital in Isfahan in 2011 to receive routine prenatal care. The 32 pregnant women were selected for acupressure during the second NST. The statistical processing was performed by descriptive, paired t -test through SPSS version 20. There was no significant difference in mean number of accelerations in fetal heart rate and mean number of fetal movement before and after intervention; however, there was a significant difference in mean time to the second acceleration before and after the intervention ( P = 0.04). No difference between parameters of the fetal heart rate before and after stimulation and lack of uterine response by this method is a significant advantage and is probably why stimulating this point could not create a risk to the fetuses.

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

PubMed Central

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

2012-01-01

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

Meta-analysis of transcutaneous electrical nerve stimulation for relief of spinal pain.

PubMed

Resende, L; Merriwether, E; Rampazo, É P; Dailey, D; Embree, J; Deberg, J; Liebano, R E; Sluka, K A

2018-04-01

We conducted a systematic review and meta-analysis analysing the existing data on transcutaneous electrical nerve stimulation (TENS) or interferential current (IFC) for chronic low back pain (CLBP) and/or neck pain (CNP) taking into account intensity and timing of stimulation, examining pain, function and disability. Seven electronic databases were searched for TENS or IFC treatment in non-specific CLBP or CNP. Four reviewers independently selected randomized controlled trials (RCTs) of TENS or IFC intervention in adult individuals with non-specific CLBP or CNP. Primary outcomes were for self-reported pain intensity and back-specific disability. Two reviewers performed quality assessment, and two reviewers extracted data using a standardized form. Nine RCTs were selected (eight CLBP; one CNP), and seven studies with complete data sets were included for meta-analysis (655 participants). For CLBP, meta-analysis shows TENS/IFC intervention, independent of time of assessment, was significantly different from placebo/control (p < 0.02). TENS/IFC intervention was better than placebo/control, during therapy (p = 0.02), but not immediately after therapy (p = 0.08), or 1-3 months after therapy (p = 0.99). Analysis for adequate stimulation parameters was not significantly different, and there was no effect on disability. This systematic review provides inconclusive evidence of TENS benefits in low back pain patients because the quality of the studies was low, and adequate parameters and timing of assessment were not uniformly used or reported. Without additional high-quality clinical trials using sufficient sample sizes and adequate parameters and outcome assessments, the outcomes of this review are likely to remain unchanged. These data highlight the need for additional high-quality RCTs to examine the effects of TENS in CLBP. Trials should consider intensity of stimulation, timing of outcome assessment and assessment of pain, disability and function. © 2017 European Pain Federation - EFIC®.

Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach.

PubMed

Karamintziou, Sofia D; Custódio, Ana Luísa; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stéphan; Stathis, Pantelis G; Tagaris, George A; Sakas, Damianos E; Polychronaki, Georgia E; Tsirogiannis, George L; David, Olivier; Nikita, Konstantina S

2017-01-01

Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson's disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications.

Instrumentation to Record Evoked Potentials for Closed-Loop Control of Deep Brain Stimulation

PubMed Central

Kent, Alexander R.; Grill, Warren M.

2012-01-01

Closed-loop deep brain stimulation (DBS) systems offer promise in relieving the clinical burden of stimulus parameter selection and improving treatment outcomes. In such a system, a feedback signal is used to adjust automatically stimulation parameters and optimize the efficacy of stimulation. We explored the feasibility of recording electrically evoked compound action potentials (ECAPs) during DBS for use as a feedback control signal. A novel instrumentation system was developed to suppress the stimulus artifact and amplify the small magnitude, short latency ECAP response during DBS with clinically relevant parameters. In vitro testing demonstrated the capabilities to increase the gain by a factor of 1,000x over a conventional amplifier without saturation, reduce distortion of mock ECAP signals, and make high fidelity recordings of mock ECAPs at latencies of only 0.5 ms following DBS pulses of 50 to 100 μs duration. Subsequently, the instrumentation was used to make in vivo recordings of ECAPs during thalamic DBS in cats, without contamination by the stimulus artifact. The signal characteristics were similar across three experiments, suggesting common neural activation patterns. The ECAP recordings enabled with this novel instrumentation may provide insight into the type and spatial extent of neural elements activated during DBS, and could serve as feedback control signals for closed-loop systems. PMID:22255894

Electromechanical Nerve Stimulator

NASA Technical Reports Server (NTRS)

Tcheng, Ping; Supplee, Frank H., Jr.; Prass, Richard L.

1993-01-01

Nerve stimulator applies and/or measures precisely controlled force and/or displacement to nerve so response of nerve measured. Consists of three major components connected in tandem: miniature probe with spherical tip; transducer; and actuator. Probe applies force to nerve, transducer measures force and sends feedback signal to control circuitry, and actuator positions force transducer and probe. Separate box houses control circuits and panel. Operator uses panel to select operating mode and parameters. Stimulator used in research to characterize behavior of nerve under various conditions of temperature, anesthesia, ventilation, and prior damage to nerve. Also used clinically to assess damage to nerve from disease or accident and to monitor response of nerve during surgery.

Transcranial magnetic stimulation changes response selectivity of neurons in the visual cortex

PubMed Central

Kim, Taekjun; Allen, Elena A.; Pasley, Brian N.; Freeman, Ralph D.

2015-01-01

Background Transcranial magnetic stimulation (TMS) is used to selectively alter neuronal activity of specific regions in the cerebral cortex. TMS is reported to induce either transient disruption or enhancement of different neural functions. However, its effects on tuning properties of sensory neurons have not been studied quantitatively. Objective/Hypothesis Here, we use specific TMS application parameters to determine how they may alter tuning characteristics (orientation, spatial frequency, and contrast sensitivity) of single neurons in the cat’s visual cortex. Methods Single unit spikes were recorded with tungsten microelectrodes from the visual cortex of anesthetized and paralyzed cats (12 males). Repetitive TMS (4Hz, 4sec) was delivered with a 70mm figure-8 coil. We quantified basic tuning parameters of individual neurons for each pre- and post-TMS condition. The statistical significance of changes for each tuning parameter between the two conditions was evaluated with a Wilcoxon signed-rank test. Results We generally find long-lasting suppression which persists well beyond the stimulation period. Pre- and post-TMS orientation tuning curves show constant peak values. However, strong suppression at non-preferred orientations tends to narrow the widths of tuning curves. Spatial frequency tuning exhibits an asymmetric change in overall shape, which results in an emphasis on higher frequencies. Contrast tuning curves show nonlinear changes consistent with a gain control mechanism. Conclusions These findings suggest that TMS causes extended interruption of the balance between sub-cortical and intra-cortical inputs. PMID:25862599

Parameter Optimization Analysis of Prolonged Analgesia Effect of tDCS on Neuropathic Pain Rats

PubMed Central

Wen, Hui-Zhong; Gao, Shi-Hao; Zhao, Yan-Dong; He, Wen-Juan; Tian, Xue-Long; Ruan, Huai-Zhen

2017-01-01

Background: Transcranial direct current stimulation (tDCS) is widely used to treat human nerve disorders and neuropathic pain by modulating the excitability of cortex. The effectiveness of tDCS is influenced by its stimulation parameters, but there have been no systematic studies to help guide the selection of different parameters. Objective: This study aims to assess the effects of tDCS of primary motor cortex (M1) on chronic neuropathic pain in rats and to test for the optimal parameter combinations for analgesia. Methods: Using the chronic neuropathic pain models of chronic constriction injury (CCI), we measured pain thresholds before and after anodal-tDCS (A-tDCS) using different parameter conditions, including stimulation intensity, stimulation time, intervention time and electrode located (ipsilateral or contralateral M1 of the ligated paw on male/female CCI models). Results: Following the application of A-tDCS over M1, we observed that the antinociceptive effects were depended on different parameters. First, we found that repetitive A-tDCS had a longer analgesic effect than single stimulus, and both ipsilateral-tDCS (ip-tDCS) and contralateral-tDCS (con-tDCS) produce a long-lasting analgesic effect on neuropathic pain. Second, the antinociceptive effects were intensity-dependent and time-dependent, high intensities worked better than low intensities and long stimulus durations worked better than short stimulus durations. Third, timing of the intervention after injury affected the stimulation outcome, early use of tDCS was an effective method to prevent the development of pain, and more frequent intervention induced more analgesia in CCI rats, finally, similar antinociceptive effects of con- and ip-tDCS were observed in both sexes of CCI rats. Conclusion: Optimized protocols of tDCS for treating antinociceptive effects were developed. These findings should be taken into consideration when using tDCS to produce analgesic effects in clinical applications. PMID:28659772

Non-invasive method for selection of electrodes and stimulus parameters for FES applications with intrafascicular arrays

NASA Astrophysics Data System (ADS)

Dowden, B. R.; Frankel, M. A.; Normann, R. A.; Clark, G. A.

2012-02-01

High-channel-count intrafascicular electrode arrays provide comprehensive and selective access to the peripheral nervous system. One practical difficulty in using several electrode arrays to evoke coordinated movements in paralyzed limbs is the identification of the appropriate stimulation channels and stimulus parameters to evoke desired movements. Here we present the use of a six degree-of-freedom load cell placed under the foot of a feline to characterize the muscle activation produced by three 100-electrode Utah Slanted Electrode Arrays (USEAs) implanted into the femoral nerves, sciatic nerves, and muscular branches of the sciatic nerves of three cats. Intramuscular stimulation was used to identify the endpoint force directions produced by 15 muscles of the hind limb, and these directions were used to classify the forces produced by each intrafascicular USEA electrode as flexion or extension. For 451 USEA electrodes, stimulus intensities for threshold and saturation muscle forces were identified, and the 3D direction and linearity of the force recruitment curves were determined. Further, motor unit excitation independence for 198 electrode pairs was measured using the refractory technique. This study demonstrates the utility of 3D endpoint force monitoring as a simple and non-invasive metric for characterizing the muscle-activation properties of hundreds of implanted peripheral nerve electrodes, allowing for electrode and parameter selection for neuroprosthetic applications.

Non-invasive method for selection of electrodes and stimulus parameters for FES applications with intrafascicular arrays.

PubMed

Dowden, B R; Frankel, M A; Normann, R A; Clark, G A

2012-02-01

High-channel-count intrafascicular electrode arrays provide comprehensive and selective access to the peripheral nervous system. One practical difficulty in using several electrode arrays to evoke coordinated movements in paralyzed limbs is the identification of the appropriate stimulation channels and stimulus parameters to evoke desired movements. Here we present the use of a six degree-of-freedom load cell placed under the foot of a feline to characterize the muscle activation produced by three 100-electrode Utah Slanted Electrode Arrays (USEAs) implanted into the femoral nerves, sciatic nerves, and muscular branches of the sciatic nerves of three cats. Intramuscular stimulation was used to identify the endpoint force directions produced by 15 muscles of the hind limb, and these directions were used to classify the forces produced by each intrafascicular USEA electrode as flexion or extension. For 451 USEA electrodes, stimulus intensities for threshold and saturation muscle forces were identified, and the 3D direction and linearity of the force recruitment curves were determined. Further, motor unit excitation independence for 198 electrode pairs was measured using the refractory technique. This study demonstrates the utility of 3D endpoint force monitoring as a simple and non-invasive metric for characterizing the muscle-activation properties of hundreds of implanted peripheral nerve electrodes, allowing for electrode and parameter selection for neuroprosthetic applications.

Model-based iterative learning control of Parkinsonian state in thalamic relay neuron

NASA Astrophysics Data System (ADS)

Liu, Chen; Wang, Jiang; Li, Huiyan; Xue, Zhiqin; Deng, Bin; Wei, Xile

2014-09-01

Although the beneficial effects of chronic deep brain stimulation on Parkinson's disease motor symptoms are now largely confirmed, the underlying mechanisms behind deep brain stimulation remain unclear and under debate. Hence, the selection of stimulation parameters is full of challenges. Additionally, due to the complexity of neural system, together with omnipresent noises, the accurate model of thalamic relay neuron is unknown. Thus, the iterative learning control of the thalamic relay neuron's Parkinsonian state based on various variables is presented. Combining the iterative learning control with typical proportional-integral control algorithm, a novel and efficient control strategy is proposed, which does not require any particular knowledge on the detailed physiological characteristics of cortico-basal ganglia-thalamocortical loop and can automatically adjust the stimulation parameters. Simulation results demonstrate the feasibility of the proposed control strategy to restore the fidelity of thalamic relay in the Parkinsonian condition. Furthermore, through changing the important parameter—the maximum ionic conductance densities of low-threshold calcium current, the dominant characteristic of the proposed method which is independent of the accurate model can be further verified.

Electrical Stimulation Followed by Mesenchymal Stem Cells Improves Anal Sphincter Anatomy and Function in a Rat Model at a Time Remote From Injury.

PubMed

Sun, Li; Yeh, Judy; Xie, Zhuojun; Kuang, Mei; Damaser, Margot S; Zutshi, Massarat

2016-05-01

We have explored cell-based therapy to aid anal sphincter repair, but a conditioning injury is required to direct stem cells to the site of injury because symptoms usually manifest at a time remote from injury. We aimed to investigate the effect of local electrical stimulation followed by mesenchymal stem cell delivery on anal sphincter regeneration at a time remote from injury. With the use of a rat model, electrical stimulation parameters and cell delivery route were selected based on in vivo cytokine expression and luciferase-labeled cell imaging of the anal sphincter complex. Three weeks after a partial anal sphincter excision, rats were randomly allocated to 4 groups based on different local interventions: no treatment, daily electrical stimulation for 3 days, daily stimulation for 3 days followed by stem cell injection on the third day, and daily electrical stimulation followed by stem cell injection on the first and third days. Histology-assessed anatomy and anal manometry evaluated physiology 4 weeks after intervention. The electrical stimulation parameters that significantly upregulated gene expression of homing cytokines also achieved mesenchymal stem cell retention when injected directly in the anal sphincter complex in comparison with intravascular and intraperitoneal injections. Four weeks after intervention, there was significantly more new muscle in the area of injury and significantly improved anal resting pressure in the group that received daily electrical stimulation for 3 days followed by a single injection of 1 million stem cells on the third day at the site of injury. This was a pilot study and therefore was not powered for functional outcome. In this rat injury model with optimized parameters, electrical stimulation with a single local mesenchymal stem cell injection administered 3 weeks after injury significantly improved both new muscle formation in the area of injury and anal sphincter pressures.

From cognitive networks to seizures: Stimulus evoked dynamics in a coupled cortical network

NASA Astrophysics Data System (ADS)

Lee, Jaejin; Ermentrout, Bard; Bodner, Mark

2013-12-01

Epilepsy is one of the most common neuropathologies worldwide. Seizures arising in epilepsy or in seizure disorders are characterized generally by uncontrolled spread of excitation and electrical activity to a limited region or even over the entire cortex. While it is generally accepted that abnormal excessive firing and synchronization of neuron populations lead to seizures, little is known about the precise mechanisms underlying human epileptic seizures, the mechanisms of transitions from normal to paroxysmal activity, or about how seizures spread. Further complication arises in that seizures do not occur with a single type of dynamics but as many different phenotypes and genotypes with a range of patterns, synchronous oscillations, and time courses. The concept of preventing, terminating, or modulating seizures and/or paroxysmal activity through stimulation of brain has also received considerable attention. The ability of such stimulation to prevent or modulate such pathological activity may depend on identifiable parameters. In this work, firing rate networks with inhibitory and excitatory populations were modeled. Network parameters were chosen to model normal working memory behaviors. Two different models of cognitive activity were developed. The first model consists of a single network corresponding to a local area of the brain. The second incorporates two networks connected through sparser recurrent excitatory connectivity with transmission delays ranging from approximately 3 ms within local populations to 15 ms between populations residing in different cortical areas. The effect of excitatory stimulation to activate working memory behavior through selective persistent activation of populations is examined in the models, and the conditions and transition mechanisms through which that selective activation breaks down producing spreading paroxysmal activity and seizure states are characterized. Specifically, we determine critical parameters and architectural changes that produce the different seizure dynamics in the networks. This provides possible mechanisms for seizure generation. Because seizures arise as attractors in a multi-state system, the system may possibly be returned to its baseline state through some particular stimulation. The ability of stimulation to terminate seizure dynamics in the local and distributed models is studied. We systematically examine when this may occur and the form of the stimulation necessary for the range of seizure dynamics. In both the local and distributed network models, termination is possible for all seizure types observed by stimulation possessing some particular configuration of spatial and temporal characteristics.

Algorithmic design of a noise-resistant and efficient closed-loop deep brain stimulation system: A computational approach

PubMed Central

Karamintziou, Sofia D.; Custódio, Ana Luísa; Piallat, Brigitte; Polosan, Mircea; Chabardès, Stéphan; Stathis, Pantelis G.; Tagaris, George A.; Sakas, Damianos E.; Polychronaki, Georgia E.; Tsirogiannis, George L.; David, Olivier; Nikita, Konstantina S.

2017-01-01

Advances in the field of closed-loop neuromodulation call for analysis and modeling approaches capable of confronting challenges related to the complex neuronal response to stimulation and the presence of strong internal and measurement noise in neural recordings. Here we elaborate on the algorithmic aspects of a noise-resistant closed-loop subthalamic nucleus deep brain stimulation system for advanced Parkinson’s disease and treatment-refractory obsessive-compulsive disorder, ensuring remarkable performance in terms of both efficiency and selectivity of stimulation, as well as in terms of computational speed. First, we propose an efficient method drawn from dynamical systems theory, for the reliable assessment of significant nonlinear coupling between beta and high-frequency subthalamic neuronal activity, as a biomarker for feedback control. Further, we present a model-based strategy through which optimal parameters of stimulation for minimum energy desynchronizing control of neuronal activity are being identified. The strategy integrates stochastic modeling and derivative-free optimization of neural dynamics based on quadratic modeling. On the basis of numerical simulations, we demonstrate the potential of the presented modeling approach to identify, at a relatively low computational cost, stimulation settings potentially associated with a significantly higher degree of efficiency and selectivity compared with stimulation settings determined post-operatively. Our data reinforce the hypothesis that model-based control strategies are crucial for the design of novel stimulation protocols at the backstage of clinical applications. PMID:28222198

Engineering the next generation of clinical deep brain stimulation technology.

PubMed

McIntyre, Cameron C; Chaturvedi, Ashutosh; Shamir, Reuben R; Lempka, Scott F

2015-01-01

Deep brain stimulation (DBS) has evolved into a powerful clinical therapy for a range of neurological disorders, but even with impressive clinical growth, DBS technology has been relatively stagnant over its history. However, enhanced collaborations between neural engineers, neuroscientists, physicists, neurologists, and neurosurgeons are beginning to address some of the limitations of current DBS technology. These interactions have helped to develop novel ideas for the next generation of clinical DBS systems. This review attempts collate some of that progress with two goals in mind. First, provide a general description of current clinical DBS practices, geared toward educating biomedical engineers and computer scientists on a field that needs their expertise and attention. Second, describe some of the technological developments that are currently underway in surgical targeting, stimulation parameter selection, stimulation protocols, and stimulation hardware that are being directly evaluated for near term clinical application. Copyright © 2015 Elsevier Inc. All rights reserved.

Beyond time and space: The effect of a lateralized sustained attention task and brain stimulation on spatial and selective attention.

PubMed

Shalev, Nir; De Wandel, Linde; Dockree, Paul; Demeyere, Nele; Chechlacz, Magdalena

2017-10-03

The Theory of Visual Attention (TVA) provides a mathematical formalisation of the "biased competition" account of visual attention. Applying this model to individual performance in a free recall task allows the estimation of 5 independent attentional parameters: visual short-term memory (VSTM) capacity, speed of information processing, perceptual threshold of visual detection; attentional weights representing spatial distribution of attention (spatial bias), and the top-down selectivity index. While the TVA focuses on selection in space, complementary accounts of attention describe how attention is maintained over time, and how temporal processes interact with selection. A growing body of evidence indicates that different facets of attention interact and share common neural substrates. The aim of the current study was to modulate a spatial attentional bias via transfer effects, based on a mechanistic understanding of the interplay between spatial, selective and temporal aspects of attention. Specifically, we examined here: (i) whether a single administration of a lateralized sustained attention task could prime spatial orienting and lead to transferable changes in attentional weights (assigned to the left vs right hemi-field) and/or other attentional parameters assessed within the framework of TVA (Experiment 1); (ii) whether the effects of such spatial-priming on TVA parameters could be further enhanced by bi-parietal high frequency transcranial random noise stimulation (tRNS) (Experiment 2). Our results demonstrate that spatial attentional bias, as assessed within the TVA framework, was primed by sustaining attention towards the right hemi-field, but this spatial-priming effect did not occur when sustaining attention towards the left. Furthermore, we show that bi-parietal high-frequency tRNS combined with the rightward spatial-priming resulted in an increased attentional selectivity. To conclude, we present a novel, theory-driven method for attentional modulation providing important insights into how the spatial and temporal processes in attention interact with attentional selection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Computer-Guided Deep Brain Stimulation Programming for Parkinson's Disease.

PubMed

Heldman, Dustin A; Pulliam, Christopher L; Urrea Mendoza, Enrique; Gartner, Maureen; Giuffrida, Joseph P; Montgomery, Erwin B; Espay, Alberto J; Revilla, Fredy J

2016-02-01

Pilot study to evaluate computer-guided deep brain stimulation (DBS) programming designed to optimize stimulation settings using objective motion sensor-based motor assessments. Seven subjects (five males; 54-71 years) with Parkinson's disease (PD) and recently implanted DBS systems participated in this pilot study. Within two months of lead implantation, the subject returned to the clinic to undergo computer-guided programming and parameter selection. A motion sensor was placed on the index finger of the more affected hand. Software guided a monopolar survey during which monopolar stimulation on each contact was iteratively increased followed by an automated assessment of tremor and bradykinesia. After completing assessments at each setting, a software algorithm determined stimulation settings designed to minimize symptom severities, side effects, and battery usage. Optimal DBS settings were chosen based on average severity of motor symptoms measured by the motion sensor. Settings chosen by the software algorithm identified a therapeutic window and improved tremor and bradykinesia by an average of 35.7% compared with baseline in the "off" state (p < 0.01). Motion sensor-based computer-guided DBS programming identified stimulation parameters that significantly improved tremor and bradykinesia with minimal clinician involvement. Automated motion sensor-based mapping is worthy of further investigation and may one day serve to extend programming to populations without access to specialized DBS centers. © 2015 International Neuromodulation Society.

Transcutaneous electrical nerve stimulation for spasticity: A systematic review.

PubMed

Fernández-Tenorio, E; Serrano-Muñoz, D; Avendaño-Coy, J; Gómez-Soriano, J

2016-07-26

Although transcutaneous electrical nerve stimulation (TENS) has traditionally been used to treat pain, some studies have observed decreased spasticity after use of this technique. However, its use in clinical practice is still limited. Our purpose was twofold: to determine whether TENS is effective for treating spasticity or associated symptoms in patients with neurological involvement, and to determine which stimulation parameters exert the greatest effect on variables associated with spasticity. Two independent reviewers used PubMed, PEDro, and Cochrane databases to search for randomised clinical trials addressing TENS and spasticity published before 12 May 2015, and selected the articles that met the inclusion criteria. Of the initial 96 articles, 86 were excluded. The remaining 10 articles present results from 207 patients with a cerebrovascular accident, 84 with multiple sclerosis, and 39 with spinal cord lesions. In light of our results, we recommend TENS as a treatment for spasticity due to its low cost, ease of use, and absence of adverse reactions. However, the great variability in the types of stimulation used in the studies, and the differences in parameters and variables, make it difficult to assess and compare any results that might objectively determine the effectiveness of this technique and show how to optimise parameters. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Pulsed laser versus electrical energy for peripheral nerve stimulation

PubMed Central

Wells, Jonathon; Konrad, Peter; Kao, Chris; Jansen, E. Duco; Mahadevan-Jansen, Anita

2010-01-01

Transient optical neural stimulation has previously been shown to elicit highly controlled, artifact-free potentials within the nervous system in a non-contact fashion without resulting in damage to tissue. This paper presents the physiologic validity of elicited nerve and muscle potentials from pulsed laser induced stimulation of the peripheral nerve in a comparative study with the standard method of electrically evoked potentials. Herein, the fundamental physical properties underlying the two techniques are contrasted. Key laser parameters for efficient optical stimulation of the peripheral nerve are detailed. Strength response curves are shown to be linear for each stimulation modality, although fewer axons can be recruited with optically evoked potentials. Results compare the relative transient energy requirements for stimulation using each technique and demonstrate that optical methods can selectively excite functional nerve stimulation. Adjacent stimulation and recording of compound nerve potentials in their entirety from optical and electrical stimulation are presented, with optical responses shown to be free of any stimulation artifact. Thus, use of a pulsed laser exhibits some advantages when compared to standard electrical means for excitation of muscle potentials in the peripheral nerve in the research domain and possibly for clinical diagnostics in the future. PMID:17537515

Two-way communication for programming and measurement in a miniature implantable stimulator.

PubMed

Thil, M A; Gérard, B; Jarvis, J C; Delbeke, J

2005-07-01

Implantable stimulators are needed for chronic electrical stimulation of nerves and muscles in experimental studies. The device described exploits the versatility of current microcontrollers for stimulation and communication in a miniature implant. Their standard outputs can provide the required selectable constant-current sources. In this device, pre-programmed stimulation paradigms were selected by transcutaneous light pulses. The potential of a programmable integrated circuit (PIC) was thus exploited. Implantable devices must be biocompatible. A novel encapsulation method that require no specialised equipment and that used two classical encapsulants, silicone and Teflon was developed. It was tested for implantation periods of up to four weeks. A novel way to estimate electrode impedance in awake animals is also presented. It was thus possible to follow the evolution of the nerve-electrode interface and, if necessary, to adjust the stimulation parameters. In practice, the electrode voltage at the end of a known constant-current pulse was measured by the PIC. The binary coded value was then indicated to the user as a series of muscle twitches that represented the binary value of the impedance measurement. This neurostimulator has been successfully tested in vitro and in vivo. Thresholds and impedance values were chronically monitored following implantation of a self-sizing spiral cuff electrode. Impedance variations in the first weeks could reflect morphological changes usually observed after the implantation of such electrodes.

Higher-order power harmonics of pulsed electrical stimulation modulates corticospinal contribution of peripheral nerve stimulation.

PubMed

Chen, Chiun-Fan; Bikson, Marom; Chou, Li-Wei; Shan, Chunlei; Khadka, Niranjan; Chen, Wen-Shiang; Fregni, Felipe

2017-03-03

It is well established that electrical-stimulation frequency is crucial to determining the scale of induced neuromodulation, particularly when attempting to modulate corticospinal excitability. However, the modulatory effects of stimulation frequency are not only determined by its absolute value but also by other parameters such as power at harmonics. The stimulus pulse shape further influences parameters such as excitation threshold and fiber selectivity. The explicit role of the power in these harmonics in determining the outcome of stimulation has not previously been analyzed. In this study, we adopted an animal model of peripheral electrical stimulation that includes an amplitude-adapted pulse train which induces force enhancements with a corticospinal contribution. We report that the electrical-stimulation-induced force enhancements were correlated with the amplitude of stimulation power harmonics during the amplitude-adapted pulse train. In an exploratory analysis, different levels of correlation were observed between force enhancement and power harmonics of 20-80 Hz (r = 0.4247, p = 0.0243), 100-180 Hz (r = 0.5894, p = 0.0001), 200-280 Hz (r = 0.7002, p < 0.0001), 300-380 Hz (r = 0.7449, p < 0.0001), 400-480 Hz (r = 0.7906, p < 0.0001), 500-600 Hz (r = 0.7717, p < 0.0001), indicating a trend of increasing correlation, specifically at higher order frequency power harmonics. This is a pilot, but important first demonstration that power at high order harmonics in the frequency spectrum of electrical stimulation pulses may contribute to neuromodulation, thus warrant explicit attention in therapy design and analysis.

Effects of Stand and Step Training with Epidural Stimulation on Motor Function for Standing in Chronic Complete Paraplegics

PubMed Central

Rejc, Enrico; Angeli, Claudia A.; Bryant, Nicole

2017-01-01

Abstract Individuals affected by motor complete spinal cord injury are unable to stand, walk, or move their lower limbs voluntarily; this diagnosis normally implies severe limitations for functional recovery. We have recently shown that the appropriate selection of epidural stimulation parameters was critical to promoting full-body, weight-bearing standing with independent knee extension in four individuals with chronic clinically complete paralysis. In the current study, we examined the effects of stand training and subsequent step training with epidural stimulation on motor function for standing in the same four individuals. After stand training, the ability to stand improved to different extents in the four participants. Step training performed afterwards substantially impaired standing ability in three of the four individuals. Improved standing ability generally coincided with continuous electromyography (EMG) patterns with constant levels of ground reaction forces. Conversely, poorer standing ability was associated with more variable EMG patterns that alternated EMG bursts and longer periods of negligible activity in most of the muscles. Stand and step training also differentially affected the evoked potentials amplitude modulation induced by sitting-to-standing transition. Finally, stand and step training with epidural stimulation were not sufficient to improve motor function for standing without stimulation. These findings show that the spinal circuitry of motor complete paraplegics can generate motor patterns effective for standing in response to task-specific training with optimized stimulation parameters. Conversely, step training can lead to neural adaptations resulting in impaired motor function for standing. PMID:27566051

Current steering to activate targeted neural pathways during deep brain stimulation of the subthalamic region

PubMed Central

Chaturvedi, Ashutosh; Foutz, Thomas J.; McIntyre, Cameron C.

2012-01-01

Deep brain stimulation (DBS) has steadily evolved into an established surgical therapy for numerous neurological disorders, most notably Parkinson’s disease (PD). Traditional DBS technology relies on voltage-controlled stimulation with a single source; however, recent engineering advances are providing current-controlled devices with multiple independent sources. These new stimulators deliver constant current to the brain tissue, irrespective of impedance changes that occur around the electrode, and enable more specific steering of current towards targeted regions of interest. In this study, we examined the impact of current steering between multiple electrode contacts to directly activate three distinct neural populations in the subthalamic region commonly stimulated for the treatment of PD: projection neurons of the subthalamic nucleus (STN), globus pallidus internus (GPi) fibers of the lenticular fasiculus, and internal capsule (IC) fibers of passage. We used three-dimensional finite element electric field models, along with detailed multi-compartment cable models of the three neural populations to determine their activations using a wide range of stimulation parameter settings. Our results indicate that selective activation of neural populations largely depends on the location of the active electrode(s). Greater activation of the GPi and STN populations (without activating any side-effect related IC fibers) was achieved by current steering with multiple independent sources, compared to a single current source. Despite this potential advantage, it remains to be seen if these theoretical predictions result in a measurable clinical effect that outweighs the added complexity of the expanded stimulation parameter search space generated by the more flexible technology. PMID:22277548

Feeding and Reward Are Differentially Induced by Activating GABAergic Lateral Hypothalamic Projections to VTA.

PubMed

Barbano, M Flavia; Wang, Hui-Ling; Morales, Marisela; Wise, Roy A

2016-03-09

Electrical stimulation of the lateral hypothalamus (LH) has two motivational effects: long trains of stimulation induce drive-like effects such as eating, and short trains are rewarding. It has not been clear whether a single set of activated fibers subserves the two effects. Previous optogenetic stimulation studies have confirmed that reinforcement and induction of feeding can each be induced by selective stimulation of GABAergic fibers originating in the bed nucleus of the LH and projecting to the ventral tegmental area (VTA). In the present study we determined the optimal stimulation parameters for each of the two optogenetically induced effects in food-sated mice. Stimulation-induced eating was strongest with 5 Hz and progressively weaker with 10 and 20 Hz. Stimulation-induced reward was strongest with 40 Hz and progressively weaker with lower or higher frequencies. Mean preferred duration for continuous 40 Hz stimulation was 61.6 s in a "real-time" place preference task; mean preferred duration for 5 Hz stimulation was 45.6 s. The differential effects of high- and low-frequency stimulation of this pathway seem most likely to be due to differential effects on downstream targets. Copyright © 2016 the authors 0270-6474/16/362975-11$15.00/0.

Punishment induced behavioural and neurophysiological variability reveals dopamine-dependent selection of kinematic movement parameters

PubMed Central

Galea, Joseph M.; Ruge, Diane; Buijink, Arthur; Bestmann, Sven; Rothwell, John C.

2013-01-01

Action selection describes the high-level process which selects between competing movements. In animals, behavioural variability is critical for the motor exploration required to select the action which optimizes reward and minimizes cost/punishment, and is guided by dopamine (DA). The aim of this study was to test in humans whether low-level movement parameters are affected by punishment and reward in ways similar to high-level action selection. Moreover, we addressed the proposed dependence of behavioural and neurophysiological variability on DA, and whether this may underpin the exploration of kinematic parameters. Participants performed an out-and-back index finger movement and were instructed that monetary reward and punishment were based on its maximal acceleration (MA). In fact, the feedback was not contingent on the participant’s behaviour but pre-determined. Blocks highly-biased towards punishment were associated with increased MA variability relative to blocks with either reward or without feedback. This increase in behavioural variability was positively correlated with neurophysiological variability, as measured by changes in cortico-spinal excitability with transcranial magnetic stimulation over the primary motor cortex. Following the administration of a DA-antagonist, the variability associated with punishment diminished and the correlation between behavioural and neurophysiological variability no longer existed. Similar changes in variability were not observed when participants executed a pre-determined MA, nor did DA influence resting neurophysiological variability. Thus, under conditions of punishment, DA-dependent processes influence the selection of low-level movement parameters. We propose that the enhanced behavioural variability reflects the exploration of kinematic parameters for less punishing, or conversely more rewarding, outcomes. PMID:23447607

Focal hand dystonia: individualized intervention with repeated application of repetitive transcranial magnetic stimulation.

PubMed

Kimberley, Teresa Jacobson; Borich, Michael R; Schmidt, Rebekah L; Carey, James R; Gillick, Bernadette

2015-04-01

To examine for individual factors that may predict response to inhibitory repetitive transcranial magnetic stimulation (rTMS) in focal hand dystonia (FHD); to present the method for determining optimal stimulation to increase inhibition in a given patient; and to examine individual responses to prolonged intervention. Single-subject design to determine optimal parameters to increase inhibition for a given subject and to use the selected parameters once per week for 6 weeks, with 1-week follow-up, to determine response. Clinical research laboratory. A volunteer sample of subjects with FHD (N = 2). One participant had transcranial magnetic stimulation responses indicating impaired inhibition, and the other had responses within normative limits. There were 1200 pulses of 1-Hz rTMS delivered using 4 different stimulation sites/intensity combinations: primary motor cortex at 90% or 110% of resting motor threshold (RMT) and dorsal premotor cortex (PMd) at 90% or 110% of RMT. The parameters producing the greatest within-session increase in cortical silent period (CSP) duration were then used as the intervention. Response variables included handwriting pressure and velocity, subjective symptom rating, CSP, and short latency intracortical inhibition and facilitation. The individual with baseline transcranial magnetic stimulation responses indicating impaired inhibition responded favorably to the repeated intervention, with reduced handwriting force, an increase in the CSP, and subjective report of moderate symptom improvement at 1-week follow-up. The individual with normative baseline responses failed to respond to the intervention. In both subjects, 90% of RMT to the PMd produced the greatest lengthening of the CSP and was used as the intervention. An individualized understanding of neurophysiological measures can be an indicator of responsiveness to inhibitory rTMS in focal dystonia, with further work needed to determine likely responders versus nonresponders. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

A testbed to explore the optimal electrical stimulation parameters for suppressing inter-ictal spikes in human hippocampal slices.

PubMed

Min-Chi Hsiao; Pen-Ning Yu; Dong Song; Liu, Charles Y; Heck, Christi N; Millett, David; Berger, Theodore W

2014-01-01

New interventions using neuromodulatory devices such as vagus nerve stimulation, deep brain stimulation and responsive neurostimulation are available or under study for the treatment of refractory epilepsy. Since the actual mechanisms of the onset and termination of the seizure are still unclear, most researchers or clinicians determine the optimal stimulation parameters through trial-and-error procedures. It is necessary to further explore what types of electrical stimulation parameters (these may include stimulation frequency, amplitude, duration, interval pattern, and location) constitute a set of optimal stimulation paradigms to suppress seizures. In a previous study, we developed an in vitro epilepsy model using hippocampal slices from patients suffering from mesial temporal lobe epilepsy. Using a planar multi-electrode array system, inter-ictal activity from human hippocampal slices was consistently recorded. In this study, we have further transferred this in vitro seizure model to a testbed for exploring the possible neurostimulation paradigms to inhibit inter-ictal spikes. The methodology used to collect the electrophysiological data, the approach to apply different electrical stimulation parameters to the slices are provided in this paper. The results show that this experimental testbed will provide a platform for testing the optimal stimulation parameters of seizure cessation. We expect this testbed will expedite the process for identifying the most effective parameters, and may ultimately be used to guide programming of new stimulating paradigms for neuromodulatory devices.

[Finite element analysis of temperature field of retina by electrical stimulation with microelectrode array].

PubMed

Wang, Wei; Qiao, Qingli; Gao, Weiping; Wu, Jun

2014-12-01

We studied the influence of electrode array parameters on temperature distribution to the retina during the use of retinal prosthesis in order to avoid thermal damage to retina caused by long-term electrical stimulation. Based on real epiretinal prosthesis, a three-dimensional model of electrical stimulation for retina with 4 X 4 microelectrode array had been established using the finite element software (COMSOL Multiphysics). The steady-state temperature field of electrical stimulation of the retina was calculated, and the effects of the electrode parameters such as the distance between the electrode contacts, the materials and area of the electrode contact on temperature field were considered. The maximum increase in the retina steady temperature was about 0. 004 degrees C with practical stimulation current. When the distance between the electrode contacts was changed from 130 microm to 520 microm, the temperature was reduced by about 0.006 microC. When the contact radius was doubled from 130 microm to 260 microm, the temperature decrease was about 0.005 degrees C. It was shown that there were little temperature changes in the retina with a 4 x 4 epiretinal microelectrode array, reflecting the safety of electrical stimulation. It was also shown that the maximum temperature in the retina decreased with increasing the distance between the electrode contacts, as well as increasing the area of electrode contact. However, the change of the maximum temperature was very small when the distance became larger than the diameter of electrode contact. There was no significant difference in the effects of temperature increase among the different electrode materials. Rational selection of the distance between the electrode contacts and their area in electrode design can reduce the temperature rise induced by electrical stimulation.

Radiofrequency for the treatment of skin laxity: mith or truth*

PubMed Central

de Araújo, Angélica Rodrigues; Soares, Viviane Pinheiro Campos; da Silva, Fernanda Souza; Moreira, Tatiane da Silva

2015-01-01

The nonablative radiofrequency is a procedure commonly used for the treatment of skin laxity from an increase in tissue temperature. The goal is to induce thermal damage to thus stimulate neocollagenesis in deep layers of the skin and subcutaneous tissue. However, many of these devices haven't been tested and their parameters are still not accepted by the scientific community. Because of this, it is necessary to review the literature regarding the physiological effects and parameters for application of radiofrequency and methodological quality and level of evidence of studies. A literature search was performed in MEDLINE, PEDro, SciELO, PubMed, LILACS and CAPES and experimental studies in humans, which used radiofrequency devices as treatment for facial or body laxity, were selected. The results showed that the main physiological effect is to stimulate collagen synthesis. There was no homogeneity between studies in relation to most of the parameters used and the methodological quality of studies and level of evidence for using radiofrequency are low. This fact complicates the determination of effective parameters for clinical use of this device in the treatment of skin laxity. The analyzed studies suggest that radiofrequency is effective, however the physiological mechanisms and the required parameters are not clear in the literature. PMID:26560216

[Status and progress of stimulating parameters in acupuncture treatment of ischemic cerebrovascular disease].

PubMed

Wei, Yuan-yuan; Fan, Xiao-nong; Wang, Shu; Shi, Xue-min

2008-08-01

Acute ischemic cerebrovascular disease is one of the critical diseases seriously endangering human health. Acupuncture therapy, an effective treatment method for many types of disorders has been generally acknowledged. In recent years, many scientific researchers have studied the relationship between the effects of acupuncture in relieving cerebral ischemia-induced sequelae and the stimulating parameters. The acupuncture stimulating parameter includes the frequency of electroacupuncture (EA), the frequency of acupuncture treatment, and the acquired quantity of stimulation, etc for clinical patients and experimental animals. It was found that different stimulating parameters may have different efficacies. Current research results provide a good basis not only for analysis of the factors of acupuncture-produced effects, but also for determination of the optimal combination of stimulating parameters. However, acupuncture therapeutic effect involves multiple factors and multiple levels, and current quantitative acupuncture parameter researches have been mainly restricted to animal experiments. Hence, more researches in which statistics specialists take part are definitely needed.

Machine Learning Approach to Optimizing Combined Stimulation and Medication Therapies for Parkinson's Disease.

PubMed

Shamir, Reuben R; Dolber, Trygve; Noecker, Angela M; Walter, Benjamin L; McIntyre, Cameron C

2015-01-01

Deep brain stimulation (DBS) of the subthalamic region is an established therapy for advanced Parkinson's disease (PD). However, patients often require time-intensive post-operative management to balance their coupled stimulation and medication treatments. Given the large and complex parameter space associated with this task, we propose that clinical decision support systems (CDSS) based on machine learning algorithms could assist in treatment optimization. Develop a proof-of-concept implementation of a CDSS that incorporates patient-specific details on both stimulation and medication. Clinical data from 10 patients, and 89 post-DBS surgery visits, were used to create a prototype CDSS. The system was designed to provide three key functions: (1) information retrieval; (2) visualization of treatment, and; (3) recommendation on expected effective stimulation and drug dosages, based on three machine learning methods that included support vector machines, Naïve Bayes, and random forest. Measures of medication dosages, time factors, and symptom-specific pre-operative response to levodopa were significantly correlated with post-operative outcomes (P < 0.05) and their effect on outcomes was of similar magnitude to that of DBS. Using those results, the combined machine learning algorithms were able to accurately predict 86% (12/14) of the motor improvement scores at one year after surgery. Using patient-specific details, an appropriately parameterized CDSS could help select theoretically optimal DBS parameter settings and medication dosages that have potential to improve the clinical management of PD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuromuscular electrical stimulation of the hindlimb muscles for movement therapy in a rodent model.

PubMed

Ichihara, Kazuhiko; Venkatasubramanian, Ganapriya; Abbas, James J; Jung, Ranu

2009-01-30

Neuromuscular electrical stimulation (NMES) can provide functional movements in people after central nervous system injury. The neuroplastic effects of long-term NMES-induced repetitive limb movement are not well understood. A rodent model of neurotrauma in which NMES can be implemented may be effective for such investigations. We present a rodent model for NMES of the flexor and extensor muscles of the hip, knee, and ankle hindlimb muscles. Custom fabricated intramuscular stimulating electrodes for rodents were implanted near identified motor points of targeted muscles in ten adult, female Long Evans rats. The effects of altering NMES pulse stimulation parameters were characterized using strength duration curves, isometric joint torque recruitment curves and joint angle measures. The data indicate that short pulse widths have the advantage of producing graded torque recruitment curves when current is used as the control parameter. A stimulus frequency of 75 Hz or more produces fused contractions. The data demonstrate ability to accurately implant the electrodes and obtain selective, graded, repeatable, strong muscle contractions. Knee and ankle angular excursions comparable to those obtained in normal treadmill walking in the same rodent species can be obtained by stimulating the target muscles. Joint torques (normalized to body weight) obtained were larger than those reported in the literature for small tailed therian mammals and for peak isometric ankle plantarflexion in a different rodent species. This model system could be used for investigations of NMES assisted hindlimb movement therapy.

A systematic review investigating the relationship between efficacy and stimulation parameters when using transcutaneous electrical nerve stimulation after knee arthroplasty.

PubMed

Beckwée, David; Bautmans, Ivan; Swinnen, Eva; Vermet, Yorick; Lefeber, Nina; Lievens, Pierre; Vaes, Peter

2014-01-01

To evaluate the clinical efficacy of transcutaneous electric nerve stimulation in the treatment of postoperative knee arthroplasty pain and to relate these results to the stimulation parameters used. PubMed, Pedro and Web of Knowledge were systematically screened for studies investigating effects of transcutaneous electric nerve stimulation on postoperative knee arthroplasty pain. Studies were screened for their methodological and therapeutical quality. We appraised the influence of the stimulation settings used and indicated whether or not a neurophysiological and/or mechanistic rationale was given for these stimulation settings. A total of 5 articles met the inclusion criteria. In total, 347 patients were investigated. The number of patients who received some form of transcutaneous electric nerve stimulation was 117, and 54 patients received sham transcutaneous electric nerve stimulation. Pain was the primary outcome in all studies. The stimulation settings used in the studies (n = 2) that reported significant effects differed from the others as they implemented a submaximal stimulation intensity. Stimulation parameters were heterogeneous, and only one study provided a rationale for them. This review reveals that an effect of transcutaneous electric nerve stimulation might have been missed due to low methodological and therapeutical quality. Justifying the choice of transcutaneous electric nerve stimulation parameters may improve therapeutical quality.

Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation.

PubMed

Dmochowski, Jacek P; Koessler, Laurent; Norcia, Anthony M; Bikson, Marom; Parra, Lucas C

2017-08-15

To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4-7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation

PubMed Central

Dmochowski, Jacek P.; Koessler, Laurent; Norcia, Anthony M.; Bikson, Marom; Parra, Lucas C.

2018-01-01

To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4–7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation. PMID:28578130

Bimanual Force Coordination in Parkinson’s Disease Patients with Bilateral Subthalamic Deep Brain Stimulation

PubMed Central

Gorniak, Stacey L.; McIntyre, Cameron C.; Alberts, Jay L.

2013-01-01

Objective Studies of bimanual actions similar to activities of daily living (ADLs) are currently lacking in evaluating fine motor control in Parkinson’s disease patients implanted with bilateral subthalamic deep brain stimulators. We investigated basic time and force characteristics of a bimanual task that resembles performance of ADLs in a group of bilateral subthalamic deep brain stimulation (DBS) patients. Methods Patients were evaluated in three different DBS parameter conditions off stimulation, on clinically derived stimulation parameters, and on settings derived from a patient-specific computational model. Model-based parameters were computed as a means to minimize spread of current to non-motor regions of the subthalamic nucleus via Cicerone Deep Brain Stimulation software. Patients were evaluated off parkinsonian medications in each stimulation condition. Results The data indicate that DBS parameter state does not affect most aspects of fine motor control in ADL-like tasks; however, features such as increased grip force and grip symmetry varied with the stimulation state. In the absence of DBS parameters, patients exhibited significant grip force asymmetry. Overall UPDRS-III and UPDRS-III scores associated with hand function were lower while patients were experiencing clinically-derived or model-based parameters, as compared to the off-stimulation condition. Conclusion While bilateral subthalamic DBS has been shown to alleviate gross motor dysfunction, our results indicate that DBS may not provide the same magnitude of benefit to fine motor coordination. PMID:24244388

Microprocessor controlled movement of solid colonic content using sequential neural electrical stimulation

PubMed Central

Amaris, M A; Rashev, P Z; Mintchev, M P; Bowes, K L

2002-01-01

Background and aims: Invoked peristaltic contractions and movement of solid content have not been attempted in normal canine colon. The purpose of this study was to determine if movement of solid content through the colon could be produced by microprocessor controlled sequential stimulation. Methods: The study was performed on six anaesthetised dogs. At laparotomy, a 15 cm segment of descending colon was selected, the proximal end closed with a purse string suture, and the distal end opened into a collecting container. Four sets of subserosal stimulating electrodes were implanted at 3 cm intervals. The segment of bowel was filled with a mixture of dog food and 50 plastic pellets before each of 2–5 random sessions of non-stimulated or stimulated emptying. Propagated contractions were generated using microprocessor controlled bipolar trains of 50 Hz rectangular voltage having 20 V (peak to peak) amplitude, 18 second stimulus duration, and a nine second phase lag between stimulation trains in sequential electrode sets. Results: Electrical stimulation using the above mentioned parameters resulted in powerful phasic contractions that closed the lumen. By phase locking the stimulation voltage between adjacent sets of electrodes, propagated contractions could be produced in an aboral or orad direction. The number of evacuated pellets during the stimulation sessions was significantly higher than during the non-stimulated sessions (p<0.01). Conclusions: Microprocessor controlled electrical stimulation accelerated movement of colonic content suggesting the possibility of future implantable colonic stimulators. PMID:11889065

Human sperm Toll-like receptor 4 (TLR4) mediates acrosome reaction, oxidative stress markers, and sperm parameters in response to bacterial lipopolysaccharide in infertile men.

PubMed

Sahnoun, Sana; Sellami, Afifa; Chakroun, Nozha; Mseddi, Malek; Attia, Hammadi; Rebai, Tarek; Lassoued, Saloua

2017-08-01

To study the role of Toll-like receptor 4 (TLR4) in human spermatozoa and to assess sperm parameters, oxidative stress markers, and acrosome reaction in response to the stimulation of TLR4 by its ligand, the lipopolysaccharide (LPS), as a major endotoxin of Gram-negative bacteria. Our study was carried out in 73 sperm samples from patients undergoing semen analysis for couple infertility investigations. The studied patients were divided into three groups: normozoospermic fertile patients (n = 13), patients with abnormal and leukospermic semen (n = 13), and patients with abnormal and non-leukospermic semen (n = 47). TLR4 expression in human spermatozoa was initially analyzed by western blot. Sperm samples were incubated in the presence of LPS (200 ng/ml) for 18 h. Then, sperm motility and vitality were evaluated by microscopic observation and oxidative stress markers as malondialdehyde (MDA) and carbonyl groups (CG) were spectrophotometrically assessed in neat and selected sperm. A triple-stain technique was also performed to evaluate acrosome reaction in 15 sperm samples from infertile patients. TLR4 expression was confirmed in human spermatozoa with a molecular weight of 69 kDa. In the normozoospermic group, no significant differences in sperm parameters and oxidative stress markers were shown after incubation with LPS in neat and selected sperms. Regarding samples from the non-leukospermic group, LPS reduced spermatozoa motility and vitality rates in selected sperm (P = 0.003; P = 0.004, respectively). A significant increase of MDA and CG levels was also detected (P = 0.01; P = 0.02, respectively). However, only the MDA levels were significantly increased (P = 0.01) in neat LPS-stimulated sperm. The same results were shown within the leukospermic group. The comparison between the two groups, leukospermic and non-leukospermic, in selected sperms showed a more important LPS effect in the leukospermic group significantly on motility and MDA rates (P = 0.006; P = 0.009, respectively). Furthermore, a significant decrease in reacted spermatozoa rate was detected in response to LPS in selected sperm samples from infertile men (P = 0.03). These findings indicate that human spermatozoa express TLR4 and respond to LPS stimulation with alterations in viability, motility, and the acrosome reaction implicating reactive oxygen species (ROS) production in sperm samples from infertile patients.

Systematic study of the effects of stimulus parameters and stimulus location on afterdischarges elicited by electrical stimulation in the rat.

PubMed

Shigeto, Hiroshi; Boongird, Atthaporn; Baker, Kenneth; Kellinghaus, Christoph; Najm, Imad; Lüders, Hans

2013-03-01

Electrical brain stimulation is used in a variety of clinical situations, including cortical mapping for epilepsy surgery, cortical stimulation therapy to terminate seizure activity in the cortex, and in deep brain stimulation therapy. However, the effects of stimulus parameters are not fully understood. In this study, we systematically tested the impact of various stimulation parameters on the generation of motor symptoms and afterdischarges (ADs). Focal electrical stimulation was delivered at subdural cortical, intracortical, and hippocampal sites in a rat model. The effects of stimulus parameter on the generation of motor symptoms and on the occurrence of ADs were examined. The effect of stimulus irregularity was tested using random or regular 50Hz stimulation through subdural electrodes. Hippocampal stimulation produced ADs at lower thresholds than neocortical stimulation. Hippocampal stimulation also produced significantly longer ADs. Both in hippocampal and cortical stimulation, when the total current was kept constant with changing pulse width, the threshold for motor symptom or AD was lowest between 50 and 100Hz and higher at both low and high frequencies. However, if the pulse width was fixed, the threshold did not increase above 100Hz and it apparently continued to decrease through 800Hz even if the difference did not reach statistical significance. There was no significant difference between random and regular stimulation. Overall, these results indicate that electrode location and several stimulus parameters including frequency, pulse width, and total electricity are important in electrical stimulation to produce motor symptoms and ADs. Copyright © 2012 Elsevier B.V. All rights reserved.

A systematic review investigating the relationship between efficacy and stimulation parameters when using transcutaneous electrical nerve stimulation after knee arthroplasty

PubMed Central

Beckwée, David; Bautmans, Ivan; Swinnen, Eva; Vermet, Yorick; Lefeber, Nina; Lievens, Pierre

2014-01-01

Objective: To evaluate the clinical efficacy of transcutaneous electric nerve stimulation in the treatment of postoperative knee arthroplasty pain and to relate these results to the stimulation parameters used. Data Sources: PubMed, Pedro and Web of Knowledge were systematically screened for studies investigating effects of transcutaneous electric nerve stimulation on postoperative knee arthroplasty pain. Review Methods: Studies were screened for their methodological and therapeutical quality. We appraised the influence of the stimulation settings used and indicated whether or not a neurophysiological and/or mechanistic rationale was given for these stimulation settings. Results: A total of 5 articles met the inclusion criteria. In total, 347 patients were investigated. The number of patients who received some form of transcutaneous electric nerve stimulation was 117, and 54 patients received sham transcutaneous electric nerve stimulation. Pain was the primary outcome in all studies. The stimulation settings used in the studies (n = 2) that reported significant effects differed from the others as they implemented a submaximal stimulation intensity. Stimulation parameters were heterogeneous, and only one study provided a rationale for them. Conclusion: This review reveals that an effect of transcutaneous electric nerve stimulation might have been missed due to low methodological and therapeutical quality. Justifying the choice of transcutaneous electric nerve stimulation parameters may improve therapeutical quality. PMID:26770730

Microstimulation with Chronically Implanted Intracortical Electrodes

NASA Astrophysics Data System (ADS)

McCreery, Douglas

Stimulating microelectrodes that penetrate into the brain afford a means of accessing the basic functional units of the central nervous system. Microstimulation in the region of the cerebral cortex that subserve vision may be an alternative, or an adjunct, to a retinal prosthesis, and may be particularly attractive as a means of restoring a semblance of high-resolution central vision. There also is the intriguing possibility that such a prosthesis could convey higher order visual percepts, many of which are mediated by neural circuits in the secondary or "extra-striate" visual areas that surround the primary visual cortex. The technologies of intracortical stimulating microelectrodes and investigations of the effects of microstimulation on neural tissue have advanced to the point where a cortical-level prosthesis is at least feasible. The imperative of protecting neural tissue from stimulation-induced damage imposes constraints on the selection of stimulus parameters, as does the requirement that the stimulation not greatly affect the electrical excitability of the neurons that are to be activated. The latter is especially likely to occur when many adjacent microelectrodes are pulsed, as will be necessary in a visual prosthesis. However, data from animal studies indicates that these restrictions on stimulus parameter are compatible with those that can evoke visual percepts in humans and in experimental animals. These findings give cause to be optimistic about the prospects for realizing a visual prosthesis utilizing intracortical microstimulation.

Selecting electrode configurations for image-guided cochlear implant programming using template matching.

PubMed

Zhang, Dongqing; Zhao, Yiyuan; Noble, Jack H; Dawant, Benoit M

2018-04-01

Cochlear implants (CIs) are neural prostheses that restore hearing using an electrode array implanted in the cochlea. After implantation, the CI processor is programmed by an audiologist. One factor that negatively impacts outcomes and can be addressed by programming is cross-electrode neural stimulation overlap (NSO). We have proposed a system to assist the audiologist in programming the CI that we call image-guided CI programming (IGCIP). IGCIP permits using CT images to detect NSO and recommend deactivation of a subset of electrodes to avoid NSO. We have shown that IGCIP significantly improves hearing outcomes. Most of the IGCIP steps are robustly automated but electrode configuration selection still sometimes requires manual intervention. With expertise, distance-versus-frequency curves, which are a way to visualize the spatial relationship learned from CT between the electrodes and the nerves they stimulate, can be used to select the electrode configuration. We propose an automated technique for electrode configuration selection. A comparison between this approach and one we have previously proposed shows that our method produces results that are as good as those obtained with our previous method while being generic and requiring fewer parameters.

[Perception and selectivity of sound duration in the central auditory midbrain].

PubMed

Wang, Xin; Li, An-An; Wu, Fei-Jian

2010-08-25

Sound duration plays important role in acoustic communication. Information of acoustic signal is mainly encoded in the amplitude and frequency spectrum of different durations. Duration selective neurons exist in the central auditory system including inferior colliculus (IC) of frog, bat, mouse and chinchilla, etc., and they are important in signal recognition and feature detection. Two generally accepted models, which are "coincidence detector model" and "anti-coincidence detector model", have been raised to explain the mechanism of neural selective responses to sound durations based on the study of IC neurons in bats. Although they are different in details, they both emphasize the importance of synaptic integration of excitatory and inhibitory inputs, and are able to explain the responses of most duration-selective neurons. However, both of the hypotheses need to be improved since other sound parameters, such as spectral pattern, amplitude and repetition rate, could affect the duration selectivity of the neurons. The dynamic changes of sound parameters are believed to enable the animal to effectively perform recognition of behavior related acoustic signals. Under free field sound stimulation, we analyzed the neural responses in the IC and auditory cortex of mouse and bat to sounds with different duration, frequency and amplitude, using intracellular or extracellular recording techniques. Based on our work and previous studies, this article reviews the properties of duration selectivity in central auditory system and discusses the mechanisms of duration selectivity and the effect of other sound parameters on the duration coding of auditory neurons.

Incorporating thyroid markers in Down syndrome screening protocols.

PubMed

Dhaifalah, Ishraq; Salek, Tomas; Langova, Dagmar; Cuckle, Howard

2017-05-01

The article aimed to assess the benefit of incorporating maternal serum thyroid disease marker levels (thyroid-stimulating hormone and free thyroxine) into first trimester Down syndrome screening protocols. Statistical modelling was used to predict performance with and without the thyroid markers. Two protocols were considered: the combined test and the contingent cell-free DNA (cfDNA) test, where 15-40% women are selected for cfDNA because of increased risk based on combined test results. Published parameters were used for the combined test, cfDNA and the Down syndrome means for thyroid-stimulating hormone and free thyroxine; other parameters were derived from a series of 5230 women screened for both thyroid disease and Down syndrome. Combined test: For a fixed 85% detection rate, the predicted false positive rate was reduced from 5.3% to 3.6% with the addition of the thyroid markers. Contingent cfDNA test: For a fixed 95% detection rate, the proportion of women selected for cfDNA was reduced from 25.6% to 20.2%. When screening simultaneously for maternal thyroid disease and Down syndrome, thyroid marker levels should be used in the calculation of Down syndrome risk. The benefit is modest but can be achieved with no additional cost. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

[Effect of remifentanil on clinical and electroencephalographic parameters of depth of anesthesia in balanced anesthesia with propofol, enflurane or isoflurane].

PubMed

Bischoff, P; Plümer, L; Scholz, J; Drögemeier, K; von Knobelsdorff, G; Schulte am Esch, J

1998-01-01

Electrophysiological parameters are well-suited to detect changes in cerebral function. The present study investigates whether balanced anaesthesia with remifentanil during nociceptive stimulation is associated with changes in clinical and electrophysiological parameters indicating inadequate depth of anaesthesia. Following IRB approval and written informed consent, 23 patients (ASA: I; age: 36 +/- 11) scheduled for elective gynaecological laparoscopy were included in the study. Without any premedication, anaesthesia was induced with remifentanil (1.0 microgram/kg bolus injection), propofol (0.5 mg/kg added by repetitive (10 mg) bolus injections every 10 s until unconciousness) and vecuronium (0.1 mg/kg). Following endotracheal intubation (normoventilation: PetCO2: 36 bis 38 mmHg), remifentanil infusion was started with continuous doses of 0.5 microgram/kg/min over 5 minutes and maintained with 0.25 microgram/kg/min during surgery. Remifentanil was randomly combined with propofol (group 1: 100 micrograms/kg/min; n = 7), enflurane (group 2: 0.5 MAC; n = 8) or isoflurane (group 3: 0.5 MAC; n = 8). Monitoring included: heart rate (beats/min), mean arterial pressure (mmHg), oxygen saturation (%), endtidal CO2 (mmHg) and endtidal enflurane and isoflurane (%). EEG: 2-channel recordings of Fz versus mastoid and ECG (artefact control) during steady-state anaesthesia and surgery. Following fast-fourier-transformation (4 s; 256/s; 0.5 to 35.0 Hz), spectral power densities were calculated for the selected frequency bands. Auditory evoked potentials (AEP; middle latency) were registered simultaneously after binaural stimulation via head-phones click-stimulation (6 Hz; 75 dB above hearing threshold; 512 stimulations per average). Bandpass was 0.01 to 2.0 kHz. Na, Pa, Nb (latencies; ms) and peak-to-peak amplitudes (NaPa, PaNb; microV). EEG and AEP recording technique [15]. The study protocol included baseline values from pre-intubation, pre-surgery, the respective post-stimulation values (1 min, 3 min, 5 min) and all data at five-minute intervals during surgery until emergence from anaesthesia. During steady-state study conditions with defined remifentanil applications, mean data indicate that in response to nociceptive stimuli no changes in clinical or electrophysiological parameters were observed. In contrast to other studies using different anaesthetic techniques, the present data from remifentanil indicate very stable haemodynamic and electrophysiological parameters (EEG, AEP) during noxious stimulations. Adjustable and with no plasma accumulation, remifentanil demonstrates potent antinociceptive effects resulting in signs of adequate anaesthesia.

Focal hand dystonia: individualized intervention with repeated application of repetitive transcranial magnetic stimulation

PubMed Central

Kimberley, Teresa Jacobson; Borich, Michael R.; Schmidt, Rebekah; Carey, James R.; Gillick, Bernadette

2016-01-01

Objective Examine for individual factors that may predict response to inhibitory repetitive transcranial magnetic stimulation (rTMS) in focal hand dystonia (FHD); present method for determining the optimal stimulation to increase inhibition in a given patient; and examine individual responses to prolonged intervention. Design A single-subject design to determine optimal parameters to increase inhibition for a given subject and to employ the selected parameters 1/wk for 6 weeks, with 1 wk follow up, to determine response. Setting Clinical research laboratory Participants A volunteer sample of 2 subjects with FHD. One participant had TMS responses indicating impaired inhibition, the other had responses within normal limits. Interventions 1200 pulses of 1 Hz rTMS delivered using 4 different stimulation site/intensity combinations: primary motor cortex (M1) at 90% or 110% resting motor threshold (RMT); dorsal premotor cortex (PMd) at 90% or 110% of RMT. The parameters producing the greatest within-session increase in cortical silent period (CSP) duration were then used as intervention. Main outcome measures Response variables included handwriting pressure and velocity, subjective symptom rating, CSP, and short-latency intracortical inhibition and facilitation. Results The individual with baseline TMS responses indicating impaired inhibition responded favorably to the repeated intervention, with reduced handwriting force, increase in CSP and subjective report of “moderate” symptom improvement at 1-wk follow-up. The individual with normal baseline responses failed to respond to the intervention. In both subjects, 90% RMT to PMd produced greatest lengthening of CSP and was used as intervention. Conclusions An individualized understanding of neurophysiologic measures may be indicators of responsiveness to inhibitory rTMS in focal dystonia, with further work needed to determine 3 likely responders vs. non-responders. PMID:25256555

The effect of the combination of acids and tannin in diet on the performance and selected biochemical, haematological and antioxidant enzyme parameters in grower pigs.

PubMed

Stukelj, Marina; Valencak, Zdravko; Krsnik, Mladen; Svete, Alenka Nemec

2010-03-06

The abolition of in-feed antibiotics or chemotherapeutics as growth promoters have stimulated the swine industry to look for alternatives such as organic acids, botanicals, probiotics and tannin. The objective of the present study was to compare the effects of a combination of acids and tannin with diet with organic acids and diet without growth promoters on the growth performance and selected biochemical, haematological and antioxidant enzyme parameters in grower pigs. Tannin is more natural and cheaper but possibly with the same effectiveness as organic acids with regard to growth performance. Thirty-six 7 week old grower pigs, divided into three equal groups, were used in a three week feeding trial. Group I was fed basal diet, group II basal diet with added organic acids and group III basal diet with added organic and inorganic acids and tannin. Pigs were weighed before and after feeding and observed daily. Blood was collected before and after the feeding trial for the determination of selected biochemical, haematological and antioxidant enzyme parameters. One-way ANOVA was used to assess any diet related changes of all the parameters. Paired t-test was used to evaluate changes of blood parameters individually in each group of growers before and after feeding. No clinical health problems related to diet were noted during the three week feeding trial. The average daily gain (ADG) and selected blood parameters were not affected by the addition to basal diet of either acids and tannin or of organic acids alone. Selected blood parameters remained within the reference range before and after the feeding trial, with the exception of total serum proteins that were below the lower value of reference range at both times. The significant changes (paired t-test) observed in individual groups before and after the feeding trial are related to the growth of pigs. Diet with acids and tannin did not improve the growth performance of grower pigs but had no deleterious effects on selected blood parameters. The possibility of beneficial effects of adding acids and tannin in diets on growth performance over a longer period, however, could not be excluded.

Evaluation of focused multipolar stimulation for cochlear implants in long-term deafened cats

NASA Astrophysics Data System (ADS)

George, Shefin S.; Wise, Andrew K.; Fallon, James B.; Shepherd, Robert K.

2015-06-01

Objective. Focused multipolar (FMP) stimulation has been shown to produce restricted neural activation using intracochlear stimulation in animals with a normal population of spiral ganglion neurons (SGNs). However, in a clinical setting, the widespread loss of SGNs and peripheral fibres following deafness is expected to influence the effectiveness of FMP. Approach. We compared the efficacy of FMP stimulation to both monopolar (MP) and tripolar (TP) stimulation in long-term deafened cat cochleae (n = 8). Unlike our previous study, these cochleae contained <10% of the normal SGN population adjacent to the electrode array. We also evaluated the effect of electrode position on stimulation modes by using either modiolar facing or lateral wall facing half-band electrodes. The spread of neural activity across the inferior colliculus, a major nucleus within the central auditory pathway, was used as a measure of spatial selectivity. Main results. In cochleae with significant SGN degeneration, we observed that FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation (p < 0.001). However, thresholds were significantly higher for FMP and TP stimulation compared to MP stimulation (p < 0.001). No difference between FMP and TP stimulation was found in any measures. The high threshold levels for FMP stimulation was significantly reduced without compromising spatial selectivity by varying the degree of current focusing (referred as ‘partial-FMP’ stimulation). Spatial selectivity of all stimulation modes was unaffected by the electrode position. Finally, spatial selectivity in long-term deafened cochleae was significantly less than that of cochleae with normal SGN population (George S S et al 2014 J. Neural Eng. 11 065003). Significance. The present results indicate that the greater spatial selectivity of FMP and TP stimulation over MP stimulation is maintained in cochleae with significant neural degeneration and is not adversely affected by electrode position. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance.

Association of the expression of Th cytokines with peripheral CD4 and CD8 lymphocyte subsets after vaccination with FMD vaccine in Holstein young sires.

PubMed

Yang, Ling; Liu, Zhichao; Li, Jianbin; He, Kaili; Kong, Lingna; Guo, Runqing; Liu, Wenjiao; Gao, Yundong; Zhong, Jifeng

2018-05-25

High immune response (HIR) cows have a balanced and robust host defense and lower disease incidence, and immune response is more important to consider for selecting young sires than for selecting cows. The protective immune response against foot-and-mouth disease (FMD) virus infection is T-cell-independent in an animal experimental model. However, there is no convenient method to select young sires with a HIR to FMD virus. In this study, 39 healthy Holstein young sires were vaccinated with the trivalent (A, O and Asia 1) FMD vaccine, and T-lymphocyte subsets in peripheral blood lymphocytes (PBLs) were detected using flow cytometric analysis before and after vaccination. The expression of interferon-gamma (IFN-γ), interleukin-2 (IL-2), IL-4, and IL-6 mRNA in PBLs was analyzed after stimulation by lipopolysaccharide (LPS) or Concanavalin A (ConA) after vaccination. According to the percentage of CD4 + lymphocyte and CD4/CD8 ratio after vaccination for selecting the HIR young sires, the results showed that the percentages of CD3 + , CD4 + , CD3 + CD4 + lymphocytes and the CD4/CD8 ratio in the HIR group were higher compared to those in the medium immune response (MIR) and low immune response (LIR) groups before vaccination. Additionally, the percentage of CD4 + lymphocytes and the CD4/CD8 ratio after vaccination were positively associated with the expression level of IFN-γ mRNA in the PBLs after stimulation by LPS. In conclusion, the in vitro expression level of IFN-γ mRNA in the PBLs stimulated by LPS may serve as a parameter for selecting young sires with a HIR to FMD virus. Copyright © 2018 Elsevier Ltd. All rights reserved.

An electric stimulation system for electrokinetic particle manipulation in microfluidic devices.

PubMed

Lopez-de la Fuente, M S; Moncada-Hernandez, H; Perez-Gonzalez, V H; Lapizco-Encinas, B H; Martinez-Chapa, S O

2013-03-01

Microfluidic devices have grown significantly in the number of applications. Microfabrication techniques have evolved considerably; however, electric stimulation systems for microdevices have not advanced at the same pace. Electric stimulation of micro-fluidic devices is an important element in particle manipulation research. A flexible stimulation instrument is desired to perform configurable, repeatable, automated, and reliable experiments by allowing users to select the stimulation parameters. The instrument presented here is a configurable and programmable stimulation system for electrokinetic-driven microfluidic devices; it consists of a processor, a memory system, and a user interface to deliver several types of waveforms and stimulation patterns. It has been designed to be a flexible, highly configurable, low power instrument capable of delivering sine, triangle, and sawtooth waveforms with one single frequency or two superimposed frequencies ranging from 0.01 Hz to 40 kHz, and an output voltage of up to 30 Vpp. A specific stimulation pattern can be delivered over a single time period or as a sequence of different signals for different time periods. This stimulation system can be applied as a research tool where manipulation of particles suspended in liquid media is involved, such as biology, medicine, environment, embryology, and genetics. This system has the potential to lead to new schemes for laboratory procedures by allowing application specific and user defined electric stimulation. The development of this device is a step towards portable and programmable instrumentation for electric stimulation on electrokinetic-based microfluidic devices, which are meant to be integrated with lab-on-a-chip devices.

An electric stimulation system for electrokinetic particle manipulation in microfluidic devices

NASA Astrophysics Data System (ADS)

Lopez-de la Fuente, M. S.; Moncada-Hernandez, H.; Perez-Gonzalez, V. H.; Lapizco-Encinas, B. H.; Martinez-Chapa, S. O.

2013-03-01

Microfluidic devices have grown significantly in the number of applications. Microfabrication techniques have evolved considerably; however, electric stimulation systems for microdevices have not advanced at the same pace. Electric stimulation of micro-fluidic devices is an important element in particle manipulation research. A flexible stimulation instrument is desired to perform configurable, repeatable, automated, and reliable experiments by allowing users to select the stimulation parameters. The instrument presented here is a configurable and programmable stimulation system for electrokinetic-driven microfluidic devices; it consists of a processor, a memory system, and a user interface to deliver several types of waveforms and stimulation patterns. It has been designed to be a flexible, highly configurable, low power instrument capable of delivering sine, triangle, and sawtooth waveforms with one single frequency or two superimposed frequencies ranging from 0.01 Hz to 40 kHz, and an output voltage of up to 30 Vpp. A specific stimulation pattern can be delivered over a single time period or as a sequence of different signals for different time periods. This stimulation system can be applied as a research tool where manipulation of particles suspended in liquid media is involved, such as biology, medicine, environment, embryology, and genetics. This system has the potential to lead to new schemes for laboratory procedures by allowing application specific and user defined electric stimulation. The development of this device is a step towards portable and programmable instrumentation for electric stimulation on electrokinetic-based microfluidic devices, which are meant to be integrated with lab-on-a-chip devices.

Role of the Internal Superior Laryngeal Nerve in the Motor Responses of Vocal Cords and the Related Voice Acoustic Changes

PubMed Central

Seifpanahi, Sadegh; Izadi, Farzad; Jamshidi, Ali-Ashraf; Torabinezhad, Farhad; Sarrafzadeh, Javad; Mohammadi, Siavash

2016-01-01

Background: Repeated efforts by researchers to impose voice changes by laryngeal surface electrical stimulation (SES) have come to no avail. This present pre-experimental study employed a novel method for SES application so as to evoke the motor potential of the internal superior laryngeal nerve (ISLN) and create voice changes. Methods: Thirty-two normal individuals (22 females and 10 males) participated in this study. The subjects were selected from the students of Iran University of Medical Sciences in 2014. Two monopolar active electrodes were placed on the thyrohyoid space at the location of the ISLN entrance to the larynx and 1 dispersive electrode was positioned on the back of the neck. A current with special programmed parameters was applied to stimulate the ISLN via the active electrodes and simultaneously the resultant acoustic changes were evaluated. All the means of the acoustic parameters during SES and rest periods were compared using the paired t-test. Results: The findings indicated significant changes (P=0.00) in most of the acoustic parameters during SES presentation compared to them at rest. The mean of fundamental frequency standard deviation (SD F0) at rest was 1.54 (SD=0.55) versus 4.15 (SD=3.00) for the SES period. The other investigated parameters comprised fundamental frequency (F0), minimum F0, jitter, shimmer, harmonic-to-noise ratio (HNR), mean intensity, and minimum intensity. Conclusion: These findings demonstrated significant changes in most of the important acoustic features, suggesting that the stimulation of the ISLN via SES could induce motor changes in the vocal folds. The clinical applicability of the method utilized in the current study in patients with vocal fold paralysis requires further research. PMID:27582586

Development of a multi-electrode array for spinal cord epidural stimulation to facilitate stepping and standing after a complete spinal cord injury in adult rats.

PubMed

Gad, Parag; Choe, Jaehoon; Nandra, Mandheerej Singh; Zhong, Hui; Roy, Roland R; Tai, Yu-Chong; Edgerton, V Reggie

2013-01-21

Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

Deep brain stimulation does not change neurovascular coupling in non-motor visual cortex: an autonomic and visual evoked blood flow velocity response study.

PubMed

Azevedo, Elsa; Santos, Rosa; Freitas, João; Rosas, Maria-José; Gago, Miguel; Garrett, Carolina; Rosengarten, Bernhard

2010-11-01

In Parkinson's disease (PD) subthalamic nucleus deep brain stimulation (STN-DBS) improves motor function. Also an effect on the neurovascular coupling in motor cortex was reported due to a parallel activation of a subthalamic vasodilator area (SVA). To address this issue further we analysed neurovascular coupling in a non-motor area. Twenty PD patients selected for bilateral STN-DBS were investigated with functional transcranial Doppler (f-TCD) before and after surgery. Hemodynamic responses to visual stimulation were registered in left posterior cerebral artery (PCA) and analysed with a control-system approach (parameters gain, rate time, attenuation and natural frequency). To exclude autonomic effects of STN-DBS, we also addressed spectrum analysis of heart rate and of systolic arterial blood pressure variability, and baroreceptor gain. Findings in the PD group were compared with healthy age-matched controls. PD patients showed no neurovascular coupling changes in PCA territory, compared to controls, and STN-DBS changed neither blood flow regulatory parameters nor autonomic function. Improvement of vasoregulation in some motor cortical areas after STN-DBS might be related to an improved neuronal functional rather than indicating an effect on the neurovascular coupling or autonomic function. Copyright © 2010 Elsevier Ltd. All rights reserved.

The cultural implications of growth: Modeling nonlinear interaction of trait selection and population dynamics

NASA Astrophysics Data System (ADS)

Antoci, Angelo; Galeotti, Marcello; Russu, Paolo; Luigi Sacco, Pier

2018-05-01

In this paper, we study a nonlinear model of the interaction between trait selection and population dynamics, building on previous work of Ghirlanda et al. [Theor. Popul. Biol. 77, 181-188 (2010)] and Antoci et al. [Commun. Nonlinear Sci. Numer. Simul. 58, 92-106 (2018)]. We establish some basic properties of the model dynamics and present some simulations of the fine-grained structure of alternative dynamic regimes for chosen combinations of parameters. The role of the parameters that govern the reinforcement/corruption of maladaptive vs. adaptive traits is of special importance in determining the model's dynamic evolution. The main implication of this result is the need to pay special attention to the structural forces that may favor the emergence and consolidation of maladaptive traits in contemporary socio-economies, as it is the case, for example, for the stimulation of dysfunctional consumption habits and lifestyles in the pursuit of short-term profits.

The cultural implications of growth: Modeling nonlinear interaction of trait selection and population dynamics.

PubMed

Antoci, Angelo; Galeotti, Marcello; Russu, Paolo; Luigi Sacco, Pier

2018-05-01

In this paper, we study a nonlinear model of the interaction between trait selection and population dynamics, building on previous work of Ghirlanda et al. [Theor. Popul. Biol. 77, 181-188 (2010)] and Antoci et al. [Commun. Nonlinear Sci. Numer. Simul. 58, 92-106 (2018)]. We establish some basic properties of the model dynamics and present some simulations of the fine-grained structure of alternative dynamic regimes for chosen combinations of parameters. The role of the parameters that govern the reinforcement/corruption of maladaptive vs. adaptive traits is of special importance in determining the model's dynamic evolution. The main implication of this result is the need to pay special attention to the structural forces that may favor the emergence and consolidation of maladaptive traits in contemporary socio-economies, as it is the case, for example, for the stimulation of dysfunctional consumption habits and lifestyles in the pursuit of short-term profits.

Seizure Control in a Computational Model Using a Reinforcement Learning Stimulation Paradigm.

PubMed

Nagaraj, Vivek; Lamperski, Andrew; Netoff, Theoden I

2017-11-01

Neuromodulation technologies such as vagus nerve stimulation and deep brain stimulation, have shown some efficacy in controlling seizures in medically intractable patients. However, inherent patient-to-patient variability of seizure disorders leads to a wide range of therapeutic efficacy. A patient specific approach to determining stimulation parameters may lead to increased therapeutic efficacy while minimizing stimulation energy and side effects. This paper presents a reinforcement learning algorithm that optimizes stimulation frequency for controlling seizures with minimum stimulation energy. We apply our method to a computational model called the epileptor. The epileptor model simulates inter-ictal and ictal local field potential data. In order to apply reinforcement learning to the Epileptor, we introduce a specialized reward function and state-space discretization. With the reward function and discretization fixed, we test the effectiveness of the temporal difference reinforcement learning algorithm (TD(0)). For periodic pulsatile stimulation, we derive a relation that describes, for any stimulation frequency, the minimal pulse amplitude required to suppress seizures. The TD(0) algorithm is able to identify parameters that control seizures quickly. Additionally, our results show that the TD(0) algorithm refines the stimulation frequency to minimize stimulation energy thereby converging to optimal parameters reliably. An advantage of the TD(0) algorithm is that it is adaptive so that the parameters necessary to control the seizures can change over time. We show that the algorithm can converge on the optimal solution in simulation with slow and fast inter-seizure intervals.

Evaluation of results obtained with corifollitropin alfa after poor ovarian response in previous cycle using recombinant follicular stimulating hormone in the long-term protocol.

PubMed

Salgueiro, Lister L; Rolim, Juliana R; Moura, Bernardo R L; Machado, Suelen P P; Haddad, Carolina

2016-08-01

This study evaluated the use of Corifollitropin alfa in patients with previous poor response to recombinant follicle stimulating hormone in long-term protocols using gonadotropin-releasing hormone. Twenty-seven poor responders to previous treatment with the long term protocol using the recombinant follicle stimulating hormone (Group 1) were selected and then submitted to a second attempt using the same long term protocol with Corifollitropin alfa instead of the recombinant follicle stimulating hormone (Group 2).Ovarian down-regulation was achieved using subcutaneous administration of Leuprolide Acetate. Ovarian stimulation was performed with recombinant follicle stimulating hormone until the administration of human chorionic gonadotropin, followed by follicular aspiration (Group 1). Group 2 was submitted to this same protocol using Corifollitropin alfa instead of recombinant follicle stimulating hormone. There were significant differences in the number of aspirated oocytes, percentage of mature oocytes, amount of injected oocytes and transferred embryos - with all of these parameters being increased in the Corifollitropin alfa group. In addition, the rates of pregnancy and ongoing pregnancy were also significantly higher in the Corifollitropin alfa group. The present study demonstrated that the use of Corifollitropin alfa in the long-term protocol could be a highly effective alternative for patients with poor ovarian response, who were unsuccessful in a previous treatment with In Vitro Fertilization - Intracytoplasmic Sperm Injection.

Nonlinear predictive control for adaptive adjustments of deep brain stimulation parameters in basal ganglia-thalamic network.

PubMed

Su, Fei; Wang, Jiang; Niu, Shuangxia; Li, Huiyan; Deng, Bin; Liu, Chen; Wei, Xile

2018-02-01

The efficacy of deep brain stimulation (DBS) for Parkinson's disease (PD) depends in part on the post-operative programming of stimulation parameters. Closed-loop stimulation is one method to realize the frequent adjustment of stimulation parameters. This paper introduced the nonlinear predictive control method into the online adjustment of DBS amplitude and frequency. This approach was tested in a computational model of basal ganglia-thalamic network. The autoregressive Volterra model was used to identify the process model based on physiological data. Simulation results illustrated the efficiency of closed-loop stimulation methods (amplitude adjustment and frequency adjustment) in improving the relay reliability of thalamic neurons compared with the PD state. Besides, compared with the 130Hz constant DBS the closed-loop stimulation methods can significantly reduce the energy consumption. Through the analysis of inter-spike-intervals (ISIs) distribution of basal ganglia neurons, the evoked network activity by the closed-loop frequency adjustment stimulation was closer to the normal state. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of contacts configuration and location on selective stimulation of cuff electrode.

PubMed

Taghipour-Farshi, Hamed; Frounchi, Javad; Ahmadiasl, Nasser; Shahabi, Parviz; Salekzamani, Yaghoub

2015-01-01

Cuff electrodes have been widely used chronically in different clinical applications. Advancements have been made in selective stimulation by using multi-contact cuff electrodes. Steering anodic current is a strategy to increase selectivity by reshaping and localizing electric fields. There are two configurations for contacts to be implemented in cuff, monopolar and tripolar. A cuff electrode with tripolar configuration can restrict the activation to a more localized region within a nerve trunk compared to a cuff with monopolar configuration and improve the selectivity. Anode contacts in tripolar configuration can be made in two structures, "ring" and "dot". In this study, the stimulation capabilities of these two structures were evaluated. The recruitment properties and the selectivity of stimulation were examined by measuring the electric potential produced by stimulation currents. The results of the present study indicated that using dot configuration, the current needed to stimulate fascicles in tripolar topologies would be reduced by 10%. It was also shown that stimulation threshold was increased by moving anode contacts inward the cuff. On the other hand, stimulation threshold was decreased by moving the anode contacts outward the cuff which would decrease selectivity, too. We conclude that dot configuration is a better choice for stimulation. Also, a cuff inward placement of 10% relative to the cuff length was near optimal.

An Orientation Dependent Size Illusion Is Underpinned by Processing in the Extrastriate Visual Area, LO1.

PubMed

Mikellidou, Kyriaki; Gouws, André D; Clawson, Hannah; Thompson, Peter; Morland, Antony B; Keefe, Bruce D

2016-01-01

We use the simple, but prominent Helmholtz's squares illusion in which a vertically striped square appears wider than a horizontally striped square of identical physical dimensions to determine whether functional magnetic resonance imaging (fMRI) BOLD responses in V1 underpin illusions of size. We report that these simple stimuli which differ in only one parameter, orientation, to which V1 neurons are highly selective elicited activity in V1 that followed their physical, not perceived size. To further probe the role of V1 in the illusion and investigate plausible extrastriate visual areas responsible for eliciting the Helmholtz squares illusion, we performed a follow-up transcranial magnetic stimulation (TMS) experiment in which we compared perceptual judgments about the aspect ratio of perceptually identical Helmholtz squares when no TMS was applied against selective stimulation of V1, LO1, or LO2. In agreement with fMRI results, we report that TMS of area V1 does not compromise the strength of the illusion. Only stimulation of area LO1, and not LO2, compromised significantly the strength of the illusion, consistent with previous research that LO1 plays a role in the processing of orientation information. These results demonstrate the involvement of a specific extrastriate area in an illusory percept of size.

Effects of unilateral selective hypergravity stimulation on gait

NASA Astrophysics Data System (ADS)

Lazerges, M.; Bessou, P.

The purpose of this work is to analyse the neural mechanisms of human motor perturbations induced by dynamic changes in gravity. A unilateral selective hypergravity stimulation (USHS) was produced by stretching an elastic band between the right shoulder and foot. The consequences of the extensor muscle tone change due to the positioning (increased muscular loading) and to its removal (decreased muscular loading) by the elastic band were observed on motor gait skill. Gait spatio-temporal parameters (horizontal displacement of both feet) and lower limb functional length variations (efficiency of flexion and extension movements of the lower limbs) were measured. The latter measure was performed using a device specially designed for that purpose. The main results were: (1) during and after USHS, gait perturbations appeared on the left—the body side not directly stimulated, (2) just after the end of USHS, perturbations were present on the right (homolateral) side evidencing a post treatment effect which caused a decrease in functional shortening of the lower limb during extension and an increase of functional shortening of the lower limb during stance (opposite in sense to the modification observed during swing). Such results afford evidence that, in addition to vestibular receptors, the mechanoreceptors of extensor muscles are involved in determining the changes in motor skills observed at the beginning and at the end of space flights.

Mechanisms and targets of deep brain stimulation in movement disorders.

PubMed

Johnson, Matthew D; Miocinovic, Svjetlana; McIntyre, Cameron C; Vitek, Jerrold L

2008-04-01

Chronic electrical stimulation of the brain, known as deep brain stimulation (DBS), has become a preferred surgical treatment for medication-refractory movement disorders. Despite its remarkable clinical success, the therapeutic mechanisms of DBS are still not completely understood, limiting opportunities to improve treatment efficacy and simplify selection of stimulation parameters. This review addresses three questions essential to understanding the mechanisms of DBS. 1) How does DBS affect neuronal tissue in the vicinity of the active electrode or electrodes? 2) How do these changes translate into therapeutic benefit on motor symptoms? 3) How do these effects depend on the particular site of stimulation? Early hypotheses proposed that stimulation inhibited neuronal activity at the site of stimulation, mimicking the outcome of ablative surgeries. Recent studies have challenged that view, suggesting that although somatic activity near the DBS electrode may exhibit substantial inhibition or complex modulation patterns, the output from the stimulated nucleus follows the DBS pulse train by direct axonal excitation. The intrinsic activity is thus replaced by high-frequency activity that is time-locked to the stimulus and more regular in pattern. These changes in firing pattern are thought to prevent transmission of pathologic bursting and oscillatory activity, resulting in the reduction of disease symptoms through compensatory processing of sensorimotor information. Although promising, this theory does not entirely explain why DBS improves motor symptoms at different latencies. Understanding these processes on a physiological level will be critically important if we are to reach the full potential of this powerful tool.

Stimulation of the cochlea using green laser light

NASA Astrophysics Data System (ADS)

Wenzel, G. I.; Balster, S.; Lim, H. H.; Zhang, K.; Reich, U.; Lubatschowski, H.; Ertmer, W.; Lenarz, T.; Reuter, G.

2009-02-01

The success of conventional hearing aids and electrical cochlear implants have generally been limited to hearing in quiet situations, in part due to a lack of localized (i.e., frequency specificity) sensorineural activation and subsequent impaired speech discrimination in noise. Laser light is a source of energy that can be focused in a controlled manner and may provide more localized activation of the inner ear, the cochlea. Compound action potentials have been elicited using 2.12 µm laser pulses through activation of auditory nerve fibers (Izzo et al. 2006). Laser stimulation (813 nm) of the cochlea has shown to induce basilar membrane motion and cochlear microphonic potentials (Fridberger et al. 2006). We sought to assess if visible light (green, 532 nm, 10 ns pulses) could be used to consistently activate the cochlea. The laser parameters were selected based on our initial attempt to induce an optoacoustic effect as the energy transfer mechanism to the cochlea. Click evoked auditory brainstem responses (AABRs) were recorded preoperatively in ketamine-anesthetized guinea pigs to confirm normal hearing. The bulla and then the cochlea were exposed. Optically evoked ABRs (OABR) were recorded in response to laser stimulation with a 50 µm optical fiber (532 nm, 10 ns pulses, 500 repetitions, 10 pulses/s; Nd:YAG laser) at the round window (RW) directed towards the basilar membrane (BM). OABRs similar in morphology to acoustically evoked ABRs, except for shorter latencies, were obtained for stimulation through the RW with energy levels between 1.7-30 µJ/pulse. The OABRs increased with increasing energy level reaching a saturation level around 13-15 µJ/pulse. Furthermore the responses remained consistent across stimulation over time, including stimulation at 13 µJ/pulse for over 30 minutes, indicating minimal or no damage within the cochlea with this type of laser stimulation. Overall we have demonstrated that laser light stimulation with 532 nm has potential for a new type of auditory prosthesis that can activate the cochlea without any apparent functional damage. Further studies are needed to determine the optimal laser parameters and fiber placement locations for localized and tonotopic activation.

Closed-Loop Efficient Searching of Optimal Electrical Stimulation Parameters for Preferential Excitation of Retinal Ganglion Cells

PubMed Central

Guo, Tianruo; Yang, Chih Yu; Tsai, David; Muralidharan, Madhuvanthi; Suaning, Gregg J.; Morley, John W.; Dokos, Socrates; Lovell, Nigel H.

2018-01-01

The ability for visual prostheses to preferentially activate functionally-distinct retinal ganglion cells (RGCs) is important for improving visual perception. This study investigates the use of high frequency stimulation (HFS) to elicit RGC activation, using a closed-loop algorithm to search for optimal stimulation parameters for preferential ON and OFF RGC activation, resembling natural physiological neural encoding in response to visual stimuli. We evaluated the performance of a wide range of electrical stimulation amplitudes and frequencies on RGC responses in vitro using murine retinal preparations. It was possible to preferentially excite either ON or OFF RGCs by adjusting amplitudes and frequencies in HFS. ON RGCs can be preferentially activated at relatively higher stimulation amplitudes (>150 μA) and frequencies (2–6.25 kHz) while OFF RGCs are activated by lower stimulation amplitudes (40–90 μA) across all tested frequencies (1–6.25 kHz). These stimuli also showed great promise in eliciting RGC responses that parallel natural RGC encoding: ON RGCs exhibited an increase in spiking activity during electrical stimulation while OFF RGCs exhibited decreased spiking activity, given the same stimulation amplitude. In conjunction with the in vitro studies, in silico simulations indicated that optimal HFS parameters could be rapidly identified in practice, whilst sampling spiking activity of relevant neuronal subtypes. This closed-loop approach represents a step forward in modulating stimulation parameters to achieve appropriate neural encoding in retinal prostheses, advancing control over RGC subtypes activated by electrical stimulation. PMID:29615857

Design of robust adaptive controller and feedback error learning for rehabilitation in Parkinson's disease: a simulation study.

PubMed

Rouhollahi, Korosh; Emadi Andani, Mehran; Karbassi, Seyed Mahdi; Izadi, Iman

2017-02-01

Deep brain stimulation (DBS) is an efficient therapy to control movement disorders of Parkinson's tremor. Stimulation of one area of basal ganglia (BG) by DBS with no feedback is the prevalent opinion. Reduction of additional stimulatory signal delivered to the brain is the advantage of using feedback. This results in reduction of side effects caused by the excessive stimulation intensity. In fact, the stimulatory intensity of controllers is decreased proportional to reduction of hand tremor. The objective of this study is to design a new controller structure to decrease three indicators: (i) the hand tremor; (ii) the level of delivered stimulation in disease condition; and (iii) the ratio of the level of delivered stimulation in health condition to disease condition. For this purpose, the authors offer a new closed-loop control structure to stimulate two areas of BG simultaneously. One area (STN: subthalamic nucleus) is stimulated by an adaptive controller with feedback error learning. The other area (GPi: globus pallidus internal) is stimulated by a partial state feedback (PSF) controller. Considering the three indicators, the results show that, stimulating two areas simultaneously leads to better performance compared with stimulating one area only. It is shown that both PSF and adaptive controllers are robust regarding system parameter uncertainties. In addition, a method is proposed to update the parameters of the BG model in real time. As a result, the parameters of the controllers can be updated based on the new parameters of the BG model.

Application of describing function analysis to a model of deep brain stimulation.

PubMed

Davidson, Clare Muireann; de Paor, Annraoi M; Lowery, Madeleine M

2014-03-01

Deep brain stimulation effectively alleviates motor symptoms of medically refractory Parkinson's disease, and also relieves many other treatment-resistant movement and affective disorders. Despite its relative success as a treatment option, the basis of its efficacy remains elusive. In Parkinson's disease, increased functional connectivity and oscillatory activity occur within the basal ganglia as a result of dopamine loss. A correlative relationship between pathological oscillatory activity and the motor symptoms of the disease, in particular bradykinesia, rigidity, and tremor, has been established. Suppression of the oscillations by either dopamine replacement or DBS also correlates with an improvement in motor symptoms. DBS parameters are currently chosen empirically using a "trial and error" approach, which can be time-consuming and costly. The work presented here amalgamates concepts from theories of neural network modeling with nonlinear control engineering to describe and analyze a model of synchronous neural activity and applied stimulation. A theoretical expression for the optimum stimulation parameters necessary to suppress oscillations is derived. The effect of changing stimulation parameters (amplitude and pulse duration) on induced oscillations is studied in the model. Increasing either stimulation pulse duration or amplitude enhanced the level of suppression. The predicted parameters were found to agree well with clinical measurements reported in the literature for individual patients. It is anticipated that the simplified model described may facilitate the development of protocols to aid optimum stimulation parameter choice on a patient by patient basis.

Evaluation of focused multipolar stimulation for cochlear implants in acutely deafened cats

NASA Astrophysics Data System (ADS)

George, Shefin S.; Wise, Andrew K.; Shivdasani, Mohit N.; Shepherd, Robert K.; Fallon, James B.

2014-12-01

Objective. The conductive nature of the fluids and tissues of the cochlea can lead to broad activation of spiral ganglion neurons using contemporary cochlear implant stimulation configurations such as monopolar (MP) stimulation. The relatively poor spatial selectivity is thought to limit implant performance, particularly in noisy environments. Several current focusing techniques have been proposed to reduce the spread of activation with the aim towards achieving improved clinical performance. Approach. The present research evaluated the efficacy of focused multipolar (FMP) stimulation, a relatively new focusing technique in the cochlea, and compared its efficacy to both MP stimulation and tripolar (TP) stimulation. The spread of neural activity across the inferior colliculus (IC), measured by recording the spatial tuning curve, was used as a measure of spatial selectivity. Adult cats (n = 6) were acutely deafened and implanted with an intracochlear electrode array before multi-unit responses were recorded across the cochleotopic gradient of the contralateral IC. Recordings were made in response to acoustic and electrical stimulation using the MP, TP and FMP configurations. Main results. FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation. However, thresholds were significantly higher (p < 0.001) for FMP and TP stimulation compared to MP stimulation. There were no differences found in spatial selectivity and threshold between FMP and TP stimulation. Significance. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance. However, further research will be required to demonstrate the efficacy of these modes of stimulation after longer durations of deafness.

Flow rate, pH and calcium concentration of saliva of children and adolescents with type 1 diabetes mellitus.

PubMed

Moreira, A R; Passos, I A; Sampaio, F C; Soares, M S M; Oliveira, R J

2009-08-01

Alterations in salivary parameters may increase the caries risk in diabetic children, but, contradictory data on this issue have been reported. The aims of this study were to compare salivary parameters (flow rate, pH and calcium concentration) between healthy and type 1 diabetes mellitus (T1DM) individuals. The sample consisted of 7- to 18-year-old individuals divided into two groups: 30 subjects with T1DM (group A) and 30 healthy control subjects (group B). Fasting glucose levels were determined. Unstimulated and stimulated saliva was collected. The pH of unstimulated saliva was measured with paper strips and an electrode. Calcium concentrations in stimulated saliva were determined with a selective electrode. Group A individuals had inadequate blood glucose control (HbA(1C) >9%), with means +/- SD unstimulated salivary flow rate of 0.15 +/- 0.1 mL/min compared to 0.36 +/- 0.2 mL/min for group B (P < 0.01). Stimulated salivary flow rate was similar by both groups and above 2.0 mL/min. Saliva pH was 6.0 +/- 0.8 for group A and significantly different from 7.0 +/- 0.6 for group B (P < 0.01). Salivary calcium was 14.7 +/- 8.1 mg/L for group A and significantly higher than 9.9 +/- 6.4 mg/L for group B (P < 0.01). Except for elevated calcium concentrations in saliva, salivary parameters favoring caries such as low saliva pH and unstimulated salivary flow rate were observed in T1DM individuals.

The effect of the combination of acids and tannin in diet on the performance and selected biochemical, haematological and antioxidant enzyme parameters in grower pigs

PubMed Central

2010-01-01

Background The abolition of in-feed antibiotics or chemotherapeutics as growth promoters have stimulated the swine industry to look for alternatives such as organic acids, botanicals, probiotics and tannin. The objective of the present study was to compare the effects of a combination of acids and tannin with diet with organic acids and diet without growth promoters on the growth performance and selected biochemical, haematological and antioxidant enzyme parameters in grower pigs. Tannin is more natural and cheaper but possibly with the same effectiveness as organic acids with regard to growth performance. Methods Thirty-six 7 week old grower pigs, divided into three equal groups, were used in a three week feeding trial. Group I was fed basal diet, group II basal diet with added organic acids and group III basal diet with added organic and inorganic acids and tannin. Pigs were weighed before and after feeding and observed daily. Blood was collected before and after the feeding trial for the determination of selected biochemical, haematological and antioxidant enzyme parameters. One-way ANOVA was used to assess any diet related changes of all the parameters. Paired t-test was used to evaluate changes of blood parameters individually in each group of growers before and after feeding. Results No clinical health problems related to diet were noted during the three week feeding trial. The average daily gain (ADG) and selected blood parameters were not affected by the addition to basal diet of either acids and tannin or of organic acids alone. Selected blood parameters remained within the reference range before and after the feeding trial, with the exception of total serum proteins that were below the lower value of reference range at both times. The significant changes (paired t-test) observed in individual groups before and after the feeding trial are related to the growth of pigs. Conclusion Diet with acids and tannin did not improve the growth performance of grower pigs but had no deleterious effects on selected blood parameters. The possibility of beneficial effects of adding acids and tannin in diets on growth performance over a longer period, however, could not be excluded. PMID:20205921

Behavioral assessment of sensitivity to intracortical microstimulation of primate somatosensory cortex.

PubMed

Kim, Sungshin; Callier, Thierri; Tabot, Gregg A; Gaunt, Robert A; Tenore, Francesco V; Bensmaia, Sliman J

2015-12-08

Intracortical microstimulation (ICMS) is a powerful tool to investigate the functional role of neural circuits and may provide a means to restore sensation for patients for whom peripheral stimulation is not an option. In a series of psychophysical experiments with nonhuman primates, we investigate how stimulation parameters affect behavioral sensitivity to ICMS. Specifically, we deliver ICMS to primary somatosensory cortex through chronically implanted electrode arrays across a wide range of stimulation regimes. First, we investigate how the detectability of ICMS depends on stimulation parameters, including pulse width, frequency, amplitude, and pulse train duration. Then, we characterize the degree to which ICMS pulse trains that differ in amplitude lead to discriminable percepts across the range of perceptible and safe amplitudes. We also investigate how discriminability of pulse amplitude is modulated by other stimulation parameters-namely, frequency and duration. Perceptual judgments obtained across these various conditions will inform the design of stimulation regimes for neuroscience and neuroengineering applications.

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

PubMed

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

2016-01-01

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

The specificity of the effects of stimulant medication on classroom learning-related measures of cognitive processing for attention deficit disorder children.

PubMed

Balthazor, M J; Wagner, R K; Pelham, W E

1991-02-01

There appear to be beneficial effects of stimulant medication on daily classroom measures of cognitive functioning for Attention Deficit Disorder (ADD) children, but the specificity and origin of such effects is unclear. Consistent with previous results, 0.3 mg/kg methylphenidate improved ADD children's performance on a classroom reading comprehension measure. Using the Posner letting-matching task and four additional measures of phonological processing, we attempted to isolate the effects of methylphenidate to parameter estimates of (a) selective attention, (b) the basic cognitive process of retrieving name codes from permanent memory, and (c) a constant term that represented nonspecific aspects of information processing. Responses to the letter-matching stimuli were faster and more accurate with medication compared to placebo. The improvement in performance was isolated to the parameter estimate that reflected nonspecific aspects of information processing. A lack of medication effect on the other measures of phonological processing supported the Posner task findings in indicating that methylphenidate appears to exert beneficial effects on academic processing through general rather than specific aspects of information processing.

Assessing TMS-induced D and I waves with spinal H-reflexes.

PubMed

Niemann, Niclas; Wiegel, Patrick; Kurz, Alexander; Rothwell, John C; Leukel, Christian

2018-03-01

Transcranial magnetic stimulation (TMS) of motor cortex produces a series of descending volleys known as D (direct) and I (indirect) waves. In the present study, we questioned whether spinal H-reflexes can be used to dissect D waves and early and late I waves from TMS. We therefore probed H-reflex facilitation at arrival times of D and I waves at the spinal level and thereby changed TMS parameters that have previously been shown to have selective effects on evoked D and different I waves. We changed TMS intensity and current direction and applied a double-pulse paradigm known as short-interval intracortical inhibition (SICI). Experiments were conducted in flexor carpi radialis (FCR) in the arm and soleus (SOL) in the leg. There were two major findings: 1) in FCR, H-reflex facilitation showed characteristic modulations with altered TMS parameters that correspond to the changes of evoked D and I waves; and 2) H-reflexes in SOL did not, possibly because of increased interference from other spinal circuits. Therefore, the most significant outcome of this study is that in FCR, H-reflexes combined with TMS seem to be a useful technique to dissect TMS-induced D and I waves. NEW & NOTEWORTHY Questions that relate to corticospinal function in pathophysiology and movement control demand sophisticated techniques to provide information about corticospinal mechanisms. We introduce a noninvasive electrophysiological technique that may be useful in describing such mechanisms in more detail by dissecting D and I waves from transcranial magnetic stimulation (TMS). Based on the combination of spinal H-reflexes and TMS in the flexor carpi radialis muscle, the technique was shown to measure selective effects on D and I waves from changing TMS parameters.

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

PubMed

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

2018-01-01

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

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

PubMed Central

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

2018-01-01

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

Deep-brain-stimulation does not impair deglutition in Parkinson's disease.

PubMed

Lengerer, Sabrina; Kipping, Judy; Rommel, Natalie; Weiss, Daniel; Breit, Sorin; Gasser, Thomas; Plewnia, Christian; Krüger, Rejko; Wächter, Tobias

2012-08-01

A large proportion of patients with Parkinson's disease develop dysphagia during the course of the disease. Dysphagia in Parkinson's disease affects different phases of deglutition, has a strong impact on quality of life and may cause severe complications, i.e., aspirational pneumonia. So far, little is known on how deep-brain-stimulation of the subthalamic nucleus influences deglutition in PD. Videofluoroscopic swallowing studies on 18 patients with Parkinson's disease, which had been performed preoperatively, and postoperatively with deep-brain-stimulation-on and deep-brain-stimulation-off, were analyzed retrospectively. The patients were examined in each condition with three consistencies (viscous, fluid and solid). The 'New Zealand index for multidisciplinary evaluation of swallowing (NZIMES) Subscale One' for qualitative and 'Logemann-MBS-Parameters' for quantitative evaluation were assessed. Preoperatively, none of the patients presented with clinically relevant signs of dysphagia. While postoperatively, the mean daily levodopa equivalent dosage was reduced by 50% and deep-brain-stimulation led to a 50% improvement in motor symptoms measured by the UPDRS III, no clinically relevant influence of deep-brain-stimulation-on swallowing was observed using qualitative parameters (NZIMES). However quantitative parameters (Logemann scale) found significant changes of pharyngeal parameters with deep-brain-stimulation-on as compared to preoperative condition and deep-brain-stimulation-off mostly with fluid consistency. In Parkinson patients without dysphagia deep-brain-stimulation of the subthalamic nucleus modulates the pharyngeal deglutition phase but has no clinically relevant influence on deglutition. Further studies are needed to test if deep-brain-stimulation is a therapeutic option for patients with swallowing disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

A low-cost multichannel wireless neural stimulation system for freely roaming animals.

PubMed

Alam, Monzurul; Chen, Xi; Fernandez, Eduardo

2013-12-01

Electrical stimulation of nerve tissue and recording of neural activity are the basis of many therapies and neural prostheses. Conventional stimulation systems have a number of practical limitations, especially in experiments involving freely roaming subjects. Our main objective was to develop a modular, versatile and inexpensive multichannel wireless system able to overcome some of these constraints. We have designed and implemented a new multichannel wireless neural stimulator based on commercial components. The system is small (2 cm × 4 cm × 0.5 cm) and light in weight (9 g) which allows it to be easily carried in a small backpack. To test and validate the performance and reliability of the whole system we conducted several bench tests and in vivo experiments. The performance and accuracy of the stimulator were comparable to commercial threaded systems. Stimulation sequences can be constructed on-the-fly with 251 selectable current levels (from 0 to 250 µA) with 1 µA step resolution. The pulse widths and intervals can be as long as 65 ms in 2 µs time resolution. The system covers approximately 10 m of transmission range in a regular laboratory environment and 100 m in free space (line of sight). Furthermore it provides great flexibility for experiments since it allows full control of the stimulator and the stimulation parameters in real time. When there is no stimulation, the device automatically goes into low-power sleep mode to preserve battery power. We introduce the design of a powerful multichannel wireless stimulator assembled from commercial components. Key features of the system are their reliability, robustness and small size. The system has a flexible design that can be modified straightforwardly to tailor it to any specific experimental need. Furthermore it can be effortlessly adapted for use with any kind of multielectrode arrays.

New fracturing technique for Dean sand

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

Pugh, T.D.; McDaniel, B.W.; Seglem, R.L.

1977-01-01

A new hydraulic fracturing technique is being applied to stimulate the Dean sand of the Spraberry trend area. Results show improvement in production, effective fracture length and lower treatment costs. Production history of several wells was reviewed, and results of this study were used to select certain design parameters. These were rate, type fluid, sand size, etc. New computer programs were used to correlate this data for selected volumes. The theory and application of the new technique is discussed, and a description of the Dean sand is presented in detail. Production results using the new method are compared with themore » wells' response to conventional treatments and considerations are presented for applications for other formations.« less

New fracturing technique for Dean sand

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

Pugh, T.D.; McDaniel, B.W.; Seglem, R.L.

1977-01-01

A new hydraulic fracturing technique is being applied to stimulate the Dean sand of the Spraberry trend area. Results show improvment in production, effective fracture length and lower treatment costs. Production history of several wells was reviewed, and results of this study were used to select certain design parameters. These were rate, type fluid, sand size, etc. New computer programs were used to correlate this data for selected volumes. The theory and application of the new technique is discussed, and a description of the Dean sand is presented in detail. Production results using the new method are compared with themore » wells' response to conventional treatments and considerations are presented for applications for other formations.« less

Improving neuromodulation technique for refractory voiding dysfunctions: two-stage implant.

PubMed

Janknegt, R A; Weil, E H; Eerdmans, P H

1997-03-01

Neuromodulation is a new technique that uses electrical stimulation of the sacral nerves for patients with refractory urinary urge/frequency or urge-incontinence, and some forms of urinary retention. The limiting factor for receiving an implant is often a failure of the percutaneous nerve evaluation (PNE) test. Present publications mention only about a 50% success score for PNE of all patients, although the micturition diaries and urodynamic parameters are similar. We wanted to investigate whether PNE results improved by using a permanent electrode as a PNE test. This would show that improvement of the PNE technique is feasible. In 10 patients where the original PNE had failed to improve the micturition diary parameters more than 50%, a permanent electrode was implanted by operation. It was connected to an external stimulator. In those cases where the patients improved according to their micturition diary by more than 50% during a period of 4 days, the external stimulator was replaced by a permanent subcutaneous neurostimulator. Eight of the 10 patients had a good to very good result (60% to 90% improvement) during the testing period and received their implant 5 to 14 days after the first stage. The good results of the two-stage implant technique we used indicate that the development of better PNE electrodes may lead to an improvement of the testing technique and better selection between nonresponders and technical failures.

Evaluation of Intradural Stimulation Efficiency and Selectivity in a Computational Model of Spinal Cord Stimulation

PubMed Central

Howell, Bryan; Lad, Shivanand P.; Grill, Warren M.

2014-01-01

Spinal cord stimulation (SCS) is an alternative or adjunct therapy to treat chronic pain, a prevalent and clinically challenging condition. Although SCS has substantial clinical success, the therapy is still prone to failures, including lead breakage, lead migration, and poor pain relief. The goal of this study was to develop a computational model of SCS and use the model to compare activation of neural elements during intradural and extradural electrode placement. We constructed five patient-specific models of SCS. Stimulation thresholds predicted by the model were compared to stimulation thresholds measured intraoperatively, and we used these models to quantify the efficiency and selectivity of intradural and extradural SCS. Intradural placement dramatically increased stimulation efficiency and reduced the power required to stimulate the dorsal columns by more than 90%. Intradural placement also increased selectivity, allowing activation of a greater proportion of dorsal column fibers before spread of activation to dorsal root fibers, as well as more selective activation of individual dermatomes at different lateral deviations from the midline. Further, the results suggest that current electrode designs used for extradural SCS are not optimal for intradural SCS, and a novel azimuthal tripolar design increased stimulation selectivity, even beyond that achieved with an intradural paddle array. Increased stimulation efficiency is expected to increase the battery life of implantable pulse generators, increase the recharge interval of rechargeable implantable pulse generators, and potentially reduce stimulator volume. The greater selectivity of intradural stimulation may improve the success rate of SCS by mitigating the sensitivity of pain relief to malpositioning of the electrode. The outcome of this effort is a better quantitative understanding of how intradural electrode placement can potentially increase the selectivity and efficiency of SCS, which, in turn, provides predictions that can be tested in future clinical studies assessing the potential therapeutic benefits of intradural SCS. PMID:25536035

Optimization of geothermal well trajectory in order to minimize borehole failure

NASA Astrophysics Data System (ADS)

Dahrabou, A.; Valley, B.; Ladner, F.; Guinot, F.; Meier, P.

2017-12-01

In projects based on Enhanced Geothermal System (EGS) principle, deep boreholes are drilled to low permeability rock masses. As part of the completion operations, the permeability of existing fractures in the rock mass is enhanced by injecting large volumes of water. These stimulation treatments aim at achieving enough water circulation for heat extraction at commercial rates which makes the stimulation operations critical to the project success. The accurate placement of the stimulation treatments requires well completion with effective zonal isolation, and wellbore stability is a prerequisite to all zonal isolation techniques, be it packer sealing or cement placement. In this project, a workflow allowing a fast decision-making process for selecting an optimal well trajectory for EGS projects is developed. In fact, the well is first drilled vertically then based on logging data which are costly (100 KCHF/day), the direction in which the strongly deviated borehole section will be drilled needs to be determined in order to optimize borehole stability and to intersect the highest number of fractures that are oriented favorably for stimulation. The workflow applies to crystalline rock and includes an uncertainty and risk assessment framework. An initial sensitivity study was performed to identify the most influential parameters on borehole stability. The main challenge in these analyses is that the strength and stress profiles are unknown independently. Calibration of a geomechanical model on the observed borehole failure has been performed using data from the Basel Geothermal well BS-1. In a first approximation, a purely elastic-static analytical solution in combination with a purely cohesive failure criterion were used as it provides the most consistent prediction across failure indicators. A systematic analysis of the uncertainty on all parameters was performed to assess the reliability of the optimal trajectory selection. To each drilling scenario, failure probability and the associated risks, are computed stochastically. In addition, model uncertainty is assessed by confronting various failure modelling approaches to the available failure data from the Basel Project. Together, these results form the basis of an integrated workflow optimizing geothermal (EGS) well trajectory.

Modeling Fast-scan Cyclic Voltammetry Data from Electrically Stimulated Dopamine Neurotransmission Data Using QNsim1.0.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Wagner, Amy K

2017-06-05

Central dopaminergic (DAergic) pathways have an important role in a wide range of functions, such as attention, motivation, and movement. Dopamine (DA) is implicated in diseases and disorders including attention deficit hyperactivity disorder, Parkinson's disease, and traumatic brain injury. Thus, DA neurotransmission and the methods to study it are of intense scientific interest. In vivo fast-scan cyclic voltammetry (FSCV) is a method that allows for selectively monitoring DA concentration changes with fine temporal and spatial resolution. This technique is commonly used in conjunction with electrical stimulations of ascending DAergic pathways to control the impulse flow of dopamine neurotransmission. Although the stimulated DA neurotransmission paradigm can produce robust DA responses with clear morphologies, making them amenable for kinetic analysis, there is still much debate on how to interpret the responses in terms of their DA release and clearance components. To address this concern, a quantitative neurobiological (QN) framework of stimulated DA neurotransmission was recently developed to realistically model the dynamics of DA release and reuptake over the course of a stimulated DA response. The foundations of this model are based on experimental data from stimulated DA neurotransmission and on principles of neurotransmission adopted from various lines of research. The QN model implements 12 parameters related to stimulated DA release and reuptake dynamics to model DA responses. This work describes how to simulate DA responses using QNsim1.0 and also details principles that have been implemented to systematically discern alterations in the stimulated dopamine release and reuptake dynamics.

Efficacy of Selected Electrical Therapies on Chronic Low Back Pain: A Comparative Clinical Pilot Study.

PubMed

Rajfur, Joanna; Pasternok, Małgorzata; Rajfur, Katarzyna; Walewicz, Karolina; Fras, Beata; Bolach, Bartosz; Dymarek, Robert; Rosinczuk, Joanna; Halski, Tomasz; Taradaj, Jakub

2017-01-07

BACKGROUND In the currently available research publications on electrical therapy of low back pain, generally no control groups or detailed randomization were used, and such studies were often conducted with relatively small groups of patients, based solely on subjective questionnaires and pain assessment scales (lacking measurement methods to objectify the therapeutic progress). The available literature also lacks a comprehensive and large-scale clinical study. The purpose of this study was to assess the effects of treating low back pain using selected electrotherapy methods. The study assesses the influence of individual electrotherapeutic treatments on reduction of pain, improvement of the range of movement in lower section of the spine, and improvement of motor functions and mobility. MATERIAL AND METHODS The 127 patients qualified for the therapy (ultimately, 123 patients completed the study) and assigned to 6 comparison groups: A - conventional TENS, B - acupuncture-like TENS, C - high-voltage electrical stimulation, D - interferential current stimulation, E - diadynamic current, and F - control group. RESULTS The research showed that using electrical stimulation with interferential current penetrating deeper into the tissues results in a significant and more efficient elimination of pain, and an improvement of functional ability of patients suffering from low back pain on the basis of an analysis of both subjective and objective parameters. The TENS currents and high voltage were helpful, but not as effective. The use of diadynamic currents appears to be useless. CONCLUSIONS Selected electrical therapies (interferential current, TENS, and high voltage) appear to be effective in treating chronic low back pain.

Efficacy of Selected Electrical Therapies on Chronic Low Back Pain: A Comparative Clinical Pilot Study

PubMed Central

Rajfur, Joanna; Pasternok, Małgorzata; Rajfur, Katarzyna; Walewicz, Karolina; Fras, Beata; Bolach, Bartosz; Dymarek, Robert; Rosinczuk, Joanna; Halski, Tomasz; Taradaj, Jakub

2017-01-01

Background In the currently available research publications on electrical therapy of low back pain, generally no control groups or detailed randomization were used, and such studies were often conducted with relatively small groups of patients, based solely on subjective questionnaires and pain assessment scales (lacking measurement methods to objectify the therapeutic progress). The available literature also lacks a comprehensive and large-scale clinical study. The purpose of this study was to assess the effects of treating low back pain using selected electrotherapy methods. The study assesses the influence of individual electrotherapeutic treatments on reduction of pain, improvement of the range of movement in lower section of the spine, and improvement of motor functions and mobility. Material/Methods The 127 patients qualified for the therapy (ultimately, 123 patients completed the study) and assigned to 6 comparison groups: A – conventional TENS, B – acupuncture-like TENS, C – high-voltage electrical stimulation, D – interferential current stimulation, E – diadynamic current, and F – control group. Results The research showed that using electrical stimulation with interferential current penetrating deeper into the tissues results in a significant and more efficient elimination of pain, and an improvement of functional ability of patients suffering from low back pain on the basis of an analysis of both subjective and objective parameters. The TENS currents and high voltage were helpful, but not as effective. The use of diadynamic currents appears to be useless. Conclusions Selected electrical therapies (interferential current, TENS, and high voltage) appear to be effective in treating chronic low back pain. PMID:28062862

Closed-loop control of epileptiform activities in a neural population model using a proportional-derivative controller

NASA Astrophysics Data System (ADS)

Wang, Jun-Song; Wang, Mei-Li; Li, Xiao-Li; Ernst, Niebur

2015-03-01

Epilepsy is believed to be caused by a lack of balance between excitation and inhibitation in the brain. A promising strategy for the control of the disease is closed-loop brain stimulation. How to determine the stimulation control parameters for effective and safe treatment protocols remains, however, an unsolved question. To constrain the complex dynamics of the biological brain, we use a neural population model (NPM). We propose that a proportional-derivative (PD) type closed-loop control can successfully suppress epileptiform activities. First, we determine the stability of root loci, which reveals that the dynamical mechanism underlying epilepsy in the NPM is the loss of homeostatic control caused by the lack of balance between excitation and inhibition. Then, we design a PD type closed-loop controller to stabilize the unstable NPM such that the homeostatic equilibriums are maintained; we show that epileptiform activities are successfully suppressed. A graphical approach is employed to determine the stabilizing region of the PD controller in the parameter space, providing a theoretical guideline for the selection of the PD control parameters. Furthermore, we establish the relationship between the control parameters and the model parameters in the form of stabilizing regions to help understand the mechanism of suppressing epileptiform activities in the NPM. Simulations show that the PD-type closed-loop control strategy can effectively suppress epileptiform activities in the NPM. Project supported by the National Natural Science Foundation of China (Grant Nos. 61473208, 61025019, and 91132722), ONR MURI N000141010278, and NIH grant R01EY016281.

Effect of the selective phosphodiesterase type 5 inhibitor sildenafil on erectile dysfunction in the anesthetized dog.

PubMed

Carter, A J; Ballard, S A; Naylor, A M

1998-07-01

The effects of sildenafil, a highly selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase type 5, on erectile function in the anesthetized dog were evaluated. In pentobarbital-anesthetized dogs, increases in intracavernosal pressure in the corpus cavernosum and penile blood flow were induced by pelvic nerve stimulation over a frequency range of 1 to 16 hertz. The effects of increasing doses of sildenafil on electrically stimulated intracavernosal pressure, penile blood flow, blood pressure, and heart-rate were evaluated. In parallel experiments, the effects of the nitric oxide synthase inhibitor N omega-Nitro-L-Arginine (L-NOArg) on these same parameters also were assessed. The effects of nerve stimulation on intracavernosal pressure and blood flow to the penis were blocked by L-NOArg, 0.1-3 mg./kg., in a dose-related manner, confirming the important role of nitric oxide in producing erections. Sildenafil, 1-100 microg./kg administered intravenously, had no direct effect on intracavernosal pressure but potentiated the increase in intracavernosal pressure induced by nerve stimulation. This potentiation occurred at sildenafil plasma concentrations consistent with its relaxation effect on isolated human cavernosal tissue and its inhibition of phosphodiesterase type 5 in vitro. Sildenafil had no significant effect on blood pressure or heart rate. By inhibiting cyclic guanosine monophosphate-specific phosphodiesterase type 5, sildenafil augments the neuronal mechanism responsible for penile erection. This mechanism explains the significant improvements reported in the rigidity and duration of erections seen in patients with erectile dysfunction who have been treated with oral sildenafil.

Closed loop deep brain stimulation: an evolving technology.

PubMed

Hosain, Md Kamal; Kouzani, Abbas; Tye, Susannah

2014-12-01

Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.

Effects of stimulation parameters and electrode location on thresholds for epidural stimulation of cat motor cortex

NASA Astrophysics Data System (ADS)

Wongsarnpigoon, Amorn; Grill, Warren M.

2011-12-01

Epidural electrical stimulation (ECS) of the motor cortex is a developing therapy for neurological disorders. Both placement and programming of ECS systems may affect the therapeutic outcome, but the treatment parameters that will maximize therapeutic outcomes and minimize side effects are not known. We delivered ECS to the motor cortex of anesthetized cats and investigated the effects of electrode placement and stimulation parameters on thresholds for evoking motor responses in the contralateral forelimb. Thresholds were inversely related to stimulation frequency and the number of pulses per stimulus train. Thresholds were lower over the forelimb representation in motor cortex (primary site) than surrounding sites (secondary sites), and thresholds at sites <4 mm away from the primary site were significantly lower than at sites >4 mm away. Electrode location and montage influenced the effects of polarity on thresholds: monopolar anodic and cathodic thresholds were not significantly different over the primary site, cathodic thresholds were significantly lower than anodic thresholds over secondary sites and bipolar thresholds were significantly lower with the anode over the primary site than with the cathode over the primary site. A majority of bipolar thresholds were either between or equal to the respective monopolar thresholds, but several bipolar thresholds were greater than or less than the monopolar thresholds of both the anode and cathode. During bipolar stimulation, thresholds were influenced by both electric field superposition and indirect, synaptically mediated interactions. These results demonstrate the influence of stimulation parameters and electrode location during cortical stimulation, and these effects should be considered during the programming of systems for therapeutic cortical stimulation.

An Orientation Dependent Size Illusion Is Underpinned by Processing in the Extrastriate Visual Area, LO1

PubMed Central

Mikellidou, Kyriaki; Gouws, André D.; Clawson, Hannah; Thompson, Peter; Morland, Antony B.

2016-01-01

We use the simple, but prominent Helmholtz’s squares illusion in which a vertically striped square appears wider than a horizontally striped square of identical physical dimensions to determine whether functional magnetic resonance imaging (fMRI) BOLD responses in V1 underpin illusions of size. We report that these simple stimuli which differ in only one parameter, orientation, to which V1 neurons are highly selective elicited activity in V1 that followed their physical, not perceived size. To further probe the role of V1 in the illusion and investigate plausible extrastriate visual areas responsible for eliciting the Helmholtz squares illusion, we performed a follow-up transcranial magnetic stimulation (TMS) experiment in which we compared perceptual judgments about the aspect ratio of perceptually identical Helmholtz squares when no TMS was applied against selective stimulation of V1, LO1, or LO2. In agreement with fMRI results, we report that TMS of area V1 does not compromise the strength of the illusion. Only stimulation of area LO1, and not LO2, compromised significantly the strength of the illusion, consistent with previous research that LO1 plays a role in the processing of orientation information. These results demonstrate the involvement of a specific extrastriate area in an illusory percept of size. PMID:27733896

Evaluation of stimulation parameters on aortomyoplasty, using Latissimus Dorsi muscle in a goat model: an acute study.

PubMed

Hakami, A; Santamore, W P; Stremel, R W; Tobin, G; Hjortdal, V E

1999-08-01

Dynamic aortomyoplasty using Latissimus Dorsi muscle (LDM) has been shown to improve myocardial function. However, systematic examination of the effects of stimulation parameters on aortic wrap function has not been done. Thus, the present study measures the direct effect of stimulation voltage, pulse train duration, frequency of the pulses, and the duration of the stimulation delay from R wave on the aortic wrap function. In eight female goats, the left LDM was wrapped around the descending aorta. The muscle was then subjected to electrical stimulation, altering frequency of stimulation pulses (16.6, 20, 25, 33 and 50 Hz), amplitude (2, 4, 6, 8 and 10 V), and number of pulses (2, 4, 6, 8 and 10 pulses) in a train stimulation. Left ventricular, aortic pressure, and pressure generated by LDM on aorta (wrap pressure) was measured. The changes in hemodynamic parameters mentioned above were calculated and compared for different stimulation parameters during unassisted and assisted cardiac cycles. Aortomyoplasty counterpulsation using LDM provided significant improvement in wrap pressure (78 mmHg +/- 2), aortic diastolic pressure, and changes in aortic diastolic pressure from 2 to 4 V (P < 0.05). Further increase in amplitude did not make any significant improvements of the above mentioned parameters. Significant augmentation of wrap pressure (82 mmHg +/- 2), aortic diastolic pressure (79 mmHg +/- 3) and changes in aortic diastolic pressure (12 mmHg +/- 1) occurred at 6 pulses (P < 0.05). Other changes in number of pulses did not show any significant improvements. Significant improvement of wrap pressure (80 mmHg +/- 2), aortic diastolic pressure (73 mmHg +/- 3) and changes in aortic diastolic pressure (12 mmHg +/- 1) was observed with a frequency of 33 Hz. To examine a wide range of delays from the onset of the QRS complex to LDM stimulation, stimulation was delivered randomly. The exact delay was determined from the ECG signal and superimposed LDM stimulation pulses. In this study we present a new measurement, wrap pressure. We also present that in aortomyoplasty using LDM, the most significant improvement in wrap pressure, aortic diastolic pressure and changes in aortic diastolic pressure occurs when the stimulation consists of an amplitude of 4 V, a frequency of 33 Hz and a train stimulation of 6 pulses.

Deep Brain Stimulation of the Subthalamic Nucleus Parameter Optimization for Vowel Acoustics and Speech Intelligibility in Parkinson's Disease

ERIC Educational Resources Information Center

Knowles, Thea; Adams, Scott; Abeyesekera, Anita; Mancinelli, Cynthia; Gilmore, Greydon; Jog, Mandar

2018-01-01

Purpose: The settings of 3 electrical stimulation parameters were adjusted in 12 speakers with Parkinson's disease (PD) with deep brain stimulation of the subthalamic nucleus (STN-DBS) to examine their effects on vowel acoustics and speech intelligibility. Method: Participants were tested under permutations of low, mid, and high STN-DBS frequency,…

Transcranial electric and magnetic stimulation: technique and paradigms.

PubMed

Paulus, Walter; Peterchev, Angel V; Ridding, Michael

2013-01-01

Transcranial electrical and magnetic stimulation techniques encompass a broad physical variety of stimuli, ranging from static magnetic fields or direct current stimulation to pulsed magnetic or alternating current stimulation with an almost infinite number of possible stimulus parameters. These techniques are continuously refined by new device developments, including coil or electrode design and flexible control of the stimulus waveforms. They allow us to influence brain function acutely and/or by inducing transient plastic after-effects in a range from minutes to days. Manipulation of stimulus parameters such as pulse shape, intensity, duration, and frequency, and location, size, and orientation of the electrodes or coils enables control of the immediate effects and after-effects. Physiological aspects such as stimulation at rest or during attention or activation may alter effects dramatically, as does neuropharmacological drug co-application. Non-linear relationships between stimulus parameters and physiological effects have to be taken into account. © 2013 Elsevier B.V. All rights reserved.

[Mechanisms and applications of transcutaneous electrical nerve stimulation in analgesia].

PubMed

Tang, Zheng-Yu; Wang, Hui-Quan; Xia, Xiao-Lei; Tang, Yi; Peng, Wei-Wei; Hu, Li

2017-06-25

Transcutaneous electrical nerve stimulation (TENS), as a non-pharmacological and non-invasive analgesic therapy with low-cost, has been widely used to relieve pain in various clinical applications, by delivering current pulses to the skin area to activate the peripheral nerve fibers. Nevertheless, analgesia induced by TENS varied in the clinical practice, which could be caused by the fact that TENS with different stimulus parameters has different biological mechanisms in relieving pain. Therefore, to advance our understanding of TENS in various basic and clinical studies, we discussed (1) neurophysiological and biochemical mechanisms of TENS-induced analgesia; (2) relevant factors that may influence analgesic effects of TENS from the perspectives of stimulus parameters, including stimulated position, pulse parameters (current intensity, frequency, and pulse width), stimulus duration and used times in each day; and (3) applications of TENS in relieving clinical pain, including post-operative pain, chronic low back pain and labor pain. Finally, we propose that TENS may involve multiple and complex psychological neurophysiological mechanisms, and suggest that different analgesic effects of TENS with different stimulus parameters should be taken into consideration in clinical applications. In addition, to optimize analgesic effect, we recommend that individual-based TENS stimulation parameters should be designed by considering individual differences among patients, e.g., adaptively adjusting the stimulation parameters based on the dynamic ratings of patients' pain.

An Analysis of The Parameters Used In Speech ABR Assessment Protocols.

PubMed

Sanfins, Milaine D; Hatzopoulos, Stavros; Donadon, Caroline; Diniz, Thais A; Borges, Leticia R; Skarzynski, Piotr H; Colella-Santos, Maria Francisca

2018-04-01

The aim of this study was to assess the parameters of choice, such as duration, intensity, rate, polarity, number of sweeps, window length, stimulated ear, fundamental frequency, first formant, and second formant, from previously published speech ABR studies. To identify candidate articles, five databases were assessed using the following keyword descriptors: speech ABR, ABR-speech, speech auditory brainstem response, auditory evoked potential to speech, speech-evoked brainstem response, and complex sounds. The search identified 1288 articles published between 2005 and 2015. After filtering the total number of papers according to the inclusion and exclusion criteria, 21 studies were selected. Analyzing the protocol details used in 21 studies suggested that there is no consensus to date on a speech-ABR protocol and that the parameters of analysis used are quite variable between studies. This inhibits the wider generalization and extrapolation of data across languages and studies.

The Impact of Carrot Enriched in Iodine through Soil Fertilization on Iodine Concentration and Selected Biochemical Parameters in Wistar Rats.

PubMed

Piątkowska, Ewa; Kopeć, Aneta; Bieżanowska-Kopeć, Renata; Pysz, Mirosław; Kapusta-Duch, Joanna; Koronowicz, Aneta Agnieszka; Smoleń, Sylwester; Skoczylas, Łukasz; Ledwożyw-Smoleń, Iwona; Rakoczy, Roksana; Maślak, Edyta

2016-01-01

Iodine is one of the trace elements which are essential for mammalian life. The major objective of iodine biofortification of plants is to obtain food rich in this trace element, which may increase its consumption by various populations. Additionally, it may reduce the risk of iodine deficiency diseases. In this research for the first time we have assessed the bioavailability of iodine from raw or cooked carrot biofortified with this trace element on iodine concentration in selected tissues and various biochemical parameters as well as mRNA expression of some genes involved in iodine metabolism in Wistar rats. Statistically, a significantly higher iodine level was determined in urine, faeces and selected tissues of rats fed a diet containing biofortified raw carrot as compared to a diet without iodine and a diet containing control cooked carrot. Biofortified raw carrot significantly increased triiodothyronine concentration as compared to animals from other experimental groups. The highest thyroid stimulating hormone level was determined in rats fed control cooked carrots. mRNA expression of selected genes was affected by different dietary treatment in rats' hearts. Biofortified raw and cooked carrot could be taken into account as a potential source of iodine in daily diets to prevent iodine deficiency in various populations.

The Impact of Carrot Enriched in Iodine through Soil Fertilization on Iodine Concentration and Selected Biochemical Parameters in Wistar Rats

PubMed Central

Piątkowska, Ewa; Kopeć, Aneta; Bieżanowska-Kopeć, Renata; Pysz, Mirosław; Kapusta-Duch, Joanna; Koronowicz, Aneta Agnieszka; Smoleń, Sylwester; Skoczylas, Łukasz; Ledwożyw-Smoleń, Iwona; Rakoczy, Roksana; Maślak, Edyta

2016-01-01

Iodine is one of the trace elements which are essential for mammalian life. The major objective of iodine biofortification of plants is to obtain food rich in this trace element, which may increase its consumption by various populations. Additionally, it may reduce the risk of iodine deficiency diseases. In this research for the first time we have assessed the bioavailability of iodine from raw or cooked carrot biofortified with this trace element on iodine concentration in selected tissues and various biochemical parameters as well as mRNA expression of some genes involved in iodine metabolism in Wistar rats. Statistically, a significantly higher iodine level was determined in urine, faeces and selected tissues of rats fed a diet containing biofortified raw carrot as compared to a diet without iodine and a diet containing control cooked carrot. Biofortified raw carrot significantly increased triiodothyronine concentration as compared to animals from other experimental groups. The highest thyroid stimulating hormone level was determined in rats fed control cooked carrots. mRNA expression of selected genes was affected by different dietary treatment in rats’ hearts. Biofortified raw and cooked carrot could be taken into account as a potential source of iodine in daily diets to prevent iodine deficiency in various populations. PMID:27043135

Effects of an implantable two-channel peroneal nerve stimulator versus conventional walking device on spatiotemporal parameters and kinematics of hemiparetic gait.

PubMed

Kottink, Anke I R; Tenniglo, Martin J B; de Vries, Wiebe H K; Hermens, Hermie J; Buurke, Jaap H

2012-01-01

The aims of this study were: (i) to compare the neuro-prosthetic effect of implantable peroneal nerve stimulation to the orthotic effect of a standard of care intervention (no device, shoe or ankle foot orthosis) on walking, as assessed by spatiotemporal parameters; and (ii) to examine whether there is evidence of an enhanced lower-limb flexion reflex with peroneal nerve stimulation and compare the kinematic effect of an implantable peroneal nerve stimulation device vs standard of care intervention on initial loading response of the paretic limb, as assessed by hip, knee and ankle kinematics. Randomized controlled trial. A total of 23 chronic stroke survivors with drop foot. The intervention group received an implantable 2-channel peroneal nerve stimulator for correction of drop foot. The control group continued using a conventional walking device. Spatiotemporal parameters and hip, knee and ankle kinematics were measured while subjects walked with the device on using a 3-dimensional video camera system during baseline and after a follow-up period of 26 weeks. Peroneal nerve stimulation normalized stance and double support of the paretic limb and single support of the non-paretic limb, in comparison with using a conventional walking device. In addition, peroneal nerve stimulation is more effective to provide ankle dorsiflexion during swing and resulted in a normalized initial loading response. Although peroneal nerve stimulation and ankle foot orthosis are both prescribed to correct a drop foot in the same patient population, spatiotemporal parameters, dorsiflexion during swing and loading response are influenced in a functionally different way.

Stimulating at the right time: phase-specific deep brain stimulation.

PubMed

Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

2017-01-01

SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Stimulating at the right time: phase-specific deep brain stimulation

PubMed Central

Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

2017-01-01

Abstract See Moll and Engel (doi:10.1093/aww308) for a scientific commentary on this article. Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson’s disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient’s tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. PMID:28007997

Profile of peripheral blood neutrophil cytokines in diabetes type 1 pregnant women and its correlation with selected parameters in the newborns.

PubMed

Pertyńska-Marczewska, Magdalena; Głowacka, Ewa; Grodzicka, Alicja; Sobczak, Małgorzata; Cypryk, Katarzyna; Wilczyński, Jacek R; Wilczyński, Jan

2010-02-01

Interleukin (IL)-12, IL-10, tumor necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 alter as pregnancy progresses, implying continuous immune regulation associated with the maintenance of pregnancy. We aimed to evaluate the peripheral blood neutrophil-derived production of these cytokines in the course of pregnancy complicated by type 1 diabetes. of study These parameters were measured in samples from healthy non-pregnant (C), diabetic non-pregnant (D), healthy pregnant (P) and pregnant diabetic (PD) women. Neutrophil-derived secretion of TNF-alpha and IL-12 increased along with progression of pregnancy in PD and P groups. The concentration of IL-10 from lipopolysaccharide (LPS)-stimulated neutrophils increased during the course of uncomplicated pregnancy but decreased in diabetic pregnancy. Concentration of IL-8 decreased with the advancing gestational age in P and PD groups. LPS-stimulated neutrophil-derived IL-6 concentration increased only in PD patients. Our results show that diabetes creates pro-inflammatory environment thus potentially influencing the outcome of pregnancy. We conclude that neutrophil-derived cytokine production could contribute to the complications seen in pregnant women with type 1 diabetes.

Nerve monitoring-guided selective hypoglossal nerve stimulation in obstructive sleep apnea patients.

PubMed

Heiser, Clemens; Hofauer, Benedikt; Lozier, Luke; Woodson, B Tucker; Stark, Thomas

2016-12-01

Selective stimulation of the upper airway is a new therapy for obstructive sleep apnea. The aim of the study was to determine if a selective nerve integrity monitoring (NIM) system could aid in precise placement of the cuff electrode in selective upper-airway stimulation. Single-center, prospective clinical trial. Twenty patients who received a selective upper-airway stimulation system (Inspire Medical Systems, Maple Grove, MN) were implanted by using a NIM system. The tongue motions were recorded during surgery and 2 months postoperatively from the transoral view and by transnasal endoscopy. All patients exhibited consistent protrusion at tongue front and tongue base. The nerve monitoring system helped to place the cuff electrode around the protrusion and stiffening branches, while excluding the retractor branches of the hypoglossal nerve. This report demonstrated a novel use of a NIM system to identify the functional separation between inclusion and exclusion branches of the hypoglossal nerve for implantation of a selective upper-airway stimulation system. 4. Laryngoscope, 126:2852-2858, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

The development and validation of a LIPUS system with preliminary observations of ultrasonic effects on human adult stem cells.

PubMed

Marvel, Skylar; Okrasinski, Stan; Bernacki, Susan H; Loboa, Elizabeth; Dayton, Paul A

2010-09-01

To study the potential effects of low-intensity pulsed ultrasound (LIPUS) on cell response in vitro, the ability to alter LIPUS parameters is required. However, commercial LIPUS systems have very little control over parameter selection. In this study, a custom LIPUS system was designed and validated by exploring the effects of using different pulse repetition frequency (PRF) parameters on human adipose derived adult stem cells (hASCs) and bone marrow derived mesenchymal stem cells (hMSCs), two common stem cell sources for creating bone constructs in vitro. Changing the PRF was found to affect cellular response to LIPUS stimulation for both cell types. Proliferation of LIPUS-stimulated cells was found to decrease for hASCs by d 7 for all three groups compared with unstimulated control cells (P = 0.008, 0.011, 0.014 for 1 Hz, 100 Hz and 1 kHz PRF, respectively) and for hMSCs by d 14 (donor 1: P = 0.0005, 0.0002, 0.0003; donor 2: P = 0.0003, 0.0002, 0.0001; for PRFs of 1 Hz, 100 Hz, and 1 kHz, respectively). Additionally, LIPUS was shown to strongly accelerate osteogenic differentiation of hASCs based on amount of calcium accretion normalized by total DNA (P = 0.003, 0.001, 0.003, and 0.032 between control/100 Hz, control/1 kHz, 1 Hz/1 kHz, and 100 Hz/1 kHz pulse repetition frequencies, respectively). These findings promote the study of using LIPUS to induce osteogenic differentiation and further encourage the exploration of LIPUS parameter optimization. The custom LIPUS system was successfully designed to allow extreme parameter variation, specifically PRF, and encourages further studies.

Selecting electrode configurations for image-guided cochlear implant programming using template matching

NASA Astrophysics Data System (ADS)

Zhang, Dongqing; Zhao, Yiyuan; Noble, Jack H.; Dawant, Benoit M.

2017-03-01

Cochlear implants (CIs) are used to treat patients with severe-to-profound hearing loss. In surgery, an electrode array is implanted in the cochlea. After implantation, the CI processor is programmed by an audiologist. One factor that negatively impacts outcomes and can be addressed by programming is cross-electrode neural stimulation overlap (NSO). In the recent past, we have proposed a system to assist the audiologist in programming the CI that we call Image-Guided CI Programming (IGCIP). IGCIP permits using CT images to detect NSO and recommend which subset of electrodes should be active to avoid NSO. In an ongoing clinical study, we have shown that IGCIP leads to significant improvement in hearing outcomes. Most of the IGCIP steps are robustly automated but electrode configuration selection still sometimes requires expert intervention. With expertise, Distance-Vs-Frequency (DVF) curves, which are a way to visualize the spatial relationship learned from CT between the electrodes and the nerves they stimulate, can be used to select the electrode configuration. In this work, we propose an automated technique for electrode configuration selection. It relies on matching new patients' DVF curves to a library of DVF curves for which electrode configurations are known. We compare this approach to one we have previously proposed. We show that, generally, our new method produces results that are as good as those obtained with our previous one while being generic and requiring fewer parameters.

Cerebellar theta-burst stimulation selectively enhances lexical associative priming.

PubMed

Argyropoulos, Giorgos P

2011-09-01

Recent research in cerebellar cognitive and linguistic functions makes plausible the idea that the cerebellum is involved in processing temporally contiguous linguistic input. In order to assess this hypothesis, a simple lexical decision task was constructed to study whether the effect of transcranial magnetic stimulation on two different cerebellar sites would have a selective impact on associative as opposed to semantic priming. This is the first experiment applying transcranial magnetic stimulation of the cerebellum to a linguistic task. The results show a selective drop in lexical decision accuracy after stimulation of a medial cerebellar site in the first session of participation. Most importantly, they also demonstrate a selective increase of associative priming sizes after stimulation of the same site that cannot be attributed to changes in sensorimotor performance or in accuracy rates. The finding is discussed within the context of domain-general associative cerebellar computations.

Long-term effect of sphincteric fatigue during bladder neurostimulation.

PubMed

Li, J S; Hassouna, M; Sawan, M; Duval, F; Elhilali, M M

1995-01-01

Commercially available stimulators lack several features, including multiple channel capability and flexible stimulation parameters. These factors limit clinical application. A new computerized electrical stimulator system was developed by our team and evaluated for its efficacy in bladder evacuation in an animal model after spinal cord transection. The system can generate a wide range of stimulation characteristics and has the feature of being a programmable multichannel pacemaker. It has enabled us to induce a reversible fatigue to the external sphincter that results in proper bladder emptying on stimulation. Using this new bladder pacemaker, 8 dogs were studied. We applied the concept of fatiguing of the external sphincter via the pudendal nerve to avoid rhizotomy. We determined the optimal stimulation parameters that can reliably empty the dog's bladder for the duration of the experiment, which lasted for 8 months. The new computerized electrical stimulation system achieved the objective of reducing bladder outlet resistance without the need for sacral rhizotomy.

Myoelectric intuitive control and transcutaneous electrical stimulation of the forearm for vibrotactile sensation feedback applied to a 3D printed prosthetic hand.

PubMed

Germany, Enrique I; Pino, Esteban J; Aqueveque, Pablo E

2016-08-01

This paper presents the development of a myoelectric prosthetic hand based on a 3D printed model. A myoelectric control strategy based on artificial neural networks is implemented on a microcontroller for online position estimation. Position estimation performance achieves a correlation index of 0.78. Also a study involving transcutaneous electrical stimulation was performed to provide tactile feedback. A series of stimulations with controlled parameters were tested on five able-body subjects. A single channel stimulator was used, positioning the electrodes 8 cm on the wrist over the ulnar and median nerve. Controlling stimulation parameters such as intensity, frequency and pulse width, the subjects were capable of distinguishing different sensations over the palm of the hand. Three main sensations where achieved: tickling, pressure and pain. Tickling and pressure were discretized into low, moderate and high according to the magnitude of the feeling. The parameters at which each sensation was obtained are further discussed in this paper.

Use of electroacupuncture and transcutaneous electrical acupoint stimulation in reproductive medicine: a group consensus.

PubMed

Qu, Fan; Li, Rong; Sun, Wei; Lin, Ge; Zhang, Rong; Yang, Jing; Tian, Li; Xing, Guo-Gang; Jiang, Hui; Gong, Fei; Liang, Xiao-Yan; Meng, Yan; Liu, Jia-Yin; Zhou, Li-Ying; Wang, Shu-Yu; Wu, Yan; He, Yi-Jing; Ye, Jia-Yu; Han, Song-Ping; Han, Ji-Sheng

With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS), become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of EA/TEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/TEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome (PCOS), pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligospermia/ asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.

Vestibular evoked myogenic potential (Vemp): evaluation of responses in normal subjects.

PubMed

Felipe, Lilian; Santos, Marco Aurélio Rocha; Gonçalves, Denise Utsch

2008-01-01

the Vestibular Evoked Myogenic Potential (Vemp) is formed by myogenic neurophysiologic responses activated by high-intensity sound stimulation. The response is registered through surface electromyography of the cervical muscles during muscle contraction. The acoustic stimuli activate the saccular macula, the vestibular inferior nerve and the pathways related to the vestibule-spinal descendant nerves. to describe Vemp parameters in a normal population. thirty adults, 13 men and 17 women with no otoneurological complaints were selected. The stimuli were 200 tone burst, with a frequency of 1Hz and intensity of 118 dB Na, band-pass filter ranging from 10Hz to 1500Hz. The first potential biphasic P13-N23 wave was analyzed. no significant difference was observed between the sides of stimulation in terms of latency and amplitude. However, a statistically significant difference was found for amplitude between genders. Vemp demonstrated to be a reliable instrument in the clinical assessment of the vestibular function.

Synthesis and characterization of luminescent materials for thermal sensing and proton dosimetry

NASA Astrophysics Data System (ADS)

Doull, Brandon Arthur

The work presented in this thesis is the materials synthesis, investigation of synthesis parameters, and basic luminescent characterizations of MgB 4O7, Li2B4O7, and MgO for the applications of thermal sensing using thermoluminescence (TL) and proton dosimetry using optically stimulated luminescence (OSL). The materials were synthesized using solution combustion synthesis and characterized by x-ray diffraction, radioluminescence, thermoluminescence, and optically stimulated luminescence. Based upon the basic characterizations MgB 4O7:Li,Dy and Li2B4O7:Cu,Ag were selected for their potential for use as TL materials for thermal sensing while MgB4O7:Li,Ce and MgO:Li were chosen for use as OSL materials in proton dosimetry. Furthermore, MgB4O7:Li,Ce and MgO:Li were fabricated into detector assemblies and exposed to a clinical proton beam for analysis.

Acute damage threshold for infrared neural stimulation of the cochlea: functional and histological evaluation.

PubMed

Goyal, Vinay; Rajguru, Suhrud; Matic, Agnella I; Stock, Stuart R; Richter, Claus-Peter

2012-11-01

This article provides a mini review of the current state of infrared neural stimulation (INS), and new experimental results concerning INS damage thresholds. INS promises to be an attractive alternative for neural interfaces. With this method, one can attain spatially selective neural stimulation that is not possible with electrical stimulation. INS is based on the delivery of short laser pulses that result in a transient temperature increase in the tissue and depolarize the neurons. At a high stimulation rate and/or high pulse energy, the method bears the risk of thermal damage to the tissue from the instantaneous temperature increase or from potential accumulation of thermal energy. With the present study, we determined the injury thresholds in guinea pig cochleae for acute INS using functional measurements (compound action potentials) and histological evaluation. The selected laser parameters for INS were the wavelength (λ = 1,869 nm), the pulse duration (100 μs), the pulse repetition rate (250 Hz), and the radiant energy (0-127 μJ/pulse). For up to 5 hr of continuous irradiation at 250 Hz and at radiant energies up to 25 μJ/pulse, we did not observe any functional or histological damage in the cochlea. Functional loss was observed for energies above 25 μJ/pulse and the probability of injury to the target tissue resulting in functional loss increased with increasing radiant energy. Corresponding cochlear histology from control animals and animals exposed to 98 or 127 μJ/pulse at 250 Hz pulse repetition rate did not show a loss of spiral ganglion cells, hair cells, or other soft tissue structures of the organ of Corti. Light microscopy did not reveal any structural changes in the soft tissue either. Additionally, microcomputed tomography was used to visualize the placement of the optical fiber within the cochlea. Copyright © 2012 Wiley Periodicals, Inc.

Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory.

PubMed

Censor, Nitzan; Cohen, Leonardo G

2011-01-01

In the last two decades, there has been a rapid development in the research of the physiological brain mechanisms underlying human motor learning and memory. While conventional memory research performed on animal models uses intracellular recordings, microfusion of protein inhibitors to specific brain areas and direct induction of focal brain lesions, human research has so far utilized predominantly behavioural approaches and indirect measurements of neural activity. Repetitive transcranial magnetic stimulation (rTMS), a safe non-invasive brain stimulation technique, enables the study of the functional role of specific cortical areas by evaluating the behavioural consequences of selective modulation of activity (excitation or inhibition) on memory generation and consolidation, contributing to the understanding of the neural substrates of motor learning. Depending on the parameters of stimulation, rTMS can also facilitate learning processes, presumably through purposeful modulation of excitability in specific brain regions. rTMS has also been used to gain valuable knowledge regarding the timeline of motor memory formation, from initial encoding to stabilization and long-term retention. In this review, we summarize insights gained using rTMS on the physiological and neural mechanisms of human motor learning and memory. We conclude by suggesting possible future research directions, some with direct clinical implications.

Motor Cortex Stimulation in Patients Suffering from Chronic Neuropathic Pain: Summary of Expert Meeting and Premeeting Questionnaire, Combined with Literature Review.

PubMed

Kurt, Erkan; Henssen, Dylan J H A; Steegers, Monique; Staal, Michiel; Beese, Ulrich; Maarrawi, Joseph; Pirotte, Benoit; Garcia-Larrea, Luis; Rasche, Dirk; Vesper, Jan; Holsheimer, Jan; Duyvendak, Wim; Herregodts, Patrick; van Dongen, Robert; Moens, Maarten

2017-12-01

Motor cortex stimulation (MCS) was introduced in the early 1990s by Tsubokawa and his group for patients diagnosed with drug-resistant, central neuropathic pain. Inconsistencies concerning the details of this therapy and its outcomes and poor methodology of most clinical essays divide the neuromodulation society worldwide into "believers" and "nonbelievers." A European expert meeting was organized in Brussels, Belgium by the Benelux Neuromodulation Society in order to develop uniform MCS protocols in the preoperative, intraoperative, and postoperative courses. An expert meeting was organized, and a questionnaire was sent out to all the invited participants before this expert meeting. An extensive literature research was conducted in order to enrich the results. Topics that were addressed during the expert meeting were 1) inclusion and exclusion criteria, 2) targeting and methods of stimulation, 3) effects of MCS, and 4) results from the questionnaire. Substantial commonalities but also important methodologic divergencies emerged from the discussion of MCS experts from 7 European Centers. From this meeting and questionnaire, all participants concluded that there is a need for more homogenous standardized protocols for MCS regarding patient selection, implantation procedure, stimulation parameters, and follow-up-course. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional screening identifies miRNAs inducing cardiac regeneration.

PubMed

Eulalio, Ana; Mano, Miguel; Dal Ferro, Matteo; Zentilin, Lorena; Sinagra, Gianfranco; Zacchigna, Serena; Giacca, Mauro

2012-12-20

In mammals, enlargement of the heart during embryonic development is primarily dependent on the increase in cardiomyocyte numbers. Shortly after birth, however, cardiomyocytes stop proliferating and further growth of the myocardium occurs through hypertrophic enlargement of the existing myocytes. As a consequence of the minimal renewal of cardiomyocytes during adult life, repair of cardiac damage through myocardial regeneration is very limited. Here we show that the exogenous administration of selected microRNAs (miRNAs) markedly stimulates cardiomyocyte proliferation and promotes cardiac repair. We performed a high-content microscopy, high-throughput functional screening for human miRNAs that promoted neonatal cardiomyocyte proliferation using a whole-genome miRNA library. Forty miRNAs strongly increased both DNA synthesis and cytokinesis in neonatal mouse and rat cardiomyocytes. Two of these miRNAs (hsa-miR-590 and hsa-miR-199a) were further selected for testing and were shown to promote cell cycle re-entry of adult cardiomyocytes ex vivo and to promote cardiomyocyte proliferation in both neonatal and adult animals. After myocardial infarction in mice, these miRNAs stimulated marked cardiac regeneration and almost complete recovery of cardiac functional parameters. The miRNAs identified hold great promise for the treatment of cardiac pathologies consequent to cardiomyocyte loss.

A low-cost multichannel wireless neural stimulation system for freely roaming animals

NASA Astrophysics Data System (ADS)

Alam, Monzurul; Chen, Xi; Fernandez, Eduardo

2013-12-01

Objectives. Electrical stimulation of nerve tissue and recording of neural activity are the basis of many therapies and neural prostheses. Conventional stimulation systems have a number of practical limitations, especially in experiments involving freely roaming subjects. Our main objective was to develop a modular, versatile and inexpensive multichannel wireless system able to overcome some of these constraints. Approach. We have designed and implemented a new multichannel wireless neural stimulator based on commercial components. The system is small (2 cm × 4 cm × 0.5 cm) and light in weight (9 g) which allows it to be easily carried in a small backpack. To test and validate the performance and reliability of the whole system we conducted several bench tests and in vivo experiments. Main results. The performance and accuracy of the stimulator were comparable to commercial threaded systems. Stimulation sequences can be constructed on-the-fly with 251 selectable current levels (from 0 to 250 µA) with 1 µA step resolution. The pulse widths and intervals can be as long as 65 ms in 2 µs time resolution. The system covers approximately 10 m of transmission range in a regular laboratory environment and 100 m in free space (line of sight). Furthermore it provides great flexibility for experiments since it allows full control of the stimulator and the stimulation parameters in real time. When there is no stimulation, the device automatically goes into low-power sleep mode to preserve battery power. Significance. We introduce the design of a powerful multichannel wireless stimulator assembled from commercial components. Key features of the system are their reliability, robustness and small size. The system has a flexible design that can be modified straightforwardly to tailor it to any specific experimental need. Furthermore it can be effortlessly adapted for use with any kind of multielectrode arrays.

Photobiomodulation of distinct lineages of human dermal fibroblasts: a rational approach towards the selection of effective light parameters for skin rejuvenation and wound healing

NASA Astrophysics Data System (ADS)

Mignon, Charles; Uzunbajakava, Natallia E.; Raafs, Bianca; Moolenaar, Mitchel; Botchkareva, Natalia V.; Tobin, Desmond J.

2016-03-01

Distinct lineages of human dermal fibroblasts play complementary roles in skin rejuvenation and wound healing, which makes them a target of phototherapy. However, knowledge about differential responses of specific cell lineages to different light parameters and moreover the actual molecular targets remain to be unravelled. The goal of this study was to investigate the impact of a range of parameters of light on the metabolic activity, collagen production, and cell migration of distinct lineages of human dermal fibroblasts. A rational approach was used to identify parameters with high therapeutic potential. Fibroblasts exhibited both inhibitory and cytotoxic change when exposed to a high dose of blue and cyan light in tissue culture medium containing photo-reactive species, but were stimulated by high dose red and near infrared light. Cytotoxic effects were eliminated by refreshing the medium after light exposure by removing potential ROS formed by extracellular photo-reactive species. Importantly, distinct lineages of fibroblasts demonstrated opposite responses to low dose blue light treatment when refreshing the medium after exposure. Low dose blue light treatment also significantly increased collagen production by papillary fibroblasts; high dose significantly retarded closure of the scratch wound without signs of cytotoxicity, and this is likely to have involved effects on both cell migration and proliferation. We recommend careful selection of fibroblast subpopulations and their culture conditions, a systematic approach in choosing and translating treatment parameters, and pursuit of fundamental research on identification of photoreceptors and triggered molecular pathways, while seeking effective parameters to address different stages of skin rejuvenation and wound healing.

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

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

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

1996-12-31

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

Flow-injection analysis of catecholamine secretion from bovine adrenal medulla cells on microbeads.

PubMed

Herrera, M; Kao, L S; Curran, D J; Westhead, E W

1985-01-01

Bovine adrenal medullary cells have been cultured on microbeads which are placed in a low-volume flow system for measurements of stimulation-response parameters. Electronically controlled stream switching allows stimulation of cells with pulse lengths from 1 s to many minutes; pulses may be repeated indefinitely. Catecholamines secreted are detected by an electrochemical detector downstream from the cells. This flow-injection analysis technique provides a new level of sensitivity and precision for measurement of kinetic parameters of secretion. A manual injection valve allows stimulation by higher levels of stimulant in the presence of constant low levels of stimulant. Such experiments show interesting differences between the effects of K+ and acetylcholine on cells partially desensitized to acetylcholine.

Dorsal column stimulator applications

PubMed Central

Yampolsky, Claudio; Hem, Santiago; Bendersky, Damián

2012-01-01

Background: Spinal cord stimulation (SCS) has been used to treat neuropathic pain since 1967. Following that, technological progress, among other advances, helped SCS become an effective tool to reduce pain. Methods: This article is a non-systematic review of the mechanism of action, indications, results, programming parameters, complications, and cost-effectiveness of SCS. Results: In spite of the existence of several studies that try to prove the mechanism of action of SCS, it still remains unknown. The mechanism of action of SCS would be based on the antidromic activation of the dorsal column fibers, which activate the inhibitory interneurons within the dorsal horn. At present, the indications of SCS are being revised constantly, while new applications are being proposed and researched worldwide. Failed back surgery syndrome (FBSS) is the most common indication for SCS, whereas, the complex regional pain syndrome (CRPS) is the second one. Also, this technique is useful in patients with refractory angina and critical limb ischemia, in whom surgical or endovascular treatment cannot be performed. Further indications may be phantom limb pain, chronic intractable pain located in the head, face, neck, or upper extremities, spinal lumbar stenosis in patients who are not surgical candidates, and others. Conclusion: Spinal cord stimulation is a useful tool for neuromodulation, if an accurate patient selection is carried out prior, which should include a trial period. Undoubtedly, this proper selection and a better knowledge of its underlying mechanisms of action, will allow this cutting edge technique to be more acceptable among pain physicians. PMID:23230533

Evidence Gaps in the Use of Spinal Cord Stimulation for Treating Chronic Spine Conditions.

PubMed

Provenzano, David A; Amirdelfan, Kasra; Kapural, Leonardo; Sitzman, B Todd

2017-07-15

A review of literature. The aim of this study was to define and explore the current evidence gaps in the use of spinal cord stimulation (SCS) for treating chronic spine conditions. Although over the last 40 years SCS therapy has undergone significant technological advancements, evidence gaps still exist. A literature review was conducted to define current evidence gaps for the use of SCS. Areas of focus included 1) treatment of cervical spine conditions, 2) treatment of lumbar spine conditions, 3) technological advancement and device selection, 4) appropriate patient selection, 5) the ability to curb pharmacological treatment, and 6) methods to prolong efficacy over time. New SCS strategies using advanced waveforms are explored. The efficacy, safety, and cost-effectiveness of traditional SCS for chronic pain conditions are well-established. Evidence gaps do exist. Recently, advancement in waveforms and programming parameters have allowed for paresthesia-reduced/free stimulation that in specific clinical areas may improve clinical outcomes. New waveforms such as 10-kHz high-frequency have resulted in an improvement in back coverage. To date, clinical efficacy data are more prevalent for the treatment of painful conditions originating from the lumbar spine in comparison to the cervical spine. Evidence gaps still exist that require appropriate study designs with long-term follow-up to better define and improve the use of this therapy for the treatment of chronic spine pain in both the cervical and lumbar regions. N/A.

Selective stimulation of facial muscles with a penetrating electrode array in the feline model

PubMed Central

Sahyouni, Ronald; Bhatt, Jay; Djalilian, Hamid R.; Tang, William C.; Middlebrooks, John C.; Lin, Harrison W.

2017-01-01

Objective Permanent facial nerve injury is a difficult challenge for both patients and physicians given its potential for debilitating functional, cosmetic, and psychological sequelae. Although current surgical interventions have provided considerable advancements in facial nerve rehabilitation, they often fail to fully address all impairments. We aim to introduce an alternative approach to facial nerve rehabilitation. Study design Acute experiments in animals with normal facial function. Methods The study included three anesthetized cats. Four facial muscles (levator auris longus, orbicularis oculi, nasalis, and orbicularis oris) were monitored with a standard electromyographic (EMG) facial nerve monitoring system with needle electrodes. The main trunk of the facial nerve was exposed and a 16-channel penetrating electrode array was placed into the nerve. Electrical current pulses were delivered to each stimulating electrode individually. Elicited EMG voltage outputs were recorded for each muscle. Results Stimulation through individual channels selectively activated restricted nerve populations, resulting in selective contraction of individual muscles. Increasing stimulation current levels resulted in increasing EMG voltage responses. Typically, selective activation of two or more distinct muscles was successfully achieved via a single placement of the multi-channel electrode array by selection of appropriate stimulation channels. Conclusion We have established in the animal model the ability of a penetrating electrode array to selectively stimulate restricted fiber populations within the facial nerve and to selectively elicit contractions in specific muscles and regions of the face. These results show promise for the development of a facial nerve implant system. PMID:27312936

Matching initial torque with different stimulation parameters influences skeletal muscle fatigue.

PubMed

Bickel, C Scott; Gregory, Chris M; Azuero, Andres

2012-01-01

A fundamental barrier to using electrical stimulation in the clinical setting is an inability to maintain torque production secondary to muscle fatigue. Electrical stimulation parameters are manipulated to influence muscle torque production, and they may also influence fatigability during repetitive stimulation. Our purpose was to determine the response of the quadriceps femoris to three different fatigue protocols using the same initial torque obtained by altering stimulator parameter settings. Participants underwent fatigue protocols in which either pulse frequency (lowHz), pulse duration (lowPD), or voltage (lowV) was manipulated to obtain an initial torque that equaled 25% of maximum voluntary isometric contraction. Muscle soreness was reported on a visual analog scale 48 h after each fatigue test. The lowHz protocol resulted in the least fatigue (25% +/- 14%); the lowPD (50% +/- 13%) and lowV (48% +/- 14%) protocols had similar levels of fatigue. The lowHz protocol resulted in significantly less muscle soreness than the higher frequency protocols. Stimulation protocols that use a lower frequency coupled with long pulse durations and high voltages result in lesser amounts of muscle fatigue and perceived soreness. The identification of optimal stimulation patterns to maximize muscle performance will reduce the effect of muscle fatigue and potentially improve clinical efficacy.

Synchronization of coupled different chaotic FitzHugh-Nagumo neurons with unknown parameters under communication-direction-dependent coupling.

PubMed

Iqbal, Muhammad; Rehan, Muhammad; Khaliq, Abdul; Saeed-ur-Rehman; Hong, Keum-Shik

2014-01-01

This paper investigates the chaotic behavior and synchronization of two different coupled chaotic FitzHugh-Nagumo (FHN) neurons with unknown parameters under external electrical stimulation (EES). The coupled FHN neurons of different parameters admit unidirectional and bidirectional gap junctions in the medium between them. Dynamical properties, such as the increase in synchronization error as a consequence of the deviation of neuronal parameters for unlike neurons, the effect of difference in coupling strengths caused by the unidirectional gap junctions, and the impact of large time-delay due to separation of neurons, are studied in exploring the behavior of the coupled system. A novel integral-based nonlinear adaptive control scheme, to cope with the infeasibility of the recovery variable, for synchronization of two coupled delayed chaotic FHN neurons of different and unknown parameters under uncertain EES is derived. Further, to guarantee robust synchronization of different neurons against disturbances, the proposed control methodology is modified to achieve the uniformly ultimately bounded synchronization. The parametric estimation errors can be reduced by selecting suitable control parameters. The effectiveness of the proposed control scheme is illustrated via numerical simulations.

Electric stimulation of the tuberomamillary nucleus affects epileptic activity and sleep-wake cycle in a genetic absence epilepsy model.

PubMed

Blik, Vitaliya

2015-01-01

Deep brain stimulation (DBS) is a promising approach for epilepsy treatment, but the optimal targets and parameters of stimulation are yet to be investigated. Tuberomamillary nucleus (TMN) is involved in EEG desynchronization-one of the proposed mechanisms for DBS action. We studied whether TMN stimulation could interfere with epileptic spike-wave discharges (SWDs) in WAG/Rij rats with inherited absence epilepsy and whether such stimulation would affect sleep-wake cycle. EEG and video registration were used to determine SWD occurrence and stages of sleep and wake during three-hours recording sessions. Stimulation (100Hz) was applied in two modes: closed-loop (with previously determined interruption threshold intensity) or open-loop mode (with 50% or 70% threshold intensity). Closed-loop stimulation successfully interrupted SWDs but elevated their number by 148 ± 54% compared to baseline. It was accompanied by increase in number of episodes but not total duration of both active and passive wakefulness. Open-loop stimulation with amplitude 50% threshold did not change measured parameters, though 70% threshold stimulation reduced SWDs number by 40 ± 9%, significantly raised the amount of active wakefulness and decreased the amount of both slow-wave and rapid eye movement sleep. These results suggest that the TMN is unfavorable as a target for DBS as its stimulation may cause alterations in sleep-wake cycle. A careful choosing of parameters and control of sleep-wake activity is necessary when applying DBS in epilepsy. Copyright © 2014 Elsevier B.V. All rights reserved.

New stimulation pattern design to improve P300-based matrix speller performance at high flash rate

NASA Astrophysics Data System (ADS)

Polprasert, Chantri; Kukieattikool, Pratana; Demeechai, Tanee; Ritcey, James A.; Siwamogsatham, Siwaruk

2013-06-01

Objective. We propose a new stimulation pattern design for the P300-based matrix speller aimed at increasing the minimum target-to-target interval (TTI). Approach. Inspired by the simplicity and strong performance of the conventional row-column (RC) stimulation, the proposed stimulation is obtained by modifying the RC stimulation through alternating row and column flashes which are selected based on the proposed design rules. The second flash of the double-flash components is then delayed for a number of flashing instants to increase the minimum TTI. The trade-off inherited in this approach is the reduced randomness within the stimulation pattern. Main results. We test the proposed stimulation pattern and compare its performance in terms of selection accuracy, raw and practical bit rates with the conventional RC flashing paradigm over several flash rates. By increasing the minimum TTI within the stimulation sequence, the proposed stimulation has more event-related potentials that can be identified compared to that of the conventional RC stimulations, as the flash rate increases. This leads to significant performance improvement in terms of the letter selection accuracy, the raw and practical bit rates over the conventional RC stimulation. Significance. These studies demonstrate that significant performance improvement over the RC stimulation is obtained without additional testing or training samples to compensate for low P300 amplitude at high flash rate. We show that our proposed stimulation is more robust to reduced signal strength due to the increased flash rate than the RC stimulation.

A Suprachoroidal Electrical Retinal Stimulator Design for Long-Term Animal Experiments and In Vivo Assessment of Its Feasibility and Biocompatibility in Rabbits

PubMed Central

Zhou, J. A.; Woo, S. J.; Park, S. I.; Kim, E. T.; Seo, J. M.; Chung, H.; Kim, S. J.

2008-01-01

This article reports on a retinal stimulation system for long-term use in animal electrical stimulation experiments. The presented system consisted of an implantable stimulator which provided continuous electrical stimulation, and an external component which provided preset stimulation patterns and power to the implanted stimulator via a paired radio frequency (RF) coil. A rechargeable internal battery and a parameter memory component were introduced to the implanted retinal stimulator. As a result, the external component was not necessary during the stimulation mode. The inductive coil pair was used to pass the parameter data and to recharge the battery. A switch circuit was used to separate the stimulation mode from the battery recharging mode. The implantable stimulator was implemented with IC chips and the electronics, except for the stimulation electrodes, were hermetically packaged in a biocompatible metal case. A polyimide-based gold electrode array was used. Surgical implantation into rabbits was performed to verify the functionality and safety of this newly designed system. The electrodes were implanted in the suprachoroidal space. Evoked cortical potentials were recorded during electrical stimulation of the retina. Long-term follow-up using OCT showed no chorioretinal abnormality after implantation of the electrodes. PMID:18317521

Respiratory and Pulse Changes Due to Vestibular Stimulations in a Motion-Based Simulator.

PubMed

Ilbasmis, Savas; Yildiz, Safak

2017-01-01

One of the mechanisms leading to spatial disorientation (SD) is overstimulation of the vestibular system by various aircraft maneuvers. The objective of this study was to observe respiratory rate and pulse changes during vestibular system stimulations with the help of two selected SD training profiles. The respiration and pulse rates of 15 subjects were recorded in response to 2 sequential SD training profiles on a motion-based simulator. The session started with a motionless instruction period (IP), continued with a Coriolis profile (CP) which stimulated the semicircular canals, and ended with a Dark Takeoff profile (DP) which stimulated the otolith organs. Recorded parameter means during profiles were statistically compared with IP mean values. The average age of all subjects was 23.67 ± 1.11. Mean CP respiratory rate (23.43 ± 3.21) was higher than mean IP respiratory rate (21.39 ± 4.27) and mean DP pulse rate (79.88 ± 10.39) was lower than mean IP pulse rate (84.76 ± 14.26) of the subjects. These differences were statistically significant. Data indicate that stimulation of the semicircular canals increased respiration rate while stimulation of the otoliths caused a reduction in pulse rate. This was considered to be a result of vestibulorespiratory reflex. Inputs from the vestibular otolith organs contribute to the control of blood pressure during movement and changes in posture. Predicting pulse and respiratory changes due to aerial maneuvers may be important for pilot safety during flight.Ilbasmis S, Yildiz S. Respiratory and pulse changes due to vestibular stimulations in a motion-based simulator. Aerosp Med Hum Perform. 2017; 88(1):48-51.

Facial nerve stimulation in normal pigs and healthy human volunteers: transitional development of a medical device for the emergency treatment of ischemic stroke.

PubMed

Sanchez, Olivia; García, Andrea; Castro-Prado, Fernando; Perez, Miriam; Lara-Estrada, Rafael; Ramirez-Meza, Martin; Godinez, Montserrat; Coco, Michael L; Azpiroz, Joaquín; Borsody, Mark K; Sacristán, Emilio

2018-02-15

Magnetic stimulation of the facial nerve has been tested in preclinical studies as a new, non-invasive emergency treatment of ischemic stroke that acts by increasing cerebral blood flow (CBF). The objective of the studies reported herein was to identify minimal stimulation parameters that increase CBF in large animals and then test those stimulation parameters in healthy volunteers for safety, tolerability, and effectiveness at increasing CBF. This translational research is necessary preparation for clinical studies in ischemic stroke patients. Initial experiments in anesthetized Yorkshire pigs were undertaken in order to identify the lowest stimulus power and duration that increase CBF. A full 3 × 3 factorial design was used to evaluate magnetic stimulation of the facial nerve at various stimulation powers (1.3, 1.6, and 1.9 Tesla field strength at coil surface) and for various durations (2, 3.5, and 5 min). CBF was measured with contrast MRI perfusion imaging and the internal carotid arteries were assessed with MR angiography. Magnetic facial nerve stimulation with parameters identified in the pig study was then applied to 35 healthy volunteers. Safety was assessed with adverse event reports and by medical examination. Tolerability was defined as each volunteer's ability to withstand at least 2 min of stimulation. Volunteers could determine the maximum power of stimulation they received during a ramp-up period. In pigs, unilateral facial nerve stimulation increased CBF by as much as 77% over pre-stimulation baseline when administered across a range of 1.3-1.9 Tesla power and for 2- to 5-min duration. No clear dose-response relationship could be observed across this range, but lower powers and durations than these were markedly less effective. The effect of a single stimulation lasted 90 min. A second stimulation delivered 100 min after the first stimulation sustained the increased CBF without evidence of tachyphylaxis. In human, bilateral facial nerve stimulation caused only non-serious adverse events that were limited to the 2-min stimulation period. Tolerability was greatly improved by gentle encouragement from the study staff, which enabled most volunteers to tolerate 1.6-1.8 Tesla of stimulation power. CBF measures taken approximately 10 min after stimulation demonstrated on average a 32 ± 6% increase in CBF, with ≥ 25% increases in CBF occurring in 10 of the 31 volunteers who had adequate CBF measurements. The minimal effective stimulation parameters defined by increased CBF, as identified in the pig study, translated into safe, tolerable, and effective stimulation of healthy volunteers. These results support the future development and evaluation of non-invasive facial nerve stimulation for the emergency treatment of ischemic stroke. Trial Registration retrospectively registered with clinicaltrials.gov NRV_P1_01_15 on June 6, 2017.

Transient stimulation of distinct subpopulations of striatal neurons mimics changes in action value

PubMed Central

Tai, Lung-Hao; Lee, A. Moses; Benavidez, Nora; Bonci, Antonello; Wilbrecht, Linda

2012-01-01

In changing environments animals must adaptively select actions to achieve their goals. In tasks involving goal-directed action selection, striatal neural activity has been shown to represent the value of competing actions. Striatal representations of action value could potentially bias responses toward actions of higher value. However, no study to date has demonstrated the direct impact of distinct striatal pathways in goal-directed action selection. Here we show in mice that transient optogenetic stimulation of dorsal striatal dopamine D1 and D2 receptor-expressing neurons during decision-making introduces opposing biases in the distribution of choices. The effect of stimulation on choice is dependent on recent reward history and mimics an additive change in the action value. While stimulation prior to and during movement initiation produces a robust bias in choice behavior, this bias is significantly diminished when stimulation is delayed after response initiation. Together, our data demonstrate the role of striatal activity in goal-directed action selection. PMID:22902719

Parkinsonian gait improves with bilateral subthalamic nucleus deep brain stimulation during cognitive multi-tasking.

PubMed

Chenji, Gaurav; Wright, Melissa L; Chou, Kelvin L; Seidler, Rachael D; Patil, Parag G

2017-05-01

Gait impairment in Parkinson's disease reduces mobility and increases fall risk, particularly during cognitive multi-tasking. Studies suggest that bilateral subthalamic deep brain stimulation, a common surgical therapy, degrades motor performance under cognitive dual-task conditions, compared to unilateral stimulation. To measure the impact of bilateral versus unilateral subthalamic deep brain stimulation on walking kinematics with and without cognitive dual-tasking. Gait kinematics of seventeen patients with advanced Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation were examined off medication under three stimulation states (bilateral, unilateral left, unilateral right) with and without a cognitive challenge, using an instrumented walkway system. Consistent with earlier studies, gait performance declined for all six measured parameters under cognitive dual-task conditions, independent of stimulation state. However, bilateral stimulation produced greater improvements in step length and double-limb support time than unilateral stimulation, and achieved similar performance for other gait parameters. Contrary to expectations from earlier studies of dual-task motor performance, bilateral subthalamic deep brain stimulation may assist in maintaining temporal and spatial gait performance under cognitive dual-task conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Simple fMRI Compatible Robotic Stimulator to Study the Neural Mechanisms of Touch and Pain.

PubMed

Riillo, F; Bagnato, C; Allievi, A G; Takagi, A; Fabrizi, L; Saggio, G; Arichi, T; Burdet, E

2016-08-01

This paper presents a simple device for the investigation of the human somatosensory system with functional magnetic imaging (fMRI). PC-controlled pneumatic actuation is employed to produce innocuous or noxious mechanical stimulation of the skin. Stimulation patterns are synchronized with fMRI and other relevant physiological measurements like electroencephalographic activity and vital physiological parameters. The system allows adjustable regulation of stimulation parameters and provides consistent patterns of stimulation. A validation experiment demonstrates that the system safely and reliably identifies clusters of functional activity in brain regions involved in the processing of pain. This new device is inexpensive, portable, easy-to-assemble and customizable to suit different experimental requirements. It provides robust and consistent somatosensory stimulation, which is of crucial importance to investigating the mechanisms of pain and its strong connection with the sense of touch.

Toward rational design of electrical stimulation strategies for epilepsy control

PubMed Central

Sunderam, Sridhar; Gluckman, Bruce; Reato, Davide; Bikson, Marom

2009-01-01

Electrical stimulation is emerging as a viable alternative for epilepsy patients whose seizures are not alleviated by drugs or surgery. Its attractions are temporal and spatial specificity of action, flexibility of waveform parameters and timing, and the perception that its effects are reversible unlike resective surgery. However, despite significant advances in our understanding of mechanisms of neural electrical stimulation, clinical electrotherapy for seizures relies heavily on empirical tuning of parameters and protocols. We highlight concurrent treatment goals with potentially conflicting design constraints that must be resolved when formulating rational strategies for epilepsy electrotherapy: namely seizure reduction versus cognitive impairment, stimulation efficacy versus tissue safety, and mechanistic insight versus clinical pragmatism. First, treatment markers, objectives, and metrics relevant to electrical stimulation for epilepsy are discussed from a clinical perspective. Then the experimental perspective is presented, with the biophysical mechanisms and modalities of open-loop electrical stimulation, and the potential benefits of closed-loop control for epilepsy. PMID:19926525

Sacral neuromodulation in the treatment of the unstable bladder.

PubMed

Bosch, J L

1998-07-01

Sacral neuromodulation as a treatment for urge incontinence in patients with an unstable bladder is the subject of ongoing clinical studies. Although approximately 75% of the patients treated with a permanent sacral foramen electrode implant have experienced significant improvements, it is now also clear that there is an initial failure rate of about 25%. Recent studies have pointed out the importance of improved patient selection on the basis of sex differences, urodynamic parameters and psychological factors. Also, newer forms of test stimulation and permanent electrode implantation are being explored in an effort to improve on the present results.

An animal model of functional electrical stimulation: evidence that the central nervous system modulates the consequences of training

PubMed Central

Hook, MA; Grau, JW

2011-01-01

Study Design Review of how spinal neurons can modulate the consequences of functional electrical stimulation (FES) in an animal model. Methods Spinal effects of FES are examined in male Sprague–Dawley rats transected at the second thoracic vertebra. The rats are exposed to FES training 24–48 h after surgery. Experimental manipulations of stimulation parameters, combined with physiological and pharmacological procedures, are used to examine the potential role of spinal neurons. Results The isolated spinal cord is inherently capable of learning the response–outcome relations imposed in FES training contingencies. Adaptive behavioral modifications are observed when an outcome (electrical stimulation) is contingent on a behavioral response. In contrast, a lack of correlation between the response and outcome in training produces a learning deficit in the spinal cord, rendering it incapable of adaptive learning for up to 48 h. The N-methyl-D-aspartic acid receptor appears to mediate both the adaptive plasticity and loss of plasticity, seen in this spinal model. Conclusion The behavioral effects observed with FES therapies are not simply due to the direct (motor) consequences of stimulation elicited by the activation of efferent motor neurons and/or selected muscles. FES training has the capacity to shape inherent spinal circuits and to produce a long-lasting behavioral modification. Further understanding of the spinal mechanisms underlying adaptive behavioral modification will be integral for establishing functional neural connections in a regenerating spinal system. PMID:17700514

Predicting non-isometric fatigue induced by electrical stimulation pulse trains as a function of pulse duration

PubMed Central

2013-01-01

Background Our previous model of the non-isometric muscle fatigue that occurs during repetitive functional electrical stimulation included models of force, motion, and fatigue and accounted for applied load but not stimulation pulse duration. Our objectives were to: 1) further develop, 2) validate, and 3) present outcome measures for a non-isometric fatigue model that can predict the effect of a range of pulse durations on muscle fatigue. Methods A computer-controlled stimulator sent electrical pulses to electrodes on the thighs of 25 able-bodied human subjects. Isometric and non-isometric non-fatiguing and fatiguing knee torques and/or angles were measured. Pulse duration (170–600 μs) was the independent variable. Measurements were divided into parameter identification and model validation subsets. Results The fatigue model was simplified by removing two of three non-isometric parameters. The third remained a function of other model parameters. Between 66% and 77% of the variability in the angle measurements was explained by the new model. Conclusion Muscle fatigue in response to different stimulation pulse durations can be predicted during non-isometric repetitive contractions. PMID:23374142

Selective recurrent laryngeal nerve stimulation using a penetrating electrode array in the feline model.

PubMed

Haidar, Yarah M; Sahyouni, Ronald; Moshtaghi, Omid; Wang, Beverly Y; Djalilian, Hamid R; Middlebrooks, John C; Verma, Sunil P; Lin, Harrison W

2017-10-31

Laryngeal muscles (LMs) are controlled by the recurrent laryngeal nerve (RLN), injury of which can result in vocal fold (VF) paralysis (VFP). We aimed to introduce a bioelectric approach to selective stimulation of LMs and graded muscle contraction responses. Acute experiments in cats. The study included six anesthetized cats. In four cats, a multichannel penetrating microelectrode array (MEA) was placed into an uninjured RLN. For RLN injury experiments, one cat received a standardized hemostat-crush injury, and one cat received a transection-reapproximation injury 4 months prior to testing. In each experiment, three LMs (thyroarytenoid, posterior cricoarytenoid, and cricothyroid muscles) were monitored with an electromyographic (EMG) nerve integrity monitoring system. Electrical current pulses were delivered to each stimulating channel individually. Elicited EMG voltage outputs were recorded for each muscle. Direct videolaryngoscopy was performed for visualization of VF movement. Stimulation through individual channels led to selective activation of restricted nerve populations, resulting in selective contraction of individual LMs. Increasing current levels resulted in rising EMG voltage responses. Typically, activation of individual muscles was successfully achieved via single placement of the MEA by selection of appropriate stimulation channels. VF abduction was predominantly observed on videolaryngoscopy. Nerve histology confirmed injury in cases of RLN crush and transection experiments. We demonstrated the ability of a penetrating MEA to selectively stimulate restricted fiber populations within the feline RLN and selectively elicit contractions of discrete LMs in both acute and injury-model experiments, suggesting a potential role for intraneural MEA implantation in VFP management. NA Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Comparative analysis of transverse intrafascicular multichannel, longitudinal intrafascicular and multipolar cuff electrodes for the selective stimulation of nerve fascicles

NASA Astrophysics Data System (ADS)

Badia, Jordi; Boretius, Tim; Andreu, David; Azevedo-Coste, Christine; Stieglitz, Thomas; Navarro, Xavier

2011-06-01

The selection of a suitable nerve electrode for neuroprosthetic applications implies a trade-off between invasiveness and selectivity, wherein the ultimate goal is achieving the highest selectivity for a high number of nerve fascicles by the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME) is intended to be transversally inserted into the peripheral nerve and to be useful to selectively activate subsets of axons in different fascicles within the same nerve. We present a comparative study of TIME, LIFE and multipolar cuff electrodes for the selective stimulation of small nerves. The electrodes were implanted on the rat sciatic nerve, and the activation of gastrocnemius, plantar and tibialis anterior muscles was recorded by EMG signals. Thus, the study allowed us to ascertain the selectivity of stimulation at the interfascicular and also at the intrafascicular level. The results of this study indicate that (1) intrafascicular electrodes (LIFE and TIME) provide excitation circumscribed to the implanted fascicle, whereas extraneural electrodes (cuffs) predominantly excite nerve fascicles located superficially; (2) the minimum threshold for muscle activation with TIME and LIFE was significantly lower than with cuff electrodes; (3) TIME allowed us to selectively activate the three tested muscles when stimulating through different active sites of one device, both at inter- and intrafascicular levels, whereas selective activation using multipolar cuff (with a longitudinal tripolar stimulation configuration) was only possible for two muscles, at the interfascicular level, and LIFE did not activate selectively more than one muscle in the implanted nerve fascicle.

A Role for Sigma Receptors in Stimulant Self-Administration and Addiction.

PubMed

Katz, Jonathan L; Hiranita, Takato; Hong, Weimin C; Job, Martin O; McCurdy, Christopher R

2017-01-01

Sigma receptors (σRs) are structurally unique proteins that function intracellularly as chaperones. Historically, σRs have been implicated as modulators of psychomotor stimulant effects and have at times been proposed as potential avenues for modifying stimulant abuse. However, the influence of ligands for σRs on the effects of stimulants, such as cocaine or methamphetamine, in various preclinical procedures related to drug abuse has been varied. The present paper reviews the effects of σR agonists and antagonists in three particularly relevant procedures: stimulant discrimination, place conditioning, and self-administration. The literature to date suggests limited σR involvement in the discriminative-stimulus effects of psychomotor stimulants, either with σR agonists substituting for the stimulant or with σR antagonists blocking stimulant effects. In contrast, studies of place conditioning suggest that administration of σR antagonists or down-regulation of σR protein can block the place conditioning induced by stimulants. Despite place conditioning results, selective σR antagonists are inactive in blocking the self-administration of stimulants. However, compounds binding to the dopamine transporter and blocking σRs can selectively decrease stimulant self-administration. Further, after self-administration of stimulants, σR agonists are self-administered, an effect not seen in subjects without that specific history. These findings suggest that stimulants induce unique changes in σR activity, and once established, the changes induced create redundant, and dopamine independent reinforcement pathways. Concomitant targeting of both dopaminergic pathways and σR proteins produces a selective antagonism of those pathways, suggesting new avenues for combination chemotherapies to specifically combat stimulant abuse.

Deep brain stimulation of the pedunculopontine nucleus for treatment of gait and balance disorder in progressive supranuclear palsy: Effects of frequency modulations and clinical outcome.

PubMed

Galazky, Imke; Kaufmann, Jörn; Lorenzl, Stefan; Ebersbach, Georg; Gandor, Florin; Zaehle, Tino; Specht, Sylke; Stallforth, Sabine; Sobieray, Uwe; Wirkus, Edyta; Casjens, Franziska; Heinze, Hans-Jochen; Kupsch, Andreas; Voges, Jürgen

2018-05-01

The pedunculopontine nucleus has been suggested as a potential deep brain stimulation target for axial symptoms such as gait and balance impairment in idiopathic Parkinson's disease as well as atypical Parkinsonian disorders. Seven consecutive patients with progressive supranuclear palsy received bilateral pedunculopontine nucleus deep brain stimulation. Inclusion criteria comprised of the clinical diagnosis of progressive supranuclear palsy, a levodopa-resistant gait and balance disorder, age <75 years, and absence of dementia or major psychiatric co-morbidities. Effects of stimulation frequencies at 8, 20, 60 and 130 Hz on motor scores and gait were assessed. Motor scores were followed up for two years postoperatively. Activities of daily living, frequency of falls, health-related quality of life, cognition and mood at 12 months were compared to baseline parameters. Surgical and stimulation related adverse events were assessed. Bilateral pedunculopontine nucleus deep brain stimulation at 8 Hz significantly improved axial motor symptoms and cyclic gait parameters, while high frequency stimulation did not ameliorate gait and balance but improved hypokinesia. This improvement however did not translate into clinically relevant benefits. Frequency of falls was not reduced. Activities of daily living, quality of life and frontal cognitive functions declined, while mood remained unchanged. Bilateral pedunculopontine nucleus deep brain stimulation in progressive supranuclear palsy generates frequency-dependent effects with improvement of cyclic gait parameters at low frequency and amelioration of hypokinesia at high frequency stimulation. However, these effects do not translate into a clinically important improvement. Copyright © 2018. Published by Elsevier Ltd.

MagPy: A Python toolbox for controlling Magstim transcranial magnetic stimulators.

PubMed

McNair, Nicolas A

2017-01-30

To date, transcranial magnetic stimulation (TMS) studies manipulating stimulation parameters have largely used blocked paradigms. However, altering these parameters on a trial-by-trial basis in Magstim stimulators is complicated by the need to send regular (1Hz) commands to the stimulator. Additionally, effecting such control interferes with the ability to send TMS pulses or simultaneously present stimuli with high-temporal precision. This manuscript presents the MagPy toolbox, a Python software package that provides full control over Magstim stimulators via the serial port. It is able to maintain this control with no impact on concurrent processing, such as stimulus delivery. In addition, a specially-designed "QuickFire" serial cable is specified that allows MagPy to trigger TMS pulses with very low-latency. In a series of experimental simulations, MagPy was able to maintain uninterrupted remote control over the connected Magstim stimulator across all testing sessions. In addition, having MagPy enabled had no effect on stimulus timing - all stimuli were presented for precisely the duration specified. Finally, using the QuickFire cable, MagPy was able to elicit TMS pulses with sub-millisecond latencies. The MagPy toolbox allows for experiments that require manipulating stimulation parameters from trial to trial. Furthermore, it can achieve this in contexts that require tight control over timing, such as those seeking to combine TMS with fMRI or EEG. Together, the MagPy toolbox and QuickFire serial cable provide an effective means for controlling Magstim stimulators during experiments while ensuring high-precision timing. Copyright © 2016 Elsevier B.V. All rights reserved.

Independent Causal Contributions of Alpha- and Beta-Band Oscillations during Movement Selection.

PubMed

Brinkman, Loek; Stolk, Arjen; Marshall, Tom R; Esterer, Sophie; Sharp, Poppy; Dijkerman, H Chris; de Lange, Floris P; Toni, Ivan

2016-08-17

To select a movement, specific neuronal populations controlling particular features of that movement need to be activated, whereas other populations are downregulated. The selective (dis)inhibition of cortical sensorimotor populations is governed by rhythmic neural activity in the alpha (8-12 Hz) and beta (15-25 Hz) frequency range. However, it is unclear whether and how these rhythms contribute independently to motor behavior. Building on a recent dissociation of the sensorimotor alpha- and beta-band rhythms, we test the hypothesis that the beta-band rhythm governs the disinhibition of task-relevant neuronal populations, whereas the alpha-band rhythm suppresses neurons that may interfere with task performance. Cortical alpha- and beta-band rhythms were manipulated with transcranial alternating current stimulation (tACS) while human participants selected how to grasp an object. Stimulation was applied at either 10 or 20 Hz and was imposed on the sensorimotor cortex contralaterally or ipsilaterally to the grasping hand. In line with task-induced changes in endogenous spectral power, the effect of the tACS intervention depended on the frequency and site of stimulation. Whereas tACS stimulation generally increased movement selection times, 10 Hz stimulation led to relatively faster selection times when applied to the hemisphere ipsilateral to the grasping hand, compared with other stimulation conditions. These effects occurred selectively when multiple movements were considered. These observations functionally differentiate the causal contribution of alpha- and beta-band oscillations to movement selection. The findings suggest that sensorimotor beta-band rhythms disinhibit task-relevant populations, whereas alpha-band rhythms inhibit neuronal populations that could interfere with movement selection. This study shows dissociable effects of 10 Hz and 20 Hz tACS on the duration of movement selection. These observations have two elements of general relevance. First, the finding that alpha- and beta-band oscillations contribute independently to movement selection provides insight in how oscillations orchestrate motor behavior, which is key to understand movement selection deficits in neurodegenerative disorders. Second, the findings highlight the potential of 10 Hz stimulation as a neurophysiologically grounded intervention to enhance human performance. In particular, this intervention can potentially be exploited to boost rehabilitation after neural damage by targeting the unaffected hemisphere. Copyright © 2016 Brinkman et al.

DC type 2 polarization depends on both the allergic status of the individual and protease activity of Per a 10.

PubMed

Goel, Chhavi; Gaur, S N; Bhati, Gaurav; Arora, Naveen

2015-10-01

Cockroach proteases are important risk factors for asthma development in predisposed individuals. In the present study, effect of allergic status of patients on DCs polarization in response to protease allergen Per a 10 was investigated. Cockroach-allergic, other-allergic patients and healthy individuals were selected following the guidelines of ATS/ARIA. Monocyte-derived dendritic cells (DCs) were generated from the selected individuals and stimulated with Per a 10. Flow cytometric analysis showed a significantly high expression of CD80 and CD86 on DCs from cockroach-allergic patients after Per a 10 stimulation as compared to healthy individuals or other-allergic patients (P<0.05). Per a 10 induced comparable level of CD83 expression on DCs from all the 3 groups, showing it was irrespective of the allergic status. CD40 expression was significantly low (P<0.05) on the DCs from cockroach-allergic patients as compared to healthy individuals or other-allergic patients. Further, proteolytically active Per a 10 induced lower CD40 expression on DCs than the heat-inactivated Per a 10 (P<0.05) indicating role of protease activity in the generation of an immune response. The sCD40 level in active Per a 10 stimulated DC cultures was significantly higher than in heat-inactivated Per a 10 (P<0.05). There was two-fold decrease (P<0.05) in IL-12 production by active Per a 10-stimulated DCs than heat-inactivated Per a 10-stimulated DCs. Per a 10-stimulated DCs from cockroach-allergic patients secreted high levels of IL-5, IL-6, TNF-α than that from healthy individuals or other-allergic patients (P<0.05). Furthermore, Per a 10-stimulated DCs from cockroach-allergic patients induced increased secretions of IL-4, IL-5, IL-6, TNF-α and low IL-12 by T cells as compared to those from other groups (P<0.05). Thus, in presence of Per a 10 allergen, polarization of DCs shifts toward type 2 in cockroach-allergic patients but not in the healthy individuals or other-allergic patients. In conclusion, both allergic status of the individual and protease activity of Per a 10 are important parameters that participate in DCs polarization. Copyright © 2015 Elsevier GmbH. All rights reserved.

Spatiotemporal mapping of scalp potentials.

PubMed

Fender, D H; Santoro, T P

1977-11-01

Computerized analysis and display techniques are applied to the problem of identifying the origins of visually evoked scalped potentials (VESP's). A new stimulus for VESP work, white noise, is being incorporated in the solution of this problem. VESP's for white-noise stimulation exhibit time domain behavior similar to the classical response for flash stimuli but with certain significant differences. Contour mapping algorithms are used to display the time behavior of equipotential surfaces on the scalp during the VESP. The electrical and geometrical parameters of the head are modeled. Electrical fields closely matching those obtained experimentally are generated on the surface of the model head by optimally selecting the location and strength parameters of one or two dipole current sources contained within the model. Computer graphics are used to display as a movie the actual and model scalp potential field and the parameters of the dipole generators whithin the model head during the time course of the VESP. These techniques are currently used to study retinotopic mapping, fusion, and texture perception in the human.

Optogenetic stimulation in a computational model of the basal ganglia biases action selection and reward prediction error.

PubMed

Berthet, Pierre; Lansner, Anders

2014-01-01

Optogenetic stimulation of specific types of medium spiny neurons (MSNs) in the striatum has been shown to bias the selection of mice in a two choices task. This shift is dependent on the localisation and on the intensity of the stimulation but also on the recent reward history. We have implemented a way to simulate this increased activity produced by the optical flash in our computational model of the basal ganglia (BG). This abstract model features the direct and indirect pathways commonly described in biology, and a reward prediction pathway (RP). The framework is similar to Actor-Critic methods and to the ventral/dorsal distinction in the striatum. We thus investigated the impact on the selection caused by an added stimulation in each of the three pathways. We were able to reproduce in our model the bias in action selection observed in mice. Our results also showed that biasing the reward prediction is sufficient to create a modification in the action selection. However, we had to increase the percentage of trials with stimulation relative to that in experiments in order to impact the selection. We found that increasing only the reward prediction had a different effect if the stimulation in RP was action dependent (only for a specific action) or not. We further looked at the evolution of the change in the weights depending on the stage of learning within a block. A bias in RP impacts the plasticity differently depending on that stage but also on the outcome. It remains to experimentally test how the dopaminergic neurons are affected by specific stimulations of neurons in the striatum and to relate data to predictions of our model.

FSH treatment in infertile males candidate to assisted reproduction improved sperm DNA fragmentation and pregnancy rate.

PubMed

Garolla, Andrea; Ghezzi, Marco; Cosci, Ilaria; Sartini, Barbara; Bottacin, Alberto; Engl, Bruno; Di Nisio, Andrea; Foresta, Carlo

2017-05-01

The purpose of this study is to evaluate whether follicle-stimulating hormone treatment improves sperm DNA parameters and pregnancy outcome in infertile male candidates to in-vitro fertilization.Observational study in 166 infertile male partners of couples undergoing in-vitro fertilization. Eighty-four patients were receiving follicle-stimulating hormone treatment (cases) and 82 refused treatment (controls). Semen parameters, sexual hormones, and sperm nucleus (fluorescence in-situ hybridization, acridine orange, TUNEL, and γH2AX) were evaluated at baseline (T0) and after 3 months (T1), when all subjects underwent assisted reproduction techniques. Statistical analysis was performed by analysis of variance.Compared to baseline, cases showed significant improvements in seminal parameters and DNA fragmentation indexes after follicle-stimulating hormone therapy (all P < 0.05), whereas no changes were observed in controls. Within cases, follicle-stimulating hormone treatment allowed to perform intrauterine insemination in 35 patients with a pregnancy rate of 23.2 %. Intracytoplasmic sperm injection was performed in all controls and in 49 patients from cases, with pregnancy rates of 23.2 and 40.8 %, respectively (P < 0.05). After 3 months (T0 vs. T1) of follicle-stimulating hormone therapy, cases with positive outcome had reduced DNA fragmentation index and lower double strand breaks (P < 0.05 and P < 0.001 vs. negative outcome, respectively).In this observational study, we showed that follicle-stimulating hormone treatment improves sperm DNA fragmentation, which in turn leads to increased pregnancy rates in infertile males undergoing in-vitro fertilization. In particular, double strand breaks (measured with γH2AX test) emerged as the most sensible parameter to follicle-stimulating hormone treatment in predicting reproductive outcome.

Quantitative structure-activity relationship analysis of the pharmacology of para-substituted methcathinone analogues.

PubMed

Bonano, J S; Banks, M L; Kolanos, R; Sakloth, F; Barnier, M L; Glennon, R A; Cozzi, N V; Partilla, J S; Baumann, M H; Negus, S S

2015-05-01

Methcathinone (MCAT) is a potent monoamine releaser and parent compound to emerging drugs of abuse including mephedrone (4-CH3 MCAT), the para-methyl analogue of MCAT. This study examined quantitative structure-activity relationships (QSAR) for MCAT and six para-substituted MCAT analogues on (a) in vitro potency to promote monoamine release via dopamine and serotonin transporters (DAT and SERT, respectively), and (b) in vivo modulation of intracranial self-stimulation (ICSS), a behavioural procedure used to evaluate abuse potential. Neurochemical and behavioural effects were correlated with steric (Es ), electronic (σp ) and lipophilic (πp ) parameters of the para substituents. For neurochemical studies, drug effects on monoamine release through DAT and SERT were evaluated in rat brain synaptosomes. For behavioural studies, drug effects were tested in male Sprague-Dawley rats implanted with electrodes targeting the medial forebrain bundle and trained to lever-press for electrical brain stimulation. MCAT and all six para-substituted analogues increased monoamine release via DAT and SERT and dose- and time-dependently modulated ICSS. In vitro selectivity for DAT versus SERT correlated with in vivo efficacy to produce abuse-related ICSS facilitation. In addition, the Es values of the para substituents correlated with both selectivity for DAT versus SERT and magnitude of ICSS facilitation. Selectivity for DAT versus SERT in vitro is a key determinant of abuse-related ICSS facilitation by these MCAT analogues, and steric aspects of the para substituent of the MCAT scaffold (indicated by Es ) are key determinants of this selectivity. © 2014 The British Pharmacological Society.

Quantitative structure–activity relationship analysis of the pharmacology of para-substituted methcathinone analogues

PubMed Central

Bonano, J S; Banks, M L; Kolanos, R; Sakloth, F; Barnier, M L; Glennon, R A; Cozzi, N V; Partilla, J S; Baumann, M H; Negus, S S

2015-01-01

Background and Purpose Methcathinone (MCAT) is a potent monoamine releaser and parent compound to emerging drugs of abuse including mephedrone (4-CH3 MCAT), the para-methyl analogue of MCAT. This study examined quantitative structure–activity relationships (QSAR) for MCAT and six para-substituted MCAT analogues on (a) in vitro potency to promote monoamine release via dopamine and serotonin transporters (DAT and SERT, respectively), and (b) in vivo modulation of intracranial self-stimulation (ICSS), a behavioural procedure used to evaluate abuse potential. Neurochemical and behavioural effects were correlated with steric (Es), electronic (σp) and lipophilic (πp) parameters of the para substituents. Experimental Approach For neurochemical studies, drug effects on monoamine release through DAT and SERT were evaluated in rat brain synaptosomes. For behavioural studies, drug effects were tested in male Sprague-Dawley rats implanted with electrodes targeting the medial forebrain bundle and trained to lever-press for electrical brain stimulation. Key Results MCAT and all six para-substituted analogues increased monoamine release via DAT and SERT and dose- and time-dependently modulated ICSS. In vitro selectivity for DAT versus SERT correlated with in vivo efficacy to produce abuse-related ICSS facilitation. In addition, the Es values of the para substituents correlated with both selectivity for DAT versus SERT and magnitude of ICSS facilitation. Conclusions and Implications Selectivity for DAT versus SERT in vitro is a key determinant of abuse-related ICSS facilitation by these MCAT analogues, and steric aspects of the para substituent of the MCAT scaffold (indicated by Es) are key determinants of this selectivity. PMID:25438806

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

PubMed

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

1998-09-01

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

Prefrontal transcranial direct current stimulation (tDCS) as treatment for major depression: study design and methodology of a multicenter triple blind randomized placebo controlled trial (DepressionDC).

PubMed

Padberg, Frank; Kumpf, Ulrike; Mansmann, Ulrich; Palm, Ulrich; Plewnia, Christian; Langguth, Berthold; Zwanzger, Peter; Fallgatter, Andreas; Nolden, Jana; Burger, Max; Keeser, Daniel; Rupprecht, Rainer; Falkai, Peter; Hasan, Alkomiet; Egert, Silvia; Bajbouj, Malek

2017-12-01

Transcranial direct current stimulation (tDCS) has been proposed as novel treatment for major depressive disorder (MDD) based on clinical pilot studies as well as randomized controlled monocentric trials. The DepressionDC trial is a triple-blind (blinding of rater, operator and patient), randomized, placebo controlled multicenter trial investigating the efficacy and safety of prefrontal tDCS used as additive treatment in MDD patients who have not responded to selective serotonin reuptake inhibitors (SSRI). At 5 study sites, 152 patients with MDD receive a 6-weeks treatment with active tDCS (anode F3 and cathode F4, 2 mA intensity, 30 min/day) or sham tDCS add-on to a stable antidepressant medication with an SSRI. Follow-up visits are at 3 and 6 months after the last tDCS session. The primary outcome measure is the change of the Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 6 post-randomisation compared to baseline. Secondary endpoints also cover other psychopathological domains, and a comprehensive safety assessment includes measures of cognition. Patients undergo optional investigations comprising genetic testing and functional magnetic resonance imaging (fMRI) of structural and functional connectivity. The study uses also an advanced tDCS technology including standard electrode positioning and recording of technical parameters (current, impedance, voltage) in every tDCS session. Aside reporting the study protocol here, we present a novel approach for monitoring technical parameters of tDCS which will allow quality control of stimulation and further analysis of the interaction between technical parameters and clinical outcome. The DepressionDC trial will hopefully answer the important clinical question whether prefrontal tDCS is a safe and effective antidepressant intervention in patients who have not sufficiently responded to SSRIs. ClinicalTrials.gov Identifier NCT0253016.

Separability of stimulus parameter encoding by on-off directionally selective rabbit retinal ganglion cells

PubMed Central

Nowak, Przemyslaw; Dobbins, Allan C.; Gawne, Timothy J.; Grzywacz, Norberto M.

2011-01-01

The ganglion cell output of the retina constitutes a bottleneck in sensory processing in that ganglion cells must encode multiple stimulus parameters in their responses. Here we investigate encoding strategies of On-Off directionally selective retinal ganglion cells (On-Off DS RGCs) in rabbits, a class of cells dedicated to representing motion. The exquisite axial discrimination of these cells to preferred vs. null direction motion is well documented: it is invariant with respect to speed, contrast, spatial configuration, spatial frequency, and motion extent. However, these cells have broad direction tuning curves and their responses also vary as a function of other parameters such as speed and contrast. In this study, we examined whether the variation in responses across multiple stimulus parameters is systematic, that is the same for all cells, and separable, such that the response to a stimulus is a product of the effects of each stimulus parameter alone. We extracellularly recorded single On-Off DS RGCs in a superfused eyecup preparation while stimulating them with moving bars. We found that spike count responses of these cells scaled as independent functions of direction, speed, and luminance. Moreover, the speed and luminance functions were common across the whole sample of cells. Based on these findings, we developed a model that accurately predicted responses of On-Off DS RGCs as products of separable functions of direction, speed, and luminance (r = 0.98; P < 0.0001). Such a multiplicatively separable encoding strategy may simplify the decoding of these cells' outputs by the higher visual centers. PMID:21325684

Transcranial direct current stimulation in the male mouse to promote recovery after stroke.

PubMed

Pikhovych, Anton; Walter, Helene L; Mahabir, Esther; Fink, Gereon Rudolf; Graf, Rudolf; Schroeter, Michael; Rueger, Maria Adele

2016-06-01

Transcranial direct current stimulation (tDCS) constitutes a promising approach for promoting recovery of function after stroke, although the underlying neurobiological mechanisms are unclear. To conduct translational research in animal models, stimulation parameters should not lead to neuronal lesions. Liebetanz et al. recommend charge densities for cathodal stimulation in rats, but parameters for mice are not established. We established tDCS in the wild-type mouse, enabling studies with genetically-engineered mice (GEM). tDCS equipment was adapted to fit the mouse skull. Using different polarities and charge densities, tDCS was safe to apply in the mouse where the charge density was below 198 kC/m(2) for single or repeated stimulations. These findings are crucial for future investigations of the neurobiological mechanisms underlying tDCS using GEM. © The Author(s) 2015.

Threshold Evolution as an Analysis of the Different Pulse Frequencies in Rechargeable Systems for Spinal Cord Stimulation.

PubMed

Abejón, David; Rueda, Pablo; Vallejo, Ricardo

2016-04-01

Pulse frequency (Fc) is one of the most important parameters in neurostimulation, with Pulse Amplitude (Pw) and Amplitude (I). Up to certain Fc, increasing the number of pulses will generate action potentials in neighboring neural structures and may facilitate deeper penetration of the electromagnetic fields. In addition, changes in frequency modify the patient's sensation with stimulation. Fifty patients previously implanted with rechargeable current control spinal cord stimulation. With pulse width fixed at 300 μsec, we stimulated at 26 different Fc values between 40 and 1200 Hz and determine the influence of these changes on different stimulation thresholds: perception threshold (Tp ), therapeutic perception (Tt), and discomfort threshold (Td). Simultaneously, paresthesia coverage of the painful area and patient's sensation and satisfaction related to the quality of stimulation were recorded. Pulse Fc is inversely proportional to stimulation thresholds and this influence is statistically significant (p < 0.05). As Pulse Fc increased from 40 to 1200 Hz, the mean threshold decreases from 7.25 to 1.38 mA (Tp ), 8.17 to 1.63 (Tt ), and 9.20 to 1.85 (Td). Significant differences for Tp and Tt began at 750 Hz (Tp , Tt ) and at 650 Hz for Td. No significant influence was found regarding paresthesia coverage. As expected, Fc affects significantly patient's sensation and satisfaction. Changes in Fc affect the quality of paresthesias. Within the evaluated parameters higher frequencies are inversely proportional to stimulation thresholds and Tt. It seems that Fc is a vital parameter to achieve therapeutic success. Changes in Fc is a useful parameter to modulate the patient's sensory perception. Fc can be successfully used to adjust the quality of the paresthesias and to modify patient's subjective sensation. We showed that as the frequency increases, the patient's satisfaction with the perceived sensation decreases, suggesting that higher Fc may need to be set up at subthreshold amplitude to achieve positive response. © 2016 International Neuromodulation Society.

Vestibular stimulation, spatial hemineglect and dysphasia, selective effects.

PubMed

Vallar, G; Papagno, C; Rusconi, M L; Bisiach, E

1995-09-01

The selectivity of the effects of vestibular stimulation was investigated in a left brain-damaged patient suffering from right visuo-spatial hemineglect and severe dysplasia. Vestibular stimulation temporarily improved the former but not the latter disorder. These results support the view that this treatment improves hemineglect by a specific effect, running counter the rightward distortion of egocentric co-ordinates, rather than by a general hemispheric activation.

Considerations in high resolution skeletal muscle DTI using single-shot EPI with stimulated echo preparation and SENSE

PubMed Central

Karampinos, Dimitrios C.; Banerjee, Suchandrima; King, Kevin F.; Link, Thomas M.; Majumdar, Sharmila

2011-01-01

Previous studies have shown that skeletal muscle diffusion tensor imaging (DTI) can non-invasively probe changes in the muscle fiber architecture and microstructure in diseased and damaged muscles. However, DTI fiber reconstruction in small muscles and in muscle regions close to aponeuroses and tendons remains challenging because of partial volume effects. Increasing the spatial resolution of skeletal muscle single-shot diffusion weighted (DW)-EPI can be hindered by the inherently low SNR of muscle DW-EPI due to the short muscle T2 and the high sensitivity of single-shot EPI to off-resonance effects and T2* blurring. In the present work, eddy-current compensated diffusion-weighted stimulated echo preparation is combined with sensitivity encoding (SENSE) to maintain good SNR properties and reduce the sensitivity to distortions and T2* blurring in high resolution skeletal muscle single-shot DW-EPI. An analytical framework is developed for optimizing the reduction factor and diffusion weighting time to achieve maximum SNR. Arguments for the selection of the experimental parameters are then presented considering the compromise between SNR, B0-induced distortions, T2* blurring effects and tissue incoherent motion effects. Based on the selected parameters in a high resolution skeletal muscle single-shot DW-EPI protocol, imaging protocols at lower acquisition matrix sizes are defined with matched bandwidth in the phase-encoding direction and SNR. In vivo results show that high resolution skeletal muscle DTI with minimized sensitivity to geometric distortions and T2* blurring is feasible using the proposed methodology. In particular, a significant benefit is demonstrated from reducing partial volume effects on resolving multi-pennate muscles and muscles with small cross sections in calf muscle DTI. PMID:22081519

Five-day course of paired associative stimulation fails to improve motor function in stroke patients.

PubMed

Tarri, Mohamed; Brimhat, Nabila; Gasq, David; Lepage, Benoît; Loubinoux, Isabelle; De Boissezon, Xavier; Marque, Philippe; Castel-Lacanal, Evelyne

2018-03-01

Non-invasive brain stimulation has been studied as a therapeutic adjunct for upper-limb recovery in patients with stroke. One type of stimulation, paired associative stimulation (PAS), has effects on plasticity in both patients and healthy participants. Lasting several hours, these effects are reversible and topographically specific. The goal was to investigate the presence of a lasting increase in motor cortex plasticity for extensor wrist muscles - extensor carpi radialis (ECR) - and an improvement in upper-limb function after 5 days of daily PAS in patients at the subacute post-stroke stage. A total of 24 patients (mean [SD] age 50.1 [12.1] years, weeks since stroke 10.1 [5.3]) were included in a double-blind, placebo-controlled trial and randomly assigned to the PAS or sham group (n=13 and n=11). For the PAS group, patients underwent a 5-day course of electrical peripheral stimulation combined with magnetic cortical stimulation applied to the ECR muscle in a single daily session at 0.1Hz for 30min; patients with sham treatment received minimal cortical stimulation. Both patient groups underwent 2 hr of conventional physiotherapy. Variations in the motor evoked potential (MEP) surface area of the ECR muscle and Fugl-Meyer Assessment-Upper-Limb motor scores were analysed up to day 12. The 2 groups did not differ in electrophysiological or motor parameters. Repeated PAS sessions seemed to affect only patients with low initial cortical excitability. We found considerable variability in PAS effects between patients and across the sessions. We failed to induce a lasting effect with PAS in the present study. PAS does not seem to be the main method for post-stroke brain stimulation. Perhaps recruitment of patients could be more selective, possibly targeting those with a wide altered ipsilesional corticomotor pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Vibrational pumping and heating under SERS conditions: fact or myth?

PubMed

Le Ru, E C; Etchegoin, P G

2006-01-01

We address in this paper the long debated issue of the possibility of vibrational pumping under Surface Enhanced Raman Scattering (SERS) conditions, both theoretically and experimentally. We revisit with simple theoretical models the mechanisms of vibrational pumping and its relation to heating. This presentation provides a clear classification of the various regimes of heating/pumping, from simple global laser heating to selective pumping of a single vibrational mode. We also propose the possibility of extreme pumping driven by stimulated phonon emission, and we introduce and apply a new experimental technique to study these effects in SERS. Our method relies on correlations between Raman peak parameters, and cross-correlation for two Raman peaks. We find strong evidence for local and dynamical heating, but no convincing evidence for selective pumping under our specific experimental SERS conditions.

21 CFR 890.5860 - Ultrasound and muscle stimulator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ultrasound and muscle stimulator. 890.5860 Section... Ultrasound and muscle stimulator. (a) Ultrasound and muscle stimulator for use in applying therapeutic deep heat for selected medical conditions—(1) Identification. An ultrasound and muscle stimulator for use in...

21 CFR 890.5860 - Ultrasound and muscle stimulator.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ultrasound and muscle stimulator. 890.5860 Section... Ultrasound and muscle stimulator. (a) Ultrasound and muscle stimulator for use in applying therapeutic deep heat for selected medical conditions—(1) Identification. An ultrasound and muscle stimulator for use in...

21 CFR 890.5860 - Ultrasound and muscle stimulator.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ultrasound and muscle stimulator. 890.5860 Section... Ultrasound and muscle stimulator. (a) Ultrasound and muscle stimulator for use in applying therapeutic deep heat for selected medical conditions—(1) Identification. An ultrasound and muscle stimulator for use in...

21 CFR 890.5860 - Ultrasound and muscle stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ultrasound and muscle stimulator. 890.5860 Section... Ultrasound and muscle stimulator. (a) Ultrasound and muscle stimulator for use in applying therapeutic deep heat for selected medical conditions—(1) Identification. An ultrasound and muscle stimulator for use in...

21 CFR 890.5860 - Ultrasound and muscle stimulator.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ultrasound and muscle stimulator. 890.5860 Section... Ultrasound and muscle stimulator. (a) Ultrasound and muscle stimulator for use in applying therapeutic deep heat for selected medical conditions—(1) Identification. An ultrasound and muscle stimulator for use in...

Salivary Parameters (Salivary Flow, pH and Buffering Capacity) in Stimulated Saliva of Mexican Elders 60 Years Old and Older

PubMed Central

Islas-Granillo, H; Borges-Yañez, SA; Medina-Solís, CE; Galan-Vidal, CA; Navarrete-Hernández, JJ; Escoffié-Ramirez, M; Maupomé, G

2014-01-01

ABSTRACT Objective: To compare a limited array of chewing-stimulated saliva features (salivary flow, pH and buffer capacity) in a sample of elderly Mexicans with clinical, sociodemographic and socio-economic variables. Subjects and Methods: A cross-sectional study was carried out in 139 adults, 60 years old and older, from two retirement homes and a senior day care centre in the city of Pachuca, Mexico. Socio-demographic, socio-economic and behavioural variables were collected through a questionnaire. A trained and standardized examiner obtained the oral clinical variables. Chewing-stimulated saliva (paraffin method) was collected and the salivary flow rate, pH and buffer capacity were measured. The analysis was performed using non-parametric tests in Stata 9.0. Results: Mean age was 79.1 ± 9.8 years. Most of the subjects included were women (69.1%). Mean chewing-stimulated salivary flow was 0.75 ± 0.80 mL/minute, and the pH and buffer capacity were 7.88 ± 0.83 and 4.20 ± 1.24, respectively. Mean chewing-stimulated salivary flow varied (p < 0.05) across type of retirement home, tooth brushing frequency, number of missing teeth and use of dental prostheses. pH varied across the type of retirement home (p < 0.05) and marginally by age (p = 0.087); buffer capacity (p < 0.05) varied across type of retirement home, tobacco consumption and the number of missing teeth. Conclusions: These exploratory data add to the body of knowledge with regard to chewing-stimulated salivary features (salivary flow rate, pH and buffer capacity) and outline the variability of those features across selected sociodemographic, socio-economic and behavioural variables in a group of Mexican elders. PMID:25867562

Salivary Parameters (Salivary Flow, pH and Buffering Capacity) in Stimulated Saliva of Mexican Elders 60 Years Old and Older.

PubMed

Islas-Granillo, H; Borges-Yañez, S A; Medina-Solís, C E; Galan-Vidal, C A; Navarrete-Hernández, J J; Escoffié-Ramirez, M; Maupomé, G

2014-12-01

To compare a limited array of chewing-stimulated saliva features (salivary flow, pH and buffer capacity) in a sample of elderly Mexicans with clinical, sociodemographic and socio-economic variables. A cross-sectional study was carried out in 139 adults, 60 years old and older, from two retirement homes and a senior day care centre in the city of Pachuca, Mexico. Sociodemographic, socio-economic and behavioural variables were collected through a questionnaire. A trained and standardized examiner obtained the oral clinical variables. Chewing-stimulated saliva (paraffin method) was collected and the salivary flow rate, pH and buffer capacity were measured. The analysis was performed using non-parametric tests in Stata 9.0. Mean age was 79.1 ± 9.8 years. Most of the subjects included were women (69.1%). Mean chewing-stimulated salivary flow was 0.75 ± 0.80 mL/minute, and the pH and buffer capacity were 7.88 ± 0.83 and 4.20 ± 1.24, respectively. Mean chewing-stimulated salivary flow varied (p < 0.05) across type of retirement home, tooth brushing frequency, number of missing teeth and use of dental prostheses. pH varied across the type of retirement home (p < 0.05) and marginally by age (p = 0.087); buffer capacity (p < 0.05) varied across type of retirement home, tobacco consumption and the number of missing teeth. These exploratory data add to the body of knowledge with regard to chewing-stimulated salivary features (salivary flow rate, pH and buffer capacity) and outline the variability of those features across selected sociodemographic, socio-economic and behavioural variables in a group of Mexican elders.

Neurostimulation for the treatment of axial back pain: a review of mechanisms, techniques, outcomes, and future advances.

PubMed

Deer, Timothy; Pope, Jason; Hayek, Salim; Narouze, Samer; Patil, Parag; Foreman, Robert; Sharan, Ashwini; Levy, Robert

2014-10-01

The use of spinal cord stimulation (SCS) is well established in the treatment of neuropathic pain. This procedure has been approved in the United States for neuropathic pain of the trunk and limbs from various conditions. International use is variable based on governmental policy. Most studies showing efficacy have focused on pain primarily in the limbs for such conditions as complex regional pain syndrome (CRPS), sciatica, radiculitis, ischemic limb pain, and peripheral neuropathy. Data on success in neuropathic pain of the trunk and particularly of the axial back are limited. New understanding about the targets of neuromodulation and their treatment with novel neurostimulation approaches has led to a new dawn of enthusiasm for spinal cord stimulation for axial low back pain. The authors review mechanisms, current and future targets, techniques, and their outcomes for treating axial back pain with neurostimulation. The paper discusses many newer methods and targets that may substantially improve results for the treatment of this patient group. The continuing evolution of technology and new data may well change these recommendations over time and regular updates of this manuscript will be critical moving forward. Improved technology and a better understanding of the goals of stimulation have led to a new ability to stimulate the axial low back and increase the effectiveness of these therapies to reduce pain. New paddle lead constructs, percutaneous paddle lead introduction, and other new technologies have led to an increased number of potential candidates for spinal cord stimulation. Optimizing the application of neurostimulation for chronic axial back pain will depend upon answering questions relating to patient selection, implantation technique, and stimulation parameters. © 2014 International Neuromodulation Society.

In vitro evidence for efficacy in food intolerance for the multispecies probiotic formulation Ecologic® Tolerance (Syngut™).

PubMed

Besseling-van der Vaart, I; Heath, M D; Guagnini, F; Kramer, M F

2016-02-01

The beneficial effects of probiotics are currently the subject of extensive studies in health and medical research. The aim of this research was to specifically design a new probiotic formulation for supplementation in people suffering from food intolerance. The selection of strains was focussed on the capacity to influence mechanisms of action that are important in development of food intolerance with the following parameters measure: in vitro capacity to produce β-galactosidase, in vitro strengthening of the epithelial barrier, in vitro stimulation of cytokines produced by regulatory T cells, in addition to assessing fundamental quality criteria (stability, gastrointestinal (GI)-survival, multispecies concept, allergen-free). Ecologic®Tolerance/Syngut™ was subsequently developed consisting of a multispecies concept using 4 different probiotic strains (Bifidobacterium lactis W51, Lactobacillus acidophilus W22, Lactobacillus plantarum W21 and Lactococcus lactis W19). Each of these strains demonstrated ability to survive the GI-tract and strain specific effects in producing β-galactosidase, strengthening the gut barrier function after immunological-induced stress and inhibiting Th2 cytokines (IL-4, IL-5 and IL-13 (≥50%), in addition to stimulating interleukin-10 levels; thus, providing in vitro evidence for the efficacy of the selected strains to provide beneficial effects in patients suffering from food intolerance.

Neuromodulation by implant for treating lower urinary tract symptoms and dysfunction.

PubMed

Bemelmans, B L; Mundy, A R; Craggs, M D

1999-08-01

Patients with irritative micturition complaints, pelvic pain, involuntary urine loss or urinary retention are sometimes difficult to treat. The advent of direct sacral nerve stimulation offers a therapeutic alternative if conservative measures fail and surgery is considered. This paper reviews therapeutic neuromodulation by implant for treating lower urinary tract symptoms and dysfunction. The international literature is reviewed on topics such as the physiological basis of neuromodulation, techniques of acute testing and chronic implantation, and clinical results. Future developments and ways for possible improvement are discussed. The mode of action of neuromodulation is probably through restoring the correct balance between excitatory and inhibitory impulses from and to the pelvic organs at a sacral and supra-sacral level. Depending on the predefined success criteria, average success rates of definitive implants vary from 50 to 70%. From the data it seems that patients with urge incontinence and urinary retention are the best candidates for neuromodulation. In the literature the lack of standardisation of selection criteria, stimulation parameters and definitions of success is striking. Neuromodulation by implant is a useful therapeutic alternative. It should at least be considered in patients with therapy-resistant urge incontinence and urinary retention before proceeding to surgery. Issues such as underlying physiology, methodological standardisation, technical improvements, and patient selection must be addressed in future research.

Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive

PubMed Central

Fiore, Vincenzo G.; Rigoli, Francesco; Stenner, Max-Philipp; Zaehle, Tino; Hirth, Frank; Heinze, Hans-Jochen; Dolan, Raymond J.

2016-01-01

Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model. PMID:27004463

Metabolic alterations induced in cultured skeletal muscle by stretch-relaxation activity

NASA Technical Reports Server (NTRS)

Hatfaludy, Sophia; Shansky, Janet; Vandenburgh, Herman H.

1989-01-01

Muscle cells differentiated in vitro are repetitively stretched and relaxed in order to determine the presence of short- and long-term alterations occurring in glucose uptake and lactate efflux that are similar to the metabolic alterations occurring in stimulated organ-cultured muscle and in vivo skeletal muscle during the active state. It is observed that whereas mechanical stimulation increases these metabolic parameters within 4-6 h of starting activity, unstimulated basal rates in control cultures also increase during this period of time, and by 8 h, their rates have reached or exceeded the rates in continuously stimulated cells. Measurements of these parameters in media of different compositions show that activity-induced long-term alterations in the parameters occur independently of growth factors in serium and embryo extracts.

Responses of human sensory characteristics to 532 nm pulse laser stimuli.

PubMed

Kim, Ji-Sun; Oh, Han-Byeol; Kim, A-Hee; Kim, Jun-Sik; Lee, Eun-Suk; Goh, Bong-Jun; Kim, Jae-Young; Jang, Kyungmin; Park, Jong-Rak; Chung, Soon-Cheol; Jun, Jae-Hoon

2016-04-29

Lasers are advantageous in some applications to stimulate a small target area and is used in various fields such as optogenetic, photoimmunological and neurophysiological studies. This study aims to implement a non-contact sense of touch without damaging biological tissues using laser. Various laser parameters were utilized in safety range to induce a sense of touch and investigate the human responses. With heat distribution simulation, the amount of changes in the temperature and the tendency in laser parameters of sensory stimulation were analyzed. The results showed the identified tactile responses in safety range with various laser parameters and temperature distribution for the laser stimulus was obtained through the simulation. This study can be applied to the areas of sensory receptor stimulation, neurophysiology and clinical medicine.

Blood pressure control with selective vagal nerve stimulation and minimal side effects

NASA Astrophysics Data System (ADS)

Plachta, Dennis T. T.; Gierthmuehlen, Mortimer; Cota, Oscar; Espinosa, Nayeli; Boeser, Fabian; Herrera, Taliana C.; Stieglitz, Thomas; Zentner, Joseph

2014-06-01

Objective. Hypertension is the largest threat to patient health and a burden to health care systems. Despite various options, 30% of patients do not respond sufficiently to medical treatment. Mechanoreceptors in the aortic arch relay blood pressure (BP) levels through vagal nerve (VN) fibers to the brainstem and trigger the baroreflex, lowering the BP. Selective electrical stimulation of these nerve fibers reduced BP in rats. However, there is no technique described to localize and stimulate these fibers inside the VN without inadvertent stimulation of non-baroreceptive fibers causing side effects like bradycardia and bradypnea. Approach. We present a novel method for selective VN stimulation to reduce BP without the aforementioned side effects. Baroreceptor compound activity of rat VN (n = 5) was localized using a multichannel cuff electrode, true tripolar recording and a coherent averaging algorithm triggered by BP or electrocardiogram. Main results. Tripolar stimulation over electrodes near the barofibers reduced the BP without triggering significant bradycardia and bradypnea. The BP drop was adjusted to 60% of the initial value by varying the stimulation pulse width and duration, and lasted up to five times longer than the stimulation. Significance. The presented method is robust to impedance changes, independent of the electrode's relative position, does not compromise the nerve and can run on implantable, ultra-low power signal processors.

Selective binding and oligomerization of the murine granulocyte colony-stimulating factor receptor by a low molecular weight, nonpeptidyl ligand.

PubMed

Doyle, Michael L; Tian, Shin-Shay; Miller, Stephen G; Kessler, Linda; Baker, Audrey E; Brigham-Burke, Michael R; Dillon, Susan B; Duffy, Kevin J; Keenan, Richard M; Lehr, Ruth; Rosen, Jon; Schneeweis, Lumelle A; Trill, John; Young, Peter R; Luengo, Juan I; Lamb, Peter

2003-03-14

Granulocyte colony-stimulating factor regulates neutrophil production by binding to a specific receptor, the granulocyte colony-stimulating factor receptor, expressed on cells of the granulocytic lineage. Recombinant forms of granulocyte colony-stimulating factor are used clinically to treat neutropenias. As part of an effort to develop granulocyte colony-stimulating factor mimics with the potential for oral bioavailability, we previously identified a nonpeptidyl small molecule (SB-247464) that selectively activates murine granulocyte colony-stimulating factor signal transduction pathways and promotes neutrophil formation in vivo. To elucidate the mechanism of action of SB-247464, a series of cell-based and biochemical assays were performed. The activity of SB-247464 is strictly dependent on the presence of zinc ions. Titration microcalorimetry experiments using a soluble murine granulocyte colony-stimulating factor receptor construct show that SB-247464 binds to the extracellular domain of the receptor in a zinc ion-dependent manner. Analytical ultracentrifugation studies demonstrate that SB-247464 induces self-association of the N-terminal three-domain fragment in a manner that is consistent with dimerization. SB-247464 induces internalization of granulocyte colony-stimulating factor receptor on intact cells, consistent with a mechanism involving receptor oligomerization. These data show that small nonpeptidyl compounds are capable of selectively binding and inducing productive oligomerization of cytokine receptors.

Why intra-epidermal electrical stimulation achieves stimulation of small fibres selectively: a simulation study

NASA Astrophysics Data System (ADS)

Motogi, Jun; Sugiyama, Yukiya; Laakso, Ilkka; Hirata, Akimasa; Inui, Koji; Tamura, Manabu; Muragaki, Yoshihiro

2016-06-01

The in situ electric field in the peripheral nerve of the skin is investigated to discuss the selective stimulation of nerve fibres. Coaxial planar electrodes with and without intra-epidermal needle tip were considered as electrodes of a stimulator. From electromagnetic analysis, the tip depth of the intra-epidermal electrode should be larger than the thickness of the stratum corneum, the electrical conductivity of which is much lower than the remaining tissue. The effect of different radii of the outer ring electrode on the in situ electric field is marginal. The minimum threshold in situ electric field (rheobase) for free nerve endings is estimated to be 6.3 kV m-1. The possible volume for electrostimulation, which can be obtained from the in situ electric field distribution, becomes deeper and narrower with increasing needle depth, suggesting that possible stimulation sites may be controlled by changing the needle depth. The injection current amplitude should be adjusted when changing the needle depth because the peak field strength also changes. This study shows that intra-epidermal electrical stimulation can achieve stimulation of small fibres selectively, because Aβ-, Aδ-, and C-fibre terminals are located at different depths in the skin.

Psychomotor development, environmental stimulation, and socioeconomic level of preschoolers in Temuco, Chile.

PubMed

Doussoulin Sanhueza, Arlette

2006-01-01

This research was designed to describe the psychomotor development, environmental stimulation, and the socioeconomic condition of preschool children attending three educational institutions in the city of Temuco, Chile. The sample included 81 boys and girls whose age ranged from three to four years. The Test de Desarrollo Psicomotor (The Psychomotor Development Test), or TEPSI, was used to assess psychomotor development; the Home Observation Measurement of the Environment (HOME) Scale was used to evaluate environmental stimulation; and the Socioeconomic Standardization Model was used to categorize children's socioeconomic status. The highest statistical correlation was observed between psychomotor development and environmental stimulation when comparing all three parameters across the sample. Environmental stimulation may be the most relevant parameter in the study of psychomotor development of children. Socioeconomic status alone does not seem to be strongly related to children's psychomotor development in the Temuco region of Chile.

The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease.

PubMed

Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M; Tan, Huiling; Brown, Peter

2017-04-01

Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson's disease, and helps inform how adaptive deep brain stimulation might best be delivered. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson’s disease

PubMed Central

Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M.; Tan, Huiling

2017-01-01

Abstract Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson’s disease, elevations in beta activity (13–35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson’s disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could be more efficacious than conventional continuous deep brain stimulation in the treatment of Parkinson’s disease, and helps inform how adaptive deep brain stimulation might best be delivered. PMID:28334851

Deep brain stimulation for movement disorders.

PubMed

Thevathasan, Wesley; Gregory, Ralph

2010-02-01

Deep brain stimulation is now considered a routine treatment option for selected patients with advanced Parkinson's disease, primary segmental and generalised dystonia, and essential tremor. The neurosurgeon is responsible for the accurate and safe placement of the electrodes and the neurologist for the careful selection of patients and titration of medication against the effects of stimulation. A multidisciplinary team approach involving specialist nurses, neuropsychologists and neurophysiologists is required for a successful outcome. In this article we will summarise the key points in patient selection, provide an overview of the surgical technique, and discuss the beneficial and adverse outcomes that can occur.

Sensory Optimization by Stochastic Tuning

PubMed Central

Jurica, Peter; Gepshtein, Sergei; Tyukin, Ivan; van Leeuwen, Cees

2013-01-01

Individually, visual neurons are each selective for several aspects of stimulation, such as stimulus location, frequency content, and speed. Collectively, the neurons implement the visual system’s preferential sensitivity to some stimuli over others, manifested in behavioral sensitivity functions. We ask how the individual neurons are coordinated to optimize visual sensitivity. We model synaptic plasticity in a generic neural circuit, and find that stochastic changes in strengths of synaptic connections entail fluctuations in parameters of neural receptive fields. The fluctuations correlate with uncertainty of sensory measurement in individual neurons: the higher the uncertainty the larger the amplitude of fluctuation. We show that this simple relationship is sufficient for the stochastic fluctuations to steer sensitivities of neurons toward a characteristic distribution, from which follows a sensitivity function observed in human psychophysics, and which is predicted by a theory of optimal allocation of receptive fields. The optimal allocation arises in our simulations without supervision or feedback about system performance and independently of coupling between neurons, making the system highly adaptive and sensitive to prevailing stimulation. PMID:24219849

Comparison of 2-dimensional, 3-dimensional, and vascular ultrasonographic parameters for endometrial receptivity between 2 consecutive stimulated in vitro fertilization cycles.

PubMed

Ng, Ernest Hung Yu; Chan, Carina Chi Wai; Tang, Oi Shan; Ho, Pak Chung

2007-07-01

We compared the ultrasonographic parameters for endometrial receptivity between 2 consecutive in vitro fertilization (IVF) cycles in the same patients. Patients who had undergone 2 in vitro fertilization cycles between November 2002 and December 2004 were recruited. A 3-dimensional ultrasonographic examination with power Doppler imaging was performed on the day of oocyte retrieval to determine the endometrial thickness, endometrial pattern, pulsatility and resistive indices of uterine vessels, endometrial volume, vascularization index, flow index, and vascularization flow index of endometrial and subendometrial regions. Of 662 patients, 95 (14.4%) underwent 2 consecutive cycles using the same stimulation regimen during the study period. There were no significant differences in these ultrasonographic parameters between the first and second cycles. The intraclass correlation coefficient (ICC) for endometrial volume was significantly higher than that of other ultrasonographic parameters. The ICC for the endometrial thickness, uterine pulsatility index, and endometrial 3-dimensional power Doppler flow indices were similar. Ultrasonographic parameters for endometrial receptivity were comparable in the 2 consecutive stimulated cycles. The endometrial volume had the highest ICC among these ultrasonographic parameters and was most reproducible between 2 cycles.

Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells

NASA Astrophysics Data System (ADS)

Suarez Castellanos, Ivan M.

Type 2 diabetes (T2D) mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. Controlling T2D is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. The objective of this dissertation was to explore a novel, non-pharmacological approach that utilizes the application of ultrasound energy to stimulate insulin release. Our experiments have focused on determination of effectiveness and safety of ultrasound application in stimulation of insulin release from the pancreatic beta cells. Our results showed that ultrasound treatment, applied at frequencies of 800 kHz and 1 MHz and intensities of 0.5 W/cm2 and 1 W/cm2, did not produce any significant effects on cell viability compared to sham group as assessed with trypan blue dye exclusion test and MTT cytotoxicity assay. ELISA quantification of insulin release from beta cells resulting from ultrasound treatment showed clinically-significant amounts of released insulin as compared to sham-treated beta cells. Carbon fiber amperometry detection of secretory events from dopamine-loaded beta cells treated with ultrasound showed that release of secretory content could be temporally controlled by careful selection of ultrasound parameters. Both ELISA and amperometry experiments demonstrated that ultrasound-stimulated insulin release is a calcium-dependent process, potentially mediated by the mechanical effects of ultrasound. This study demonstrated that therapeutic ultrasound is a technique capable of stimulating the release of insulin from pancreatic beta cells in a safe, effective and controlled manner.

The "neuro-mapping locator" software. A real-time intraoperative objective paraesthesia mapping tool to evaluate paraesthesia coverage of the painful zone in patients undergoing spinal cord stimulation lead implantation.

PubMed

Guetarni, F; Rigoard, P

2015-03-01

Conventional spinal cord stimulation (SCS) generates paraesthesia, as the efficacy of this technique is based on the relationship between the paraesthesia provided by SCS on the painful zone and an analgesic effect on the stimulated zone. Although this basic postulate is based on clinical evidence, it is clear that this relationship has never been formally demonstrated by scientific studies. There is a need for objective evaluation tools ("transducers") to transpose electrical signals to clinical effects and to guide therapeutic choices. We have developed a software at Poitiers University hospital allowing real-time objective mapping of the paraesthesia generated by SCS lead placement and programming during the implantation procedure itself, on a touch screen interface. The purpose of this article is to describe this intraoperative mapping software, in terms of its concept and technical aspects. The Neuro-Mapping Locator (NML) software is dedicated to patients with failed back surgery syndrome, candidates for SCS lead implantation, to actively participate in the implantation procedure. Real-time geographical localization of the paraesthesia generated by percutaneous or multicolumn surgical SCS lead implanted under awake anaesthesia allows intraoperative lead programming and possibly lead positioning to be modified with the patient's cooperation. Software updates should enable us to refine objectives related to the use of this tool and minimize observational biases. The ultimate goals of NML software should not be limited to optimize one specific device implantation in a patient but also allow to compare instantaneously various stimulation strategies, by characterizing new technical parameters as "coverage efficacy" and "device specificity" on selected subgroups of patients. Another longer-term objective would be to organize these predictive factors into computer science ontologies, which could constitute robust and helpful data for device selection and programming of tomorrow's neurostimulators. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

One year double blind study of high vs low frequency subcallosal cingulate stimulation for depression.

PubMed

Eitan, Renana; Fontaine, Denys; Benoît, Michel; Giordana, Caroline; Darmon, Nelly; Israel, Zvi; Linesky, Eduard; Arkadir, David; Ben-Naim, Shiri; Iserlles, Moshe; Bergman, Hagai; Hulse, Natasha; Abdelghani, Mohamed; McGuffin, Peter; Farmer, Anne; DeLea, Peichel; Ashkan, Keyoumars; Lerer, Bernard

2018-01-01

Subcallosal Brodmann's Area 25 (Cg25) Deep Brain Stimulation (DBS) is a new promising therapy for treatment resistant major depressive disorder (TR-MDD). While different DBS stimulating parameters may have an impact on the efficacy and safety of the therapy, there is no data to support a protocol for optimal stimulation parameters for depression. Here we present a prospective multi-center double-blind randomized crossed-over 13-month study that evaluated the effects of High (130 Hz) vs Low (20 Hz) frequency Cg25 stimulation for nine patients with TR-MDD. Four out of nine patients achieved response criteria (≥40% reduction of symptom score) compared to mean baseline values at the end of the study. The mean percent change of MADRS score showed a similar improvement in the high and low frequency stimulation groups after 6 months of stimulation (-15.4 ± 21.1 and -14.7 ± 21.1 respectively). The mean effect at the end of the second period (6 months after cross-over) was higher than the first period (first 6 months of stimulation) in all patients (-23.4 ± 19.9 (n = 6 periods) and -13.0 ± 22 (n = 9 periods) respectively). At the end of the second period, the mean percent change of the MADRS scores improved more in the high than low frequency groups (-31.3 ± 19.3 (n = 4 patients) and -7.7 ± 10.9 (n = 2 patients) respectively). Given the small numbers, detailed statistical analysis is challenging. Nonetheless the results of this study suggest that long term high frequency stimulation might confer the best results. Larger scale, randomized double blind trials are needed in order to evaluate the most effective stimulation parameters. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of Epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study

PubMed Central

Harkema, Susan; Gerasimenko, Yury; Hodes, Jonathan; Burdick, Joel; Angeli, Claudia; Chen, Yangsheng; Ferreira, Christie; Willhite, Andrea; Rejc, Enrico; Grossman, Robert G.; Edgerton, V. Reggie

2011-01-01

Summary Background Repeated periods of stimulation of the spinal cord and training seems to have amplified the ability to consciously control movement. Methods An individual three years post C7-T1 subluxation presented with a complete loss of clinically detectable voluntary motor function and partial preservation of sensation below the T1 cord segment. Following 170 locomotor training sessions, a 16-electrode array was surgically placed on the dura (L1-S1 cord segments) to allow for chronic electrical stimulation. After implantation and throughout stand retraining with epidural stimulation, 29 experiments were performed. Extensive stimulation combinations and parameters were tested to achieve standing and stepping. Findings Epidural stimulation enabled the human lumbosacral spinal circuitry to dynamically elicit full weight-bearing standing with assistance provided only for balance for 4·25 minutes in a subject with a clinically motor complete SCI. This occurred when using stimulation at parameters optimized for standing while providing bilateral load-bearing proprioceptive input. Locomotor-like patterns were also observed when stimulation parameters were optimized for stepping. In addition, seven months after implantation, the subject recovered supraspinal control of certain leg movements, but only during epidural stimulation. Interpretation Even after a severe low cervical spinal injury, the neural networks remaining within the lumbosacral segments can be reactivated into functional states so that it can recognize specific details of ensembles of sensory input to the extent that it can serve as the source of neural control. In addition, newly formed supraspinal input to this same lumbosacral segments can re-emerge as another source of control. Task specific training with epidural stimulation may have reactivated previously silent spared neural circuits or promoted plasticity. This suggests that these interventions could be a viable clinical approach for functional recovery after severe paralysis. Funding National Institutes of Health and Christopher and Dana Reeve Foundation. PMID:21601270

Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex.

PubMed

Major, Alex J; Vijayraghavan, Susheel; Everling, Stefan

2018-01-31

Acetylcholine is released in the prefrontal cortex (PFC) and is a key modulator of cognitive performance in primates. Cholinergic stimulation has been shown to have beneficial effects on performance of cognitive tasks, and cholinergic receptors are being actively explored as promising targets for ameliorating cognitive deficits in Alzheimer's disease. We hypothesized that cholinergic stimulation of PFC during performance of a cognitive task would augment neuronal activity and neuronal coding of task attributes. We iontophoretically applied the general cholinergic receptor agonist carbachol onto neurons in dorsolateral PFC (DLPFC) of male rhesus macaques performing rule-guided prosaccades and antisaccades, a well established oculomotor task for testing cognitive control. Carbachol application had heterogeneous effects on neuronal excitability, with both excitation and suppression observed in significant proportions. Contrary to our prediction, neurons with rule-selective activity exhibited a reduction in selectivity during carbachol application. Cholinergic stimulation disrupted rule selectivity regardless of whether it had suppressive or excitatory effects on these neurons. In addition, cholinergic stimulation excited putative pyramidal neurons, whereas the activity of putative interneurons remained unchanged. Moreover, cholinergic stimulation attenuated saccade direction selectivity in putative pyramidal neurons due to nonspecific increases in activity. Our results suggest excessive cholinergic stimulation has detrimental effects on DLPFC representations of task attributes. These findings delineate the complexity and heterogeneity of neuromodulation of cerebral cortex by cholinergic stimulation, an area of active exploration with respect to the development of cognitive enhancers. SIGNIFICANCE STATEMENT The neurotransmitter acetylcholine is known to be important for cognitive processes in the prefrontal cortex. Removal of acetylcholine from prefrontal cortex can disrupt short-term memory performance and is reminiscent of Alzheimer's disease, which is characterized by degeneration of acetylcholine-producing neurons. Stimulation of cholinergic receptors is being explored to create cognitive enhancers for the treatment of Alzheimer's disease and other psychiatric diseases. Here, we stimulated cholinergic receptors in prefrontal cortex and examined its effects on neurons that are engaged in cognitive behavior. Surprisingly, cholinergic stimulation decreased neurons' ability to discriminate between rules. This work suggests that overstimulation of acetylcholine receptors could disrupt neuronal processing during cognition and is relevant to the design of cognitive enhancers based on stimulating the cholinergic system. Copyright © 2018 the authors 0270-6474/18/381137-14$15.00/0.

A Systematic Review and Meta-Analysis of the Effects of Transcranial Direct Current Stimulation (tDCS) Over the Dorsolateral Prefrontal Cortex in Healthy and Neuropsychiatric Samples: Influence of Stimulation Parameters.

PubMed

Dedoncker, Josefien; Brunoni, Andre R; Baeken, Chris; Vanderhasselt, Marie-Anne

2016-01-01

Research into the effects of transcranial direct current stimulation of the dorsolateral prefrontal cortex on cognitive functioning is increasing rapidly. However, methodological heterogeneity in prefrontal tDCS research is also increasing, particularly in technical stimulation parameters that might influence tDCS effects. To systematically examine the influence of technical stimulation parameters on DLPFC-tDCS effects. We performed a systematic review and meta-analysis of tDCS studies targeting the DLPFC published from the first data available to February 2016. Only single-session, sham-controlled, within-subject studies reporting the effects of tDCS on cognition in healthy controls and neuropsychiatric patients were included. Evaluation of 61 studies showed that after single-session a-tDCS, but not c-tDCS, participants responded faster and more accurately on cognitive tasks. Sub-analyses specified that following a-tDCS, healthy subjects responded faster, while neuropsychiatric patients responded more accurately. Importantly, different stimulation parameters affected a-tDCS effects, but not c-tDCS effects, on accuracy in healthy samples vs. increased current density and density charge resulted in improved accuracy in healthy samples, most prominently in females; for neuropsychiatric patients, task performance during a-tDCS resulted in stronger increases in accuracy rates compared to task performance following a-tDCS. Healthy participants respond faster, but not more accurate on cognitive tasks after a-tDCS. However, increasing the current density and/or charge might be able to enhance response accuracy, particularly in females. In contrast, online task performance leads to greater increases in response accuracy than offline task performance in neuropsychiatric patients. Possible implications and practical recommendations are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcranial direct current stimulation improves long-term memory deficits in an animal model of attention-deficit/hyperactivity disorder and modulates oxidative and inflammatory parameters.

PubMed

Leffa, Douglas Teixeira; Bellaver, Bruna; Salvi, Artur Alban; de Oliveira, Carla; Caumo, Wolnei; Grevet, Eugenio Horacio; Fregni, Felipe; Quincozes-Santos, André; Rohde, Luis Augusto; Torres, Iraci L S

2018-04-05

Transcranial direct current stimulation (tDCS) is a technique that modulates neuronal activity and has been proposed as a potential therapeutic tool for attention-deficit/hyperactivity disorder (ADHD) symptoms. Although pilot studies have shown evidence of efficacy, its mechanism of action remains unclear. We evaluated the effects of tDCS on behavioral (working and long-term memory) and neurochemical (oxidative and inflammatory parameters) outcomes related to ADHD pathophysiology. We used the most widely accepted animal model of ADHD: spontaneously hypertensive rats (SHR). The selected behavioral outcomes have been shown to be altered in both ADHD patients and animal models, and were chosen for their relation to the proposed mechanistic action of tDCS. Adult male SHR and their control, the Wistar Kyoto rats (WKY), were subjected to 20 min of bicephalic tDCS or sham stimulation for 8 consecutive days. Working memory, long-term memory, and neurochemical outcomes were evaluated. TDCS improved long-term memory deficits presented by the SHR. No change in working memory performance was observed. In the hippocampus, tDCS increased both the production of reactive oxygen species in SHR and the levels of the antioxidant molecule glutathione in both strains. TDCS also modulated inflammatory response in the brains of WKY by downregulating pro-inflammatory cytokines. TDCS had significant effects that were specific for strain, type of behavioral and neurochemical outcomes. The long-term memory improvement in the SHR may point to a possible therapeutic role of tDCS in ADHD that does not seem to be mediated by inflammatory markers. Additionally, the anti-inflammatory effects observed in the brain of WKY after tDCS needs to be further explored. Copyright © 2018 Elsevier Inc. All rights reserved.

Electrical and optical co-stimulation in the deaf white cat

NASA Astrophysics Data System (ADS)

Cao, Zhiping; Xu, Yingyue; Tan, Xiaodong; Suematsu, Naofumi; Robinson, Alan; Richter, Claus-Peter

2018-02-01

Spatial selectivity of neural stimulation with photons, such as infrared neural stimulation (INS) is higher than the selectivity obtained with electrical stimulation. To obtain more independent channels for stimulation in neural prostheses, INS may be implemented to better restore the fidelity of the damaged neural system. However, irradiation with infrared light also bares the risk of heat accumulation in the target tissue with subsequent neural damage. Lowering the threshold for stimulation could reduce the amount of heat delivered to the tissue and the risk for subsequent tissue damage. It has been shown in the rat sciatic nerve that simultaneous irradiation with infrared light and the delivery of biphasic sub-threshold electrical pulses can reduce the threshold for INS [1]. In this study, deaf white cats have been used to test whether opto-electrical co-stimulation can reduce the stimulation threshold for INS in the auditory system too. The cochleae of the deaf white cats have largely reduced spiral ganglion neuron counts and significant degeneration of the organ of Corti and do not respond to acoustic stimuli. Combined electrical and optical stimulation was used to demonstrate that simultaneous stimulation with infrared light and biphasic electrical pulses can reduce the threshold for stimulation.

Staggered transverse tripoles with quadripolar lateral anodes using percutaneous and surgical leads in spinal cord stimulation.

PubMed

Sankarasubramanian, Vishwanath; Buitenweg, Jan R; Holsheimer, Jan; Veltink, Peter H

2013-03-01

In spinal cord stimulation for low-back pain, the use of electrode arrays with both low-power requirements and selective activation of target dorsal column (DC) fibers is desired. The aligned transverse tripolar lead configuration offers the best DC selectivity. Electrode alignment of the same configuration using 3 parallel percutaneous leads is possible, but compromised by longitudinal migration, resulting in loss of DC selectivity. This loss might be repaired by using the adjacent anodal contacts on the lateral leads. To investigate if stimulation using adjacent anodal contacts on the lateral percutaneous leads of a staggered transverse tripole can restore DC selectivity. Staggered transverse tripoles with quadripolar lateral anodes were modeled on the low-thoracic vertebral region (T10-T12) of the spinal cord using (a) percutaneous lead with staggered quadripolar lateral anodal configuration (PERC QD) and (b) laminotomy lead with staggered quadripolar lateral anodal configuration (LAM QD), of the same contact dimensions. The commercially available LAM 565 surgical lead with 16 widely spaced contacts was also modeled. For comparison with PERC QD, staggered transverse tripoles with dual lateral anodes were modeled by using percutaneous lead with staggered dual lateral anodal configuration (PERC ST). The PERC QD improved the depth of DC penetration and enabled selective recruitment of DCs in comparison with PERC ST. Mediolateral selectivity of DCs could not be achieved with the LAM 565. Stimulation using PERC QD improves anodal shielding of dorsal roots and restores DC selectivity. Based on our modeling study, we hypothesize that, in clinical practice, LAM QD can provide an improved performance compared with the PERC QD. Our model also predicts that the same configuration realized on the commercial LAM 565 surgical lead with widely spaced contacts cannot selectively stimulate DCs essential in treating low-back pain.

Selective Radiofrequency Stimulation of the Dorsal Root Ganglion (DRG) as a Method for Predicting Targets for Neuromodulation in Patients With Post Amputation Pain: A Case Series.

PubMed

Hunter, Corey W; Yang, Ajax; Davis, Tim

2017-10-01

While spinal cord stimulation (SCS) has established itself as an accepted and validated treatment for neuropathic pain, there are a number of conditions where it has experienced less, long-term success: post amputee pain (PAP) being one of them. Dorsal root ganglion (DRG) stimulation has shown great promise, particularly in conditions where traditional SCS has fallen short. One major difference between DRG stimulation and traditional SCS is the ability to provide focal stimulation over targeted areas. While this may be a contributing factor to its superiority, it can also be a limitation insofar stimulating the wrong DRG(s) can lead to failure. This is particularly relevant in conditions like PAP where neuroplastic maladaptation occurs causing the pain to deviate from expected patterns, thus creating uncertainty and variability in predicting targets for stimulation. We propose selective radiofrequency (RF) stimulation of the DRG as a method for preoperatively predicting targets for neuromodulation in patients with PAP. We present four patients with PAP of the lower extremities. RF stimulation was used to selectively stimulate individual DRG's, creating areas of paresthesias to see which most closely correlated/overlapped with the painful area(s). RF stimulation to the DRG's that resulted in the desirable paresthesia coverage in the residual or the missing limb(s) was recorded as "positive." Trial DRG leads were placed based on the positive RF stimulation findings. In each patient, stimulating one or more DRG(s) produced paresthesias patterns that were contradictory to know dermatomal patterns. Upon completion of a one-week trial all four patients reported 60-90% pain relief, with coverage over the painful areas, and opted for permanent implant. Mapping the DRG via RF stimulation appears to provide improved accuracy for determining lead placement in the setting of PAP where pain patterns are known to deviate from conventional dermatomal mapping. © 2017 International Neuromodulation Society.

Subthalamic nucleus stimulation influences expression and suppression of impulsive behaviour in Parkinson’s disease

PubMed Central

Ridderinkhof, K. Richard; Elias, William J.; Frysinger, Robert C.; Bashore, Theodore R.; Downs, Kara E.; van Wouwe, Nelleke C.; van den Wildenberg, Wery P. M.

2010-01-01

Past studies show beneficial as well as detrimental effects of subthalamic nucleus deep-brain stimulation on impulsive behaviour. We address this paradox by investigating individuals with Parkinson’s disease treated with subthalamic nucleus stimulation (n = 17) and healthy controls without Parkinson’s disease (n = 17) on performance in a Simon task. In this reaction time task, conflict between premature response impulses and goal-directed action selection is manipulated. We applied distributional analytic methods to separate the strength of the initial response impulse from the proficiency of inhibitory control engaged subsequently to suppress the impulse. Patients with Parkinson’s disease were tested when stimulation was either turned on or off. Mean conflict interference effects did not differ between controls and patients, or within patients when stimulation was on versus off. In contrast, distributional analyses revealed two dissociable effects of subthalamic nucleus stimulation. Fast response errors indicated that stimulation increased impulsive, premature responding in high conflict situations. Later in the reaction process, however, stimulation improved the proficiency with which inhibitory control was engaged to suppress these impulses selectively, thereby facilitating selection of the correct action. This temporal dissociation supports a conceptual framework for resolving past paradoxical findings and further highlights that dynamic aspects of impulse and inhibitory control underlying goal-directed behaviour rely in part on neural circuitry inclusive of the subthalamic nucleus. PMID:20861152

Body growth and reproduction of individuals of the sciaenid fish Stellifer rastrifer in a shallow tropical bight: A cautionary tale for assumptions regarding population parameters

NASA Astrophysics Data System (ADS)

Pombo, Maíra; Denadai, Márcia Regina; Turra, Alexander

2013-05-01

Knowledge of population parameters and the ability to predict their responses to environmental changes are useful tools to aid in the appropriate management and conservation of natural resources. Samples of the sciaenid fish Stellifer rastrifer were taken from August 2003 through October 2004 in shallow areas of Caraguatatuba Bight, southeastern Brazil. The results showed a consistent presence of length-frequency classes throughout the year and low values of the gonadosomatic index of this species, indicating that the area is not used for spawning or residence of adults, but rather shelters individuals in late stages of development. The results may serve as a caveat for assessments of transitional areas such as the present one, the nursery function of which is neglected compared to estuaries and mangroves. The danger of mismanaging these areas by not considering their peculiarities is emphasized by using these data as a study case for the development of some broadly used population-parameter analyses. The individuals' body growth parameters from the von Bertalanffy model were estimated based on the most common approaches, and the best values obtained from traditional quantification methods of selection were very prone to bias. The low gonadosomatic index (GSI) estimated during the period was an important factor in stimulating us to select more reliable parameters of body growth (L∞ = 20.9, K = 0.37 and Z = 2.81), which were estimated based on assuming the existence of spatial segregation by size. The data obtained suggest that the estimated mortality rate included a high rate of migration of older individuals to deeper areas, where we assume that they completed their development.

Parameters for calcium metabolism in women with polycystic ovary syndrome who undergo clomiphene citrate stimulation: a prospective cohort study.

PubMed

Ott, J; Wattar, L; Kurz, C; Seemann, R; Huber, J C; Mayerhofer, K; Vytiska-Binstorfer, E

2012-05-01

To evaluate whether parameters for calcium metabolism were associated with characteristics of polycystic ovary syndrome (PCOS). A prospective cohort study. Ninety-one anovulatory, infertile women with PCOS patients underwent clomiphene citrate (CC) stimulation. Main outcome measures were parathyroid hormone (PTH); 25-hydroxyvitamin D3 (25OHD3); serum levels of calcium, phosphorus, magnesium, albumin, and total protein; the serum calcium-phosphorus product; LH; FSH; sexual hormone binding globulin; testosterone; and androstenedione. PTH correlated inversely with serum calcium (r=-0.235; P=0.004) and 25OHD3 (r=-0.664; P<0.001), whereas positive correlations were found between PTH and body mass index (BMI; r=0.270; P=0.010) and between PTH and testosterone (r=0.347; P=0.001). After stimulation with 50 mg CC, 57.1% (52/91) developed a follicle, whereas 26.4% (24/91) became pregnant. In a multivariate model to predict both follicle development and pregnancy, BMI and 25OHD3 deficiency were significant predictive parameters. 25OHD3 deficiency was an independent predictive parameter of CC stimulation outcome, in terms of follicle development and pregnancy. Our results suggest a substantial role of vitamin D in PCOS and infertility treatment in these patients.

StimDuino: an Arduino-based electrophysiological stimulus isolator.

PubMed

Sheinin, Anton; Lavi, Ayal; Michaelevski, Izhak

2015-03-30

Electrical stimulus isolator is a widely used device in electrophysiology. The timing of the stimulus application is usually automated and controlled by the external device or acquisition software; however, the intensity of the stimulus is adjusted manually. Inaccuracy, lack of reproducibility and no automation of the experimental protocol are disadvantages of the manual adjustment. To overcome these shortcomings, we developed StimDuino, an inexpensive Arduino-controlled stimulus isolator allowing highly accurate, reproducible automated setting of the stimulation current. The intensity of the stimulation current delivered by StimDuino is controlled by Arduino, an open-source microcontroller development platform. The automatic stimulation patterns are software-controlled and the parameters are set from Matlab-coded simple, intuitive and user-friendly graphical user interface. The software also allows remote control of the device over the network. Electrical current measurements showed that StimDuino produces the requested current output with high accuracy. In both hippocampal slice and in vivo recordings, the fEPSP measurements obtained with StimDuino and the commercial stimulus isolators showed high correlation. Commercial stimulus isolators are manually managed, while StimDuino generates automatic stimulation patterns with increasing current intensity. The pattern is utilized for the input-output relationship analysis, necessary for assessment of excitability. In contrast to StimuDuino, not all commercial devices are capable for remote control of the parameters and stimulation process. StimDuino-generated automation of the input-output relationship assessment eliminates need for the current intensity manually adjusting, improves stimulation reproducibility, accuracy and allows on-site and remote control of the stimulation parameters. Copyright © 2015 Elsevier B.V. All rights reserved.

Using Transcranial Direct Current Stimulation to Enhance Creative Cognition: Interactions between Task, Polarity, and Stimulation Site

PubMed Central

Weinberger, Adam B.; Green, Adam E.; Chrysikou, Evangelia G.

2017-01-01

Creative cognition is frequently described as involving two primary processes, idea generation and idea selection. A growing body of research has used transcranial direct current stimulation (tDCS) to examine the neural mechanisms implicated in each of these processes. This literature has yielded a diverse set of findings that vary depending on the location and type (anodal, cathodal, or both) of electrical stimulation employed, as well as the task’s reliance on idea generation or idea selection. As a result, understanding the interactions between stimulation site, polarity and task demands is required to evaluate the potential of tDCS to enhance creative performance. Here, we review tDCS designs that have elicited reliable and dissociable enhancements for creative cognition. Cathodal stimulation over the left inferior frontotemporal cortex has been associated with improvements on tasks that rely primarily on idea generation, whereas anodal tDCS over left dorsolateral prefrontal cortex (DLPFC) and frontopolar cortex has been shown to augment performance on tasks that impose high demands on creative idea selection. These results highlight the functional selectivity of tDCS for different components of creative thinking and confirm the dissociable contributions of left dorsal and inferior lateral frontotemporal cortex for different creativity tasks. We discuss promising avenues for future research that can advance our understanding of the effectiveness of tDCS as a method to enhance creative cognition. PMID:28559804

Restoration of vision in blind individuals using bionic devices: a review with a focus on cortical visual prostheses.

PubMed

Lewis, Philip M; Ackland, Helen M; Lowery, Arthur J; Rosenfeld, Jeffrey V

2015-01-21

The field of neurobionics offers hope to patients with sensory and motor impairment. Blindness is a common cause of major sensory loss, with an estimated 39 million people worldwide suffering from total blindness in 2010. Potential treatment options include bionic devices employing electrical stimulation of the visual pathways. Retinal stimulation can restore limited visual perception to patients with retinitis pigmentosa, however loss of retinal ganglion cells precludes this approach. The optic nerve, lateral geniculate nucleus and visual cortex provide alternative stimulation targets, with several research groups actively pursuing a cortically-based device capable of driving several hundred stimulating electrodes. While great progress has been made since the earliest works of Brindley and Dobelle in the 1960s and 1970s, significant clinical, surgical, psychophysical, neurophysiological, and engineering challenges remain to be overcome before a commercially-available cortical implant will be realized. Selection of candidate implant recipients will require assessment of their general, psychological and mental health, and likely responses to visual cortex stimulation. Implant functionality, longevity and safety may be enhanced by careful electrode insertion, optimization of electrical stimulation parameters and modification of immune responses to minimize or prevent the host response to the implanted electrodes. Psychophysical assessment will include mapping the positions of potentially several hundred phosphenes, which may require repetition if electrode performance deteriorates over time. Therefore, techniques for rapid psychophysical assessment are required, as are methods for objectively assessing the quality of life improvements obtained from the implant. These measures must take into account individual differences in image processing, phosphene distribution and rehabilitation programs that may be required to optimize implant functionality. In this review, we detail these and other challenges facing developers of cortical visual prostheses in addition to briefly outlining the epidemiology of blindness, and the history of cortical electrical stimulation in the context of visual prosthetics. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Orientation selective deep brain stimulation

NASA Astrophysics Data System (ADS)

Lehto, Lauri J.; Slopsema, Julia P.; Johnson, Matthew D.; Shatillo, Artem; Teplitzky, Benjamin A.; Utecht, Lynn; Adriany, Gregor; Mangia, Silvia; Sierra, Alejandra; Low, Walter C.; Gröhn, Olli; Michaeli, Shalom

2017-02-01

Objective. Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS. Approach. This concept, which involves orienting the electric field along an axonal pathway, was tested in the corpus callosum of the rat brain by freely controlling the direction of the electric field on a plane using a three-electrode bundle, and monitoring the response of the neurons using functional magnetic resonance imaging (fMRI). Computational models were developed to further analyze axonal excitability for varied electric field orientation. Main results. Our results demonstrated that the strongest fMRI response was observed when the electric field was oriented parallel to the axons, while almost no response was detected with the perpendicular orientation of the electric field relative to the primary fiber tract. These results were confirmed by computational models of the experimental paradigm quantifying the activation of radially distributed axons while varying the primary direction of the electric field. Significance. The described strategies identify a new course for selective neuromodulation paradigms in DBS based on axonal fiber orientation.

Development of network-based multichannel neuromuscular electrical stimulation system for stroke rehabilitation.

PubMed

Qu, Hongen; Xie, Yongji; Liu, Xiaoxuan; He, Xin; Hao, Manzhao; Bao, Yong; Xie, Qing; Lan, Ning

2016-01-01

Neuromuscular electrical stimulation (NMES) is a promising assistive technology for stroke rehabilitation. Here we present the design and development of a multimuscle stimulation system as an emerging therapy for people with paretic stroke. A network-based multichannel NMES system was integrated based on dual bus architecture of communication and an H-bridge current regulator with a power booster. The structure of the system was a body area network embedded with multiple stimulators and a communication protocol of controlled area network to transmit muscle stimulation parameter information to individual stimulators. A graphical user interface was designed to allow clinicians to specify temporal patterns and muscle stimulation parameters. We completed and tested a prototype of the hardware and communication software modules of the multichannel NMES system. The prototype system was first verified in nondisabled subjects for safety, and then tested in subjects with stroke for feasibility with assisting multijoint movements. Results showed that synergistic stimulation of multiple muscles in subjects with stroke improved performance of multijoint movements with more natural velocity profiles at elbow and shoulder and reduced acromion excursion due to compensatory trunk rotation. The network-based NMES system may provide an innovative solution that allows more physiological activation of multiple muscles in multijoint task training for patients with stroke.

Efficiency Analysis of Waveform Shape for Electrical Excitation of Nerve Fibers

PubMed Central

Wongsarnpigoon, Amorn; Woock, John P.; Grill, Warren M.

2011-01-01

Stimulation efficiency is an important consideration in the stimulation parameters of implantable neural stimulators. The objective of this study was to analyze the effects of waveform shape and duration on the charge, power, and energy efficiency of neural stimulation. Using a population model of mammalian axons and in vivo experiments on cat sciatic nerve, we analyzed the stimulation efficiency of four waveform shapes: square, rising exponential, decaying exponential, and rising ramp. No waveform was simultaneously energy-, charge-, and power-optimal, and differences in efficiency among waveform shapes varied with pulse width (PW) For short PWs (≤ 0.1 ms), square waveforms were no less energy-efficient than exponential waveforms, and the most charge-efficient shape was the ramp. For long PWs (≥0.5 ms), the square was the least energy-efficient and charge-efficient shape, but across most PWs, the square was the most power-efficient shape. Rising exponentials provided no practical gains in efficiency over the other shapes, and our results refute previous claims that the rising exponential is the energy-optimal shape. An improved understanding of how stimulation parameters affect stimulation efficiency will help improve the design and programming of implantable stimulators to minimize tissue damage and extend battery life. PMID:20388602

Autonomous Parameter Adjustment for SSVEP-Based BCIs with a Novel BCI Wizard.

PubMed

Gembler, Felix; Stawicki, Piotr; Volosyak, Ivan

2015-01-01

Brain-Computer Interfaces (BCIs) transfer human brain activities into computer commands and enable a communication channel without requiring movement. Among other BCI approaches, steady-state visual evoked potential (SSVEP)-based BCIs have the potential to become accurate, assistive technologies for persons with severe disabilities. Those systems require customization of different kinds of parameters (e.g., stimulation frequencies). Calibration usually requires selecting predefined parameters by experienced/trained personnel, though in real-life scenarios an interface allowing people with no experience in programming to set up the BCI would be desirable. Another occurring problem regarding BCI performance is BCI illiteracy (also called BCI deficiency). Many articles reported that BCI control could not be achieved by a non-negligible number of users. In order to bypass those problems we developed a SSVEP-BCI wizard, a system that automatically determines user-dependent key-parameters to customize SSVEP-based BCI systems. This wizard was tested and evaluated with 61 healthy subjects. All subjects were asked to spell the phrase "RHINE WAAL UNIVERSITY" with a spelling application after key parameters were determined by the wizard. Results show that all subjects were able to control the spelling application. A mean (SD) accuracy of 97.14 (3.73)% was reached (all subjects reached an accuracy above 85% and 25 subjects even reached 100% accuracy).

What Do We Know About the Influence of the Cerebellum on Walking Ability? Promising Findings from Transcranial Alternating Current Stimulation.

PubMed

Naro, Antonino; Milardi, Demetrio; Cacciola, Alberto; Russo, Margherita; Sciarrone, Francesca; La Rosa, Gianluca; Bramanti, Alessia; Bramanti, Placido; Calabrò, Rocco Salvatore

2017-08-01

Several cerebellar functions related to upper limb motor control have been studied using non-invasive brain stimulation paradigms. We have recently shown that transcranial alternating current stimulation (tACS) may be a promising approach in shaping the plasticity of cerebellum-brain pathways in a safe and effective manner. This study aimed to assess whether cerebellar tACS at different frequencies may tune M1-leg excitability and modify gait control in healthy human subjects. To this end, we tested the effects of different cerebellar tACS frequencies over the right cerebellar hemisphere (at 10, 50, and 300 Hz, besides a sham-tACS) on M1-leg excitability, cerebellum-brain inhibition (CBI), and gait parameters in a sample of 25 healthy volunteers. Fifty and 300 Hz tACS differently modified M1-leg excitability and CBI from both lower limbs, without significant gait perturbations. We hypothesize that tACS aftereffect may depend on a selective entrainment of distinct cerebellar networks related to lower limb motor functions. Therefore, cerebellar tACS might represent a useful tool to modulate walking training in people with cerebellum-related gait impairment, given that tACS may potentially reset abnormal cerebellar circuitries.

Emerging strategies in the management of essential tremor

PubMed Central

Hedera, Peter

2016-01-01

Currently available therapies for essential tremor (ET) provide sufficient control only for less than a half of patients and many unmet needs exist. This is in part due to the empiric nature of existing treatment options and persisting uncertainties about the pathogenesis of ET. The emerging concept of ET as a possible neurodegenerative disorder, better understanding of associated biochemical changes, including alterations in the γ-aminobutyric acid (GABA)-ergic system and gap junctions, and the identification of the role of the leucine-rich repeat and immunoglobulin-like domain-containing 1 (LINGO-1) gene in ET pathogenesis suggest new avenues for more targeted therapies. Here we review the most promising new approaches to treating ET, including allosteric modulation of GABA receptors and modifications of the LINGO-1 pathway. Medically refractory tremor can be successfully treated by high-frequency deep brain stimulation (DBS) of the ventral intermediate nucleus, but surgical therapies are also fraught with limitations due to adverse effects of stimulation and the loss of therapeutic response. The selection of additional thalamic and extrathalamic targets for electrode placements and the development of a closed-loop DBS system enabling automatic adjustment of stimulation parameters in response to changes in electrophysiologic brain activity are also reviewed. Tremor cancellation methods using exoskeleton and external hand-held devices are also briefly discussed. PMID:28382111

Neuronal and behavioural modulations by pathway-selective optogenetic stimulation of the primate oculomotor system

PubMed Central

Inoue, Ken-ichi; Takada, Masahiko; Matsumoto, Masayuki

2015-01-01

Optogenetics enables temporally and spatially precise control of neuronal activity in vivo. One of the key advantages of optogenetics is that it can be used to control the activity of targeted neural pathways that connect specific brain regions. While such pathway-selective optogenetic control is a popular tool in rodents, attempts at modulating behaviour using pathway-selective optogenetics have not yet been successful in primates. Here we develop a methodology for pathway-selective optogenetics in macaque monkeys, focusing on the pathway from the frontal eye field (FEF) to the superior colliculus (SC), part of the complex oculomotor network. We find that the optogenetic stimulation of FEF projections to the SC modulates SC neuron activity and is sufficient to evoke saccadic eye movements towards the response field corresponding to the stimulation site. Thus, our results demonstrate the feasibility of using pathway-selective optogenetics to elucidate neural network function in primates. PMID:26387804

Neuronal and behavioural modulations by pathway-selective optogenetic stimulation of the primate oculomotor system.

PubMed

Inoue, Ken-ichi; Takada, Masahiko; Matsumoto, Masayuki

2015-09-21

Optogenetics enables temporally and spatially precise control of neuronal activity in vivo. One of the key advantages of optogenetics is that it can be used to control the activity of targeted neural pathways that connect specific brain regions. While such pathway-selective optogenetic control is a popular tool in rodents, attempts at modulating behaviour using pathway-selective optogenetics have not yet been successful in primates. Here we develop a methodology for pathway-selective optogenetics in macaque monkeys, focusing on the pathway from the frontal eye field (FEF) to the superior colliculus (SC), part of the complex oculomotor network. We find that the optogenetic stimulation of FEF projections to the SC modulates SC neuron activity and is sufficient to evoke saccadic eye movements towards the response field corresponding to the stimulation site. Thus, our results demonstrate the feasibility of using pathway-selective optogenetics to elucidate neural network function in primates.

Systematic Review of Three Electrical Stimulation Techniques for Rehabilitation After Total Knee Arthroplasty.

PubMed

Yue, Chen; Zhang, Xue; Zhu, Yingjie; Jia, Yudong; Wang, Huichao; Liu, Youwen

2018-07-01

The comparative effectiveness of neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and electroacupuncture (EA) for improving patient rehabilitation following total knee arthroplasty (TKA) is controversial. Therefore we conducted this systematic review to assess the available evidence. The PubMed, OVID, and ScienceDirect databases were comprehensively searched and studies were selected and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Data were extracted and qualitatively synthesized for several outcomes. Data were analyzed from 17 randomized controlled trials involving 1285 procedures: 8 NMES studies (608 procedures), 7 TENS studies (560 procedures), and 2 EA studies (117 procedures). Qualitative analysis suggested that NMES was associated with higher quadriceps strength and functional recovery after TKA. Recovery benefits were maximal when the stimulation was performed once or twice a day for 4-6 weeks at an intensity of 100-120 mA and frequency of 30-100 Hz. The electrode should be sufficiently large (100-200 cm 2 ) to reduce discomfort. TENS at an intensity of 15-40 mA and frequency of 70-150 Hz provided effective analgesia after TKA. EA at an intensity of 2 mA and frequency of 2 Hz may also provide postoperative analgesia of TKA. As adjunct modalities, NMES and TENS can effectively improve rehabilitation after TKA without triggering significant intolerance, and maximal benefits depend on optimized parameters and intervention protocols. EA may be an effective adjunct modality for analgesia after TKA. Copyright © 2018 Elsevier Inc. All rights reserved.

Ocular vestibular evoked myogenic potentials in response to air-conducted 500 Hz short tones: Effect of stimulation procedure (monaural or binaural), age and gender.

PubMed

Versino, Maurizio; Colnaghi, Silvia; Ranzani, Marina; Alloni, Roberto; Bolis, Carlotta; Sacco, Simone; Moglia, Arrigo; Callieco, Roberto

2015-01-01

The ocular vestibular myogenic potentials (oVEMP) can be elicited by monaural air-conducted sound stimulation, and are usually recorded from the contralateral eye. In clinical setting a binaural stimulation would save time and require less effort from the subjects. We evaluated the differences between monaural and binaural stimulation, and the possible effect of age and gender on oVEMP parameters. Air-conducted oVEMP were recorded by binaural and by monaural stimulation in a group of 54 normal subjects, aged from 12 to 83 years, and in 50 vestibular patients. From each side, we measured the latency of the N1 component, and the peak-to-peak N1-P1 amplitude. For both parameters we also computed the asymmetry ratio. In normal subjects binaural stimulation produced slightly larger responses than monaural stimulation; detectability, latency and amplitude ratio were the same for the two techniques. We found no differences related to gender, and the age-induced amplitude decline was likely to be negligible.oVEMP recorded not in an acute phase of their disorder, proved to be abnormal in about 20% of the patients, and the normal or abnormal findings obtained either with monaural or with binaural stimulation were always concordant. The oVEMP obtained after binaural and monaural stimulation are very similar, and they are largely independent from age and gender.

The effect of losartan on differential reflex control of sympathetic nerve activity in chronic kidney disease.

PubMed

Yao, Yimin; Hildreth, Cara M; Farnham, Melissa M; Saha, Manash; Sun, Qi-Jian; Pilowsky, Paul M; Phillips, Jacqueline K

2015-06-01

The effect of angiotensin II type I receptor (AT1R) inhibition on the pattern of reflex sympathetic nerve activity (SNA) to multiple target organs in the Lewis polycystic kidney (LPK) rat model of chronic kidney disease was determined. Mean arterial pressure (MAP), splanchnic SNA (sSNA), renal SNA (rSNA) and lumbar SNA (lSNA) were recorded in urethane-anaesthetized LPK and Lewis controls (total n = 39). Baroreflex, peripheral and central chemoreflex, and somatosensory reflex control of SNA (evoked by phenylephrine/sodium nitroprusside infusion, 10% O2 in N2 or 100% N2 ventilation, 5% CO2 ventilation and sciatic nerve stimulation, respectively) were determined before and after administration of losartan (AT1R antagonist 3 mg/kg, intravenous). Baseline MAP was higher in LPK rats and baroreflex control of sSNA and rSNA, but not lSNA, was reduced. Losartan reduced MAP in both strains and selectively improved baroreflex gain for sSNA (-1.2 ± 0.1 vs. -0.7 ± 0.07 %/mmHg; P < 0.05) in LPK. The peripheral and central chemoreflex increased MAP and all SNA in Lewis controls, but reduced or had no effect on these parameters, respectively, in LPK. The SNA response to somatosensory stimulation was biphasic, with latency to second peak less in LPK. Losartan ameliorated the depressor and sympathoinhibitory responses to peripheral chemoreflex stimulation in the LPK, but did not alter the central chemoreflex or somatosympathetic responses. Inhibition of the AT1R selectively improved baroreflex control of sSNA and peripheral chemoreflex control of all three sympathetic nerve outflows in the LPK rat, suggesting these anomalies in reflex function are driven in part by angiotensin II.

Does transcranial electrical stimulation enhance corticospinal excitability of the motor cortex in healthy individuals? A systematic review and meta-analysis.

PubMed

Dissanayaka, Thusharika; Zoghi, Maryam; Farrell, Michael; Egan, Gary F; Jaberzadeh, Shapour

2017-08-01

Numerous studies have explored the effects of transcranial electrical stimulation (tES) - including anodal transcranial direct current stimulation (a-tDCS), cathodal transcranial direct current stimulation (c-tDCS), transcranial alternative current stimulation (tACS), transcranial random noise stimulation (tRNS) and transcranial pulsed current stimulation (tPCS) - on corticospinal excitability (CSE) in healthy populations. However, the efficacy of these techniques and their optimal parameters for producing robust results has not been studied. Thus, the aim of this systematic review was to consolidate current knowledge about the effects of various parameters of a-tDCS, c-tDCS, tACS, tRNS and tPCS on the CSE of the primary motor cortex (M1) in healthy people. Leading electronic databases were searched for relevant studies published between January 1990 and February 2017; 126 articles were identified, and their results were extracted and analysed using RevMan software. The meta-analysis showed that a-tDCS application on the dominant side significantly increases CSE (P < 0.01) and that the efficacy of a-tDCS is dependent on current density and duration of application. Similar results were obtained for stimulation of M1 on the non-dominant side (P = 0.003). The effects of a-tDCS reduce significantly after 24 h (P = 0.006). Meta-analysis also revealed significant reduction in CSE following c-tDCS (P < 0.001) and significant increases after tRNS (P = 0.03) and tPCS (P = 0.01). However, tACS effects on CSE were only significant when the stimulation frequency was ≥140 Hz. This review provides evidence that tES has substantial effects on CSE in healthy individuals for a range of stimulus parameters. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The effects of chronic intracortical microstimulation on neural tissue and fine motor behavior.

PubMed

Rajan, Alexander T; Boback, Jessica L; Dammann, John F; Tenore, Francesco V; Wester, Brock A; Otto, Kevin J; Gaunt, Robert A; Bensmaia, Sliman J

2015-12-01

One approach to conveying sensory feedback in neuroprostheses is to electrically stimulate sensory neurons in the cortex. For this approach to be viable, it is critical that intracortical microstimulation (ICMS) causes minimal damage to the brain. Here, we investigate the effects of chronic ICMS on the neuronal tissue across a variety of stimulation regimes in non-human primates. We also examine each animal's ability to use their hand--the cortical representation of which is targeted by the ICMS--as a further assay of possible neuronal damage. We implanted electrode arrays in the primary somatosensory cortex of three Rhesus macaques and delivered ICMS four hours per day, five days per week, for six months. Multiple regimes of ICMS were delivered to investigate the effects of stimulation parameters on the tissue and behavior. Parameters included current amplitude (10-100 μA), pulse train duration (1, 5 s), and duty cycle (1/1, 1/3). We then performed a range of histopathological assays on tissue near the tips of both stimulated and unstimulated electrodes to assess the effects of chronic ICMS on the tissue and their dependence on stimulation parameters. While the implantation and residence of the arrays in the cortical tissue did cause significant damage, chronic ICMS had no detectable additional effect; furthermore, the animals exhibited no impairments in fine motor control. Chronic ICMS may be a viable means to convey sensory feedback in neuroprostheses as it does not cause significant damage to the stimulated tissue.

A proposal for refining the forced swim test in Swiss mice.

PubMed

Costa, Ana Paula Ramos; Vieira, Cintia; Bohner, Lauren O L; Silva, Cristiane Felisbino; Santos, Evelyn Cristina da Silva; De Lima, Thereza Christina Monteiro; Lino-de-Oliveira, Cilene

2013-08-01

The forced swim test (FST) is a preclinical test to the screening of antidepressants based on rats or mice behaviours, which is also sensitive to stimulants of motor activity. This work standardised and validated a method to register the active and passive behaviours of Swiss mice during the FST in order to strength the specificity of the test. Adult male Swiss mice were subjected to the FST for 6 min without any treatment or after intraperitoneal injection of saline (0.1 ml/10 g), antidepressants (imipramine, desipramine, or fluoxetine, 30 mg/kg) or stimulants (caffeine, 30 mg/kg or apomorphine, 10mg/kg). The latency, frequency and duration of behaviours (immobility, swimming, and climbing) were scored and summarised in bins of 6, 4, 2 or 1 min. Parameters were first analysed using Principal Components Analysis generating components putatively related to antidepressant (first and second) or to stimulant effects (third). Antidepressants and stimulants affected similarly the parameters grouped into all components. Effects of stimulants on climbing were better distinguished of antidepressants when analysed during the last 4 min of the FST. Surprisingly, the effects of antidepressants on immobility were better distinguished from saline when parameters were scored in the first 2 min. The method proposed here is able to distinguish antidepressants from stimulants of motor activity using Swiss mice in the FST. This refinement should reduce the number of mice used in preclinical evaluation of antidepressants. Copyright © 2013 Elsevier Inc. All rights reserved.

The effects of chronic intracortical microstimulation on neural tissue and fine motor behavior

NASA Astrophysics Data System (ADS)

Rajan, Alexander T.; Boback, Jessica L.; Dammann, John F.; Tenore, Francesco V.; Wester, Brock A.; Otto, Kevin J.; Gaunt, Robert A.; Bensmaia, Sliman J.

2015-12-01

Objective. One approach to conveying sensory feedback in neuroprostheses is to electrically stimulate sensory neurons in the cortex. For this approach to be viable, it is critical that intracortical microstimulation (ICMS) causes minimal damage to the brain. Here, we investigate the effects of chronic ICMS on the neuronal tissue across a variety of stimulation regimes in non-human primates. We also examine each animal’s ability to use their hand—the cortical representation of which is targeted by the ICMS—as a further assay of possible neuronal damage. Approach. We implanted electrode arrays in the primary somatosensory cortex of three Rhesus macaques and delivered ICMS four hours per day, five days per week, for six months. Multiple regimes of ICMS were delivered to investigate the effects of stimulation parameters on the tissue and behavior. Parameters included current amplitude (10-100 μA), pulse train duration (1, 5 s), and duty cycle (1/1, 1/3). We then performed a range of histopathological assays on tissue near the tips of both stimulated and unstimulated electrodes to assess the effects of chronic ICMS on the tissue and their dependence on stimulation parameters. Main results. While the implantation and residence of the arrays in the cortical tissue did cause significant damage, chronic ICMS had no detectable additional effect; furthermore, the animals exhibited no impairments in fine motor control. Significance. Chronic ICMS may be a viable means to convey sensory feedback in neuroprostheses as it does not cause significant damage to the stimulated tissue.

Enhanced Soft Tissue Attachment and Fixation Using a Mechanically-Stimulated Cytoselective Tissue-Specific ECM Coating

DTIC Science & Technology

2013-01-01

of stimulation parameters . The deposited ECM was quantified. It was observed that the entirely strained stretching regime produced slightly higher... parameters (such as, % strain, strain duration, number of cycles, lag between cycles, etc.) that were commonly reported in the literature. There are many... hydroxyapatite . Biomaterials 2007;28(3):383-92. 18. Johnson GA, Tramaglini DM, Levine RE, Ohno K, Choi NY, Woo SL. Tensile and viscoelastic

Why the impact of mechanical stimuli on stem cells remains a challenge.

PubMed

Goetzke, Roman; Sechi, Antonio; De Laporte, Laura; Neuss, Sabine; Wagner, Wolfgang

2018-05-04

Mechanical stimulation affects growth and differentiation of stem cells. This may be used to guide lineage-specific cell fate decisions and therefore opens fascinating opportunities for stem cell biology and regenerative medicine. Several studies demonstrated functional and molecular effects of mechanical stimulation but on first sight these results often appear to be inconsistent. Comparison of such studies is hampered by a multitude of relevant parameters that act in concert. There are notorious differences between species, cell types, and culture conditions. Furthermore, the utilized culture substrates have complex features, such as surface chemistry, elasticity, and topography. Cell culture substrates can vary from simple, flat materials to complex 3D scaffolds. Last but not least, mechanical forces can be applied with different frequency, amplitude, and strength. It is therefore a prerequisite to take all these parameters into consideration when ascribing their specific functional relevance-and to only modulate one parameter at the time if the relevance of this parameter is addressed. Such research questions can only be investigated by interdisciplinary cooperation. In this review, we focus particularly on mesenchymal stem cells and pluripotent stem cells to discuss relevant parameters that contribute to the kaleidoscope of mechanical stimulation of stem cells.

More attention when speaking: does it help or does it hurt?

PubMed Central

Nozari, Nazbanou; Thompson-Schill, Sharon L.

2013-01-01

Paying selective attention to a word in a multi-word utterance results in a decreased probability of error on that word (benefit), but an increased probability of error on the other words (cost). We ask whether excitation of the prefrontal cortex helps or hurts this cost. One hypothesis (the resource hypothesis) predicts a decrease in the cost due to the deployment of more attentional resources, while another (the focus hypothesis) predicts even greater costs due to further fine-tuning of selective attention. Our results are more consistent with the focus hypothesis: prefrontal stimulation caused a reliable increase in the benefit and a marginal increase in the cost of selective attention. To ensure that the effects are due to changes to the prefrontal cortex, we provide two checks: We show that the pattern of results is quite different if, instead, the primary motor cortex is stimulated. We also show that the stimulation-related benefits in the verbal task correlate with the stimulation-related benefits in an N-back task, which is known to tap into a prefrontal function. Our results shed light on how selective attention affects language production, and more generally, on how selective attention affects production of a sequence over time. PMID:24012690

Corticospinal excitability is dependent on the parameters of peripheral electric stimulation: a preliminary study.

PubMed

Chipchase, Lucy S; Schabrun, Siobhan M; Hodges, Paul W

2011-09-01

To evaluate the effect of 6 electric stimulation paradigms on corticospinal excitability. Using a same subject pre-post test design, transcranial magnetic stimulation (TMS) was used to measure the responsiveness of corticomotor pathway to biceps and triceps brachii muscles before and after 30 minutes of electric stimulation over the biceps brachii. Six different electric stimulation paradigms were applied in random order, at least 3 days apart. Motor control research laboratory. Healthy subjects (N=10; 5 women, 5 men; mean age ± SD, 26 ± 3.6y). Six different electric stimulation paradigms with varied stimulus amplitude, frequency, and ramp settings. Amplitudes of TMS-induced motor evoked potentials at biceps and triceps brachii normalized to maximal M-wave amplitudes. Electric stimulation delivered at stimulus amplitude sufficient to evoke a sensory response at both 10 Hz and 100 Hz, and stimulus amplitude to create a noxious response at 10 Hz decreased corticomotor responsiveness (all P<0.01). Stimulation sufficient to induce a motor contraction (30 Hz) applied in a ramped pattern to mimic a voluntary activation increased corticomotor responsiveness (P=0.002), whereas constant low- and high-intensity motor stimulation at 10 Hz did not. Corticomotor excitability changes were similar for both the stimulated muscle and its antagonist. Stimulus amplitude (intensity) and the nature (muscle flicker vs contraction) of motor stimulation have a significant impact on changes in corticospinal excitability induced by electric stimulation. Here, we demonstrate that peripheral electric stimulation at stimulus amplitude to create a sensory response reduces corticomotor responsiveness. Conversely, stimulus amplitude to create a motor response increases corticomotor responsiveness, but only the parameters that create a motor response that mimics a voluntary muscle contraction. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Neuromuscular Electrical Stimulation for Skeletal Muscle Function

PubMed Central

Doucet, Barbara M.; Lam, Amy; Griffin, Lisa

2012-01-01

Lack of neural innervation due to neurological damage renders muscle unable to produce force. Use of electrical stimulation is a medium in which investigators have tried to find a way to restore movement and the ability to perform activities of daily living. Different methods of applying electrical current to modify neuromuscular activity are electrical stimulation (ES), neuromuscular electrical stimulation (NMES), transcutaneous electrical nerve stimulation (TENS), and functional electrical stimulation (FES). This review covers the aspects of electrical stimulation used for rehabilitation and functional purposes. Discussed are the various parameters of electrical stimulation, including frequency, pulse width/duration, duty cycle, intensity/amplitude, ramp time, pulse pattern, program duration, program frequency, and muscle group activated, and how they affect fatigue in the stimulated muscle. PMID:22737049

Quantitative Analysis of Energy Metabolic Pathways in MCF-7 Breast Cancer Cells by Selected Reaction Monitoring Assay*

PubMed Central

Drabovich, Andrei P.; Pavlou, Maria P.; Dimitromanolakis, Apostolos; Diamandis, Eleftherios P.

2012-01-01

To investigate the quantitative response of energy metabolic pathways in human MCF-7 breast cancer cells to hypoxia, glucose deprivation, and estradiol stimulation, we developed a targeted proteomics assay for accurate quantification of protein expression in glycolysis/gluconeogenesis, TCA cycle, and pentose phosphate pathways. Cell growth conditions were selected to roughly mimic the exposure of cells in the cancer tissue to the intermittent hypoxia, glucose deprivation, and hormonal stimulation. Targeted proteomics assay allowed for reproducible quantification of 76 proteins in four different growth conditions after 24 and 48 h of perturbation. Differential expression of a number of control and metabolic pathway proteins in response to the change of growth conditions was found. Elevated expression of the majority of glycolytic enzymes was observed in hypoxia. Cancer cells, as opposed to near-normal MCF-10A cells, exhibited significantly increased expression of key energy metabolic pathway enzymes (FBP1, IDH2, and G6PD) that are known to redirect cellular metabolism and increase carbon flux through the pentose phosphate pathway. Our quantitative proteomic protocol is based on a mass spectrometry-compatible acid-labile detergent and is described in detail. Optimized parameters of a multiplex selected reaction monitoring (SRM) assay for 76 proteins, 134 proteotypic peptides, and 401 transitions are included and can be downloaded and used with any SRM-compatible mass spectrometer. The presented workflow is an integrated tool for hypothesis-driven studies of mammalian cells as well as functional studies of proteins, and can greatly complement experimental methods in systems biology, metabolic engineering, and metabolic transformation of cancer cells. PMID:22535206

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

PubMed

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

2015-11-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to treat movement disorders, including advanced Parkinson's disease (PD). The pathogenesis of PD and the therapeutic mechanisms of DBS are not well understood. Large animal models are essential for investigating the mechanisms of PD and DBS. The purpose of this study was to develop a novel sheep model of STN DBS and quantify the stimulation-evoked motor behaviors. To do so, a large sample of animals was chronically-implanted with commercial DBS systems. Neuroimaging and histology revealed that the DBS leads were implanted accurately relative to the neurosurgical plan and also precisely relative to the STN. It was also possible to repeatedly conduct controlled evaluations of stimulation-evoked motor behavior in the awake-state. The evoked motor responses depended on the neuroanatomical location of the electrode contact selected for stimulation, as contacts proximal to the STN evoked movements at significantly lower voltages. Tissue stimulation modeling demonstrated that selecting any of the contacts stimulated the STN, whereas selecting the relatively distal contacts often also stimulated thalamus but only the distal-most contact stimulated internal capsule. The types of evoked motor behaviors were specific to the stimulation frequency, as low but not high frequencies consistently evoked movements resembling human tremor or dyskinesia. Electromyography confirmed that the muscle activity underlying the tremor-like movements in the sheep was consistent with human tremor. Overall, this work establishes that the sheep is a viable a large-animal platform for controlled testing of STN DBS with objective motor outcomes. Moreover, the results support the hypothesis that exaggerated low-frequency activity within individual nodes of the motor network can drive symptoms of human movement disorders, including tremor and dyskinesia. Copyright © 2015 Elsevier Inc. All rights reserved.

Transcutaneous vagus nerve stimulation (tVNS) enhances divergent thinking.

PubMed

Colzato, Lorenza S; Ritter, Simone M; Steenbergen, Laura

2018-03-01

Creativity is one of the most important cognitive skills in our complex and fast-changing world. Previous correlative evidence showed that gamma-aminobutyric acid (GABA) is involved in divergent but not convergent thinking. In the current study, a placebo/sham-controlled, randomized between-group design was used to test a causal relation between vagus nerve and creativity. We employed transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain stimulation technique to stimulate afferent fibers of the vagus nerve and speculated to increase GABA levels, in 80 healthy young volunteers. Creative performance was assessed in terms of divergent thinking (Alternate Uses Task) and convergent thinking tasks (Remote Associates Test, Creative Problem Solving Task, Idea Selection Task). Results demonstrate active tVNS, compared to sham stimulation, enhanced divergent thinking. Bayesian analysis reported the data to be inconclusive regarding a possible effect of tVNS on convergent thinking. Therefore, our findings corroborate the idea that the vagus nerve is causally involved in creative performance. Even thought we did not directly measure GABA levels, our results suggest that GABA (likely to be increased in active tVNS condition) supports the ability to select among competing options in high selection demand (divergent thinking) but not in low selection demand (convergent thinking). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Electrodes for high-definition transcutaneous DC stimulation for applications in drug delivery and electrotherapy, including tDCS.

PubMed

Minhas, Preet; Bansal, Varun; Patel, Jinal; Ho, Johnson S; Diaz, Julian; Datta, Abhishek; Bikson, Marom

2010-07-15

Transcutaneous electrical stimulation is applied in a range of biomedical applications including transcranial direct current stimulation (tDCS). tDCS is a non-invasive procedure where a weak direct current (<2 mA) is applied across the scalp to modulate brain function. High-definition tDCS (HD-tDCS) is a technique used to increase the spatial focality of tDCS by passing current across the scalp using <12 mm diameter electrodes. The purpose of this study was to design and optimize "high-definition" electrode-gel parameters for electrode durability, skin safety and subjective pain. Anode and cathode electrode potential, temperature, pH and subjective sensation over time were assessed during application of 2 mA direct current, for up to 22 min on agar gel or subject forearms. A selection of five types of solid-conductors (Ag pellet, Ag/AgCl pellet, rubber pellet, Ag/AgCl ring and Ag/AgCl disc) and seven conductive gels (Signa, Spectra, Tensive, Redux, BioGel, Lectron and CCNY-4) were investigated. The Ag/AgCl ring in combination with CCNY-4 gel resulted in the most favorable outcomes. Under anode stimulations, electrode potential and temperature rises were generally observed in all electrode-gel combinations except for Ag/AgCl ring and disc electrodes. pH remained constant for all solid-conductors except for both Ag and rubber pellet electrodes with Signa and CCNY-4 gels. Sensation ratings were independent of stimulation polarity. Ag/AgCl ring electrodes were found to be the most comfortable followed by Ag, rubber and Ag/AgCl pellet electrodes across all gels. Copyright 2010 Elsevier B.V. All rights reserved.

Electrodes for high-definition transcutaneous DC stimulation for applications in drug-delivery and electrotherapy, including tDCS

PubMed Central

Minhas, Preet; Bansal, Varun; Patel, Jinal; Ho, Johnson S.; Diaz, Julian; Datta, Abhishek; Bikson, Marom

2010-01-01

Transcutaneous electrical stimulation is applied in a range of biomedical applications including Transcranial Direct Current Stimulation (tDCS). tDCS is a non-invasive procedure where a weak direct current (<2 mA) is applied across the scalp to modulate brain function. High-Definition tDCS (HD-tDCS) is a technique used to increase the spatial focality of tDCS by passing current across the scalp using <12 mm diameter electrodes. The purpose of this study was to design and optimize “high-definition” electrode-gel parameters for electrode durability, skin safety, and subjective pain. Anode and cathode electrode potential, temperature, pH, and subjective sensation over time were assessed during application of 2 mA direct current, for up to 22 minutes on agar gel or subject forearms. A selection of 5 types of solid-conductors (Ag pellet, Ag/AgCl pellet, Rubber pellet, Ag/AgCl ring, and Ag/AgCl disc) and 7 conductive gels (Signa, Spectra, Tensive, Redux, BioGel, Lectron, and CCNY-4) were investigated. The Ag/AgCl ring in combination with CCNY-4 gel resulted in the most favorable outcomes. Under anode stimulations, electrode potential and temperature rises were generally observed in all electrode-gel combinations except for Ag/AgCl ring and disc electrodes. pH remained constant for all solid-conductors except for both Ag and Rubber pellet electrodes with Signa and CCNY-4 gels. Sensation ratings were independent of stimulation polarity. Ag/AgCl ring electrodes were found to be the most comfortable followed by Ag, Rubber, and Ag/AgCl pellet electrodes across all gels. PMID:20488204

Dilation of the oropharynx via selective stimulation of the hypoglossal nerve

NASA Astrophysics Data System (ADS)

Huang, Jingtao; Sahin, Mesut; Durand, Dominique M.

2005-12-01

The functional effects of selective hypoglossal nerve (HG) stimulation with a multi-contact peripheral nerve electrode were assessed using images of the upper airways and the tongue in anesthetized beagles. A biphasic pulse train of 50 Hz frequency and 2 s duration was applied through each one of the tripolar contact sets of the nerve electrode while the pharyngeal images were acquired into a computer. The stimulation current was limited to 20% above the activation threshold for maximum selectivity. The images showed that various contact sets could generate several different activation patterns of the tongue muscles resulting in medial and/or lateral dilation and closing of the airways at the tongue root. Some of these patterns translated into an increase in the oropharyngeal size while others did not have any effect. The pharyngeal sizes were not statistically different during stimulation either between the two different positions of the head (30° and 60°), or when the lateral contacts were compared with the medial ones. The contacts that had the least effect generated an average of 53 ± 15% pharyngeal dilation relative to the best contacts, indicating that the results are marginally sensitive to the contact position around the HG nerve trunk. These results suggest that selective HG nerve stimulation can be a useful technique to produce multiple tongue activation patterns that can dilate the pharynx. This may in turn increase the size of the patient population who can benefit from HG nerve stimulation as a treatment method for obstructive sleep apnea.

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2011-01-01

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

Parametric changes in response equilibrium during an intra-cranial self stimulation (ICSS) task: can reward value be assessed independently of absolute threshold?

PubMed

Easterling, K W; Holtzman, S G

1997-01-01

Traditional ICSS methodologies have attempted to evaluate changes in the rewarding value of brain stimulation by assessing the lowest value of the stimulation that will support responding. However, orderly changes in suprathreshold indicants of hedonic magnitude such as titration point have been shown. In the present experiments, rats were trained to respond on two ICSS autotitration schedules in which every response on one lever produced stimulation of the medial forebrain bundle, and every Xth response decreased either the stimulation current or the stimulation frequency. At any time, a response on a second "reset" lever restored the stimulation current or frequency available on the stimulation lever to its starting level and operationally defined changes in "reward value". In order to study this titration point measure, two response requirements (responses/stepdown; step size) and two stimulation parameters (initial stimulation level; train duration) were systematically varied. Under both current and frequency titration schedules, data indicated that response rate and titration point remained stable over repeated trials and multiple testing days--parameters being constant. Across all conditions, compared to the frequency titration schedule, subjects responding under the current titration schedule showed significantly higher titration points and lower rates of responding. Indicating the independence of rate and titration point data, parametric manipulations did not affect titration point and rate data concurrently. Results support the conclusion that titration point is a relative measure of "reward value" that is generally independent of response rate, but that is affected by manipulations that alter the amount of stimulation available between "resets". Additional work is needed in order to determine the relationship between the magnitude of stimulation needed to maintain minimal responding and that needed to maintain response equilibrium in an autotitration task.

Facial Vibrotactile Stimulation Activates the Parasympathetic Nervous System: Study of Salivary Secretion, Heart Rate, Pupillary Reflex, and Functional Near-Infrared Spectroscopy Activity

PubMed Central

Hiraba, Hisao; Inoue, Motoharu; Gora, Kanako; Sato, Takako; Nishimura, Satoshi; Yamaoka, Masaru; Kumakura, Ayano; Ono, Shinya; Wakasa, Hirotugu; Nakayama, Enri; Abe, Kimiko; Ueda, Koichiro

2014-01-01

We previously found that the greatest salivation response in healthy human subjects is produced by facial vibrotactile stimulation of 89 Hz frequency with 1.9 μm amplitude (89 Hz-S), as reported by Hiraba et al. (2012, 20011, and 2008). We assessed relationships between the blood flow to brain via functional near-infrared spectroscopy (fNIRS) in the frontal cortex and autonomic parameters. We used the heart rate (HRV: heart rate variability analysis in RR intervals), pupil reflex, and salivation as parameters, but the interrelation between each parameter and fNIRS measures remains unknown. We were to investigate the relationship in response to established paradigms using simultaneously each parameter-fNIRS recording in healthy human subjects. Analysis of fNIRS was examined by a comparison of various values between before and after various stimuli (89 Hz-S, 114 Hz-S, listen to classic music, and “Ahh” vocalization). We confirmed that vibrotactile stimulation (89 Hz) of the parotid glands led to the greatest salivation, greatest increase in heart rate variability, and the most constricted pupils. Furthermore, there were almost no detectable differences between fNIRS during 89 Hz-S and fNIRS during listening to classical music of fans. Thus, vibrotactile stimulation of 89 Hz seems to evoke parasympathetic activity. PMID:24511550

Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia.

PubMed

Ratnadurai-Giridharan, Shivakeshavan; Cheung, Chung C; Rubchinsky, Leonid L

2017-11-01

Conventional deep brain stimulation of basal ganglia uses high-frequency regular electrical pulses to treat Parkinsonian motor symptoms but has a series of limitations. Relatively new and not yet clinically tested, optogenetic stimulation is an effective experimental stimulation technique to affect pathological network dynamics. We compared the effects of electrical and optogenetic stimulation of the basal gangliaon the pathologicalParkinsonian rhythmic neural activity. We studied the network response to electrical stimulation and excitatory and inhibitory optogenetic stimulations. Different stimulations exhibit different interactions with pathological activity in the network. We studied these interactions for different network and stimulation parameter values. Optogenetic stimulation was found to be more efficient than electrical stimulation in suppressing pathological rhythmicity. Our findings indicate that optogenetic control of neural synchrony may be more efficacious than electrical control because of the different ways of how stimulations interact with network dynamics.

The numeric calculation of eddy current distributions in transcranial magnetic stimulation.

PubMed

Tsuyama, Seichi; Hyodo, Akira; Sekino, Masaki; Hayami, Takehito; Ueno, Shoogo; Iramina, Keiji

2008-01-01

Transcranial magnetic stimulation (TMS) is a method to stimulate neurons in the brain. It is necessary to obtain eddy current distributions and determine parameters such as position, radius and bend-angle of the coil to stimulate target area exactly. In this study, we performed FEM-based numerical simulations of eddy current induced by TMS using three-dimentional human head model with inhomogeneous conductivity. We used double-cone coil and changed the coil radius and bend-angle of coil. The result of computer simulation showed that as coil radius increases, the eddy current became stronger everywhere. And coil with bend-angle of 22.5 degrees induced stronger eddy current than the coil with bendangle of 0 degrees. Meanwhile, when the bend-angle was 45 degrees, eddy current became weaker than these two cases. This simulation allowed us to determine appropriate parameter easier.

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

PubMed Central

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

2017-01-01

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

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

PubMed

Quessy, Stephan; Freedman, Edward G

2004-06-01

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

Signal and response properties indicate an optoacoustic effect underlying the intra-cochlear laser-optical stimulation

NASA Astrophysics Data System (ADS)

Kallweit, Nicole; Baumhoff, Peter; Krueger, Alexander; Tinne, Nadine; Heisterkamp, Alexander; Kral, Andrej; Maier, Hannes; Ripken, Tammo

2016-02-01

Optical cochlea stimulation is under investigation as a potential alternative to conventional electric cochlea implants in treatment of sensorineural hearing loss. If direct optical stimulation of spiral ganglion neurons (SGNs) would be feasible, a smaller stimulation volume and, therefore, an improved frequency resolution could be achieved. However, it is unclear whether the mechanism of optical stimulation is based on direct neuronal stimulation or on optoacoustics. Animal studies on hearing vs. deafened guinea pigs already identified the optoacoustic effect as potential mechanism for intra-cochlear optical stimulation. In order to characterize the optoacoustic stimulus more thoroughly the acoustic signal along the beam path of a pulsed laser in water was quantified and compared to the neuronal response properties of hearing guinea pigs stimulated with the same laser parameters. Two pulsed laser systems were used for analyzing the influence of variable pulse duration, pulse energy, pulse peak power and absorption coefficient. Preliminary results of the experiments in water and in vivo suggesta similar dependency of response signals on the applied laser parameters: Both datasets show an onset and offset signal at the beginning and the end of the laser pulse. Further, the resulting signal amplitude depends on the pulse peak power as well as the temporal development of the applied laser pulse. The data indicates the maximum of the first derivative of power as the decisive factor. In conclusion our findings strengthen the hypothesis of optoacoustics as the underlying mechanism for optical stimulation of the cochlea.

A pilot study of planar coil based magnetic stimulation using acute hippocampal slice in mice.

PubMed

Park, H J; Kang, H K; Wang, M; Jo, J; Chung, E; Kim, S

2017-07-01

Micromagnetic stimulation using small-sized implantable coils has recently been studied. The main advantage of this method is that it can provide sustainable stimulation performance even if a fibrotic encapsulation layer is formed around the implanted coil by inflammation response, because indirectly induced currents are used to induce neural responses. In previous research, we optimized the geometrical and control parameters used in implantable magnetic stimulation. Based on those results, we fabricated the planar coil and studied the LTP effect in the hippocampal slice by two different magnetic stimulation protocols using the quadripulse stimulation (QPS) pattern. We found that direct magnetic stimulation (DMS) induced insignificant LTP effect and priming magnetic stimulation (PMS) occluded LTP effect after tetanic stimulation, when QPS patterned magnetic stimulation with 1 A current pulse was applied to the planar coil.

Effect of bilateral stimulation of the subthalamic nucleus on different speech subsystems in patients with Parkinson's disease.

PubMed

Pützer, Manfred; Barry, William J; Moringlane, Jean Richard

2008-12-01

The effect of deep brain stimulation on the two speech-production subsystems, articulation and phonation, of nine Parkinsonian patients is examined. Production parameters (stop closure voicing; stop closure, VOT, vowel) in fast syllable-repetitions were defined and measured and quantitative, objective metrics of vocal fold function were obtained during vowel production. Speech material was recorded for patients (with and without stimulation) and for a reference group of healthy control speakers. With stimulation, precision of the glottal and supraglottal articulation as well as the phonatory function is reduced for some individuals, whereas for other individuals an improvement is observed. Importantly, the improvement or deterioration is determined not only on the basis of the direction of parameter change but also on the individuals' position relative to the healthy control data. This study also notes differences within an individual in the effects of stimulation on the two speech subsystems. These findings qualify the value of global statements about the effect of neurostimulatory operations on Parkinsonian patients. They also underline the importance of careful consideration of individual differences in the effect of deep brain stimulation on different speech subsystems.

Sex-biased dispersal, kin selection and the evolution of sexual conflict.

PubMed

Faria, Gonçalo S; Varela, Susana A M; Gardner, Andy

2015-10-01

There is growing interest in resolving the curious disconnect between the fields of kin selection and sexual selection. Rankin's (2011, J. Evol. Biol. 24, 71-81) theoretical study of the impact of kin selection on the evolution of sexual conflict in viscous populations has been particularly valuable in stimulating empirical research in this area. An important goal of that study was to understand the impact of sex-specific rates of dispersal upon the coevolution of male-harm and female-resistance behaviours. But the fitness functions derived in Rankin's study do not flow from his model's assumptions and, in particular, are not consistent with sex-biased dispersal. Here, we develop new fitness functions that do logically flow from the model's assumptions, to determine the impact of sex-specific patterns of dispersal on the evolution of sexual conflict. Although Rankin's study suggested that increasing male dispersal always promotes the evolution of male harm and that increasing female dispersal always inhibits the evolution of male harm, we find that the opposite can also be true, depending upon parameter values. © 2015 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.

Motor neuron activation in peripheral nerves using infrared neural stimulation

NASA Astrophysics Data System (ADS)

Peterson, E. J.; Tyler, D. J.

2014-02-01

Objective. Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach. The rabbit sciatic nerve was stimulated extraneurally with 1875 nm wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results. 81% of nerves tested were sensitive to INS, with 1.7 ± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2-9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance. The observed selectivity of INS indicates that it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS.

Motor Neuron Activation in Peripheral Nerves Using Infrared Neural Stimulation

PubMed Central

Peterson, EJ; Tyler, DJ

2014-01-01

Objective Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach The rabbit sciatic nerve was stimulated extraneurally with 1875 nm-wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results 81% of nerves tested were sensitive to INS, with 1.7± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2–9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance The observed selectivity of INS indicates it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS. PMID:24310923

A new universal dynamic model to describe eating rate and cumulative intake curves123

PubMed Central

Paynter, Jonathan; Peterson, Courtney M; Heymsfield, Steven B

2017-01-01

Background: Attempts to model cumulative intake curves with quadratic functions have not simultaneously taken gustatory stimulation, satiation, and maximal food intake into account. Objective: Our aim was to develop a dynamic model for cumulative intake curves that captures gustatory stimulation, satiation, and maximal food intake. Design: We developed a first-principles model describing cumulative intake that universally describes gustatory stimulation, satiation, and maximal food intake using 3 key parameters: 1) the initial eating rate, 2) the effective duration of eating, and 3) the maximal food intake. These model parameters were estimated in a study (n = 49) where eating rates were deliberately changed. Baseline data was used to determine the quality of model's fit to data compared with the quadratic model. The 3 parameters were also calculated in a second study consisting of restrained and unrestrained eaters. Finally, we calculated when the gustatory stimulation phase is short or absent. Results: The mean sum squared error for the first-principles model was 337.1 ± 240.4 compared with 581.6 ± 563.5 for the quadratic model, or a 43% improvement in fit. Individual comparison demonstrated lower errors for 94% of the subjects. Both sex (P = 0.002) and eating duration (P = 0.002) were associated with the initial eating rate (adjusted R2 = 0.23). Sex was also associated (P = 0.03 and P = 0.012) with the effective eating duration and maximum food intake (adjusted R2 = 0.06 and 0.11). In participants directed to eat as much as they could compared with as much as they felt comfortable with, the maximal intake parameter was approximately double the amount. The model found that certain parameter regions resulted in both stimulation and satiation phases, whereas others only produced a satiation phase. Conclusions: The first-principles model better quantifies interindividual differences in food intake, shows how aspects of food intake differ across subpopulations, and can be applied to determine how eating behavior factors influence total food intake. PMID:28077377

OCT-based angiography of human dermal microvascular reactions to local stimuli: Implications for increasing capillary blood collection volumes.

PubMed

Men, Shaojie; Wong, Jennifer Manyu; Welch, Emily J; Xu, Jingjiang; Song, Shaozhen; Deegan, Anthony J; Ravichander, Aarthi; Casavant, Benjamin; Berthier, Erwin; Wang, Ruikang K

2018-05-25

To measure and compare microvascular responses within the skin of the upper arm to local stimuli, such as heating or rubbing, through the use of optical coherence tomography angiography (OCTA), and to investigate its impact on blood volume collection. With the use of heat packs or rubbing, local stimulation was applied to the skin of either the left or right upper arm. Data from the stimulated sites were obtained using OCTA comparing pre- and post-stimulation microvascular parameters, such as vessel density, mean vessel diameter, and mean avascular pore size. Additionally, blood was collected using a newly designed collection device and volume was recorded to evaluate the effect of the skin stimulation. Nineteen subjects were recruited for local stimulation study (including rubbing and heating) and 21 subjects for blood drawn study. Of these subjects, 14 agreed to participate in both studies. OCTA was successful in monitoring and measuring minute changes in the microvasculature of the stimulated skin. Compared to baseline, significant changes after local heating and rubbing were respectively found in vessel density (16% [P = 0.0004] and 33% [P < 0.0001] increase), mean vessel diameter (14% and 11% increase) and mean avascular pore size (5% [P = 0.0068] and 8% [P = 0.0005] decrease) after stimulations. A gradual recovery was recorded for each parameter, with no difference being measured after 30 minutes. Blood collection volumes significantly increased after stimulations of heating (48% increase; P = 0.049) and rubbing (78% increase; P = 0.048). Significant correlations were found between blood volume and microvascular parameters except mean avascular pore size under the heating condition. OCTA can provide important information regarding microvascular adaptations to local stimuli. With that, both heating and rubbing of the skin have positive effects on blood collection capacity, with rubbing having the most significant effect. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Studies of stimulus parameters for seizure disruption using neural network simulations.

PubMed

Anderson, William S; Kudela, Pawel; Cho, Jounhong; Bergey, Gregory K; Franaszczuk, Piotr J

2007-08-01

A large scale neural network simulation with realistic cortical architecture has been undertaken to investigate the effects of external electrical stimulation on the propagation and evolution of ongoing seizure activity. This is an effort to explore the parameter space of stimulation variables to uncover promising avenues of research for this therapeutic modality. The model consists of an approximately 800 mum x 800 mum region of simulated cortex, and includes seven neuron classes organized by cortical layer, inhibitory or excitatory properties, and electrophysiological characteristics. The cell dynamics are governed by a modified version of the Hodgkin-Huxley equations in single compartment format. Axonal connections are patterned after histological data and published models of local cortical wiring. Stimulation induced action potentials take place at the axon initial segments, according to threshold requirements on the applied electric field distribution. Stimulation induced action potentials in horizontal axonal branches are also separately simulated. The calculations are performed on a 16 node distributed 32-bit processor system. Clear differences in seizure evolution are presented for stimulated versus the undisturbed rhythmic activity. Data is provided for frequency dependent stimulation effects demonstrating a plateau effect of stimulation efficacy as the applied frequency is increased from 60 to 200 Hz. Timing of the stimulation with respect to the underlying rhythmic activity demonstrates a phase dependent sensitivity. Electrode height and position effects are also presented. Using a dipole stimulation electrode arrangement, clear orientation effects of the dipole with respect to the model connectivity is also demonstrated. A sensitivity analysis of these results as a function of the stimulation threshold is also provided.

CO2 laser nerve stimulator with flat-top irradiance profile for human pain research

NASA Astrophysics Data System (ADS)

McCaughey, Ryan Gerard

Human pain research aims to further the understanding of how pain is processed by the body. Studies require a reproducible, quantifiable, scalable, pain specific and safe stimulus. Using laser light to raise the temperature of the skin to painful levels is a good method of satisfying these conditions. The CO[2] laser is an ideal source because its infrared radiation is readily absorbed in the upper layers of the skin, where the free nerve endings of pain-conveying fibres are located, causing localised heating and evoking pain. A pain stimulator based on a CO[2] laser has been developed. It is computer controlled with a graphical interface so that non specialists can easily operate the laser. Safety features have been incorporated to protect the operator and the subject. These include activation of a shutter to block the beam and shut-down of the laser, when, for example, potentially harmful laser parameters are selected or abnormal signals are sent to the laser. The CO[2] laser normally operates in TEM[00] mode, i.e. the irradiance of the beam decreases roughly exponentially from the centre. This is not ideal for thermal stimulation, since it will generate a temperature that also has a peak in the centre of the beam. This will result in non-uniform activation of nerve fibres. Lenses have been developed to redistribute the energy of the beam to produce a flattened super Gaussian irradiance profile for uniform heating of the skin. The shape of the lenses was determined by geometrical optics. They work by refracting the more intense central part of the beam towards the periphery. Solution of the heat transfer equation by a finite differences method, confirmed that the super Gaussian profile generated by the bean shaper produces a more uniform temperature distribution in skin. The model was also used to predict how varying skin parameters, such as thickness and water content, affects the temperature generated by irradiation with a CO[2] laser beam. The predicted skin temperatures matched the temperatures measured during thermal stimulation with the laser. The risk of damaging the tissue was also calculated from the modelled temperature distribution. Psychophysical techniques were used to characterise the laser stimulator compared to an existing laser stimulator. Differences in the temporal provides of the lasers resulted in different pain sensations for beams of the same energy. The conduction velocities of thermally stimulated fibres were estimated by recording the reaction time to laser irradiation. It was found that the super Gaussian beam evokes pain at a lower temperature than a TEM[00] beam. It is, therefore, a safer source for evoking pain in human pain studies.

The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve

PubMed Central

Li, Yongping; Lao, Jie; Zhao, Xin; Tian, Dong; Zhu, Yi; Wei, Xiaochun

2014-01-01

The distance between the two electrode tips can greatly influence the parameters used for recording compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spacings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance between two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed significantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no significant change. Different distances between recording and stimulating sites did not produce significant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference (however also required a higher threshold and higher supramaximal stimulus), was found to be superior to the antidromic compound action potential. PMID:25206798

Pedunculopontine nucleus stimulation improves akinesia in a Parkinsonian monkey.

PubMed

Jenkinson, Ned; Nandi, Dipankar; Miall, R Chris; Stein, John F; Aziz, Tipu Z

2004-12-03

We have studied the effects of stimulating the pedunculopontine nuclei through a fully implanted macroelectrode with a s.c. implantable pulse generator whose parameters can be programmed telemetrically, in a macaque before and after inducing Parkinsonian akinesia with MPTP. Our results show that in the normal monkey high frequency stimulation of the pedunculopontine nuclei reduces motor activity while low frequency stimulation increases it significantly over baseline. After making the monkey Parkinsonian with MPTP, unilateral low frequency stimulation of the pedunculopontine nuclei led to significant increases in activity. These results suggest that pedunculopontine nuclei stimulation could be clinically effective in treating advanced Parkinson's disease and other akinetic disorders.

More attention when speaking: does it help or does it hurt?

PubMed

Nozari, Nazbanou; Thompson-Schill, Sharon L

2013-11-01

Paying selective attention to a word in a multi-word utterance results in a decreased probability of error on that word (benefit), but an increased probability of error on the other words (cost). We ask whether excitation of the prefrontal cortex helps or hurts this cost. One hypothesis (the resource hypothesis) predicts a decrease in the cost due to the deployment of more attentional resources, while another (the focus hypothesis) predicts even greater costs due to further fine-tuning of selective attention. Our results are more consistent with the focus hypothesis: prefrontal stimulation caused a reliable increase in the benefit and a marginal increase in the cost of selective attention. To ensure that the effects are due to changes to the prefrontal cortex, we provide two checks: We show that the pattern of results is quite different if, instead, the primary motor cortex is stimulated. We also show that the stimulation-related benefits in the verbal task correlate with the stimulation-related benefits in an N-back task, which is known to tap into a prefrontal function. Our results shed light on how selective attention affects language production, and more generally, on how selective attention affects production of a sequence over time. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sensory optimization by stochastic tuning.

PubMed

Jurica, Peter; Gepshtein, Sergei; Tyukin, Ivan; van Leeuwen, Cees

2013-10-01

Individually, visual neurons are each selective for several aspects of stimulation, such as stimulus location, frequency content, and speed. Collectively, the neurons implement the visual system's preferential sensitivity to some stimuli over others, manifested in behavioral sensitivity functions. We ask how the individual neurons are coordinated to optimize visual sensitivity. We model synaptic plasticity in a generic neural circuit and find that stochastic changes in strengths of synaptic connections entail fluctuations in parameters of neural receptive fields. The fluctuations correlate with uncertainty of sensory measurement in individual neurons: The higher the uncertainty the larger the amplitude of fluctuation. We show that this simple relationship is sufficient for the stochastic fluctuations to steer sensitivities of neurons toward a characteristic distribution, from which follows a sensitivity function observed in human psychophysics and which is predicted by a theory of optimal allocation of receptive fields. The optimal allocation arises in our simulations without supervision or feedback about system performance and independently of coupling between neurons, making the system highly adaptive and sensitive to prevailing stimulation. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Energy absorption buildup factors, exposure buildup factors and Kerma for optically stimulated luminescence materials and their tissue equivalence for radiation dosimetry

NASA Astrophysics Data System (ADS)

Singh, Vishwanath P.; Badiger, N. M.

2014-11-01

Optically stimulated luminescence (OSL) materials are sensitive dosimetric materials used for precise and accurate dose measurement for low-energy ionizing radiation. Low dose measurement capability with improved sensitivity makes these dosimeters very useful for diagnostic imaging, personnel monitoring and environmental radiation dosimetry. Gamma ray energy absorption buildup factors and exposure build factors were computed for OSL materials using the five-parameter Geometric Progression (G-P) fitting method in the energy range 0.015-15 MeV for penetration depths up to 40 mean free path. The computed energy absorption buildup factor and exposure buildup factor values were studied as a function of penetration depth and incident photon energy. Effective atomic numbers and Kerma relative to air of the selected OSL materials and tissue equivalence were computed and compared with that of water, PMMA and ICRU standard tissues. The buildup factors and kerma relative to air were found dependent upon effective atomic numbers. Buildup factors determined in the present work should be useful in radiation dosimetry, medical diagnostics and therapy, space dosimetry, accident dosimetry and personnel monitoring.

Surface plasmon resonance immunoassay analysis of pituitary hormones in urine and serum samples.

PubMed

Treviño, Juan; Calle, Ana; Rodríguez-Frade, José Miguel; Mellado, Mario; Lechuga, Laura M

2009-05-01

Direct determination of four pituitary peptide hormones: human thyroid stimulating hormone (hTSH), growth hormone (hGH), follicle stimulating hormone (hFSH), and luteinizing hormone (hLH) has been carried out using a portable surface plasmon resonance (SPR) immunosensor. A commercial SPR biosensor was employed. The immobilization of the hormones was optimized and monoclonal antibodies were selected in order to obtain the best sensor performance. Assay parameters as running buffer and regeneration solution composition or antibody concentration were adjusted to achieve a sensitive analyte detection. The performance of the assays was assessed in buffer solution, serum and urine, showing sensitivity in the range from 1 to 6 ng/mL. The covalent attachment of the hormones ensured the stability of the SPR signal through repeated use in up to 100 consecutive assay cycles. Mean intra- and inter-day coefficients of variation were all <7%, while batch-assay variability using different sensor surfaces was <5%. Taking account both the excellent reutilization performance and the outstanding reproducibility, this SPR immunoassay method turns on a highly reliable tool for endocrine monitoring in laboratory and point-of-care (POC) settings.

Light intensity modulation in phototherapy

NASA Astrophysics Data System (ADS)

Lukyanovich, P. A.; Zon, B. A.; Kunin, A. A.; Pankova, S. N.

2015-04-01

A hypothesis that blocking ATP synthesis is one of the main causes of the stimulating effect is considered based on analysis of the primary photostimulation mechanisms. The light radiation intensity modulation is substantiated and the estimates of such modulation parameters are made. An explanation is offered to the stimulation efficiency decrease phenomenon at the increase of the radiation dose during the therapy. The results of clinical research of the medical treatment in preventive dentistry are presented depending on the spectrum and parameters of the light flux modulation.

Non-invasive electric current stimulation for restoration of vision after unilateral occipital stroke.

PubMed

Gall, Carolin; Silvennoinen, Katri; Granata, Giuseppe; de Rossi, Francesca; Vecchio, Fabrizio; Brösel, Doreen; Bola, Michał; Sailer, Michael; Waleszczyk, Wioletta J; Rossini, Paolo M; Tatlisumak, Turgut; Sabel, Bernhard A

2015-07-01

Occipital stroke often leads to visual field loss, for which no effective treatment exists. Little is known about the potential of non-invasive electric current stimulation to ameliorate visual functions in patients suffering from unilateral occipital stroke. One reason is the traditional thinking that visual field loss after brain lesions is permanent. Since evidence is available documenting vision restoration by means of vision training or non-invasive electric current stimulation future studies should also consider investigating recovery processes after visual cortical strokes. Here, protocols of repetitive transorbital alternating current stimulation (rtACS) and transcranial direct current stimulation (tDCS) are presented and the European consortium for restoration of vision (REVIS) is introduced. Within the consortium different stimulation approaches will be applied to patients with unilateral occipital strokes resulting in homonymous hemianopic visual field defects. The aim of the study is to evaluate effects of current stimulation of the brain on vision parameters, vision-related quality of life, and physiological parameters that allow concluding about the mechanisms of vision restoration. These include EEG-spectra and coherence measures, and visual evoked potentials. The design of stimulation protocols involves an appropriate sham-stimulation condition and sufficient follow-up periods to test whether the effects are stable. This is the first application of non-invasive current stimulation for vision rehabilitation in stroke-related visual field deficits. Positive results of the trials could have far-reaching implications for clinical practice. The ability of non-invasive electrical current brain stimulation to modulate the activity of neuronal networks may have implications for stroke rehabilitation also in the visual domain. Copyright © 2015 Elsevier Inc. All rights reserved.

Cochlear-implant spatial selectivity with monopolar, bipolar and tripolar stimulation.

PubMed

Zhu, Ziyan; Tang, Qing; Zeng, Fan-Gang; Guan, Tian; Ye, Datian

2012-01-01

Sharp spatial selectivity is critical to auditory performance, particularly in pitch-related tasks. Most contemporary cochlear implants have employed monopolar stimulation that produces broad electric fields, which presumably contribute to poor pitch and pitch-related performance by implant users. Bipolar or tripolar stimulation can generate focused electric fields but requires higher current to reach threshold and, more interestingly, has not produced any apparent improvement in cochlear-implant performance. The present study addressed this dilemma by measuring psychophysical and physiological spatial selectivity with both broad and focused stimulations in the same cohort of subjects. Different current levels were adjusted by systematically measuring loudness growth for each stimulus, each stimulation mode, and in each subject. Both psychophysical and physiological measures showed that, although focused stimulation produced significantly sharper spatial tuning than monopolar stimulation, it could shift the tuning position or even split the tuning tips. The altered tuning with focused stimulation is interpreted as a result of poor electrode-to-neuron interface in the cochlea, and is suggested to be mainly responsible for the lack of consistent improvement in implant performance. A linear model could satisfactorily quantify the psychophysical and physiological data and derive the tuning width. Significant correlation was found between the individual physiological and psychophysical tuning widths, and the correlation was improved by log-linearly transforming the physiological data to predict the psychophysical data. Because the physiological measure took only one-tenth of the time of the psychophysical measure, the present model is of high clinical significance in terms of predicting and improving cochlear-implant performance. Copyright © 2011 Elsevier B.V. All rights reserved.

Cochlear Implant Spatial Selectivity with Monopolar, Bipolar and Tripolar Stimulation

PubMed Central

Zhu, Ziyan; Tang, Qing; Zeng, Fan-Gang; Guan, Tian; Ye, Datian

2011-01-01

Sharp spatial selectivity is critical to auditory performance, particularly in pitch related tasks. Most contemporary cochlear implants have employed monopolar stimulation that produces broad electric fields, which presumably contribute to poor pitch and pitch-related performance by implant users. Bipolar or tripolar stimulation can generate focused electric fields but requires higher current to reach threshold and, more interestingly, has not produced any apparent improvement in cochlear implant performance. The present study addressed this dilemma by measuring psychophysical and physiological spatial selectivity with both broad and focused stimulations in the same cohort of subjects. Different current levels were adjusted by systematically measuring loudness growth for each stimulus, each stimulation mode, and in each subject. Both psychophysical and physiological measures showed that, although focused stimulation produced significantly sharper spatial tuning than monopolar stimulation, it could shift the tuning position or even split the tuning tips. The altered tuning with focused stimulation is interpreted as a result of poor electrode-to-neuron interface in the cochlea, and is suggested to be mainly responsible for the lack of consistent improvement in implant performance. A linear model could satisfactorily quantify the psychophysical and physiological data and derive the tuning width. Significant correlation was found between the individual physiological and psychophysical tuning widths, and the correlation was improved by log-linearly transforming the physiological data to predict the psychophysical data. Because the physiological measure took only one-tenth of the time of the psychophysical measure, the present model is of high clinical significance in terms of predicting and improving cochlear implant performance. PMID:22138630

Nociceptive flexion reflexes during analgesic neurostimulation in man.

PubMed

García-Larrea, L; Sindou, M; Mauguière, F

1989-11-01

Nociceptive flexion reflexes of the lower limbs (RIII responses) have been studied in 21 patients undergoing either epidural (DCS, n = 16) or transcutaneous (TENS, n = 5) analgesic neurostimulation (AN) for chronic intractable pain. Flexion reflex RIII was depressed or suppressed by AN in 11 patients (52.4%), while no modification was observed in 9 cases and a paradoxical increase during AN was evidenced in 1 case. In all but 2 patients, RIII changes were rapidly reversible after AN interruption. RIII depression was significantly associated with subjective pain relief, as assessed by conventional self-rating; moreover, in 2 patients it was possible to ameliorate the pain-suppressing effects of AN by selecting those stimulation parameters (intensity and frequency) that maximally depressed nociceptive reflex RIII. We recorded 2 cases of RIII attenuation after contralateral neurostimulation. AN appeared to affect nociceptive reflexes rather selectively, with no or very little effect on other cutaneous, non-nociceptive responses. Recording of RIII reflexes is relatively simple to implement as a routine paraclinical procedure. It facilitates the objective assessment of AN efficacy and may help to choose the most appropriate parameters of neurostimulation. In addition, RIII behavior in patients could be relevant to the understanding of some of the mechanisms involved in AN-induced pain relief.

Genetic variation of natural antibodies in milk of Dutch Holstein-Friesian cows.

PubMed

Ploegaert, T C W; Wijga, S; Tijhaar, E; van der Poel, J J; Lam, T J G M; Savelkoul, H F J; Parmentier, H K; van Arendonk, J A M

2010-11-01

Defense mechanisms of dairy cows against diseases partly rest on their naturally present disease resistance capacity. Natural antibodies (NAb) form a soluble part of the innate immune system, being defined as antibodies circulating in animals without prior intentional antigenic stimulation. Genetic selection on NAb titers in milk, therefore, might improve disease resistance. We estimated genetic parameters of NAb titers binding lipopolysaccharide, lipoteichoic acid (LTA), peptidoglycan, and keyhole limpet hemocyanin, and titers of the NAb isotypes IgG1, IgM, and IgA binding LTA in milk of Dutch Holstein-Friesian heifers. Natural antibody titers were measured in 1 milk sample from each of 1,939 Holstein-Friesian heifers and used for estimating genetic parameters of NAb titers. The data show that phenotypic variation exists among heifers in NAb titers binding lipopolysaccharide, LTA, peptidoglycan, and keyhole limpet hemocyanin, and the NAb isotypes IgG1, IgM, and IgA binding LTA in milk. High genetic correlations among NAb (ranging from 0.45 to 0.99) indicated a common genetic basis for the levels of different NAb in bovine milk. Intra-herd heritability estimates for NAb ranged from 0.10 to 0.53. The results indicated that NAb levels have potential for genetic selection. Copyright © 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

[Normative aspects of somatosensory evoked P300 components].

PubMed

Louzã Neto, M R; Maurer, K; Neuhauser, B

1989-06-01

Using a somatosensory version of the oddball-paradigma the influence of age and gender on the P300-component and the comparison of the potential after stimulation of the right and left median nerve was studied in 30 healthy right handed volunteers (age: 20-35 years). Latency, amplitude, area and duration of the P300-potential were analysed. No relationship between age, gender and the P300-parameters were observed. The amplitude and the area of the potential obtained from the F3 electrode were greater after stimulation of the right median nerve compared to the potential after stimulation of the left median nerve. All other results were not significantly different. Strong positive correlations between the results after stimulation of the right and left median nerve were observed. These results showed that by a young group of volunteers age and gender did not influence the P300-component. Although the P300-Parameters had a between-subject variability, their mean remained constant over the study, their correlation coefficients were strong positive and the side of stimulation did not influence them (except for the electrode F3).

The influence of functional electrical stimulation on hand motor recovery in stroke patients: a review.

PubMed

Quandt, Fanny; Hummel, Friedhelm C

2014-01-01

Neuromuscular stimulation has been used as one potential rehabilitative treatment option to restore motor function and improve recovery in patients with paresis. Especially stroke patients who often regain only limited hand function would greatly benefit from a therapy that enhances recovery and restores movement. Multiple studies investigated the effect of functional electrical stimulation on hand paresis, the results however are inconsistent. Here we review the current literature on functional electrical stimulation on hand motor recovery in stroke patients. We discuss the impact of different parameters such as stage after stoke, degree of impairment, spasticity and treatment protocols on the functional outcome. Importantly, we outline the results from recent studies investigating the cortical effects elicited by functional electrical stimulation giving insights into the underlying mechanisms responsible for long-term treatment effects. Bringing together the findings from present research it becomes clear that both, treatment outcomes as well as the neurophysiologic mechanisms causing functional recovery, vary depending on patient characteristics. In order to develop unified treatment guidelines it is essential to conduct homogenous studies assessing the impact of different parameters on rehabilitative success.

The influence of functional electrical stimulation on hand motor recovery in stroke patients: a review

PubMed Central

2014-01-01

Neuromuscular stimulation has been used as one potential rehabilitative treatment option to restore motor function and improve recovery in patients with paresis. Especially stroke patients who often regain only limited hand function would greatly benefit from a therapy that enhances recovery and restores movement. Multiple studies investigated the effect of functional electrical stimulation on hand paresis, the results however are inconsistent. Here we review the current literature on functional electrical stimulation on hand motor recovery in stroke patients. We discuss the impact of different parameters such as stage after stoke, degree of impairment, spasticity and treatment protocols on the functional outcome. Importantly, we outline the results from recent studies investigating the cortical effects elicited by functional electrical stimulation giving insights into the underlying mechanisms responsible for long-term treatment effects. Bringing together the findings from present research it becomes clear that both, treatment outcomes as well as the neurophysiologic mechanisms causing functional recovery, vary depending on patient characteristics. In order to develop unified treatment guidelines it is essential to conduct homogenous studies assessing the impact of different parameters on rehabilitative success. PMID:25276333

Transcutaneous electrical nerve stimulation and interferential current demonstrate similar effects in relieving acute and chronic pain: a systematic review with meta-analysis.

PubMed

Almeida, Camila Cadena de; Silva, Vinicius Z Maldaner da; Júnior, Gerson Cipriano; Liebano, Richard Eloin; Durigan, Joao Luiz Quagliotti

2018-02-02

Transcutaneous electrical nerve stimulation and interferential current have been widely used in clinical practice. However, a systematic review comparing their effects on pain relief has not yet been performed. To investigate the effects of transcutaneous electrical nerve stimulation and interferential current on acute and chronic pain. We use Pubmed, Embase, LILACS, PEDro and Cochrane Central Register of Controlled Trials as data sources. Two independent reviewers that selected studies according to inclusion criteria, extracted information of interest and verified the methodological quality of the studies made study selection. The studies were selected if transcutaneous electrical nerve stimulation and interferential current were used as treatment and they had pain as the main outcome, as evaluated by a visual analog scale. Secondary outcomes were the Western Ontario Macmaster and Rolland Morris Disability questionnaires, which were added after data extraction. Eight studies with a pooled sample of 825 patients were included. The methodological quality of the selected studies was moderate, with an average of six on a 0-10 scale (PEDro). In general, both transcutaneous electrical nerve stimulation and interferential current improved pain and functional outcomes without a statistical difference between them. Transcutaneous electrical nerve stimulation and interferential current have similar effects on pain outcome The low number of studies included in this meta-analysis indicates that new clinical trials are needed. Copyright © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2013-12-01

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

Considerations in high-resolution skeletal muscle diffusion tensor imaging using single-shot echo planar imaging with stimulated-echo preparation and sensitivity encoding.

PubMed

Karampinos, Dimitrios C; Banerjee, Suchandrima; King, Kevin F; Link, Thomas M; Majumdar, Sharmila

2012-05-01

Previous studies have shown that skeletal muscle diffusion tensor imaging (DTI) can noninvasively probe changes in the muscle fiber architecture and microstructure in diseased and damaged muscles. However, DTI fiber reconstruction in small muscles and in muscle regions close to aponeuroses and tendons remains challenging because of partial volume effects. Increasing the spatial resolution of skeletal muscle single-shot diffusion-weighted echo planar imaging (DW-EPI) can be hindered by the inherently low signal-to-noise ratio (SNR) of muscle DW-EPI because of the short muscle T(2) and the high sensitivity of single-shot EPI to off-resonance effects and T(2)* blurring. In this article, eddy current-compensated diffusion-weighted stimulated-echo preparation is combined with sensitivity encoding (SENSE) to maintain good SNR properties and to reduce the sensitivity to distortions and T(2)* blurring in high-resolution skeletal muscle single-shot DW-EPI. An analytical framework is developed to optimize the reduction factor and diffusion weighting time to achieve maximum SNR. Arguments for the selection of the experimental parameters are then presented considering the compromise between SNR, B(0)-induced distortions, T(2)* blurring effects and tissue incoherent motion effects. On the basis of the selected parameters in a high-resolution skeletal muscle single-shot DW-EPI protocol, imaging protocols at lower acquisition matrix sizes are defined with matched bandwidth in the phase-encoding direction and SNR. In  vivo results show that high-resolution skeletal muscle DTI with minimized sensitivity to geometric distortions and T(2)* blurring is feasible using the proposed methodology. In particular, a significant benefit is demonstrated from a reduction in partial volume effects for resolving multi-pennate muscles and muscles with small cross-sections in calf muscle DTI. Copyright © 2011 John Wiley & Sons, Ltd.

Electrical Identification and Selective Microstimulation of Neuronal Compartments Based on Features of Extracellular Action Potentials

NASA Astrophysics Data System (ADS)

Radivojevic, Milos; Jäckel, David; Altermatt, Michael; Müller, Jan; Viswam, Vijay; Hierlemann, Andreas; Bakkum, Douglas J.

2016-08-01

A detailed, high-spatiotemporal-resolution characterization of neuronal responses to local electrical fields and the capability of precise extracellular microstimulation of selected neurons are pivotal for studying and manipulating neuronal activity and circuits in networks and for developing neural prosthetics. Here, we studied cultured neocortical neurons by using high-density microelectrode arrays and optical imaging, complemented by the patch-clamp technique, and with the aim to correlate morphological and electrical features of neuronal compartments with their responsiveness to extracellular stimulation. We developed strategies to electrically identify any neuron in the network, while subcellular spatial resolution recording of extracellular action potential (AP) traces enabled their assignment to the axon initial segment (AIS), axonal arbor and proximal somatodendritic compartments. Stimulation at the AIS required low voltages and provided immediate, selective and reliable neuronal activation, whereas stimulation at the soma required high voltages and produced delayed and unreliable responses. Subthreshold stimulation at the soma depolarized the somatic membrane potential without eliciting APs.

Stochastic stimulated electronic x-ray Raman spectroscopy

PubMed Central

Kimberg, Victor; Rohringer, Nina

2016-01-01

Resonant inelastic x-ray scattering (RIXS) is a well-established tool for studying electronic, nuclear, and collective dynamics of excited atoms, molecules, and solids. An extension of this powerful method to a time-resolved probe technique at x-ray free electron lasers (XFELs) to ultimately unravel ultrafast chemical and structural changes on a femtosecond time scale is often challenging, due to the small signal rate in conventional implementations at XFELs that rely on the usage of a monochromator setup to select a small frequency band of the broadband, spectrally incoherent XFEL radiation. Here, we suggest an alternative approach, based on stochastic spectroscopy, which uses the full bandwidth of the incoming XFEL pulses. Our proposed method is relying on stimulated resonant inelastic x-ray scattering, where in addition to a pump pulse that resonantly excites the system a probe pulse on a specific electronic inelastic transition is provided, which serves as a seed in the stimulated scattering process. The limited spectral coherence of the XFEL radiation defines the energy resolution in this process and stimulated RIXS spectra of high resolution can be obtained by covariance analysis of the transmitted spectra. We present a detailed feasibility study and predict signal strengths for realistic XFEL parameters for the CO molecule resonantly pumped at the O1s→π* transition. Our theoretical model describes the evolution of the spectral and temporal characteristics of the transmitted x-ray radiation, by solving the equation of motion for the electronic and vibrational degrees of freedom of the system self consistently with the propagation by Maxwell equations. PMID:26958585

Tuning Shifts of the Auditory System By Corticocortical and Corticofugal Projections and Conditioning

PubMed Central

Suga, Nobuo

2011-01-01

The central auditory system consists of the lemniscal and nonlemniscal systems. The thalamic lemniscal and non-lemniscal auditory nuclei are different from each other in response properties and neural connectivities. The cortical auditory areas receiving the projections from these thalamic nuclei interact with each other through corticocortical projections and project down to the subcortical auditory nuclei. This corticofugal (descending) system forms multiple feedback loops with the ascending system. The corticocortical and corticofugal projections modulate auditory signal processing and play an essential role in the plasticity of the auditory system. Focal electric stimulation -- comparable to repetitive tonal stimulation -- of the lemniscal system evokes three major types of changes in the physiological properties, such as the tuning to specific values of acoustic parameters of cortical and subcortical auditory neurons through different combinations of facilitation and inhibition. For such changes, a neuromodulator, acetylcholine, plays an essential role. Electric stimulation of the nonlemniscal system evokes changes in the lemniscal system that is different from those evoked by the lemniscal stimulation. Auditory signals ascending from the lemniscal and nonlemniscal thalamic nuclei to the cortical auditory areas appear to be selected or adjusted by a “differential” gating mechanism. Conditioning for associative learning and pseudo-conditioning for nonassociative learning respectively elicit tone-specific and nonspecific plastic changes. The lemniscal, corticofugal and cholinergic systems are involved in eliciting the former, but not the latter. The current article reviews the recent progress in the research of corticocortical and corticofugal modulations of the auditory system and its plasticity elicited by conditioning and pseudo-conditioning. PMID:22155273

Electromagnetic characteristics of eccentric figure-eight coils for transcranial magnetic stimulation: A numerical study

NASA Astrophysics Data System (ADS)

Kato, Takuya; Sekino, Masaki; Matsuzaki, Taiga; Nishikawa, Atsushi; Saitoh, Youichi; Ohsaki, Hiroyuki

2012-04-01

Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment of several neurological and psychiatric diseases. We proposed an eccentric figure-eight coil, which induces strong eddy currents in the target brain tissue. In this study, numerical analyses were carried out to obtain magnetic field distribution of the eccentric figure-eight coil and eddy current in the brain. The analyses were performed with various coil design parameters, such as the outer and inner diameters and number of turns, to investigate the influence of these parameters on the coil characteristics. Increases in the inner diameter, outer diameter, and number of turns caused increases in the maximum eddy current densities. Coil inductance, working voltage, and heat generation also became higher with the increases in these design parameters. In order to develop a compact stimulator system for use at home, we need to obtain strong eddy current density, keeping the working voltage as low as possible. Our results show that it is effective to enlarge the outer diameter.

Fully Implantable Deep Brain Stimulation System with Wireless Power Transmission for Long-term Use in Rodent Models of Parkinson's Disease.

PubMed

Heo, Man Seung; Moon, Hyun Seok; Kim, Hee Chan; Park, Hyung Woo; Lim, Young Hoon; Paek, Sun Ha

2015-03-01

The purpose of this study to develop new deep-brain stimulation system for long-term use in animals, in order to develop a variety of neural prostheses. Our system has two distinguished features, which are the fully implanted system having wearable wireless power transfer and ability to change the parameter of stimulus parameter. It is useful for obtaining a variety of data from a long-term experiment. To validate our system, we performed pre-clinical test in Parkinson's disease-rat models for 4 weeks. Through the in vivo test, we observed the possibility of not only long-term implantation and stability, but also free movement of animals. We confirmed that the electrical stimulation neither caused any side effect nor damaged the electrodes. We proved possibility of our system to conduct the long-term pre-clinical test in variety of parameter, which is available for development of neural prostheses.

Designing a deep brain stimulator to suppress pathological neuronal synchrony.

PubMed

Montaseri, Ghazal; Yazdanpanah, Mohammad Javad; Bahrami, Fariba

2015-03-01

Some of neuropathologies are believed to be related to abnormal synchronization of neurons. In the line of therapy, designing effective deep brain stimulators to suppress the pathological synchrony among neuronal ensembles is a challenge of high clinical relevance. The stimulation should be able to disrupt the synchrony in the presence of latencies due to imperfect knowledge about parameters of a neuronal ensemble and stimulation impacts on the ensemble. We propose an adaptive desynchronizing deep brain stimulator capable of dealing with these uncertainties. We analyze the collective behavior of the stimulated neuronal ensemble and show that, using the designed stimulator, the resulting asynchronous state is stable. Simulation results reveal the efficiency of the proposed technique. Copyright © 2014 Elsevier Ltd. All rights reserved.

Restoration of bladder function in spastic neuropathic bladder using sacral deafferentation and different techniques of neurostimulation.

PubMed

Schumacher, S; Bross, S; Scheepe, J R; Alken, P; Jünemann, K P

1999-01-01

Conventional sacral anterior root stimulation (SARS) results in simultaneous activation of both the detrusor muscle and the external urethral sphincter. We evaluated the possibilities of different neurostimulation techniques to overcome stimulation induced detrusor-sphincter-dyssynergia and to achieve a physiological voiding. The literature was reviewed on different techniques of sacral anterior root stimulation of the bladder and the significance of posterior rhizotomy in patients with supraconal spinal cord injury suffering from the loss of voluntary bladder control, detrusor hyperreflexia and sphincter spasm. The achievement of selective detrusor activation would improve current sacral neurostimulation of the bladder, including the principle of "poststimulus voiding". This is possible with the application of selective neurostimulation in techniques of anodal block, high frequency block, depolarizing prepulses and cold block. Nowadays, sacral deafferentation is a standard therapy in combination with neurostimulation of the bladder because in conclusion advantages of complete rhizotomy predominate. The combination of sacral anterior root stimulation and sacral deafferentation is a successful procedure for restoration of bladder function in patients with supraconal spinal cord injury. Anodal block technique and cryotechnique are excellent methods for selective bladder activation to avoid detrusor-sphincter-dyssynergia and thus improve stimulation induced voiding.

A technique for sequential segmental neuromuscular stimulation with closed loop feedback control.

PubMed

Zonnevijlle, Erik D H; Abadia, Gustavo Perez; Somia, Naveen N; Kon, Moshe; Barker, John H; Koenig, Steven; Ewert, D L; Stremel, Richard W

2002-01-01

In dynamic myoplasty, dysfunctional muscle is assisted or replaced with skeletal muscle from a donor site. Electrical stimulation is commonly used to train and animate the skeletal muscle to perform its new task. Due to simultaneous tetanic contractions of the entire myoplasty, muscles are deprived of perfusion and fatigue rapidly, causing long-term problems such as excessive scarring and muscle ischemia. Sequential stimulation contracts part of the muscle while other parts rest, thus significantly improving blood perfusion. However, the muscle still fatigues. In this article, we report a test of the feasibility of using closed-loop control to economize the contractions of the sequentially stimulated myoplasty. A simple stimulation algorithm was developed and tested on a sequentially stimulated neo-sphincter designed from a canine gracilis muscle. Pressure generated in the lumen of the myoplasty neo-sphincter was used as feedback to regulate the stimulation signal via three control parameters, thereby optimizing the performance of the myoplasty. Additionally, we investigated and compared the efficiency of amplitude and frequency modulation techniques. Closed-loop feedback enabled us to maintain target pressures within 10% deviation using amplitude modulation and optimized control parameters (correction frequency = 4 Hz, correction threshold = 4%, and transition time = 0.3 s). The large-scale stimulation/feedback setup was unfit for chronic experimentation, but can be used as a blueprint for a small-scale version to unveil the theoretical benefits of closed-loop control in chronic experimentation.

Reference values in ovarian response to controlled ovarian stimulation throughout the reproductive period.

PubMed

La Marca, Antonio; Grisendi, Valentina; Spada, Elena; Argento, Cindy; Milani, Silvano; Plebani, Maddalena; Seracchioli, Renato; Volpe, Annibale

2014-01-01

Abstract The age-related decline in ovarian response to gonadotropins has been well known since the beginning of ovarian stimulation in IVF cycles and has been considered secondary to the age-related decline in ovarian reserve. The objective of this study was to establish reference values and to construct nomograms of ovarian response for any specific age to gonadotropins in IVF/ICSI cycles. We analyzed our database containing information on IVF cycles. According to inclusion and exclusion criteria, a total of 703 patients were selected. Among inclusion criteria, there were regular menstrual cycle, treatment with a long GnRH agonist protocol and starting follicle-stimulating hormone (FSH) dose of at least 200 IU per day. To estimate the reference values of ovarian response, the CG-LMS method was used. A linear decline in the parameters of ovarian response with age was observed: the median number of oocytes decreases approximately by one every three years, and the median number of follicles >16 mm by one every eight years. The number of oocytes and growing follicles corresponding to the 5th, 25th, 50th, 75th and 95th centiles has been calculated. This study confirmed the well known negative relationship between ovarian response to FSH and female ageing and permitted the construction of nomograms of ovarian response.

Deep brain stimulation: a return journey from psychiatry to neurology.

PubMed

Ashkan, Keyoumars; Shotbolt, Paul; David, Anthony S; Samuel, Michael

2013-06-01

Deep brain stimulation (DBS) has emerged as an effective neurosurgical tool to treat a range of conditions. Its use in movement disorders such as Parkinson's disease, tremor and dystonia is now well established and has been approved by the National Institute of Clinical Excellence (NICE). The NICE does, however, emphasise the need for a multidisciplinary team to manage these patients. Such a team is traditionally composed of neurologists, neurosurgeons and neuropsychologists. Neuropsychiatrists, however, are increasingly recognised as essential members given many psychiatric considerations that may arise in patients undergoing DBS. Patient selection, assessment of competence to consent and treatment of postoperative psychiatric disease are just a few areas where neuropsychiatric input is invaluable. Partly driven by this close team working and partly based on the early history of DBS for psychiatric disorders, there is increasing interest in re-exploring the potential of neurosurgery to treat patients with psychiatric disease, such as depression and obsessive-compulsive disorder. Although the clinical experience and evidence with DBS in this group of patients are steadily increasing, many questions remain unanswered. Yet, the characteristics of optimal surgical candidates, the best choice of DBS target, the most effective stimulating parameters and the extent of postoperative improvement are not clear for most psychiatric conditions. Further research is therefore required to define how DBS can be best utilised to improve the quality of life of patients with psychiatric disease.

Musical motor feedback (MMF) in walking hemiparetic stroke patients: randomized trials of gait improvement.

PubMed

Schauer, Michael; Mauritz, Karl-Heinz

2003-11-01

To demonstrate the effect of rhythmical auditory stimulation in a musical context for gait therapy in hemiparetic stroke patients, when the stimulation is played back measure by measure initiated by the patient's heel-strikes (musical motor feedback). Does this type of musical feedback improve walking more than a less specific gait therapy? The randomized controlled trial considered 23 registered stroke patients. Two groups were created by randomization: the control group received 15 sessions of conventional gait therapy and the test group received 15 therapy sessions with musical motor feedback. Inpatient rehabilitation hospital. Median post-stroke interval was 44 days and the patients were able to walk without technical aids with a speed of approximately 0.71 m/s. Gait velocity, step duration, gait symmetry, stride length and foot rollover path length (heel-on-toe-off distance). The test group showed more mean improvement than the control group: stride length increased by 18% versus 0%, symmetry deviation decreased by 58% versus 20%, walking speed increased by 27% versus 4% and rollover path length increased by 28% versus 11%. Musical motor feedback improves the stroke patient's walk in selected parameters more than conventional gait therapy. A fixed memory in the patient's mind about the song and its timing may stimulate the improvement of gait even without the presence of an external pacemaker.

Factor analytic reduction of the carotid-cardiac baroreflex parameters

NASA Technical Reports Server (NTRS)

Ludwig, David A.

1989-01-01

An accepted method for measuring the responsiveness of the carotid-cardiac baroreflex to arterial pressure changes is to artificially stimulate the baroreceptors in the neck. This is accomplished by using a pressurized neck cuff which constricts and distends the carotid artery and subsequently stimulates the baroreceptors. Nine physiological responses to this type of stimulation are quantified and used as indicators of the baroreflex. Thirty male humans between the ages 27 and 46 underwent the carotid-cardiac baroreflex test. The data for the nine response parameters were analyzed by principle component factor analysis. The results of this analysis indicated that 93 percent of the total variance across all nine parameters could be explained in four dimensions. Examination of the factor loadings following an orthogonal rotation of the principle components indicated four well defined dimensions. The first two dimensions reflected location points for R-R interval and carotid distending pressure respectively. The third dimension was composed of measures reflecting the gain of the reflex. The fourth dimension was the ratio of the resting R-R interval to R-R interval during simulated hypertension. The data suggests that the analysis of all nine baroreflex parameters is redundant.

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

PubMed Central

Vidal, Jose; Ghovanloo, Maysam

2013-01-01

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

An Electrical Muscle Stimulation Suit for Increasing Blood Pressure

DTIC Science & Technology

2008-09-01

an exploratory way in about 100 trials. Maximal indi- vidual stimulation intensity was selected to give a solid, tetanic muscle contraction without...therapy and in muscle strength training in athletes. However, if the electrical stimulation is too intense, the result will be muscle contraction pain...Each subject was instructed to have the investigator lower the intensity or stop the stimulation if muscle contraction pain was experienced

Electrical Stimulation of Lateral Habenula during Learning: Frequency-Dependent Effects on Acquisition but Not Retrieval of a Two-Way Active Avoidance Response

PubMed Central

Wetzel, Wolfram; Scheich, Henning; Ohl, Frank W.

2013-01-01

The lateral habenula (LHb) is an epithalamic structure involved in signaling reward omission and aversive stimuli, and it inhibits dopaminergic neurons during motivated behavior. Less is known about LHb involvement in the acquisition and retrieval of avoidance learning. Our previous studies indicated that brief electrical stimulation of the LHb, time-locked to the avoidance of aversive footshock (presumably during the positive affective “relief” state that occurs when an aversive outcome is averted), inhibited the acquisition of avoidance learning. In the present study, we used the same paradigm to investigate different frequencies of LHb stimulation. The effect of 20 Hz vs. 50 Hz vs. 100 Hz stimulation was investigated during two phases, either during acquisition or retrieval in Mongolian gerbils. The results indicated that 50 Hz, but not 20 Hz, was sufficient to produce a long-term impairment in avoidance learning, and was somewhat more effective than 100 Hz in this regard. None of the stimulation parameters led to any effects on retrieval of avoidance learning, nor did they affect general motor activity. This suggests that, at frequencies in excess of the observed tonic firing rates of LHb neurons (>1–20 Hz), LHb stimulation may serve to interrupt the consolidation of new avoidance memories. However, these stimulation parameters are not capable of modifying avoidance memories that have already undergone extensive consolidation. PMID:23840355

Hair growth-promotion effects of different alternating current parameter settings are mediated by the activation of Wnt/β-catenin and MAPK pathway.

PubMed

Sohn, Ki Min; Jeong, Kwan Ho; Kim, Jung Eun; Park, Young Min; Kang, Hoon

2015-12-01

Electrical stimulation is being used in variable skin therapeutic conditions. There have been clinical studies demonstrating the positive effect of electrical stimuli on hair regrowth. However, the underlying exact mechanism and optimal parameter settings are not clarified yet. To investigate the effects of different parameter settings of electrical stimuli on hair growth by examining changes in human dermal papilla cells (hDPCs) in vitro and by observing molecular changes in animal tissue. In vitro, cultured hDPCs were electrically stimulated with different parameter settings at alternating current (AC). Cell proliferation was measured by MTT assay. The Ki67 expression was measured by immunofluorescence. Hair growth-related gene expressions were measured by RT-PCR. In animal model, different parameter settings of AC were applied to the shaved dorsal skin of rabbit for 8 weeks. Expression of hair-related genes in the skin of rabbit was examined by RT-PCR. At low voltage power (3.5 V) and low frequency (1 or 2 MHz) with AC, in vitro proliferation of hDPCs was successfully induced. A significant increase in Wnt/β-catenin, Ki67, p-ERK and p-AKT expressions was observed under the aforementioned settings. In animal model, hair regrowth was observed in the entire stimulated areas under individual conditions. Expression of hair-related genes in the skin significantly increased on the 6th week of treatment. There are optimal conditions for electrical stimulated hair growth, and they might be different in the cells, animals and human tissues. Electrical stimuli induce mechanisms such as the activation of Wnt/β-catenin and MAPK pathway in hair follicles. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Selective and graded recruitment of cat hamstring muscles with intrafascicular stimulation.

PubMed

Dowden, Brett R; Wilder, Andrew M; Hiatt, Scott D; Normann, Richard A; Brown, Nicholas A T; Clark, Gregory A

2009-12-01

The muscles of the hamstring group can produce different combinations of hip and knee torque. Thus, the ability to activate the different hamstring muscles selectively is of particular importance in eliciting functional movements such as stance and gait in a person with spinal cord injury. We investigated the ability of intrafascicular stimulation of the muscular branch of the sciatic nerve to recruit the feline hamstring muscles in a selective and graded fashion. A Utah Slanted Electrode Array, consisting of 100 penetrating microelectrodes, was implanted into the muscular branch of the sciatic nerve in six cats. Muscle twitches were evoked in the three compartments of biceps femoris (anterior, middle, and posterior), as well as semitendinosus and semimembranosus, using pulse-width modulated constant-voltage pulses. The resultant compound muscle action potentials were recorded using intramuscular fine-wire electrodes. 74% of the electrodes per implant were able to evoke a threshold response in these muscles, and these electrodes were evenly distributed among the instrumented muscles. Of the five muscles instrumented, on average 2.5 could be selectively activated to 90% of maximum EMG, and 3.5 could be selectively activated to 50% of maximum EMG. The muscles were recruited selectively with a mean stimulus dynamic range of 4.14 +/- 5.05 dB between threshold and either spillover to another muscle or a plateau in the response. This selective and graded activation afforded by intrafascicular stimulation of the muscular branch of the sciatic nerve suggests that it is a potentially useful stimulation paradigm for eliciting distinct forces in the hamstring muscle group in motor neuroprosthetic applications.

Focusing the research agenda for simulation training visual system requirements

NASA Astrophysics Data System (ADS)

Lloyd, Charles J.

2014-06-01

Advances in the capabilities of the display-related technologies with potential uses in simulation training devices continue to occur at a rapid pace. Simultaneously, ongoing reductions in defense spending stimulate the services to push a higher proportion of training into ground-based simulators to reduce their operational costs. These two trends result in increased customer expectations and desires for more capable training devices, while the money available for these devices is decreasing. Thus, there exists an increasing need to improve the efficiency of the acquisition process and to increase the probability that users get the training devices they need at the lowest practical cost. In support of this need the IDEAS program was initiated in 2010 with the goal of improving display system requirements associated with unmet user needs and expectations and disrupted acquisitions. This paper describes a process of identifying, rating, and selecting the design parameters that should receive research attention. Analyses of existing requirements documents reveal that between 40 and 50 specific design parameters (i.e., resolution, contrast, luminance, field of view, frame rate, etc.) are typically called out for the acquisition of a simulation training display system. Obviously no research effort can address the effects of this many parameters. Thus, we developed a defensible strategy for focusing limited R&D resources on a fraction of these parameters. This strategy encompasses six criteria to identify the parameters most worthy of research attention. Examples based on display design parameters recommended by stakeholders are provided.

A neurochemical closed-loop controller for deep brain stimulation: toward individualized smart neuromodulation therapies.

PubMed

Grahn, Peter J; Mallory, Grant W; Khurram, Obaid U; Berry, B Michael; Hachmann, Jan T; Bieber, Allan J; Bennet, Kevin E; Min, Hoon-Ki; Chang, Su-Youne; Lee, Kendall H; Lujan, J L

2014-01-01

Current strategies for optimizing deep brain stimulation (DBS) therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. As such, development of closed-loop control systems that can respond to changing neurochemical environments, tailoring DBS therapy to individual patients, is paramount for improving the therapeutic efficacy of DBS. Evidence obtained using electrophysiology and imaging techniques in both animals and humans suggests that DBS works by modulating neural network activity. Recently, animal studies have shown that stimulation-evoked changes in neurotransmitter release that mirror normal physiology are associated with the therapeutic benefits of DBS. Therefore, to fully understand the neurophysiology of DBS and optimize its efficacy, it may be necessary to look beyond conventional electrophysiological analyses and characterize the neurochemical effects of therapeutic and non-therapeutic stimulation. By combining electrochemical monitoring and mathematical modeling techniques, we can potentially replace the trial-and-error process used in clinical programming with deterministic approaches that help attain optimal and stable neurochemical profiles. In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a "smart" neuroprosthetic system for treatment of neurologic and psychiatric disorders.

Regional differences in mu and kappa opioid receptor G-protein activation in brain in male and female prairie voles.

PubMed

Martin, T J; Sexton, T; Kim, S A; Severino, A L; Peters, C M; Young, L J; Childers, S R

2015-12-17

Prairie voles are unusual mammals in that, like humans, they are capable of forming socially monogamous pair bonds, display biparental care, and engage in alloparental behaviors. Both mu and kappa opioid receptors are involved in behaviors that either establish and maintain, or result from pair bond formation in these animals. Mu and kappa opioid receptors both utilize inhibitory G-proteins in signal transduction mechanisms, however the efficacy by which these receptor subtypes stimulate G-protein signaling across the prairie vole neuraxis is not known. Utilizing [(35)S]GTPγS autoradiography, we characterized the efficacy of G-protein stimulation in coronal sections throughout male and female prairie vole brains by [D-Ala2,NMe-Phe4,Gly-ol5]-enkephalin (DAMGO) and U50,488H, selective mu and kappa opioid agonists, respectively. DAMGO stimulation was highest in the forebrain, similar to that found with other rodent species. U-50,488H produced greater stimulation in prairie voles than is typically seen in mice and rats, particularly in select forebrain areas. DAMGO produced higher stimulation in the core versus the shell of the nucleus accumbens (NAc) in females, while the distribution of U-50,488H stimulation was the opposite. There were no gender differences for U50,488H stimulation of G-protein activity across the regions examined, while DAMGO stimulation was greater in sections from females compared to those from males for NAc core, entopeduncular nucleus, and hippocampus. These data suggest that the kappa opioid system may be more sensitive to manipulation in prairie voles compared to mice and rats, and that female prairie voles may be more sensitive to mu agonists in select brain regions than males. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Estrogen Replacement Therapy in Ovariectomized Nonpregnant Ewes Stimulates Uterine Artery Hydrogen Sulfide Biosynthesis by Selectively Up-Regulating Cystathionine β-Synthase Expression

PubMed Central

Lechuga, Thomas J.; Zhang, Hong-hai; Sheibani, Lili; Karim, Muntarin; Jia, Jason; Magness, Ronald R.; Rosenfeld, Charles R.

2015-01-01

Estrogens dramatically dilate numerous vascular beds with the greatest response in the uterus. Endogenous hydrogen sulfide (H2S) is a potent vasodilator and proangiogenic second messenger, which is synthesized from L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). We hypothesized that estrogen replacement therapy (ERT) selectively stimulates H2S biosynthesis in uterine artery (UA) and other systemic arteries. Intact and endothelium-denuded UA, mesenteric artery (MA), and carotid artery (CA) were obtained from ovariectomized nonpregnant ewes (n = 5/group) receiving vehicle or estradiol-17β replacement therapy (ERT). Total RNA and protein were extracted for measuring CBS and CSE, and H2S production was determined by the methylene blue assay. Paraffin-embedded UA rings were used to localize CBS and CSE proteins by immunofluorescence microscopy. ERT significantly stimulated CBS mRNA and protein without altering CSE mRNA or protein in intact and denuded UA. Quantitative immunofluorescence microscopic analyses showed CBS and CSE protein localization in endothelium and smooth muscle and confirmed that ERT stimulated CBS but not CSE protein expression in UA endothelium and smooth muscle. ERT also stimulated CBS, but not CSE, mRNA and protein expression in intact and denuded MA but not CA in ovariectomized ewes. Concomitantly, ERT stimulated UA and MA but not CA H2S production. ERT-stimulated UA H2S production was completely blocked by a specific CBS but not CSE inhibitor. Thus, ERT selectively stimulates UA and MA but not CA H2S biosynthesis by specifically up-regulating CBS expression, implicating a role of H2S in estrogen-induced vasodilation and postmenopausal women's health. PMID:25825818

Estrogen Replacement Therapy in Ovariectomized Nonpregnant Ewes Stimulates Uterine Artery Hydrogen Sulfide Biosynthesis by Selectively Up-Regulating Cystathionine β-Synthase Expression.

PubMed

Lechuga, Thomas J; Zhang, Hong-hai; Sheibani, Lili; Karim, Muntarin; Jia, Jason; Magness, Ronald R; Rosenfeld, Charles R; Chen, Dong-bao

2015-06-01

Estrogens dramatically dilate numerous vascular beds with the greatest response in the uterus. Endogenous hydrogen sulfide (H2S) is a potent vasodilator and proangiogenic second messenger, which is synthesized from L-cysteine by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). We hypothesized that estrogen replacement therapy (ERT) selectively stimulates H2S biosynthesis in uterine artery (UA) and other systemic arteries. Intact and endothelium-denuded UA, mesenteric artery (MA), and carotid artery (CA) were obtained from ovariectomized nonpregnant ewes (n = 5/group) receiving vehicle or estradiol-17β replacement therapy (ERT). Total RNA and protein were extracted for measuring CBS and CSE, and H2S production was determined by the methylene blue assay. Paraffin-embedded UA rings were used to localize CBS and CSE proteins by immunofluorescence microscopy. ERT significantly stimulated CBS mRNA and protein without altering CSE mRNA or protein in intact and denuded UA. Quantitative immunofluorescence microscopic analyses showed CBS and CSE protein localization in endothelium and smooth muscle and confirmed that ERT stimulated CBS but not CSE protein expression in UA endothelium and smooth muscle. ERT also stimulated CBS, but not CSE, mRNA and protein expression in intact and denuded MA but not CA in ovariectomized ewes. Concomitantly, ERT stimulated UA and MA but not CA H2S production. ERT-stimulated UA H2S production was completely blocked by a specific CBS but not CSE inhibitor. Thus, ERT selectively stimulates UA and MA but not CA H2S biosynthesis by specifically up-regulating CBS expression, implicating a role of H2S in estrogen-induced vasodilation and postmenopausal women's health.

Anatomical Parameters of tDCS to Modulate the Motor System after Stroke: A Review

PubMed Central

Lefebvre, Stephanie; Liew, Sook-Lei

2017-01-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method to modulate the local field potential in neural tissue and consequently, cortical excitability. As tDCS is relatively portable, affordable, and accessible, the applications of tDCS to probe brain–behavior connections have rapidly increased in the last 10 years. One of the most promising applications is the use of tDCS to modulate excitability in the motor cortex after stroke and promote motor recovery. However, the results of clinical studies implementing tDCS to modulate motor excitability have been highly variable, with some studies demonstrating that as many as 50% or more of patients fail to show a response to stimulation. Much effort has therefore been dedicated to understand the sources of variability affecting tDCS efficacy. Possible suspects include the placement of the electrodes, task parameters during stimulation, dosing (current amplitude, duration of stimulation, frequency of stimulation), individual states (e.g., anxiety, motivation, attention), and more. In this review, we first briefly review potential sources of variability specific to stroke motor recovery following tDCS. We then examine how the anatomical variability in tDCS placement [e.g., neural target(s) and montages employed] may alter the neuromodulatory effects that tDCS exerts on the post-stroke motor system. PMID:28232816

Redox-active cerium oxide nanoparticles protect human dermal fibroblasts from PQ-induced damage.

PubMed

von Montfort, Claudia; Alili, Lirija; Teuber-Hanselmann, Sarah; Brenneisen, Peter

2015-01-01

Recently, it has been published that cerium (Ce) oxide nanoparticles (CNP; nanoceria) are able to downregulate tumor invasion in cancer cell lines. Redox-active CNP exhibit both selective pro-oxidative and antioxidative properties, the first being responsible for impairment of tumor growth and invasion. A non-toxic and even protective effect of CNP in human dermal fibroblasts (HDF) has already been observed. However, the effect on important parameters such as cell death, proliferation and redox state of the cells needs further clarification. Here, we present that nanoceria prevent HDF from reactive oxygen species (ROS)-induced cell death and stimulate proliferation due to the antioxidative property of these particles. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Randomized, sham-controlled trial based on transcranial direct current stimulation and wrist robot-assisted integrated treatment on subacute stroke patients: Intermediate results.

PubMed

Mazzoleni, Stefano; Tran, Vi Do; Iardella, Laura; Dario, Paolo; Posteraro, Federico

2017-07-01

The main goal of this study is to analyse the effects of combined transcranial direct current stimulation (tDCS) and wrist robot-assisted therapy in subacute stroke patients. Twenty-four patients were included in this study and randomly assigned to the experimental (EG) or control group (CG). All participants performed wrist robot-assisted training a) in conjunction with tDCS (real stimulation for patients in EG) or b) without tDCS (sham stimulation for patients in CG). Clinical scales and kinematic parameters recorded by the robot were used for the assessment. Clinical outcome measures show a significant decrease in motor impairment after the treatment in both groups. Kinematic data show several significant improvements after the integrated therapy in both groups. However, no significant differences in both clinical outcome measures and kinematic parameters was found between two groups. The potential advantages of combined tDCS and wrist robot-assisted therapy in subacute stroke patients are still unclear.

Low-frequency repetitive transcranial magnetic simulation prevents chronic epileptic seizure

PubMed Central

Wang, Yinxu; Wang, Xiaoming; Ke, Sha; Tan, Juan; Hu, Litian; Zhang, Yaodan; Cui, Wenjuan

2013-01-01

Although low-frequency repetitive transcranial magnetic simulation can potentially treat epilepsy, its underlying mechanism remains unclear. This study investigated the influence of low-frequency re-petitive transcranial magnetic simulation on changes in several nonlinear dynamic electroence-phalographic parameters in rats with chronic epilepsy and explored the mechanism underlying petitive transcranial magnetic simulation-induced antiepileptic effects. An epilepsy model was es-tablished using lithium-pilocarpine intraperitoneal injection into adult Sprague-Dawley rats, which were then treated with repetitive transcranial magnetic simulation for 7 consecutive days. Nonlinear electroencephalographic parameters were obtained from the rats at 7, 14, and 28 days post-stimulation. Results showed significantly lower mean correlation-dimension and Kolmogo-rov-entropy values for stimulated rats than for non-stimulated rats. At 28 days, the complexity and point-wise correlation dimensional values were lower in stimulated rats. Low-frequency repetitive transcranial magnetic simulation has suppressive effects on electrical activity in epileptic rats, thus explaining its effectiveness in treating epilepsy. PMID:25206567

Effective intracortical microstimulation parameters applied to primary motor cortex for evoking forelimb movements to stable spatial end points

PubMed Central

Van Acker, Gustaf M.; Amundsen, Sommer L.; Messamore, William G.; Zhang, Hongyu Y.; Luchies, Carl W.; Kovac, Anthony

2013-01-01

High-frequency, long-duration intracortical microstimulation (HFLD-ICMS) applied to motor cortex is recognized as a useful and informative method for corticomotor mapping by evoking natural-appearing movements of the limb to consistent stable end-point positions. An important feature of these movements is that stimulation of a specific site in motor cortex evokes movement to the same spatial end point regardless of the starting position of the limb. The goal of this study was to delineate effective stimulus parameters for evoking forelimb movements to stable spatial end points from HFLD-ICMS applied to primary motor cortex (M1) in awake monkeys. We investigated stimulation of M1 as combinations of frequency (30–400 Hz), amplitude (30–200 μA), and duration (0.5–2 s) while concurrently recording electromyographic (EMG) activity from 24 forelimb muscles and movement kinematics with a motion capture system. Our results suggest a range of parameters (80–140 Hz, 80–140 μA, and 1,000-ms train duration) that are effective and safe for evoking forelimb translocation with subsequent stabilization at a spatial end point. The mean time for stimulation to elicit successful movement of the forelimb to a stable spatial end point was 475.8 ± 170.9 ms. Median successful frequency and amplitude were 110 Hz and 110 μA, respectively. Attenuated parameters resulted in inconsistent, truncated, or undetectable movements, while intensified parameters yielded no change to movement end points and increased potential for large-scale physiological spread and adverse focal motor effects. Establishing cortical stimulation parameters yielding consistent forelimb movements to stable spatial end points forms the basis for a systematic and comprehensive mapping of M1 in terms of evoked movements and associated muscle synergies. Additionally, the results increase our understanding of how the central nervous system may encode movement. PMID:23741044

Study on the Effect of Thermal and Magnetic Stimulation by Measuring of the Peripheral Blood Flow and Skin Temperature

NASA Astrophysics Data System (ADS)

Kubota, Kouhei; Nuruki, Atsuo; Tamari, Youzou; Yunokuchi, Kazutomo

Recently, the stiff shoulder accompanying the muscle fatigue becomes an issue of public concern. Therefore, we paid attention to the effect of the thermal and magnetic stimulation for the muscle fatigue. The maximum voluntary contraction has recovered significantly, and also peripheral blood flow has increased by stimulation. In order to evaluate if the thermal and magnetic stimulation has any effects, three parameters was measured, which are the maximum voluntary contraction, peripheral blood flow and skin temperature. The skin temperature, however, did not changed significantly.

[Parameter fitting for cochlear implant].

PubMed

Banda González, Rosa Isela; Castillo Castillo, Salvador; Roque Lee, Graciela

Programming a patient with cochlear impant follows a standardized and individualized protocol, although there is a percentage of users in which, for some reason, it is not possible to establish appropriate levels of stimulation. In these patients, the audiologist has to make adjustments in some special parameters such as a change in the strategy, stimulation rate, pulse width, among others, in order to obtain an auditory performance as expected. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

A modular, closed-loop platform for intracranial stimulation in people with neurological disorders.

PubMed

Sarma, Anish A; Crocker, Britni; Cash, Sydney S; Truccolo, Wilson

2016-08-01

Neuromodulation systems based on electrical stimulation can be used to investigate, probe, and potentially treat a range of neurological disorders. The effects of ongoing neural state and dynamics on stimulation response, and of stimulation parameters on neural state, have broad implications for the development of closed-loop neuro-modulation approaches. We describe the development of a modular, low-latency platform for pre-clinical, closed-loop neuromodulation studies with human participants. We illustrate the uses of the platform in a stimulation case study with a person with epilepsy undergoing neuro-monitoring prior to resective surgery. We demonstrate the efficacy of the system by tracking interictal epileptiform discharges in the local field potential to trigger intracranial electrical stimulation, and show that the response to stimulation depends on the neural state.

Graded activation of the intrinsic laryngeal muscles for vocal fold posturing

PubMed Central

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

2010-01-01

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

Effect of deep brain stimulation on different speech subsystems in patients with multiple sclerosis.

PubMed

Pützer, Manfred; Barry, William John; Moringlane, Jean Richard

2007-11-01

The effect of deep brain stimulation on articulation and phonation subsystems in seven patients with multiple sclerosis (MS) was examined. Production parameters in fast syllable-repetitions were defined and measured, and the phonation quality during vowel productions was analyzed. Speech material was recorded for patients (with and without stimulation) and for a group of healthy control speakers. With stimulation, the precision of glottal and supraglottal articulatory gestures is reduced, whereas phonation has a greater tendency to be hyperfunctional in comparison with the healthy control data. Different effects on the two speech subsystems are induced by electrical stimulation of the thalamus in patients with MS.

Outcomes of Upper Airway Stimulation for Obstructive Sleep Apnea in a Multicenter German Postmarket Study.

PubMed

Heiser, Clemens; Maurer, Joachim T; Hofauer, Benedikt; Sommer, J Ulrich; Seitz, Annemarie; Steffen, Armin

2017-02-01

Objective Selective stimulation of the hypoglossal nerve is a new surgical therapy for obstructive sleep apnea, with proven efficacy in well-designed clinical trials. The aim of the study is to obtain additional safety and efficacy data on the use of selective upper airway stimulation during daily clinical routine. Study Design Prospective single-arm study. Setting Three tertiary hospitals in Germany (Munich, Mannheim, Lübeck). Subjects and Methods A multicenter prospective single-arm study under a common implant and follow-up protocol took place in 3 German centers (Mannheim, Munich, Lübeck). Every patient who received an implant of selective upper airway stimulation was included in this trial (apnea-hypopnea index ≥15/h and ≤65/h and body mass index <35 kg/m 2 ). Before and 6 months after surgery, a 2-night home sleep test was performed. Data regarding the safety and efficacy were collected. Results From July 2014 through October 2015, 60 patients were included. Every subject reported improvement in sleep and daytime symptoms. The average usage time of the system was 42.9 ± 11.9 h/wk. The median apnea-hypopnea index was significantly reduced at 6 months from 28.6/h to 8.3/h. No patient required surgical revision of the implanted system. Conclusion Selective upper airway stimulation is a safe and effective therapy for patients with obstructive sleep apnea and represents a powerful option for its surgical treatment.

Electrical or repetitive transcranial magnetic stimulation of primary motor cortex for intractable neuropathic pain.

PubMed

Saitoh, Youichi; Maruo, Tomoyuki; Yokoe, Masaru; Matsuzaki, Taiga; Sekino, Masaki

2013-01-01

To assess the pain-relieving effects of motor cortex electrical stimulation (MCS) and the predictive factors retrospectively. Thirty-four patients with intractable neuropathic pain underwent MCS; 19 patients had cerebral lesions, and 15 had non-cerebral lesions. In selected 12 patients, test electrodes were implanted within the central sulcus and on the precentral gyrus. Twelve patients received both MCS and repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex. Pain reduction of >50% was observed in 12 of 32 (36%) patients with >12 months follow-ups (2 patients were excluded because of short follow-up). In 10 of the 12 patients who received test electrodes within the central sulcus and on the precentral gyrus, the optimal stimulation was MCS within the central sulcus. In 4 of these (40%) patients, positive effects were maintained at follow-ups. The pain reduction of rTMS significantly correlated with that of MCS during test stimulation. The test stimulation within the central sulcus was more effective than that of the precentral gyrus. In the selected patients, chronic stimulation within the central sulcus did not significantly improve long-term results. Repeated rTMS seems to be same effective as MCS.

Subthalamic nucleus stimulation selectively improves motor and visual memory performance in Parkinson's disease.

PubMed

Mollion, Hélène; Dominey, Peter Ford; Broussolle, Emmanuel; Ventre-Dominey, Jocelyne

2011-09-01

Although the treatment of Parkinson's disease via subthalamic stimulation yields remarkable improvements in motor symptoms, its effects on memory function are less clear. In this context, we previously demonstrated dissociable effects of levodopa therapy on parkinsonian performance in spatial and nonspatial visual working memory. Here we used the same protocol with an additional, purely motor task to investigate visual memory and motor performance in 2 groups of patients with Parkinson's disease with or without subthalamic stimulation. In each stimulation condition, subjects performed a simple motor task and 3 successive cognitive tasks: 1 conditional color-response association task and 2 visual (spatial and nonspatial) working memory tasks. The Parkinson's groups were compared with a control group of age-matched healthy subjects. Our principal results demonstrated that (1) in the motor task, stimulated patients were significantly improved with respect to nonstimulated patients and did not differ significantly from healthy controls, and (2) in the cognitive tasks, stimulated patients were significantly improved with respect to nonstimulated patients, but both remained significantly impaired when compared with healthy controls. These results demonstrate selective effects of subthalamic stimulation on parkinsonian disorders of motor and visual memory functions, with clear motor improvement for stimulated patients and a partial improvement for their visual memory processing. Copyright © 2011 Movement Disorder Society.

Comparison of Mono-, Bi-, and Tripolar Configurations for Stimulation and Recording With an Interfascicular Interface.

PubMed

Nielsen, Thomas N; Sevcencu, Cristian; Struijk, Johannes J

2014-01-01

Previous studies have indicated that electrodes placed between fascicles can provide nerve recruitment with high topological selectivity if the areas of interest in the nerve are separated with passive elements. In this study, we investigated if this separation of fascicles also can provide topologically selective nerve recordings and compared the performance of mono-, bi-, and tripolar configurations for stimulation and recording with an intra-neural interface. The interface was implanted in the sciatic nerve of 10 rabbits and achieved a median selectivity of Ŝ=0.98-0.99 for all stimulation configurations, while recording selectivity configurations was in the range of Ŝ=0.70-0.80 with the monopolar configuration providing the lowest and the average reference configuration the highest recording selectivity. Interfascicular electrodes could provide an interesting addition to the bulk of peripheral nerve interfaces available for neural prosthetic devices. The separation of the nerve into chambers by the passive elements of the electrode could ensure a higher selectivity than comparable cuff electrodes and the intra-neural location could provide an option of targeting mainly central fascicles. Further studies are, however, still required to develop biocompatible electrodes and test their stability and safety in chronic experiments.

A Selective TSH Receptor Antagonist Inhibits Stimulation of Thyroid Function in Female Mice

PubMed Central

Neumann, Susanne; Nir, Eshel A.; Eliseeva, Elena; Huang, Wenwei; Marugan, Juan; Xiao, Jingbo; Dulcey, Andrés E.

2014-01-01

Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of cAMP production stimulated by TSH, LH, or FSH. We tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 μM for TSHR and greater than 30 μM for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. In conclusion, we developed a selective TSHR antagonist that is effective in vivo in mice. This is the first report of a small-molecule TSHR antagonist active in vivo and may lead to a drug to treat Graves' disease. PMID:24169564

A selective TSH receptor antagonist inhibits stimulation of thyroid function in female mice.

PubMed

Neumann, Susanne; Nir, Eshel A; Eliseeva, Elena; Huang, Wenwei; Marugan, Juan; Xiao, Jingbo; Dulcey, Andrés E; Gershengorn, Marvin C

2014-01-01

Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of cAMP production stimulated by TSH, LH, or FSH. We tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 μM for TSHR and greater than 30 μM for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. In conclusion, we developed a selective TSHR antagonist that is effective in vivo in mice. This is the first report of a small-molecule TSHR antagonist active in vivo and may lead to a drug to treat Graves' disease.

[Selective training of the vastus medialis muscle using electrical stimulator for chondromalacia patella].

PubMed

Guo, K; Ye, Q; Lin, J; Shen, J; Yang, X

1996-04-01

Chondromalacia patella is closely related with subluxation and tilt of patella, as well as with muscular atrophy of quadriceps, especially in vastus medialis muscle. 364 cases of chondromalacia patella were treated with selective training of the vastus medialis muscle using electrical stimulator in our hospital. 211 cases were followed up after treatment from 6 months to 3 years. Among them excellent and good results were seen in 130 cases (62%), fair results were seen in 69 cases (33%) and no change was seen in 12 cases (5%). Significant reduction of CA (P < 0.01) and LPA (P < 0.001) were observed in all these patients in comparison with their primary angle. We believe that the selective training of the vastus medialis muscle using electrical stimulator is one of the effective methods for the treatment of chondromalacia patella.

Steric parameters, molecular modeling and hydropathic interaction analysis of the pharmacology of para-substituted methcathinone analogues

PubMed Central

Sakloth, F; Kolanos, R; Mosier, P D; Bonano, J S; Banks, M L; Partilla, J S; Baumann, M H; Negus, S S; Glennon, R A

2015-01-01

Background and Purpose There is growing concern over the abuse of certain psychostimulant methcathinone (MCAT) analogues. This study extends an initial quantitative structure–activity relationship (QSAR) investigation that demonstrated important steric considerations of seven 4- (or para-)substituted analogues of MCAT. Specifically, the steric character (Taft's steric ES) of the 4-position substituent affected in vitro potency to induce monoamine release via dopamine and 5-HT transporters (DAT and SERT) and in vivo modulation of intracranial self-stimulation (ICSS). Here, we have assessed the effects of other steric properties of the 4-position substituents. Experimental Approach Definitive steric parameters that more explicitly focus on the volume, width and length of the MCAT 4-position substituents were assessed. In addition, homology models of human DAT and human SERT based upon the crystallized Drosophila DAT were constructed and docking studies were performed, followed by hydropathic interaction (HINT) analysis of the docking results. Key Results The potency of seven MCAT analogues at DAT was negatively correlated with the volume and maximal width of their 4-position substituents, whereas potency at SERT increased as substituent volume and length increased. SERT/DAT selectivity, as well as abuse-related drug effects in the ICSS procedure, also correlated with the same parameters. Docking solutions offered a means of visualizing these findings. Conclusions and Implications These results suggest that steric aspects of the 4-position substituents of MCAT analogues are key determinants of their action and selectivity, and that the hydrophobic nature of these substituents is involved in their potency at SERT. PMID:25522019

Key Physiological Parameters Dictate Triggering of Activity-Dependent Bulk Endocytosis in Hippocampal Synapses

PubMed Central

Wenzel, Eva M.; Morton, Andrew; Ebert, Katrin; Welzel, Oliver; Kornhuber, Johannes; Cousin, Michael A.; Groemer, Teja W.

2012-01-01

To maintain neurotransmission in central neurons, several mechanisms are employed to retrieve synaptically exocytosed membrane. The two major modes of synaptic vesicle (SV) retrieval are clathrin-mediated endocytosis and activity-dependent bulk endocytosis (ADBE). ADBE is the dominant SV retrieval mode during intense stimulation, however the precise physiological conditions that trigger this mode are not resolved. To determine these parameters we manipulated rat hippocampal neurons using a wide spectrum of stimuli by varying both the pattern and duration of stimulation. Using live-cell fluorescence imaging and electron microscopy approaches, we established that stimulation frequency, rather than the stimulation load, was critical in the triggering of ADBE. Thus two hundred action potentials, when delivered at high frequency, were sufficient to induce near maximal bulk formation. Furthermore we observed a strong correlation between SV pool size and ability to perform ADBE. We also identified that inhibitory nerve terminals were more likely to utilize ADBE and had a larger SV recycling pool. Thus ADBE in hippocampal synaptic terminals is tightly coupled to stimulation frequency and is more likely to occur in terminals with large SV pools. These results implicate ADBE as a key modulator of both hippocampal neurotransmission and plasticity. PMID:22675521

Nonantimuscarinic treatment for overactive bladder: a systematic review.

PubMed

Olivera, Cedric K; Meriwether, Kate; El-Nashar, Sherif; Grimes, Cara L; Chen, Chi Chiung Grace; Orejuela, Francisco; Antosh, Danielle; Gleason, Jon; Kim-Fine, Shunaha; Wheeler, Thomas; McFadden, Brook; Balk, Ethan M; Murphy, Miles

2016-07-01

The purpose of the study was to determine the efficacy and safety of nonantimuscarinic treatments for overactive bladder. Medline, Cochrane, and other databases (inception to April 2, 2014) were used. We included any study design in which there were 2 arms and an n > 100, if at least 1 of the arms was a nonantimuscarinic therapy or any comparative trial, regardless of number, if at least 2 arms were nonantimuscarinic therapies for overactive bladder. Eleven reviewers double-screened citations and extracted eligible studies for study: population, intervention, outcome, effects on outcome categories, and quality. The body of evidence for categories of interventions were summarized and assessed for strength. Ninety-nine comparative studies met inclusion criteria. Interventions effective to improve subjective overactive bladder symptoms include exercise with heat and steam generating sheets (1 study), diaphragmatic (1 study), deep abdominal (1 study), and pelvic floor muscle training exercises (2 studies). Pelvic floor exercises are more effective in subjective and objective outcomes with biofeedback or verbal feedback. Weight loss with diet and exercise, caffeine reduction, 25-50% reduction in fluid intake, and pelvic floor muscle exercises with verbal instruction and or biofeedback were all efficacious. Botulinum toxin A improves urge incontinence episodes, urgency, frequency, quality of life, nocturia, and urodynamic testing parameters. Acupuncture improves quality of life and urodynamic testing parameters. Extracorporeal magnetic stimulation improves urodynamic parameters. Mirabegron improves daily incontinence episodes, nocturia, number of daily voids, and urine volume per void, whereas solabegron improves daily incontinence episodes. Short-term posterior tibial nerve stimulation is more efficacious than pelvic floor muscle training exercises and behavioral therapy for improving: urgency, urinary incontinence episodes, daily voids, volume per void, and overall quality of life. Sacral neuromodulation is more efficacious than antimuscarinic treatment for subjective improvement of overactive bladder and quality of life. Transvaginal electrical stimulation demonstrates subjective improvement in overactive bladder symptoms and urodynamic parameters. Multiple therapies, including physical therapy, behavioral therapy, botulinum toxin A, acupuncture, magnetic stimulation, mirabegron, posterior tibial nerve stimulation, sacral neuromodulation, and transvaginal electrical stimulation, are efficacious in the treatment of overactive bladder. Copyright © 2016 Elsevier Inc. All rights reserved.

The Effects of Electroacupuncture on Cyclophosphamide-Induced Emesis in Ferrets.

DTIC Science & Technology

1996-07-01

Other studies conducted by Dundee’s group showed that acupressure and transcutaneous electrical stimulation ( TENS ) of the same acupoints also benefited...typically left in place for 20-30 minutes. The effects of acupuncture may be augmented with electrical stimulation (EA) and/or heat (e.g. moxibustion). Side...electrodes (Grass) were attached to the end of the needles and electrical stimulation was applied (the EA parameters will be described in detail later

New Stimulation Strategy to Improve the Bladder Function in Paraplegics: Chronic Experiments in Dogs

DTIC Science & Technology

2001-10-25

urinary system [4]. More recently, neurostimulation and neuromodulation of the sacral nerve root seems to be one of the most promising options to enhance...day. Expelled and residual urine volumes were measured. Also the applied parameters for the continuous low frequency / low amplitude neuromodulation ...VCUG) with neurostimulation was carried out after IVU study. Low-frequency only stimulation During the 7th month, daily stimulations were performed

A nerve stimulation method to selectively recruit smaller motor-units in rat skeletal muscle.

PubMed

van Bolhuis, A I; Holsheimer, J; Savelberg, H H

2001-05-30

Electrical stimulation of peripheral nerve results in a motor-unit recruitment order opposite to that attained by natural neural control, i.e. from large, fast-fatiguing to progressively smaller, fatigue-resistant motor-units. Yet animal studies involving physiological exercise protocols of low intensity and long duration require minimal fatigue. The present study sought to apply a nerve stimulation method to selectively recruit smaller motor-units in rat skeletal muscle. Two pulse generators were used, independently supplying short supramaximal cathodal stimulating pulses (0.5 ms) and long subthreshold cathodal inactivating pulses (1.5 s) to the sciatic nerve. Propagation of action potentials was selectively blocked in nerve fibres of different diameter by adjusting the strength of the inactivating current. A tensile-testing machine was used to gauge isometric muscle force of the plantaris and both heads of the gastrocnemius muscle. The order of motor-unit recruitment was estimated from twitch characteristics, i.e. peak force and relaxation time. The results showed prolonged relaxation at lower twitch peak forces as the intensity of the inactivating current increased, indicating a reduction of the number of large motor-units to force production. It is shown that the nerve stimulation method described is effective in mimicking physiological muscle control.

Repetitive transcranial magnetic stimulation for hallucination in schizophrenia spectrum disorders: A meta-analysis

PubMed Central

Zhang, Yingli; Liang, Wei; Yang, Shichang; Dai, Ping; Shen, Lijuan; Wang, Changhong

2013-01-01

Objective: This study assessed the efficacy and tolerability of repetitive transcranial magnetic stimulation for treatment of auditory hallucination of patients with schizophrenia spectrum disorders. Data Sources: Online literature retrieval was conducted using PubMed, ISI Web of Science, EMBASE, Medline and Cochrane Central Register of Controlled Trials databases from January 1985 to May 2012. Key words were “transcranial magnetic stimulation”, “TMS”, “repetitive transcranial magnetic stimulation”, and “hallucination”. Study Selection: Selected studies were randomized controlled trials assessing therapeutic efficacy of repetitive transcranial magnetic stimulation for hallucination in patients with schizophrenia spectrum disorders. Experimental intervention was low-frequency repetitive transcranial magnetic stimulation in left temporoparietal cortex for treatment of auditory hallucination in schizophrenia spectrum disorders. Control groups received sham stimulation. Main Outcome Measures: The primary outcome was total scores of Auditory Hallucinations Rating Scale, Auditory Hallucination Subscale of Psychotic Symptom Rating Scale, Positive and Negative Symptom Scale-Auditory Hallucination item, and Hallucination Change Scale. Secondary outcomes included response rate, global mental state, adverse effects and cognitive function. Results: Seventeen studies addressing repetitive transcranial magnetic stimulation for treatment of schizophrenia spectrum disorders were screened, with controls receiving sham stimulation. All data were completely effective, involving 398 patients. Overall mean weighted effect size for repetitive transcranial magnetic stimulation versus sham stimulation was statistically significant (MD = –0.42, 95%CI: –0.64 to –0.20, P = 0.000 2). Patients receiving repetitive transcranial magnetic stimulation responded more frequently than sham stimulation (OR = 2.94, 95%CI: 1.39 to 6.24, P = 0.005). No significant differences were found between active repetitive transcranial magnetic stimulation and sham stimulation for positive or negative symptoms. Compared with sham stimulation, active repetitive transcranial magnetic stimulation had equivocal outcome in cognitive function and commonly caused headache and facial muscle twitching. Conclusion: Repetitive transcranial magnetic stimulation is a safe and effective treatment for auditory hallucination in schizophrenia spectrum disorders. PMID:25206578

Augmenting distractor filtering via transcranial magnetic stimulation of the lateral occipital cortex.

PubMed

Eštočinová, Jana; Lo Gerfo, Emanuele; Della Libera, Chiara; Chelazzi, Leonardo; Santandrea, Elisa

2016-11-01

Visual selective attention (VSA) optimizes perception and behavioral control by enabling efficient selection of relevant information and filtering of distractors. While focusing resources on task-relevant information helps counteract distraction, dedicated filtering mechanisms have recently been demonstrated, allowing neural systems to implement suitable policies for the suppression of potential interference. Limited evidence is presently available concerning the neural underpinnings of these mechanisms, and whether neural circuitry within the visual cortex might play a causal role in their instantiation, a possibility that we directly tested here. In two related experiments, transcranial magnetic stimulation (TMS) was applied over the lateral occipital cortex of healthy humans at different times during the execution of a behavioral task which entailed varying levels of distractor interference and need for attentional engagement. While earlier TMS boosted target selection, stimulation within a restricted time epoch close to (and in the course of) stimulus presentation engendered selective enhancement of distractor suppression, by affecting the ongoing, reactive instantiation of attentional filtering mechanisms required by specific task conditions. The results attest to a causal role of mid-tier ventral visual areas in distractor filtering and offer insights into the mechanisms through which TMS may have affected ongoing neural activity in the stimulated tissue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys

NASA Astrophysics Data System (ADS)

Brill, N. A.; Naufel, S. N.; Polasek, K.; Ethier, C.; Cheesborough, J.; Agnew, S.; Miller, L. E.; Tyler, D. J.

2018-06-01

Objective. The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. Approach. To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294-303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. Main result. A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. Significance. FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.

A selective androgen receptor modulator with minimal prostate hypertrophic activity restores lean body mass in aged orchidectomized male rats.

PubMed

Allan, George; Sbriscia, Tifanie; Linton, Olivia; Lai, Muh-Tsann; Haynes-Johnson, Donna; Bhattacharjee, Sheela; Ng, Raymond; Sui, Zhihua; Lundeen, Scott

2008-06-01

Androgens are required for the maintenance of normal sexual activity in adulthood and for enhancing muscle growth and lean body mass in adolescents and adults. Androgen receptor (AR) ligands with tissue selectivity (selective androgen receptor modulators, or SARMs) have potential for treating muscle wasting, hypogonadism of aging, osteoporosis, female sexual dysfunction, and other indications. JNJ-37654032 is a nonsteroidal AR ligand with mixed agonist and antagonist activity in androgen-responsive cell-based assays. It is an orally active SARM with muscle selectivity in orchidectomized rat models. It stimulated growth of the levator ani muscle with ED(50) 0.8 mg/kg, stimulating maximal growth at a dose of 3mg/kg. In contrast, it stimulated ventral prostate growth to 21% of its full size at 3mg/kg. At the same time, JNJ-37654032 reduced prostate weight in intact rats by 47% at 3mg/kg, while having no inhibitory effect on muscle. Using magnetic resonance imaging to monitor body composition, JNJ-37654032 restored about 20% of the lean body mass lost following orchidectomy in aged rats. JNJ-37654032 reduced follicle-stimulating hormone levels in orchidectomized rats and reduced testis size in intact rats. JNJ-37654032 is a potent prostate-sparing SARM with the potential for clinical benefit in muscle-wasting diseases.

Standardizing therapeutic parameters of acupuncture for pain suppression in rats: preliminary study.

PubMed

Yeo, Sujung; Lim, Hyungtaeck; Choe, Ilwhan; Kim, Sung-Hoon; Lim, Sabina

2014-01-15

Despite acupuncture's wide and successful use, it is still considered as lacking scientifically rigorous evidence, especially with respect to its effectiveness. To address this problem, it is necessary to re-examine the practice of acupuncture using scientific methodology. The standardization of acupuncture practices may offer a solution. As a preliminary step towards the standardization of acupuncture stimulation in animal experiments, this study attempted to clarify the various therapeutic parameters that contribute to acupuncture's efficacy. This study identified specific acupoints, temporal point of needling, rotation of the needle, duration of acupuncture, and diameter of the needle as the parameters, through formalin test. In this test, acupuncture was performed on either the ST36 or LR2 point immediately after pain induction and 5 minutes after pain induction. The formalin test yielded no significant suppression of pain in the case of ST36 and LR2 acupuncture stimulation immediately following pain induction. When acupuncture was applied 5 minutes after pain induction, however, the ST36 stimulation resulted in a significant decrease in pain, while the LR2 stimulation produced no change. The duration of acupuncture, but not the diameter of the needle, was also significant. As for the rotation of the needle, there was no significant difference in the pain reduction achieved in the rotation and non-rotation groups. We determined that specific acupoint, temporal point of needling, and duration of treatment are important factors in the inhibition of pain. These finding strongly suggest that in animal experiments, the application of a set of appropriate therapeutic parameters can significantly influence the outcome.

Comparison of Effects Produced by Nicotine and the α4β2-Selective Agonist 5-I-A-85380 On Intracranial Self-Stimulation in Rats

PubMed Central

Freitas, Kelen; Carroll, F. Ivy; Negus, S. Stevens

2015-01-01

Intracranial self-stimulation (ICSS) is one type of preclinical procedure for research on pharmacological mechanisms that mediate abuse potential of drugs acting at various targets including nicotinic acetylcholine receptors (nAChRs). This study compared effects of the non-selective nAChR agonist nicotine (0.032-1.0 mg/kg) and the α4β2-selective nAChR agonist 5-I-A-85380 (0.01-1.0 mg/kg) on ICSS in male Sprague-Dawley rats. Rats were implanted with electrodes targeting the medial forebrain bundle at the level of the lateral hypothalamus and trained to respond under a fixed-ratio 1 schedule for a range of brain stimulation frequencies (158-56 Hz). A broad range of 5-I-A-85380 doses produced an abuse-related increase (or “facilitation”) of low ICSS rates maintained by low brain-stimulation frequencies, and this effect was blocked by both the nonselective nAChR antagonist mecamylamine and the selective α4β2 antagonist dihyrdo-ß-erythroidine (DHßE). Conversely, nicotine produced weaker ICSS facilitation across a narrower range of doses, and higher nicotine doses decreased high rates of ICSS maintained by high brain- stimulation frequencies. The rate-decreasing effects of a high nicotine dose were blocked by mecamylamine but not DHßE. Chronic nicotine treatment produced selective tolerance to rate-decreasing effects of nicotine but did not alter ICSS rate-increasing effects of nicotine. These results suggest that α4β2 receptors are sufficient to mediate abuse-related rate-increasing effects of nAChR agonists in this ICSS procedure. Conversely, nicotine effects at non-α4β2 nAChRs appear to oppose and limit abuse-related effects mediated by α4β2 receptors, although tolerance can develop to these non-α4β2 effects. Selective α4β2 agonists may have higher abuse potential than nicotine. PMID:26461167

Cardiac effects produced by long-term stimulation of thoracic autonomic ganglia or nerves: implications for interneuronal interactions within the thoracic autonomic nervous system.

PubMed

Butler, C; Watson-Wright, W M; Wilkinson, M; Johnstone, D E; Armour, J A

1988-03-01

Electrical stimulation of an acutely decentralized stellate or middle cervical ganglion or cardiopulmonary nerve augments cardiac chronotropism or inotropism; as the stimulation continues there is a gradual reduction of this augmentation following the peak response, i.e., an inhibition of augmentation. The amount of this inhibition was found to be dependent upon the region of the heart investigated and the neural structure stimulated. The cardiac parameters which were augmented the most displayed the greatest inhibition. Maximum augmentation or inhibition occurred, in most instances, when 5-20 Hz stimuli were used. Inhibition of augmentation was overcome when the stimulation frequency was subsequently increased or following the administration of nicotine or tyramine, indicating that the inhibition was not primarily due to the lack of availability of noradrenaline in the nerve terminals of the efferent postganglionic sympathetic neurons. Furthermore, as infusions of isoproterenol or noradrenaline during the period of inhibition could still augment cardiac responses, whereas during the early peak responses they did not, the inhibition of augmentation does not appear to be due primarily to down regulation of cardiac myocyte beta-adrenergic receptors. The inhibition was modified by hexamethonium but not by phentolamine or atropine. Inhibition occurred when all ipsilateral cardiopulmonary nerves connected with acutely decentralized middle cervical and stellate ganglia were stimulated, whereas significant inhibition did not occur when these nerves were stimulated after they had been disconnected from the ipsilateral decentralized ganglia. Taken together these data indicate that the inhibition of cardiac augmentation which occurs during relatively long-term stimulation of intrathoracic sympathetic neural elements is due in large part to nicotinic cholinergic synaptic mechanisms that lie primarily in the major thoracic autonomic ganglia. They also indicate that long-term stimulation in intrathoracic sympathetic neural elements with frequencies as low as 2 Hz may augment the heart as much as higher stimulation frequencies, depending upon the structure stimulated and the cardiovascular parameter monitored.

Electronic enhancement of tear secretion

NASA Astrophysics Data System (ADS)

Brinton, Mark; Lim Chung, Jae; Kossler, Andrea; Kook, Koung Hoon; Loudin, Jim; Franke, Manfred; Palanker, Daniel

2016-02-01

Objective. To study electrical stimulation of the lacrimal gland and afferent nerves for enhanced tear secretion, as a potential treatment for dry eye disease. We investigate the response pathways and electrical parameters to safely maximize tear secretion. Approach. We evaluated the tear response to electrical stimulation of the lacrimal gland and afferent nerves in isofluorane-anesthetized rabbits. In acute studies, electrical stimulation was performed using bipolar platinum foil electrodes, implanted beneath the inferior lacrimal gland, and a monopolar electrode placed near the afferent ethmoid nerve. Wireless microstimulators with bipolar electrodes were implanted beneath the lacrimal gland for chronic studies. To identify the response pathways, we applied various pharmacological inhibitors. To optimize the stimulus, we measured tear secretion rate (Schirmer test) as a function of pulse amplitude (1.5-12 mA), duration (0.1-1 ms) and repetition rate (10-100 Hz). Main results. Stimulation of the lacrimal gland increased tear secretion by engaging efferent parasympathetic nerves. Tearing increased with stimulation amplitude, pulse duration and repetition rate, up to 70 Hz. Stimulation with 3 mA, 500 μs pulses at 70 Hz provided a 4.5 mm (125%) increase in Schirmer score. Modulating duty cycle further increased tearing up to 57%, compared to continuous stimulation in chronically implanted animals (36%). Ethmoid (afferent) nerve stimulation increased tearing similar to gland stimulation (3.6 mm) via a reflex pathway. In animals with chronically implanted stimulators, a nearly 6 mm increase (57%) was achieved with 12-fold less charge density per pulse (0.06-0.3 μC mm-2 with 170-680 μs pulses) than the damage threshold (3.5 μC mm-2 with 1 ms pulses). Significance. Electrical stimulation of the lacrimal gland or afferent nerves may be used as a treatment for dry eye disease. Clinical trials should validate this approach in patients with aqueous tear deficiency, and further optimize electrical parameters for maximum clinical efficacy.

Neuropsychology of selective attention and magnetic cortical stimulation.

PubMed

Sabatino, M; Di Nuovo, S; Sardo, P; Abbate, C S; La Grutta, V

1996-01-01

Informed volunteers were asked to perform different neuropsychological tests involving selective attention under control conditions and during transcranial magnetic cortical stimulation. The tests chosen involved the recognition of a specific letter among different letters (verbal test) and the search for three different spatial orientations of an appendage to a square (visuo-spatial test). For each test the total time taken and the error rate were calculated. Results showed that cortical stimulation did not cause a worsening in performance. Moreover, magnetic stimulation of the temporal lobe neither modified completion time in both verbal and visuo-spatial tests nor changed error rate. In contrast, magnetic stimulation of the pre-frontal area induced a significant reduction in the performance time of both the verbal and visuo-spatial tests always without an increase in the number of errors. The experimental findings underline the importance of the pre-frontal area in performing tasks requiring a high level of controlled attention and suggest the need to adopt an interdisciplinary approach towards the study of neurone/mind interface mechanisms.

Otolithic influences on extraocular and intraocular muscles

NASA Technical Reports Server (NTRS)

Gernandt, B. E.

1973-01-01

Selective stimulation of utricular gravireceptors leads to gross activation of the bulbar reticular formation where a strong interaction with evoked spino-bulbo-spinal reflex activity occurs. The utricular neurons encountered by microelectrodes in the lateral vestibular nuclei show four types of elicited activity; two of these display an increased firing rate, and two exhibit pronounced inhibitory effects. Application of a stimulus of long duration and constant intensity to the utricle has shown that rapid adaptation of the peripheral receptors is a prominent feature. The effects of selective utricular stimulation upon eye movements, as recorded by the corneoretinal potential method, have been studied in experiments on cats and monkeys and it can be firmly stated that prolonged stimulation of the utricle can evoke strong primary nystagmus, followed by a secondary nystagmus at the cessation of stimulation. The action of utricular stimulation on ocular reflexes has been examined further, with particular attention to evoked pupillary reactions in both cats and monkeys: constriction during the fast phase of the brisk conjugate eye movement, and dilatation during the flow phase.

Optogenetic control of contractile function in skeletal muscle

PubMed Central

Bruegmann, Tobias; van Bremen, Tobias; Vogt, Christoph C.; Send, Thorsten; Fleischmann, Bernd K.; Sasse, Philipp

2015-01-01

Optogenetic stimulation allows activation of cells with high spatial and temporal precision. Here we show direct optogenetic stimulation of skeletal muscle from transgenic mice expressing the light-sensitive channel Channelrhodopsin-2 (ChR2). Largest tetanic contractions are observed with 5-ms light pulses at 30 Hz, resulting in 84% of the maximal force induced by electrical stimulation. We demonstrate the utility of this approach by selectively stimulating with a light guide individual intralaryngeal muscles in explanted larynges from ChR2-transgenic mice, which enables selective opening and closing of the vocal cords. Furthermore, systemic injection of adeno-associated virus into wild-type mice provides sufficient ChR2 expression for optogenetic opening of the vocal cords. Thus, direct optogenetic stimulation of skeletal muscle generates large force and provides the distinct advantage of localized and cell-type-specific activation. This technology could be useful for therapeutic purposes, such as restoring the mobility of the vocal cords in patients suffering from laryngeal paralysis. PMID:26035411

Cooperative role of electrical stimulation on microbial metabolism and selection of thermophilic communities for p-fluoronitrobenzene treatment.

PubMed

Zhang, Xueqin; Shen, Dongsheng; Feng, Huajun; Wang, Yanfeng; Li, Na; Han, Jingyi; Long, Yuyang

2015-01-01

A novel thermophilic bioelectrochemical system (TBES) based on electrical stimulation was established for the enhanced treatment of p-fluoronitrobenzene (p-FNB) wastewater. p-FNB removal rate constant in the TBES was 78.6% higher than that of the mesophilic BES (MBES), the elevation of which owing to high-temperature overtook the rate improvement of 50.8% in the electrocatalytic system (ECS). Additionally, an overwhelming mineralization efficiency of 91.96% ± 5.70% was obtained in the TBES. The superiority of TBES was attributed to the integrated role of electrical stimulation and high-temperature. Electrical stimulation provided an alternative for the microbial growth independent energy requirements, compensating insufficient energy support from p-FNB metabolism under the high-temperature stress. Besides, electrical stimulation facilitated microbial community evolution to form specific thermophilic biocatalysis. The uniquely selected thermophilic microorganisms including Coprothermobacter sp. and other ones cooperated to enhance p-FNB mineralization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson's disease: a systematic review and meta-analysis.

PubMed

Goodwill, Alicia M; Lum, Jarrad A G; Hendy, Ashlee M; Muthalib, Makii; Johnson, Liam; Albein-Urios, Natalia; Teo, Wei-Peng

2017-11-01

Parkinson's disease (PD) is a neurodegenerative disorder affecting motor and cognitive abilities. There is no cure for PD, therefore identifying safe therapies to alleviate symptoms remains a priority. This meta-analysis quantified the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (TES) to improve motor and cognitive dysfunction in PD. PubMed, EMBASE, Web of Science, Google Scholar, Scopus, Library of Congress and Cochrane library were searched. 24 rTMS and 9 TES studies (n = 33) with a sham control group were included for analyses. The Physiotherapy Evidence Database and Cochrane Risk of Bias showed high quality (7.5/10) and low bias with included studies respectively. Our results showed an overall positive effect in favour of rTMS (SMD = 0.394, CI [0.106-0.683], p = 0.007) and TES (SMD = 0.611, CI [0.188-1.035], p = 0.005) compared with sham stimulation on motor function, with no significant differences detected between rTMS and TES (Q [1] = 0.69, p = 0.406). Neither rTMS nor TES improved cognition. No effects for stimulation parameters on motor or cognitive function were observed. To enhance the clinical utility of non-invasive brain stimulation (NBS), individual prescription of stimulation parameters based upon symptomology and resting excitability state should be a priority of future research.

cAMP Stimulates Transepithelial Short-Circuit Current and Fluid Transport Across Porcine Ciliary Epithelium.

PubMed

Cheng, Angela King-Wah; Civan, Mortimer M; To, Chi-Ho; Do, Chi-Wai

2016-12-01

To investigate the effects of cAMP on transepithelial electrical parameters and fluid transport across porcine ciliary epithelium. Transepithelial electrical parameters were determined by mounting freshly isolated porcine ciliary epithelium in a modified Ussing chamber. Similarly, fluid movement across intact ciliary body was measured with a custom-made fluid flow chamber. Addition of 1, 10, and 100 μM 8-Br-cAMP (cAMP) to the aqueous side (nonpigmented ciliary epithelium, NPE) induced a sustained increase in short-circuit current (Isc). Addition of niflumic acid (NFA) to the aqueous surface effectively blocked the cAMP-induced Isc stimulation. The administration of cAMP to the stromal side (pigmented ciliary epithelium, PE) triggered a significant stimulation of Isc only at 100 μM. No additive effect was observed with bilateral application of cAMP. Likewise, forskolin caused a significant stimulation of Isc when applied to the aqueous side. Concomitantly, cAMP and forskolin increased fluid transport across porcine ciliary epithelium, and this stimulation was effectively inhibited by aqueous NFA. Depleting Cl- in the bathing solution abolished the baseline Isc and inhibited the subsequent stimulation by cAMP. Pretreatment with protein kinase A (PKA) blockers (H89/KT5720) significantly inhibited the cAMP- and forskolin-induced Isc responses. Our results suggest that cAMP triggers a sustained stimulation of Cl- and fluid transport across porcine ciliary epithelium; Cl- channels in the NPE cells are potentially a cellular site for this PKA-sensitive cAMP-mediated response.

Design and in vivo evaluation of more efficient and selective deep brain stimulation electrodes

NASA Astrophysics Data System (ADS)

Howell, Bryan; Huynh, Brian; Grill, Warren M.

2015-08-01

Objective. Deep brain stimulation (DBS) is an effective treatment for movement disorders and a promising therapy for treating epilepsy and psychiatric disorders. Despite its clinical success, the efficiency and selectivity of DBS can be improved. Our objective was to design electrode geometries that increased the efficiency and selectivity of DBS. Approach. We coupled computational models of electrodes in brain tissue with cable models of axons of passage (AOPs), terminating axons (TAs), and local neurons (LNs); we used engineering optimization to design electrodes for stimulating these neural elements; and the model predictions were tested in vivo. Main results. Compared with the standard electrode used in the Medtronic Model 3387 and 3389 arrays, model-optimized electrodes consumed 45-84% less power. Similar gains in selectivity were evident with the optimized electrodes: 50% of parallel AOPs could be activated while reducing activation of perpendicular AOPs from 44 to 48% with the standard electrode to 0-14% with bipolar designs; 50% of perpendicular AOPs could be activated while reducing activation of parallel AOPs from 53 to 55% with the standard electrode to 1-5% with an array of cathodes; and, 50% of TAs could be activated while reducing activation of AOPs from 43 to 100% with the standard electrode to 2-15% with a distal anode. In vivo, both the geometry and polarity of the electrode had a profound impact on the efficiency and selectivity of stimulation. Significance. Model-based design is a powerful tool that can be used to improve the efficiency and selectivity of DBS electrodes.

Stimulated Raman scattering: old physics, new applications.

PubMed

Yakovlev, Vladislav V; Petrov, Georgi I; Zhang, Hao F; Noojin, Gary D; Denton, Michael L; Thomas, Robert J; Scully, Marlan O

2009-10-01

Stimulated Raman scattering as a promising way of expanding the tunability of ultrafast lasers and as an exciting new biomedical imaging modality capable of selective excitation and chemically-specific diagnostics of molecular species.

Short-pulse amplification by strongly coupled stimulated Brillouin scattering

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

Edwards, Matthew R., E-mail: mredward@princeton.edu; Mikhailova, Julia M.; Jia, Qing

2016-08-15

We examine the feasibility of strongly coupled stimulated Brillouin scattering as a mechanism for the plasma-based amplification of sub-picosecond pulses. In particular, we use fluid theory and particle-in-cell simulations to compare the relative advantages of Raman and Brillouin amplification over a broad range of achievable parameters.

Causal Measurement Models: Can Criticism Stimulate Clarification?

ERIC Educational Resources Information Center

Markus, Keith A.

2016-01-01

In their 2016 work, Aguirre-Urreta et al. provided a contribution to the literature on causal measurement models that enhances clarity and stimulates further thinking. Aguirre-Urreta et al. presented a form of statistical identity involving mapping onto the portion of the parameter space involving the nomological net, relationships between the…

Apigenin in Combination with Akt Inhibition Significantly Enhances Thyrotropin-Stimulated Radioiodide Accumulation in Thyroid Cells

PubMed Central

Lakshmanan, Aparna; Doseff, Andrea I.; Ringel, Matthew D.; Saji, Motoyasu; Rousset, Bernard; Zhang, Xiaoli

2014-01-01

Background: Selectively increased radioiodine accumulation in thyroid cells by thyrotropin (TSH) allows targeted treatment of thyroid cancer. However, the extent of TSH-stimulated radioiodine accumulation in some thyroid tumors is not sufficient to confer therapeutic efficacy. Hence, it is of clinical importance to identify novel strategies to selectively further enhance TSH-stimulated thyroidal radioiodine accumulation. Methods: PCCl3 rat thyroid cells, PCCl3 cells overexpressing BRAFV600E, or primary cultured tumor cells from a thyroid cancer mouse model, under TSH stimulation were treated with various reagents for 24 hours. Cells were then subjected to radioactive iodide uptake, kinetics, efflux assays, and protein extraction followed by Western blotting against selected antibodies. Results: We previously reported that Akt inhibition increased radioiodine accumulation in thyroid cells under chronic TSH stimulation. Here, we identified Apigenin, a plant-derived flavonoid, as a reagent to further enhance the iodide influx rate increased by Akt inhibition in thyroid cells under acute TSH stimulation. Akt inhibition is permissive for Apigenin's action, as Apigenin alone had little effect. This action of Apigenin requires p38 MAPK activity but not PKC-δ. The increase in radioiodide accumulation by Apigenin with Akt inhibition was also observed in thyroid cells expressing BRAFV600E and in primary cultured thyroid tumor cells from TRβPV/PV mice. Conclusion: Taken together, Apigenin may serve as a dietary supplement in combination with Akt inhibitors to enhance therapeutic efficacy of radioiodine for thyroid cancer. PMID:24400871

Auditory beat stimulation and its effects on cognition and mood States.

PubMed

Chaieb, Leila; Wilpert, Elke Caroline; Reber, Thomas P; Fell, Juergen

2015-01-01

Auditory beat stimulation may be a promising new tool for the manipulation of cognitive processes and the modulation of mood states. Here, we aim to review the literature examining the most current applications of auditory beat stimulation and its targets. We give a brief overview of research on auditory steady-state responses and its relationship to auditory beat stimulation (ABS). We have summarized relevant studies investigating the neurophysiological changes related to ABS and how they impact upon the design of appropriate stimulation protocols. Focusing on binaural-beat stimulation, we then discuss the role of monaural- and binaural-beat frequencies in cognition and mood states, in addition to their efficacy in targeting disease symptoms. We aim to highlight important points concerning stimulation parameters and try to address why there are often contradictory findings with regard to the outcomes of ABS.

Parameter-specific analgesic effects of electroacupuncture mediated by degree of regulation TRPV1 and P2X3 in inflammatory pain in rats.

PubMed

Fang, J Q; Du, J Y; Fang, J F; Xiao, T; Le, X Q; Pan, N F; Yu, J; Liu, B Y

2018-05-01

Observing the parameter-specific anti-hyperalgesic effects of EA with different stimulation times and frequencies on painful hyperalgesia mediated by the level of TRPV1 and P2X3 expression in DRG after CFA injection. The model was induced by the injection of CFA in each rat's right hind paw. EA treatment was applied to the bilateral ST36 and BL60. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were tested with Von Frey filaments and the radiant heat source of the test instrument, respectively. TRPV1 and P2X3 expressions were measured by immunofluorescence and western blot. αβ-meATP and capsaicine combined with EA were further utilized to investigate the change in PWL. Different stimulation times (20, 30, 45 min) combined with different frequencies (2 Hz, 100 Hz, 2/100 Hz) of EA have analgesic effects on the PWT and PWL; however, the level of the hypoalgesic efficacy of EA was primarily associated with EA frequency. The analgesic effect of EA was better at 100 Hz than at 2 Hz. The level of regulation of 100 Hz EA on TRPV1 and P2X3 in DRG was greater than that of 2 Hz. Furthermore, both TRPV1 agonist and P2X3 agonist may impair the level of EA analgesia. EA has a parameter-specific effect on chronic inflammatory pain relief, which primarily depend on the stimulation frequency and not on the stimulation time at a certain stimulation time. The parameter-specific analgesic effect of EA is at least partially related to mediation of the protein level of TRPV1 and P2X3 expression in DRG of CFA rats. Copyright © 2018 Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

Short pulse gastric electrical stimulation for cisplatin-induced emesis in dogs.

PubMed

Song, J; Zhong, D-X; Qian, W; Hou, X-H; Chen, J D Z

2011-05-01

In a previous study, we investigated the ameliorating effect of gastric electrical stimulation (GES) with a single set of parameters on emesis and behaviors suggestive of nausea induced by cisplatin in dogs. The aim of this study was to investigate the effects of GES with different parameters on cisplatin-induced emesis in dogs. Seven dogs implanted with gastric serosal electrodes were studied in six randomized sessions: one control session with cisplatin (2 mg kg(-1)) and five sessions with cisplatin plus GES of different parameters: GES-A: 14 Hz, 5 mA, 0.3 ms, 0.1 s on and 5 s off; GES-B: increased frequency and on-time; GES-C: increased frequency; GES-D: increased frequency and pulse width; and GES-E: increased frequency and amplitude. Gastric slow waves and emetic responses were recorded in each session. (i) Cisplatin induced emetic responses and gastric dysrhythmia. The peak time of the emetic response was during the fourth hour after cisplatin. (ii) GES with appropriate parameters reduced cisplatin-induced emesis. The number of vomiting times during the 6 h after cisplatin was 7.0 ± 1.4 in the control, 4.7 ± 1.2 with GES-A (P = 0.179), 4.2 ± 1.2 with GES-B (P = 0.109), 7.0 ± 0.8 with GES-C (P = 0.928), 2.1 ± 0.3 with GES-D (P = 0.005) and 4.7 ± 1.5 with GES-E (P = 0.129). However, none of the GES parameters could improve gastric dysrhythmia. Gastric electrical stimulation with appropriate parameters reduces cisplatin-induced emetic responses and behaviors suggestive of nausea in dogs. Among the tested parameters, GES with increased pulse width seems to produce better relief of cisplatin-induced emesis. © 2011 Blackwell Publishing Ltd.

A microcontroller-based implantable nerve stimulator used for rats.

PubMed

Sha, Hong; Zheng, Zheng; Wang, Yan; Ren, Chaoshi

2005-01-01

A microcontroller-based stimulator that can be flexible programmed after it has been implanted into a rat was studied. Programmability enables implanted stimulators to generate customized, complex protocols for experiments. After implantation, a coded light pulse train that contains information of specific identification will unlock a certain stimulator. If a command that changing the parameters is received, the microcontroller will update its flash memory after it affirms the commands. The whole size of it is only 1.6 cubic centimeters, and it can work for a month. The devices have been successfully used in animal behavior experiments, especially on rats.

Improved selectivity from a wavelength addressable device for wireless stimulation of neural tissue

PubMed Central

Seymour, Elif Ç.; Freedman, David S.; Gökkavas, Mutlu; Özbay, Ekmel; Sahin, Mesut; Ünlü, M. Selim

2014-01-01

Electrical neural stimulation with micro electrodes is a promising technique for restoring lost functions in the central nervous system as a result of injury or disease. One of the problems related to current neural stimulators is the tissue response due to the connecting wires and the presence of a rigid electrode inside soft neural tissue. We have developed a novel, optically activated, microscale photovoltaic neurostimulator based on a custom layered compound semiconductor heterostructure that is both wireless and has a comparatively small volume (<0.01 mm3). Optical activation provides a wireless means of energy transfer to the neurostimulator, eliminating wires and the associated complications. This neurostimulator was shown to evoke action potentials and a functional motor response in the rat spinal cord. In this work, we extend our design to include wavelength selectivity and thus allowing independent activation of devices. As a proof of concept, we fabricated two different microscale devices with different spectral responsivities in the near-infrared region. We assessed the improved addressability of individual devices via wavelength selectivity as compared to spatial selectivity alone through on-bench optical measurements of the devices in combination with an in vivo light intensity profile in the rat cortex obtained in a previous study. We show that wavelength selectivity improves the individual addressability of the floating stimulators, thus increasing the number of devices that can be implanted in close proximity to each other. PMID:24600390

Specific LED-based red light photo-stimulation procedures improve overall sperm function and reproductive performance of boar ejaculates

PubMed Central

Yeste, Marc; Codony, Francesc; Estrada, Efrén; Lleonart, Miquel; Balasch, Sam; Peña, Alejandro; Bonet, Sergi; Rodríguez-Gil, Joan E.

2016-01-01

The present study evaluated the effects of exposing liquid-stored boar semen to different red light LED regimens on sperm quality and reproductive performance. Of all of the tested photo-stimulation procedures, the best pattern consisted of 10 min light, 10 min rest and 10 min of further light (10-10-10 pattern). This pattern induced an intense and transient increase in the majority of motility parameters, without modifying sperm viability and acrosome integrity. While incubating non-photo-stimulated sperm at 37 °C for 90 min decreased all sperm quality parameters, this reduction was prevented when the previously-described light procedure was applied. This effect was concomitant with an increase in the percentage of sperm with high mitochondrial membrane potential. When sperm were subjected to ‘in vitro’ capacitation, photo-stimulation also increased the percentage of sperm with capacitation-like changes in membrane structure. On the other hand, treating commercial semen doses intended for artificial insemination with the 10-10-10 photo-stimulation pattern significantly increased farrowing rates and the number of both total and live-born piglets for parturition. Therefore, our results indicate that a precise photo-stimulation procedure is able to increase the fertilising ability of boar sperm via a mechanism that could be related to mitochondrial function. PMID:26931070

The temporary and accumulated effects of transcranial direct current stimulation for the treatment of advanced Parkinson’s disease monkeys

PubMed Central

Li, Hao; Lei, Xiaoguang; Yan, Ting; Li, Hongwei; Huang, Baihui; Li, Ling; Xu, Liqi; Liu, Li; Chen, Nanhui; Lü, Longbao; Ma, Yuanye; Xu, Lin; Li, Jiali; Wang, Zhengbo; Zhang, Baorong; Hu, Xintian

2015-01-01

Transcranial direct current stimulation (tDCS) is a useful noninvasive technique of cortical brain stimulation for the treatment of neurological disorders. Clinical research has demonstrated tDCS with anodal stimulation of primary motor cortex (M1) in Parkinson’s disease (PD) patients significantly improved their motor function. However, few studies have been focused on the optimization of parameters which contributed significantly to the treatment effects of tDCS and exploration of the underline neuronal mechanisms. Here, we used different stimulation parameters of anodal tDCS on M1 for the treatment of aged advanced PD monkeys induced with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) administration, and then analyzed the temporary and accumulated effects of tDCS treatment. The results indicated anodal tDCS on M1 very significantly improved motor ability temporarily; importantly, the treatment effects of anodal tDCS on M1 were quantitatively correlated to the accumulated stimulation instead of the stimuli intensity or duration respectively. In addition, c-fos staining showed tDCS treatment effects activated the neurons both in M1 and substantia nigra (SN). Therefore, we propose that long time and continue anodal tDCS on M1 is a better strategy to improve the motor symptoms of PD than individual manipulation of stimuli intensity or duration. PMID:26220760

Effects of the conjugated equine estrogen/bazedoxifene tissue-selective estrogen complex (TSEC) on mammary gland and breast cancer in mice.

PubMed

Song, Yan; Santen, Richard J; Wang, Ji-ping; Yue, Wei

2012-12-01

A tissue-selective estrogen complex (TSEC), combining a selective estrogen receptor modulator, bazedoxifene (BZA), with conjugated equine estrogen (CEE), represents a novel strategy of menopausal hormone therapy without involving a progestin. We hypothesized that the antiestrogenic properties of BZA can also block the estrogenic effects of CEE on breast tissue and thereby prevent breast cancer in women. To test our hypothesis, the effects of estradiol (E(2)), CEE, and BZA on mammary gland and breast cancer xenografts were assessed in mouse models. In immature castrate mice, BZA completely blocked CEE- or E(2)-stimulated ductal and terminal end bud growth of mammary gland as well as estrogen-responsive gene expression. As a positive control, E(2) stimulated tumor growth in nude mice bearing MCF-7 xenografts. This effect was completely blocked by BZA as were E(2)-stimulated expression of PR, pS2 (trefoil factor 1), cMyc, and AREG; the enhancement of Ki67 and proliferating cell nuclear antigen (PCNA); and the antiapoptotic effect. CEE was much less potent than E(2) in stimulating Ki67, reducing apoptosis, and stimulating gene expression, but all effects were blocked by BZA. Unexpectedly, CEE alone, even at high doses, did not stimulate tumor growth. As confirmation of its absorption and deconjugation, CEE caused a 6-fold increase in uterine weight and stimulation of gene expression. These data support our hypothesis that the net effect of the CEE/BZA TSEC is to block estrogen action in benign and malignant breast tissue. These findings provide a rationale for a clinical study to determine whether this TSEC prevents breast cancer in women.

[Corifollitropin alfa in women stimulated for the first time in in vitro fertilization programme].

PubMed

Vraná-Mardešićová, N; Vobořil, J; Melicharová, L; Jelínková, L; Vilímová, Š; Mardešić, T

2017-01-01

To compare results after stimulation with corifollitropin alfa (Elonva) in unselected group of women entering for the first time in in vitro fertilization programme (IVF) with results from Phase III randomized trials with selected groups of women. Prospective study. Sanatorium Pronatal, Praha. 40 unselected women with adequat ovarian reserve entering for the first time in IVF programme were stimulated with corifollitropin alfa and GnRH antagonists. Avarage age in the study group was 32,8 years (29-42 years), women younger then 36 and less then 60 kg received Elonva 100 µg , all others (age > 36 let, weight > 60 kg) Elonva 150 µg. Five days after egg retrieval one blastocyst was transferred (single embryo transfer - eSET). Our results were compared with the resuls in higly selected groups of women from Phase III randomized trials. After stimulation with corifollitropin alfa and GnRH antagonists on average 10,6 (9,2 ± 4,2) eggs could be retrieved, among them 7,3 (6,6 ± 3,9) were M II oocytes (68,9%) and fertilisation rate was 84,6%. After first embryo transfer ("fresh" embryos and embryos from "freeze all" cycles) 14 pregnancies were achieved (37,8%), three pregnancies were achieved later from transfer of frozen-thawed embryos (cumulative pregnancy rate 45,9%). There were three abortions. No severe hyperstimulation syndrom occured. Our results in unselected group of women stimulated for the first in an IVF programme with corifollitropin alfa are fully comparable with results published in randomized trials with selected group of patiens. Corifollitropin alfa in combination with daily GnRH antagonist can be successfully used in normal-responder patients stimulated for the first time in an IVF programmeKeywords: corifollitropin alfa, GnRH antagonists, ovarian stimulation, pregnancy.

Attentional modulation of cell-class specific gamma-band synchronization in awake monkey area V4

PubMed Central

Vinck, Martin; Womelsdorf, Thilo; Buffalo, Elizabeth A.; Desimone, Robert; Fries, Pascal

2013-01-01

Summary Selective visual attention is subserved by selective neuronal synchronization, entailing precise orchestration among excitatory and inhibitory cells. We tentatively identified these as broad (BS) and narrow spiking (NS) cells and analyzed their synchronization to the local field potential in two macaque monkeys performing a selective visual attention task. Across cells, gamma phases scattered widely but were unaffected by stimulation or attention. During stimulation, NS cells lagged BS cells on average by ~60° and gamma synchronized twice as strongly. Attention enhanced and reduced the gamma locking of strongly and weakly activated cells, respectively. During a pre-stimulus attentional cue period, BS cells showed weak gamma synchronization, while NS cells gamma synchronized as strongly as with visual stimulation. These analyses reveal the cell-type specific dynamics of the gamma cycle in macaque visual cortex and suggest that attention affects neurons differentially depending on cell type and activation level. PMID:24267656

Surgical anatomy of the hypoglossal nerve: A new classification system for selective upper airway stimulation.

PubMed

Heiser, Clemens; Knopf, Andreas; Hofauer, Benedikt

2017-12-01

Selective upper airway stimulation (UAS) has shown effectiveness in treating patients with obstructive sleep apnea (OSA). The terminating branches of the hypoglossal nerve show a wide complexity, requiring careful discernment of a functional breakpoint between branches for inclusion and exclusion from the stimulation cuff electrode. The purpose of this study was to describe and categorize the topographic phenotypes of these branches. Thirty patients who received an implant with selective UAS from July 2015 to June 2016 were included. All implantations were recorded using a microscope and resultant tongue motions were captured perioperatively for comparison. Eight different variations of the branches were encountered and described, both in a tabular numeric fashion and in pictorial schema. The examinations showed the complex phenotypic surgical anatomy of the hypoglossal nerve. A schematic classification system has been developed to help surgeons identify the optimal location for cuff placement in UAS. © 2017 Wiley Periodicals, Inc.

Spontaneous and stimulated emission spectroscopy of a Nd(3+)-doped phosphate glass under wavelength selective pumping.

PubMed

Iparraguirre, I; Azkargorta, J; Balda, R; Venkata Krishnaiah, K; Jayasankar, C K; Al-Saleh, M; Fernández, J

2011-09-26

The influence of the host matrix on the spectroscopic and laser properties of Nd(3+) in a K-Ba-Al phosphate glass has been investigated as a function of rare-earth concentration. Site-selective time resolved laser spectroscopy and stimulated emission experiments under selective wavelength laser pumping show the existence of a very complex crystal field site distribution of Nd(3+) ions in this glass. The peak of the broad stimulated (4)F(3/2)→(4)I(11/2) emission shifts in a non monotonous way up to 3 nm as a function of the excitation wavelength. This behavior can be explained by the relatively moderate inter-site energy transfer among Nd(3+) ions found in this system and measured by using fluorescence line narrowing spectroscopy. The best slope efficiency obtained for the laser emission was 40%. © 2011 Optical Society of America

Computational modeling of epidural cortical stimulation

NASA Astrophysics Data System (ADS)

Wongsarnpigoon, Amorn; Grill, Warren M.

2008-12-01

Epidural cortical stimulation (ECS) is a developing therapy to treat neurological disorders. However, it is not clear how the cortical anatomy or the polarity and position of the electrode affects current flow and neural activation in the cortex. We developed a 3D computational model simulating ECS over the precentral gyrus. With the electrode placed directly above the gyrus, about half of the stimulus current flowed through the crown of the gyrus while current density was low along the banks deep in the sulci. Beneath the electrode, neurons oriented perpendicular to the cortical surface were depolarized by anodic stimulation, and neurons oriented parallel to the boundary were depolarized by cathodic stimulation. Activation was localized to the crown of the gyrus, and neurons on the banks deep in the sulci were not polarized. During regulated voltage stimulation, the magnitude of the activating function was inversely proportional to the thickness of the CSF and dura. During regulated current stimulation, the activating function was not sensitive to the thickness of the dura but was slightly more sensitive than during regulated voltage stimulation to the thickness of the CSF. Varying the width of the gyrus and the position of the electrode altered the distribution of the activating function due to changes in the orientation of the neurons beneath the electrode. Bipolar stimulation, although often used in clinical practice, reduced spatial selectivity as well as selectivity for neuron orientation.

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

PubMed

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

2017-04-01

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

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

NS-398, a selective COX-2 inhibitor, inhibits proliferation of IL-1{beta}-stimulated vascular smooth muscle cells by induction of {eta}{omicron}-1

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

Choi, Hyoung Chul; Kim, Hee Sun; Lee, Kwang Youn

2008-11-28

We investigated whether NS-398, a selective inhibitor of COX-2, induces HO-1 in IL-1{beta}-stimulated vascular smooth muscle cells (VSMC). NS-398 reduced the production of PGE{sub 2} without modulation of expression of COX-2 in IL-1{beta}-stimulated VSMC. NS-398 increased HO-1 mRNA and protein in a dose-dependent manner, but inhibited proliferation of IL-1{beta}-stimulated VSMC. Furthermore, SnPPIX, a HO-1 inhibitor, reversed the effects of NS-398 on PGE{sub 2} production, suggesting that COX-2 activity can be affected by HO-1. Hemin, a HO-1 inducer, also reduced the production of PGE{sub 2} and proliferation of IL-1{beta}-stimulated VSMC. CORM-2, a CO-releasing molecule, but not bilirubin inhibited proliferation of IL-1{beta}-stimulatedmore » VSMC. NS-398 inhibited proliferation of IL-1{beta}-stimulated VSMC in a HbO{sub 2}-sensitive manner. In conclusion, NS-398 inhibits proliferation of IL-1{beta}-stimulated VSMC by HO-1-derived CO. Thus, NS-398 may facilitate the healing process of vessels in vascular inflammatory disorders such as atherosclerosis.« less

From amusic to musical?--Improving pitch memory in congenital amusia with transcranial alternating current stimulation.

PubMed

Schaal, Nora K; Pfeifer, Jasmin; Krause, Vanessa; Pollok, Bettina

2015-11-01

Brain imaging studies highlighted structural differences in congenital amusia, a life-long perceptual disorder that is associated with pitch perception and pitch memory deficits. A functional anomaly characterized by decreased low gamma oscillations (30-40 Hz range) in the right dorsolateral prefrontal cortex (DLPFC) during pitch memory has been revealed recently. Thus, the present study investigates whether applying transcranial alternating current stimulation (tACS) at 35 Hz to the right DLPFC would improve pitch memory. Nine amusics took part in two tACS sessions (either 35 Hz or 90 Hz) and completed a pitch and visual memory task before and during stimulation. 35 Hz stimulation facilitated pitch memory significantly. No modulation effects were found with 90 Hz stimulation or on the visual task. While amusics showed a selective impairment of pitch memory before stimulation, the performance during 35 Hz stimulation was not significantly different to healthy controls anymore. Taken together, the study shows that modulating the right DLPFC with 35 Hz tACS in congenital amusia selectively improves pitch memory performance supporting the hypothesis that decreased gamma oscillations within the DLPFC are causally involved in disturbed pitch memory and highlight the potential use of tACS to interact with cognitive processes. Copyright © 2015 Elsevier B.V. All rights reserved.

Entrainment of prefrontal beta oscillations induces an endogenous echo and impairs memory formation.

PubMed

Hanslmayr, Simon; Matuschek, Jonas; Fellner, Marie-Christin

2014-04-14

Brain oscillations across all frequency bands play a key role for memory formation. Specifically, desynchronization of local neuronal assemblies in the left inferior prefrontal cortex (PFC) in the beta frequency (∼18 Hz) has been shown to be central for encoding of verbal memories. However, it remains elusive whether prefrontal beta desynchronization is causally relevant for memory formation and whether these endogenous beta oscillations can be entrained by external stimulation. By using combined EEG-TMS (transcranial magnetic stimulation), we here address these fundamental questions in human participants performing a word-list learning task. Confirming our predictions, memory encoding was selectively impaired when the left inferior frontal gyrus (IFG) was driven at beta (18.7 Hz) compared to stimulation at other frequencies (6.8 Hz and 10.7 Hz) and to ineffective sham stimulation (18.7 Hz). Furthermore, a sustained oscillatory "echo" in the left IFG, which outlasted the stimulation period by approximately 1.5 s, was observed solely after beta stimulation. The strength of this beta echo was related to memory impairment on a between-subjects level. These results show endogenous oscillatory entrainment effects and behavioral impairment selectively in beta frequency for stimulation of the left IFG, demonstrating an intimate causal relationship between prefrontal beta desynchronization and memory formation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of low-intensity pulsed ultrasound stimulation on gap healing in a rabbit osteotomy model evaluated by quantitative micro-computed tomography-based cross-sectional moment of inertia.

PubMed

Tobita, Kenji; Matsumoto, Takuya; Ohashi, Satoru; Bessho, Masahiko; Kaneko, Masako; Ohnishi, Isao

2012-07-01

It has been previously demonstrated that low-intensity pulsed ultrasound stimulation (LIPUS) enhances formation of the medullary canal and cortex in a gap-healing model of the tibia in rabbits, shortens the time required for remodeling, and enhances mineralization of the callus. In the current study, the mechanical integrity of these models was confirmed. In order to do this, the cross-sectional moment of inertia (CSMI) obtained from quantitative micro-computed tomography scans was calculated, and a comparison was made with a four-point bending test. This parameter can be analyzed in any direction, and three directions were selected in order to adopt an XYZ coordinate (X and Y for bending; Z for torsion). The present results demonstrated that LIPUS improved earlier restoration of bending stiffness at the healing site. In addition, LIPUS was effective not only in the ultrasound-irradiated plane, but also in the other two planes. CSMI may provide the structural as well as compositional determinants to assess fracture healing and would be very useful to replace the mechanical testing.

Stress-Strain Characterization for Reversed Loading Path and Constitutive Modeling for AHSS Springback Predictions

NASA Astrophysics Data System (ADS)

Zhu, Hong; Huang, Mai; Sadagopan, Sriram; Yao, Hong

2017-09-01

With increasing vehicle fuel economy standards, automotive OEMs are widely using various AHSS grades including DP, TRIP, CP and 3rd Gen AHSS to reduce vehicle weight due to their good combination of strength and formability. As one of enabling technologies for AHSS application, the requirement for requiring accurate prediction of springback for cold stamped AHSS parts stimulated a large number of investigations in the past decade with reversed loading path at large strains followed by constitutive modeling. With a spectrum of complex loading histories occurring in production stamping processes, there were many challenges in this field including issues of test data reliability, loading path representability, constitutive model robustness and non-unique constitutive parameter-identification. In this paper, various testing approaches and constitutive modeling will be reviewed briefly and a systematic methodology from stress-strain characterization, constitutive model parameter identification for material card generation will be presented in order to support automotive OEM’s need on virtual stamping. This systematic methodology features a tension-compression test at large strain with robust anti-buckling device with concurrent friction force correction, properly selected loading paths to represent material behavior during different springback modes as well as the 10-parameter Yoshida model with knowledge-based parameter-identification through nonlinear optimization. Validation cases for lab AHSS parts will also be discussed to check applicability of this methodology.

Spatiotemporal, kinematic, and kinetic effects of a peroneal nerve stimulator versus an ankle foot orthosis in hemiparetic gait.

PubMed

Sheffler, Lynne R; Bailey, Stephanie Nogan; Wilson, Richard D; Chae, John

2013-06-01

The relative effect of a transcutaneous peroneal nerve stimulator (tPNS) and an ankle foot orthosis (AFO) on spatiotemporal, kinematic, and kinetic parameters of hemiparetic gait has not been well described. To compare the relative neuroprosthetic effect of a tPNS with the orthotic effect of an AFO using quantitative gait analysis (QGA). In all, 12 stroke survivors underwent QGA under 3 device conditions: (1) no device (ND), (2) AFO, and (3) tPNS. A series of repeated-measures analyses of variance (rmANOVAs) were performed with dorsiflexion status (presence or absence of volitional dorsiflexion) as a covariate to compare selected spatiotemporal, kinematic, and kinetic parameters for each device condition. Post hoc pairwise comparisons and/or subset analysis by dorsiflexion status were performed for significant effect. Stride length was improved with both the AFO (P = .035) and the tPNS (P = .029) relative to ND. Those with absent dorsiflexion had longer stride length with the tPNS relative to ND (P = .034) and a higher walking velocity with a tPNS relative to the AFO (P = .015). There was no device effect on dorsiflexion angle at initial contact; however, a significant Device × Dorsiflexion status interaction effect favored the AFO relative to ND (P = .025) in those with dorsiflexion present. This study suggests that level of motor impairment may influence the relative effects of the tPNS and AFO devices in chronic hemiparetic gait; however, the small sample size limits generalizability. Future studies are necessary to determine if motor impairment level should be considered in the clinical prescription of these devices.

Inhibition of glycogen-synthase kinase 3 stimulates glycogen synthase and glucose transport by distinct mechanisms in 3T3-L1 adipocytes.

PubMed

Oreña, S J; Torchia, A J; Garofalo, R S

2000-05-26

The role of glycogen-synthase kinase 3 (GSK3) in insulin-stimulated glucose transport and glycogen synthase activation was investigated in 3T3-L1 adipocytes. GSK3 protein was clearly present in adipocytes and was found to be more abundant than in muscle and liver cell lines. The selective GSK3 inhibitor, LiCl, stimulated glucose transport and glycogen synthase activity (20 and 65%, respectively, of the maximal (1 microm) insulin response) and potentiated the responses to a submaximal concentration (1 nm) of insulin. LiCl- and insulin-stimulated glucose transport were abolished by the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, wortmannin; however, LiCl stimulation of glycogen synthase was not. In contrast to the rapid stimulation of glucose transport by insulin, transport stimulated by LiCl increased gradually over 3-5 h reaching 40% of the maximal insulin-stimulated level. Both LiCl- and insulin-stimulated glycogen synthase activity were maximal at 25 min. However, insulin-stimulated glycogen synthase activity returned to basal after 2 h, coincident with reactivation of GSK3. After a 2-h exposure to insulin, glycogen synthase was refractory to restimulation with insulin, indicating selective desensitization of this pathway. However, LiCl could partially stimulate glycogen synthase in desensitized cells. Furthermore, coincubation with LiCl during the 2 h exposure to insulin completely blocked desensitization of glycogen synthase activity. In summary, inhibition of GSK3 by LiCl: 1) stimulated glycogen synthase activity directly and independently of PI3-kinase, 2) stimulated glucose transport at a point upstream of PI3-kinase, 3) stimulated glycogen synthase activity in desensitized cells, and 4) prevented desensitization of glycogen synthase due to chronic insulin treatment. These data are consistent with GSK3 playing a central role in the regulation of glycogen synthase activity and a contributing factor in the regulation of glucose transport in 3T3-L1 adipocytes.

Contractile Skeletal Muscle Cells Cultured with a Conducting Soft Wire for Effective, Selective Stimulation.

PubMed

Nagamine, Kuniaki; Sato, Hirotaka; Kai, Hiroyuki; Kaji, Hirokazu; Kanzaki, Makoto; Nishizawa, Matsuhiko

2018-02-02

Contractile skeletal muscle cells were cultured so as to wrap around an electrode wire to enable their selective stimulation even when they were co-cultured with other electrically-excitable cells. Since the electrode wire was composed of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and polyurethane (PU), which is soft and highly capacitive (~10 mF cm -2 ), non-faradaic electrical stimulation with charge/discharge currents could be applied to the surrounding cells without causing significant damage even for longer periods (more than a week). The advantage of this new culture system was demonstrated in the study of chemotactic interaction of monocytes and skeletal muscle cells via myokines.

Optimal parameters of transcorneal electrical stimulation (TES) to be neuroprotective of axotomized RGCs in adult rats.

PubMed

Morimoto, Takeshi; Miyoshi, Tomomitsu; Sawai, Hajime; Fujikado, Takashi

2010-02-01

We previously showed that transcorneal electrical stimulation (TES) promoted the survival of axotomized retinal ganglion cells (RGCs) of rats. However the relationship between the parameters of TES and the neuroprotective effect of TES on axotomized RGCs was unclear. In the present study, we determined whether the neuroprotective effect of TES is affected by the parameters of TES. Adult male Wistar rats received TES just after transection of the left optic nerve (ON). The pulse duration, current intensity, frequency, waveform, and numbers of sessions of the TES were changed systematically. The alterations of the retina were examined histologically seven days or fourteen days after the ON transection. The optimal neuroprotective parameters were pulse duration of 1 and 2 ms/phase (P < 0.001, each), current intensity of 100 and 200 muA (P < 0.05, each), and stimulation frequency of 1, 5, and 20 Hz (P < 0.001, respectively). More than 30 min of TES was necessary to have a neuroprotective effect (P < 0.001). Symmetric pulses without an inter-pulse interval were most effective (P < 0.001). Repeated TES was more neuroprotective than a single TES at 14 days after ON transection (P < 0.001). Our results indicate that there is a range of optimal neuroprotective parameters of TES for axotomized RGCs of rats. These values will provide a guideline for the use of TES in patients with different retinal and optic nerve diseases. Copyright 2009 Elsevier Ltd. All rights reserved.

Explanation of the cw operation of the Er3+ 3-μm crystal laser

NASA Astrophysics Data System (ADS)

Pollnau, M.; Graf, Th.; Balmer, J. E.; Lüthy, W.; Weber, H. P.

1994-05-01

A computer simulation of the Er3+ 3-μm crystal laser considering the full rate-equation scheme up to the 4F7/2 level has been performed. The influence of the important system parameters on lasing and the interaction of these parameters has been clarified with multiple-parameter variations. Stimulated emission is fed mainly by up-conversion from the lower laser level and in many cases is reduced by the quenching of the lifetime of this level. However, also without up-conversion a set of parameters can be found that allows lasing. Up-conversion from the upper laser level is detrimental to stimulated emission but may be compensated by cross relaxation from the 4S3/2 level. For a typical experimental situation we started with the parameters of Er3+:LiYF4. In addition, the host materials Y3Al5O12 (YAG), YAlO3, Y3Sc2Al3O12 (YSGG), and BaY2F8, as well as the possibilities of codoping, are discussed. In view of the consideration of all excited levels up to 4F7/2, all lifetimes and branching ratios, ground-state depletion, excited-state absorption, three up-conversion processes as well as their inverse processes, stimulated emission, and a realistic resonator design, this is, to our knowledge, the most detailed investigation of the Er3+ 3-μm crystal laser performed so far.

Transverse versus longitudinal tripolar configuration for selective stimulation with multipolar cuff electrodes.

PubMed

Nielsen, Thomas N; Kurstjens, G A Mathijs; Struijk, Johannes J

2011-04-01

The ability to stimulate subareas of a nerve selectively is highly desirable, since it has the potential of simplifying surgery to implanting one cuff on a large nerve instead of many cuffs on smaller nerves or muscles, or alternatively can improve function where surgical access to the smaller nerves is limited. In this paper, stimulation was performed with a four-channel multipolar cuff electrode implanted on the sciatic nerve of nine rabbits to compare the extensively researched longitudinal tripolar configuration with the transverse tripolar configuration, which has received less interest. The performance of these configurations was evaluated in terms of selectivity in recruitment of the three branches of the sciatic nerve. The results showed that the transverse configuration was able to selectively activate the sciatic nerve branches to a functionally relevant level in more cases than the longitudinal configuration (20/27 versus 11/27 branches) and overall achieved a higher mean selectivity [0.79 ± 0.13 versus 0.61 ± 0.09 (mean ± standard deviation)]. The transverse configuration was most successful at recruiting the small cutaneous and medium-sized peroneal branches, and less successful at recruiting the large tibial nerve.

Selectivity of beta-adrenergic stimulating and blocking agents.

PubMed

Löfdahl, C G; Svedmyr, N

1984-01-01

Studies have been performed to answer two questions: whether there are subgroups of beta 2-receptors separating effects in bronchial and skeletal muscle and whether beta 1-receptors in asthmatic airways mediate bronchoconstriction. Asthmatic patients have been studied in randomised cross-over trials. Effects on FEV1, heart rate and skeletal muscle tremor have been monitored. In some experimental studies, two new compounds, D2343 and QH-25, have shown a selectivity for beta 2-receptors in bronchial muscle compared to skeletal muscle. Studies in asthmatics did not confirm this. Thus, the beta 2-receptors in the two organs appear to be identical. The clinical effect of beta 1-receptors in the the airways was studied by giving selective beta 1-receptor blocking agents. It was shown that pafenolol , a beta-blocker more beta 1-selective than metoprolol, had less effect on FEV1 than metoprolol given in equipotent beta 1-blocking doses. Beta 1-receptor stimulation with a new selective beta 1-stimulating agent, prenalterol, did not give bronchodilation in doses which gave a significant increase of heart rate. Thus, beta 1-receptors do not contribute to bronchodilation in asthmatic patients.

Lack of Effect of Stimulant Combination with Second-Generation Antipsychotics on Weight Gain, Metabolic Changes, Prolactin Levels, and Sedation in Youth with Clinically Relevant Aggression or Oppositionality

PubMed Central

Penzner, Julie B.; Dudas, Melissa; Saito, Ema; Olshanskiy, Vladimir; Parikh, Umesh H.; Kapoor, Sandeep; Chekuri, Raja; Gadaleta, Dominick; Avedon, Jennifer; Sheridan, Eva M.; Randell, Jane; Malhotra, Anil K.; Kane, John M.

2009-01-01

Abstract Background Second-generation antipsychotics (SGAs) are associated with weight gain, metabolic abnormalities, sedation/sleep disturbance, and prolactin abnormalities, especially in youths. Although stimulants have opposing dopamine receptor and adverse effects, it is unclear whether stimulant co-treatment counteracts the therapeutic or side effects of antipsychotics. Methods This was a naturalistic cohort study including 153 antipsychotic trials in youths aged 4–19 (mean, 11.3 ± 3.0) years, started on an SGA for clinically significant aggression or oppositionality associated with oppositional defiant disorder, conduct disorder, disruptive behavior disorder not otherwise specified (NOS), impulse control disorder NOS, intermittent explosive disorder, Tourette's disorder, autistic disorder, and pervasive developmental disorder NOS. Patients underwent fasting assessments of body composition, lipids, glucose, insulin, prolactin, sedation, and general efficacy at baseline, weeks 4, 8, and 12, comparing patients co-prescribed stimulants (n = 71) with those not co-prescribed stimulants (n = 82). Results Patients received risperidone (33.3%), aripiprazole (29.4%), quetiapine (18.4%), olanzapine (11.8%), ziprasidone (5.9%), or clozapine (0.7%). With and without adjustment for differences in baseline variables (sex, prior stimulant use, primary Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV] disorders, co-morbid attention-deficit/hyperactivity disorder [ADHD], present in 46.3% of youths not receiving stimulants, and some body composition parameters), patients on versus off stimulants did not differ on any of the assessed outcomes (all p values ≥ 0.1). Conclusions In contrast to guidelines, stimulant use did not precede or accompany antipsychotic use during the current episode of aggression/oppositionality in almost half of those youths who had aggressive/oppositional behavior and a DSM-IV diagnosis of ADHD. At the clinically prescribed doses, stimulant co-treatment of SGAs did not seem to significantly reduce antipsychotic effects on body composition, metabolic parameters, prolactin, sedation, and broad efficacy. PMID:19877981

[Macroscopic evaluation of the oral mucosa and analysis of salivary pH in patients with anorexia nervosa].

PubMed

Paszyńska, Elzbieta; Słopień, Agnieszka; Slebioda, Zuzanna S; Dyszkiewicz-Konwińska, Marta; Weglarz, Monika; Rajewski, Andrzej

2014-01-01

The aim of the study was to evaluate the status of the oral mucosa, to assess the prevalence of Candida in the oral cavity and to analyze the pH values of total saliva in patients with anorexia nervosa (AN) in comparison to the general population. A controlled clinical trial was designed for two, age-matched, female groups: patients with AN (Group A, n=31) and healthy women (Group 0, n = 40). Total saliva was collected at rest and after stimulation by chewing paraffin wax. Salivary pH was measured and macroscopic evaluation of the oral mucosa was performed with a qualitative and quantitative mycological analysis. The smear layer was collected from three different areas in the oral cavity. Selected Candida broths were used for incubation. Changes in the macroscopic structure of the oral mucosa due to multifactorial etiologies were observed. The prevalence of Candida in patients with AN was comparable to that in the general population. Salivary pH values were significantly lower in the AN patients than in the control group. The incidence of pathological changes in the oral mucosa is associated with the loss of the salivary protective barrier. This is shown by the significant reduction in the pH values of stimulated and non-stimulated saliva of the AN patients. In these patients, the monitoring of salivary parameters such as salivary flow rate and pH is indicated, and a regular dental checkup, together with soft tissue evaluation, is advised.

Effect of granulocyte colony-stimulating factor on myocardium recovery in postinfarction period.

PubMed

Gol'dberg, E D; Dygai, A M; Zhdanov, V V; Stavrova, L A; Fomina, T I; Plotnikov, M B; Aliev, O I; Chernyshova, G A; Masycheva, V I; Sotnikova, N V

2005-03-01

The effect of Neutrostim (preparation of granulocytic colony-stimulating factor) on recovery of myocardial tissue after acute myocardial infarction was studied in rats. A course of Neutrostim after ligation of the left coronary artery led to normalization of electrocardiographic and morphological parameters of the myocardium after one month.

A urodynamic study of surface neuromodulation versus sham in detrusor instability and sensory urgency.

PubMed

Bower, W F; Moore, K H; Adams, R D; Shepherd, R

1998-12-01

We studied the effect of surface neuromodulation on cystometric pressure and volume parameters in women with detrusor instability or sensory urgency. Electrical current was delivered to the suprapubic region and third sacral foramina via a transcutaneous electrical nerve stimulator with sham neuromodulation control. A consecutive series of women with proved detrusor instability or sensory urgency were randomized to 3 surface neuromodulation groups. Volume and pressure parameters were the main outcomes of transcutaneous electrical nerve stimulation applied during second cystometric fill. Sham transcutaneous electrical nerve stimulation did not alter the outcome measures. However, neuromodulation delivered across the suprapubic and sacral skin effected a reduction in mean maximum height of detrusor contraction. A current which inhibits motor activity was not superior to that which inhibits sensory perception in reducing detrusor pressure. Response in sensory urgency was poor. Results from our sham controlled study suggest that short-term surface neuromodulation via transcutaneous electrical nerve stimulation may have a role in the treatment of detrusor instability. Future studies must examine the clinical effect of long-term surface neuromodulation.

Tourette syndrome and other chronic tic disorders: an update on clinical management.

PubMed

Martino, Davide; Pringsheim, Tamara M

2018-02-01

The management of Tourette syndrome (TS) and other chronic tic disorders occurs in multiple stages and begins with comprehensive assessment and complex psychoeducation. Behavioral and pharmacological interventions (second stage) are needed when tics cause physical or psychosocial impairment. Deep brain stimulation surgery or experimental therapies represent the third stage. Areas covered: Discussed are recent advances in assessment and therapy of chronic tic disorders, encompassing the three stages of intervention, with the addition of experimental, non-invasive brain stimulation strategies. A PubMed search was performed using as keywords: 'tic disorders', 'Tourette syndrome', 'assessment', 'rating scales', 'behavioral treatment', 'pharmacological treatment', 'deep brain stimulation', 'transcranial magnetic (or current) stimulation', and 'transcranial current stimulation'. More than 300 peer-reviewed articles were evaluated. The studies discussed have been selected on the basis of novelty and impact. Expert commentary: Comprehensive assessment of tic disorders and psychoeducation are crucial to a correct active management approach. Behavioral treatments represent first line of active interventions, with increasing potential offered by telehealth. Antipsychotics and alpha agonists remain first line pharmacological interventions for tics, although VMAT-2 inhibitors appear promising. Deep brain stimulation is a potential option for medically refractory, severely disabled patients with tics, but age and target selection require further investigation.

Phantom somatosensory evoked potentials following selective intraneural electrical stimulation in two amputees.

PubMed

Granata, Giuseppe; Di Iorio, Riccardo; Romanello, Roberto; Iodice, Francesco; Raspopovic, Stanisa; Petrini, Francesco; Strauss, Ivo; Valle, Giacomo; Stieglitz, Thomas; Čvančara, Paul; Andreu, David; Divoux, Jean-Louis; Guiraud, David; Wauters, Loic; Hiairrassary, Arthur; Jensen, Winnie; Micera, Silvestro; Rossini, Paolo Maria

2018-06-01

The aim of the paper is to objectively demonstrate that amputees implanted with intraneural interfaces are truly able to feel a sensation in the phantom hand by recording "phantom" somatosensory evoked potentials from the corresponding brain areas. We implanted four transverse intrafascicular multichannel electrodes, available with percutaneous connections to a multichannel electrical stimulator, in the median and ulnar nerves of two left trans-radial amputees. Two channels of the implants that were able to elicit sensations during intraneural nerve stimulation were chosen, in both patients, for recording somatosensory evoked potentials. We recorded reproducible evoked responses by stimulating the median and the ulnar nerves in both cases. Latencies were in accordance with the arrival of somatosensory information to the primary somatosensory cortex. Our results provide evidence that sensations generated by intraneural stimulation are truly perceived by amputees and located in the phantom hand. Moreover, our results strongly suggest that sensations perceived in different parts of the phantom hand result in different evoked responses. Somatosensory evoked potentials obtained by selective intraneural electrical stimulation in amputee patients are a useful tool to provide an objective demonstration of somatosensory feedback in new generation bidirectional prostheses. Copyright © 2018. Published by Elsevier B.V.

Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner.

PubMed

Mitew, Stanislaw; Gobius, Ilan; Fenlon, Laura R; McDougall, Stuart J; Hawkes, David; Xing, Yao Lulu; Bujalka, Helena; Gundlach, Andrew L; Richards, Linda J; Kilpatrick, Trevor J; Merson, Tobias D; Emery, Ben

2018-01-22

Mounting evidence suggests that neuronal activity influences myelination, potentially allowing for experience-driven modulation of neural circuitry. The degree to which neuronal activity is capable of regulating myelination at the individual axon level is unclear. Here we demonstrate that stimulation of somatosensory axons in the mouse brain increases proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) within the underlying white matter. Stimulated axons display an increased probability of being myelinated compared to neighboring non-stimulated axons, in addition to being ensheathed with thicker myelin. Conversely, attenuating neuronal firing reduces axonal myelination in a selective activity-dependent manner. Our findings reveal that the process of selecting axons for myelination is strongly influenced by the relative activity of individual axons within a population. These observed cellular changes are consistent with the emerging concept that adaptive myelination is a key mechanism for the fine-tuning of neuronal circuitry in the mammalian CNS.

Electrochemical activation and inhibition of neuromuscular systems through modulation of ion concentrations with ion-selective membranes

NASA Astrophysics Data System (ADS)

Song, Yong-Ak; Melik, Rohat; Rabie, Amr N.; Ibrahim, Ahmed M. S.; Moses, David; Tan, Ara; Han, Jongyoon; Lin, Samuel J.

2011-12-01

Conventional functional electrical stimulation aims to restore functional motor activity of patients with disabilities resulting from spinal cord injury or neurological disorders. However, intervention with functional electrical stimulation in neurological diseases lacks an effective implantable method that suppresses unwanted nerve signals. We have developed an electrochemical method to activate and inhibit a nerve by electrically modulating ion concentrations in situ along the nerve. Using ion-selective membranes to achieve different excitability states of the nerve, we observe either a reduction of the electrical threshold for stimulation by up to approximately 40%, or voluntary, reversible inhibition of nerve signal propagation. This low-threshold electrochemical stimulation method is applicable in current implantable neuroprosthetic devices, whereas the on-demand nerve-blocking mechanism could offer effective clinical intervention in disease states caused by uncontrolled nerve activation, such as epilepsy and chronic pain syndromes.

Differential impact of continuous theta-burst stimulation over left and right DLPFC on planning.

PubMed

Kaller, Christoph P; Heinze, Katharina; Frenkel, Annekathrein; Läppchen, Claus H; Unterrainer, Josef M; Weiller, Cornelius; Lange, Rüdiger; Rahm, Benjamin

2013-01-01

Most neuroimaging studies on planning report bilateral activations of the dorsolateral prefrontal cortex (dlPFC). Recently, these concurrent activations of left and right dlPFC have been shown to double dissociate with different cognitive demands imposed by the planning task: Higher demands on the extraction of task-relevant information led to stronger activation in left dlPFC, whereas higher demands on the integration of interdependent information into a coherent action sequence entailed stronger activation of right dlPFC. Here, we used continuous theta-burst stimulation (cTBS) to investigate the supposed causal structure-function mapping underlying this double dissociation. Two groups of healthy subjects (left-lateralized stimulation, n = 26; right-lateralized stimulation, n = 26) were tested within-subject on a variant of the Tower of London task following either real cTBS over dlPFC or sham stimulation over posterior parietal cortex. Results revealed that, irrespective of specific task demands, cTBS over left and right dlPFC was associated with a global decrease and increase, respectively, in initial planning times compared to sham stimulation. Moreover, no interaction between task demands and stimulation type (real vs. sham) and/or stimulation side (left vs. right hemisphere) were found. Together, against expectations from previous neuroimaging data, lateralized cTBS did not lead to planning-parameter specific changes in performance, but instead revealed a global asymmetric pattern of faster versus slower task processing after left versus right cTBS. This global asymmetry in the absence of any task-parameter specific impact of cTBS suggests that different levels of information processing may span colocalized, but independent axes of functional lateralization in the dlPFC. Copyright © 2011 Wiley Periodicals, Inc.

Deep brain stimulation in the central nucleus of the amygdala decreases 'wanting' and 'liking' of food rewards.

PubMed

Ross, Shani E; Lehmann Levin, Emily; Itoga, Christy A; Schoen, Chelsea B; Selmane, Romeissa; Aldridge, J Wayne

2016-10-01

We investigated the potential of deep brain stimulation (DBS) in the central nucleus of the amygdala (CeA) in rats to modulate functional reward mechanisms. The CeA is the major output of the amygdala with direct connections to the hypothalamus and gustatory brainstem, and indirect connections with the nucleus accumbens. Further, the CeA has been shown to be involved in learning, emotional integration, reward processing, and regulation of feeding. We hypothesized that DBS, which is used to treat movement disorders and other brain dysfunctions, might block reward motivation. In rats performing a lever-pressing task to obtain sugar pellet rewards, we stimulated the CeA and control structures, and compared stimulation parameters. During CeA stimulation, animals stopped working for rewards and rejected freely available rewards. Taste reactivity testing during DBS exposed aversive reactions to normally liked sucrose tastes and even more aversive taste reactions to normally disliked quinine tastes. Interestingly, given the opportunity, animals implanted in the CeA would self-stimulate with 500 ms trains of stimulation at the same frequency and current parameters as continuous stimulation that would stop reward acquisition. Neural recordings during DBS showed that CeA neurons were still active and uncovered inhibitory-excitatory patterns after each stimulus pulse indicating possible entrainment of the neural firing with DBS. In summary, DBS modulation of CeA may effectively usurp normal neural activity patterns to create an 'information lesion' that not only decreased motivational 'wanting' of food rewards, but also blocked 'liking' of rewards. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Auditory Beat Stimulation and its Effects on Cognition and Mood States

PubMed Central

Chaieb, Leila; Wilpert, Elke Caroline; Reber, Thomas P.; Fell, Juergen

2015-01-01

Auditory beat stimulation may be a promising new tool for the manipulation of cognitive processes and the modulation of mood states. Here, we aim to review the literature examining the most current applications of auditory beat stimulation and its targets. We give a brief overview of research on auditory steady-state responses and its relationship to auditory beat stimulation (ABS). We have summarized relevant studies investigating the neurophysiological changes related to ABS and how they impact upon the design of appropriate stimulation protocols. Focusing on binaural-beat stimulation, we then discuss the role of monaural- and binaural-beat frequencies in cognition and mood states, in addition to their efficacy in targeting disease symptoms. We aim to highlight important points concerning stimulation parameters and try to address why there are often contradictory findings with regard to the outcomes of ABS. PMID:26029120

Non-scanning fiber-optic near-infrared beam led to two-photon optogenetic stimulation in-vivo.

PubMed

Dhakal, Kamal R; Gu, Ling; Shivalingaiah, Shivaranjani; Dennis, Torry S; Morris-Bobzean, Samara A; Li, Ting; Perrotti, Linda I; Mohanty, Samarendra K

2014-01-01

Stimulation of specific neurons expressing opsins in a targeted region to manipulate brain function has proved to be a powerful tool in neuroscience. However, the use of visible light for optogenetic stimulation is invasive due to low penetration depth and tissue damage owing to larger absorption and scattering. Here, we report, for the first time, in-depth non-scanning fiber-optic two-photon optogenetic stimulation (FO-TPOS) of neurons in-vivo in transgenic mouse models. In order to optimize the deep-brain stimulation strategy, we characterized two-photon activation efficacy at different near-infrared laser parameters. The significantly-enhanced in-depth stimulation efficiency of FO-TPOS as compared to conventional single-photon beam was demonstrated both by experiments and Monte Carlo simulation. The non-scanning FO-TPOS technology will lead to better understanding of the in-vivo neural circuitry because this technology permits more precise and less invasive anatomical delivery of stimulation.

High gamma power in ECoG reflects cortical electrical stimulation effects on unit activity in layers V/VI

NASA Astrophysics Data System (ADS)

Yazdan-Shahmorad, Azadeh; Kipke, Daryl R.; Lehmkuhle, Mark J.

2013-12-01

Objective. Cortical electrical stimulation (CES) has been used extensively in experimental neuroscience to modulate neuronal or behavioral activity, which has led this technique to be considered in neurorehabilitation. Because the cortex and the surrounding anatomy have irregular geometries as well as inhomogeneous and anisotropic electrical properties, the mechanism by which CES has therapeutic effects is poorly understood. Therapeutic effects of CES can be improved by optimizing the stimulation parameters based on the effects of various stimulation parameters on target brain regions. Approach. In this study we have compared the effects of CES pulse polarity, frequency, and amplitude on unit activity recorded from rat primary motor cortex with the effects on the corresponding local field potentials (LFP), and electrocorticograms (ECoG). CES was applied at the surface of the cortex and the unit activity and LFPs were recorded using a penetrating electrode array, which was implanted below the stimulation site. ECoGs were recorded from the vicinity of the stimulation site. Main results. Time-frequency analysis of LFPs following CES showed correlation of gamma frequencies with unit activity response in all layers. More importantly, high gamma power of ECoG signals only correlated with the unit activity in lower layers (V-VI) following CES. Time-frequency correlations, which were found between LFPs, ECoGs and unit activity, were frequency- and amplitude-dependent. Significance. The signature of the neural activity observed in LFP and ECoG signals provides a better understanding of the effects of stimulation on network activity, representative of large numbers of neurons responding to stimulation. These results demonstrate that the neurorehabilitation and neuroprosthetic applications of CES targeting layered cortex can be further improved by using field potential recordings as surrogates to unit activity aimed at optimizing stimulation efficacy. Likewise, the signatures of unit activity observed as changes in high gamma power in ECoGs suggest that future cortical stimulation studies could rely on less invasive feedback schemes that incorporate surface stimulation with ECoG reporting of stimulation efficacy.

An Optimized IES Method and Its Inhibitory Effects and Mechanisms on Food Intake and Body Weight in Diet-Induced Obese Rats: IES for Obesity.

PubMed

Wan, Xinyue; Yin, Jieyun; Foreman, Robert; Chen, Jiande D Z

2017-12-01

This paper aims to optimize stimulation parameters and durations for intestinal electrical stimulation (IES) and to explore the effects and mechanisms of chronic IES with optimized methodology in obesity rats. Sixteen diet-induced obese (DIO) rats were tested for food intake with four different sets of IES parameters each lasting 1 week. Then, another 12 DIO rats were used to test the effect of IES on food intake with different stimulation durations. Finally, 16 DIO rats were treated with IES or sham-IES for 4 weeks. Meal patterns, food intake, and body weight were observed. Mechanisms involving gastrointestinal motility, ghrelin, and glucagon-like peptide-1 (GLP-1) were studied. (1) Acute IES with different parameters showed different inhibitory effects on food intake, and the most effective parameters were 0.6 s on, 0.9 s off, 80 Hz, 2 ms, and 4 mA with which 26.3% decrease in food intake was noted (p < 0.001). (2) IES with daily treatment of 12 h was most effective in suppressing food intake compared with 1 or 6 h. (3) Four-week IES reduced net weight by 10.9% (p < 0.05 vs. sham-IES) and epididymal fat pad weight by 13.9% (p < 0.001). (4) IES delayed gastric emptying (p < 0.001) and accelerated intestinal transit (p < 0.05). (5) IES increased both fasting and postprandial plasma levels of GLP-1 but not ghrelin. Twelve-hour daily IES using optimized stimulation parameters reduces food intake and body weight in DIO rats by altering gastrointestinal motility and GLP-1. The IES methodology derived in this study may have a therapeutic potential for obesity.

Sensory trigeminal ULF-TENS stimulation reduces HRV response to experimentally induced arithmetic stress: A randomized clinical trial.

PubMed

Monaco, Annalisa; Cattaneo, Ruggero; Ortu, Eleonora; Constantinescu, Marian Vladimir; Pietropaoli, Davide

2017-05-01

Ultra Low Frequency Transcutaneous Electric Nervous Stimulation (ULF-TENS) is extensively used for pain relief and for the diagnosis and treatment of temporomandibular disorders (TMD). In addition to its local effects, ULF-TENS acts on the autonomic nervous system (ANS), with particular reference to the periaqueductal gray (PAG), promoting the release of endogenous opioids and modulating descending pain systems. It has been suggested that the PAG participates in the coupling between the emotional stimulus and the appropriate behavioral autonomic response. This function is successfully investigated by HRV. Therefore, our goal is to investigate the effects of trigeminal ULF-TENS stimulation on autonomic behavior in terms of HRV and respiratory parameters during an experimentally-induced arithmetic stress test in healthy subjects. Thirty healthy women between 25 and 35years of age were enrolled and randomly assigned to either the control (TENS stimulation off) or test group (TENS stimulation on). Heart (HR, LF, HF, LF/HF ratio, DET, RMSSD, PNN50, RR) and respiratory (BR) rate were evaluated under basal, T1 (TENS off/on), and stress (mathematical task) conditions. Results showed that HRV parameters and BR significantly changed during the arithmetic stress paradigm (p<0.01). Independently of stress conditions, TENS and control group could be discriminated only by non-linear HRV data, namely RR and DET (p=0.038 and p=0.027, respectively). During the arithmetic task, LF/HF ratio was the most sensitive parameter to discriminate between groups (p=0.019). Our data suggest that trigeminal sensory ULF-TENS reduces the autonomic response in terms of HRV and BR during acute mental stress in healthy subjects. Future directions of our work aim at applying the HRV and BR analysis, with and without TENS stimulation, to individuals with dysfunctional ANS among those with TMD. Copyright © 2017 Elsevier Inc. All rights reserved.

Blood flow and oxygenation changes due to low-frequency repetitive transcranial magnetic stimulation of the cerebral cortex

NASA Astrophysics Data System (ADS)

Mesquita, Rickson C.; Faseyitan, Olufunsho K.; Turkeltaub, Peter E.; Buckley, Erin M.; Thomas, Amy; Kim, Meeri N.; Durduran, Turgut; Greenberg, Joel H.; Detre, John A.; Yodh, Arjun G.; Hamilton, Roy H.

2013-06-01

Transcranial magnetic stimulation (TMS) modulates processing in the human brain and is therefore of interest as a treatment modality for neurologic conditions. During TMS administration, an electric current passing through a coil on the scalp creates a rapidly varying magnetic field that induces currents in the cerebral cortex. The effects of low-frequency (1 Hz), repetitive TMS (rTMS) on motor cortex cerebral blood flow (CBF) and tissue oxygenation in seven healthy adults, during/after 20 min stimulation, is reported. Noninvasive optical methods are employed: diffuse correlation spectroscopy (DCS) for blood flow and diffuse optical spectroscopy (DOS) for hemoglobin concentrations. A significant increase in median CBF (33%) on the side ipsilateral to stimulation was observed during rTMS and persisted after discontinuation. The measured hemodynamic parameter variations enabled computation of relative changes in cerebral metabolic rate of oxygen consumption during rTMS, which increased significantly (28%) in the stimulated hemisphere. By contrast, hemodynamic changes from baseline were not observed contralateral to rTMS administration (all parameters, p>0.29). In total, these findings provide new information about hemodynamic/metabolic responses to low-frequency rTMS and, importantly, demonstrate the feasibility of DCS/DOS for noninvasive monitoring of TMS-induced physiologic effects.

Detection of sub micro Gray dose levels using OSL phosphor LiMgPO4:Tb,B

NASA Astrophysics Data System (ADS)

Rawat, N. S.; Dhabekar, Bhushan; Muthe, K. P.; Koul, D. K.; Datta, D.

2017-04-01

Detection of sub micro Gray doses finds application in personnel and environmental monitoring, and nuclear forensics. Recently developed LiMgPO4:Tb,B (LMP) is highly sensitive Optically Stimulated Luminescence (OSL) phosphor with excellent dosimetric properties. The OSL emission spectrum of LMP consists of several peaks attributed to characteristic Tb3+ emission. The OSL emission peak at 380 nm is favorable for bi-alkali PMT used in RISO reader system. It is demonstrated that significant improvement in dose detection threshold can be realized for LMP by optimization of continuous wave (CW-) OSL parameters like stimulation intensity and readout time. The minimum measurable dose (MMD) as low as 0.49 μGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm2 has been achieved using this phosphor. The recommendations for choice of parameters for personnel and environmental monitoring are also discussed.

Designing electrical stimulated bioreactors for nerve tissue engineering

NASA Astrophysics Data System (ADS)

Sagita, Ignasius Dwi; Whulanza, Yudan; Dhelika, Radon; Nurhadi, Ibrahim

2018-02-01

Bioreactor provides a biomimetic ecosystem that is able to culture cells in a physically controlled system. In general, the controlled-parameters are temperature, pH, fluid flow, nutrition flow, etc. In this study, we develop a bioreactor that specifically targeted to culture neural stem cells. This bioreactor could overcome some limitations of conventional culture technology, such as petri dish, by providing specific range of observation area and a uniform treatment. Moreover, the microfluidic bioreactor, which is a small-controlled environment, is able to observe as small number of cells as possible. A perfusion flow is applied to mimic the physiological environment in human body. Additionally, this bioreactor also provides an electrical stimulation which is needed by neural stem cells. In conclusion, we found the correlation between the induced shear stress with geometric parameters of the bioreactor. Ultimately, this system shall be used to observe the interaction between stimulation and cell growth.

Changes induced by music therapy to physiologic parameters in patients with dental anxiety.

PubMed

Mejía-Rubalcava, Cynthia; Alanís-Tavira, Jorge; Mendieta-Zerón, Hugo; Sánchez-Pérez, Leonor

2015-11-01

The aim of this study was to determine the effect of music therapy on patients suffering dental anxiety. In addition, a second objective was to determine the correlation between salivary cortisol and other physiologic parameters. 34 patients were randomly assigned to the control group and the experimental group. For each patient was measured for salivary cortisol, stimulate salivary flow, blood pressure, heart rate, oxygen saturation and body temperature. Student t-test and Chi2 were applied to analyze significant differences between the studied variables before and after the unpleasant stimulation causes anxiety for dental treatment. Initially, both groups registered the same level of anxiety. In the second measurement, significant differences were registered in the salivary cortisol concentration, systolic and diastolic pressure, heart rate, body temperature and stimulated salivary flow for treated group with music therapy. Music therapy has a positive effect in control of dental anxiety. Copyright © 2015. Published by Elsevier Ltd.

Foraging for brain stimulation: toward a neurobiology of computation.

PubMed

Gallistel, C R

1994-01-01

The self-stimulating rat performs foraging tasks mediated by simple computations that use interreward intervals and subjective reward magnitudes to determine stay durations. This is a simplified preparation in which to study the neurobiology of the elementary computational operations that make cognition possible, because the neural signal specifying the value of a computationally relevant variable is produced by direct electrical stimulation of a neural pathway. Newly developed measurement methods yield functions relating the subjective reward magnitude to the parameters of the neural signal. These measurements also show that the decision process that governs foraging behavior divides the subjective reward magnitude by the most recent interreward interval to determine the preferability of an option (a foraging patch). The decision process sets the parameters that determine stay durations (durations of visits to foraging patches) so that the ratios of the stay durations match the ratios of the preferabilities.

Effects of short-term hypothermal and contrast exposure on immunophysiological parameters of laboratory animals.

PubMed

Kalenova, L F; Fisher, T A; Suhovey, J G; Besedin, I M

2009-05-01

Experiments on inbred animals showed that short-term exposure in cold water significantly modified structural and functional parameters of the immune system at different levels of its organization, from bone marrow hemopoiesis to effector stage of the immune response to antigen. The thermal factor caused changes in nonspecific and specific mechanisms of the immune system. Hypothermal exposure (7-9 degrees C, 5 sec) increased the thymic index and bone marrow lymphocyte count, reduced absorption capacity and stimulated metabolic activity of phagocytes, stimulated cell-mediated and suppressed humoral immunity. Contrast exposure in cold and hot water (7-9 degrees C, 5 sec/40-42 degrees C, 30 sec) increased monocyte count in bone marrow and reduced it in the their peripheral blood, reduced metabolic activity of phagocytes, stimulated cell-mediated and suppressed humoral immunity. These data demonstrate physiological mechanisms of interactions between the thermoregulatory and immune systems.

[Electrical stimulation of the facial nerve with a prognostic function in parotid surgery].

PubMed

García-Losarcos, N; González-Hidalgo, M; Franco-Carcedo, C; Poch-Broto, J

Continuous electromyography during parotidectomies and direct stimulation of the facial nerve as an intraoperative identification technique significantly lower the rate of post-operative morbidity. To determine the usefulness of intra-operative neurophysiological parameters registered by means of electrical stimulation of the facial nerve as values capable of predicting the type of lesion and the functional prognosis. Our sample consisted of a correlative series of 20 cases of monitored parotidectomies. Post-operative facial functioning, type of lesion and its prognosis were compared with the variations in latency/amplitude of the muscle response between two stimulations of the facial nerve before and after resection, as well as in the absence or presence of muscle response to stimulation after resection. All the patients except one presented motor evoked potentials (MEP) to stimulation after resection. There was no facial damage following the operation in 55% of patients and 45% presented some kind of paresis. The 21% drop in the amplitude of the intra-operative MEP and the mean increase in latency of 13.5% correspond to axonal and demyelinating insult, respectively, with a mean recovery time of three and six months. The only case of absence of response to the post-resection stimulation presented permanent paresis. The presence of MEP following resection does not ensure that functioning of the nerve remains undamaged. Nevertheless, it can be considered a piece of data that suggests a lower degree of compromise, if it is present, and a better prognosis. The variations in latency and amplitude of the MEP tend to be intra-operative parameters that indicate the degree of compromise and functional prognosis.

Repetitive transcranial magnetic stimulation of Broca's area affects verbal responses to gesture observation.

PubMed

Gentilucci, Maurizio; Bernardis, Paolo; Crisi, Girolamo; Dalla Volta, Riccardo

2006-07-01

The aim of the present study was to determine whether Broca's area is involved in translating some aspects of arm gesture representations into mouth articulation gestures. In Experiment 1, we applied low-frequency repetitive transcranial magnetic stimulation over Broca's area and over the symmetrical loci of the right hemisphere of participants responding verbally to communicative spoken words, to gestures, or to the simultaneous presentation of the two signals. We performed also sham stimulation over the left stimulation loci. In Experiment 2, we performed the same stimulations as in Experiment 1 to participants responding with words congruent and incongruent with gestures. After sham stimulation voicing parameters were enhanced when responding to communicative spoken words or to gestures as compared to a control condition of word reading. This effect increased when participants responded to the simultaneous presentation of both communicative signals. In contrast, voicing was interfered when the verbal responses were incongruent with gestures. The left stimulation neither induced enhancement on voicing parameters of words congruent with gestures nor interference on words incongruent with gestures. We interpreted the enhancement of the verbal response to gesturing in terms of intention to interact directly. Consequently, we proposed that Broca's area is involved in the process of translating into speech aspects concerning the social intention coded by the gesture. Moreover, we discussed the results in terms of evolution to support the theory [Corballis, M. C. (2002). From hand to mouth: The origins of language. Princeton, NJ: Princeton University Press] proposing spoken language as evolved from an ancient communication system using arm gestures.

Brain Stimulation in Alzheimer's Disease.

PubMed

Chang, Chun-Hung; Lane, Hsien-Yuan; Lin, Chieh-Hsin

2018-01-01

Brain stimulation techniques can modulate cognitive functions in many neuropsychiatric diseases. Pilot studies have shown promising effects of brain stimulations on Alzheimer's disease (AD). Brain stimulations can be categorized into non-invasive brain stimulation (NIBS) and invasive brain stimulation (IBS). IBS includes deep brain stimulation (DBS), and invasive vagus nerve stimulation (VNS), whereas NIBS includes transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), electroconvulsive treatment (ECT), magnetic seizure therapy (MST), cranial electrostimulation (CES), and non-invasive VNS. We reviewed the cutting-edge research on these brain stimulation techniques and discussed their therapeutic effects on AD. Both IBS and NIBS may have potential to be developed as novel treatments for AD; however, mixed findings may result from different study designs, patients selection, population, or samples sizes. Therefore, the efficacy of NIBS and IBS in AD remains uncertain, and needs to be further investigated. Moreover, more standardized study designs with larger sample sizes and longitudinal follow-up are warranted for establishing a structural guide for future studies and clinical application.

Computational analysis of transcranial magnetic stimulation in the presence of deep brain stimulation probes

NASA Astrophysics Data System (ADS)

Syeda, F.; Holloway, K.; El-Gendy, A. A.; Hadimani, R. L.

2017-05-01

Transcranial Magnetic Stimulation is an emerging non-invasive treatment for depression, Parkinson's disease, and a variety of other neurological disorders. Many Parkinson's patients receive the treatment known as Deep Brain Stimulation, but often require additional therapy for speech and swallowing impairment. Transcranial Magnetic Stimulation has been explored as a possible treatment by stimulating the mouth motor area of the brain. We have calculated induced electric field, magnetic field, and temperature distributions in the brain using finite element analysis and anatomically realistic heterogeneous head models fitted with Deep Brain Stimulation leads. A Figure of 8 coil, current of 5000 A, and frequency of 2.5 kHz are used as simulation parameters. Results suggest that Deep Brain Stimulation leads cause surrounding tissues to experience slightly increased E-field (Δ Emax =30 V/m), but not exceeding the nominal values induced in brain tissue by Transcranial Magnetic Stimulation without leads (215 V/m). The maximum temperature in the brain tissues surrounding leads did not change significantly from the normal human body temperature of 37 °C. Therefore, we ascertain that Transcranial Magnetic Stimulation in the mouth motor area may stimulate brain tissue surrounding Deep Brain Stimulation leads, but will not cause tissue damage.

Hydraulic Fracturing Treatment Controls on Induced Microseismicity Attributes

NASA Astrophysics Data System (ADS)

Reyes-Montes, J. M.; Kelly, C.; Huang, J.; Zhao, X.; Young, R. P.

2014-12-01

Hydraulic fracturing imposes stress changes in the treated rock through the injection of a mix of fluid and proppant at variable rates and can result in stimulated microseismicity (induced or triggered) with a wide range of magnitudes associated to the opening of new cracks or the mobilisation of pre-existing fractures. Optimizing the treatment is vital for the economic and sustainable development of hydrocarbon reservoir and for the minimization of potential environmental impacts. The analysis of the induced seismicity and of event parameters provide an estimate of the effect of the treatment and the extent of the changes in the rock reservoir properties affecting fluid conductivity. This gives critical feedback for the optimization of the treatment, especially during real-time monitoring. In this study, we correlate microseismic attributes such as the fracture dimensions, event distribution and b-values with the fluid treatment parameters such as the pumping pressure and the slurry rate across different reservoir treatments. Although the microseismic attributes are influenced by many different factors such as the reservoir elastic properties, the stress regime and in-situ fracturing, we consistently observed positive correlations between the slurry rate, plateau treatment pressure and the fracture dimensions. In addition, the variation and systematic deviation of b-value from the natural average of 1.0 gives an insight into the geomechanical behavior of the reservoir. Similar to b-value, another fractal dimension, D-value, indicates the fracture spatial propagation from linear advancement (D=1.0) to planar distribution (D=2.0) to full space occurrence (D=3.0). By merging microseismic events from multiple treatment stages, we statistically analyzed magnitude distribution and spatial and temporal structure of the microseismic cloud induced during the stimulation of a range of different reservoirs with a total population of ~20,000 MS events. Analysis on multiple treatment projects can provide a first order guidance on selecting optimal treatment parameters.

An Implanted, Stimulated Muscle Powered Piezoelectric Generator

NASA Technical Reports Server (NTRS)

Lewandowski, Beth; Gustafson, Kenneth; Kilgore, Kevin

2007-01-01

A totally implantable piezoelectric generator system able to harness power from electrically activated muscle could be used to augment the power systems of implanted medical devices, such as neural prostheses, by reducing the number of battery replacement surgeries or by allowing periods of untethered functionality. The features of our generator design are no moving parts and the use of a portion of the generated power for system operation and regulation. A software model of the system has been developed and simulations have been performed to predict the output power as the system parameters were varied within their constraints. Mechanical forces that mimic muscle forces have been experimentally applied to a piezoelectric generator to verify the accuracy of the simulations and to explore losses due to mechanical coupling. Depending on the selection of system parameters, software simulations predict that this generator concept can generate up to approximately 700 W of power, which is greater than the power necessary to drive the generator, conservatively estimated to be 50 W. These results suggest that this concept has the potential to be an implantable, self-replenishing power source and further investigation is underway.

Additive Manufacturing in Production: A Study Case Applying Technical Requirements

NASA Astrophysics Data System (ADS)

Ituarte, Iñigo Flores; Coatanea, Eric; Salmi, Mika; Tuomi, Jukka; Partanen, Jouni

Additive manufacturing (AM) is expanding the manufacturing capabilities. However, quality of AM produced parts is dependent on a number of machine, geometry and process parameters. The variability of these parameters affects the manufacturing drastically and therefore standardized processes and harmonized methodologies need to be developed to characterize the technology for end use applications and enable the technology for manufacturing. This research proposes a composite methodology integrating Taguchi Design of Experiments, multi-objective optimization and statistical process control, to optimize the manufacturing process and fulfil multiple requirements imposed to an arbitrary geometry. The proposed methodology aims to characterize AM technology depending upon manufacturing process variables as well as to perform a comparative assessment of three AM technologies (Selective Laser Sintering, Laser Stereolithography and Polyjet). Results indicate that only one machine, laser-based Stereolithography, was feasible to fulfil simultaneously macro and micro level geometrical requirements but mechanical properties were not at required level. Future research will study a single AM system at the time to characterize AM machine technical capabilities and stimulate pre-normative initiatives of the technology for end use applications.

ICI D7114 a novel selective beta-adrenoceptor agonist selectively stimulates brown fat and increases whole-body oxygen consumption.

PubMed Central

Holloway, B. R.; Howe, R.; Rao, B. S.; Stribling, D.; Mayers, R. M.; Briscoe, M. G.; Jackson, J. M.

1991-01-01

1. ICI D7114 is a novel, beta-adrenoceptor agonist which stimulates whole body oxygen consumption in conscious rats, cats and dogs and brown adipose tissue (BAT) activity in conscious rats. Treatment of rats with ICI D7114 stimulated oxygen consumption (ED50, 0.04 mg kg-1, p.o.) and BAT mitochondrial guanosine diphosphate (GDP)-binding (ED50, 0.15 mg kg-1, p.o.) with no chronotropic effects on the heart at these doses. 2. Reference beta-adrenoceptor agonists, isoprenaline and clenbuterol, also stimulated oxygen consumption and BAT activity but were less selective because they also produced effects on heart rate at these doses. 3. Treatment of conscious rats with ICI D7114 did not attenuate the chronotropic effects on the heart of a subsequent isoprenaline challenge. 4. Administration of ICI D7114 or of its acid metabolite had no effect in a cat soleus muscle model of tremor or on blood potassium levels in the conscious dog, indicating lack of effects at beta 2-adrenoceptors. 5. The results indicate that ICI D7114 may have activity at atypical beta-adrenoceptors in brown adipose tissue leading to increased whole body oxygen consumption. PMID:1686210

Selective modulation of intracortical inhibition by low-intensity Theta Burst Stimulation.

PubMed

McAllister, S M; Rothwell, J C; Ridding, M C

2009-04-01

Theta Burst Stimulation (TBS) is a repetitive transcranial magnetic stimulation paradigm which has effects on both excitatory and inhibitory intracortical pathways when applied at an intensity of 80% of active motor threshold. As intracortical inhibitory pathways have a lower threshold for activation than excitatory pathways, we sought to determine whether it was possible to selectively target cortical inhibitory circuitry by reducing the intensity of TBS to 70% of active motor threshold. Motor evoked potentials (MEPs), short latency intracortical facilitation (SICF), intracortical facilitation (ICF) and short interval intracortical inhibition (SICI) were measured at baseline, 5-20 and 20-35 min following continuous (cTBS) and intermittent (iTBS) low-intensity TBS in nine healthy subjects. Low-intensity cTBS significantly reduced SICI 5-20 min following stimulation, whilst having no effect on MEPs, SICF or ICF. Low-intensity iTBS had no effect on SICI, MEPs, SICF or ICF. It is possible to selectively target intracortical inhibitory networks for modulation by low-intensity TBS, however, responses may critically depend upon the particular paradigm chosen. These findings have important implications for the treatment of neurological disorders where abnormal levels of intracortical inhibition are present, such as Parkinson's disease and focal hand dystonia and requires further investigation.

Understanding Epileptiform After-Discharges as Rhythmic Oscillatory Transients.

PubMed

Baier, Gerold; Taylor, Peter N; Wang, Yujiang

2017-01-01

Electro-cortical activity in patients with epilepsy may show abnormal rhythmic transients in response to stimulation. Even when using the same stimulation parameters in the same patient, wide variability in the duration of transient response has been reported. These transients have long been considered important for the mapping of the excitability levels in the epileptic brain but their dynamic mechanism is still not well understood. To investigate the occurrence of abnormal transients dynamically, we use a thalamo-cortical neural population model of epileptic spike-wave activity and study the interaction between slow and fast subsystems. In a reduced version of the thalamo-cortical model, slow wave oscillations arise from a fold of cycles (FoC) bifurcation. This marks the onset of a region of bistability between a high amplitude oscillatory rhythm and the background state. In vicinity of the bistability in parameter space, the model has excitable dynamics, showing prolonged rhythmic transients in response to suprathreshold pulse stimulation. We analyse the state space geometry of the bistable and excitable states, and find that the rhythmic transient arises when the impending FoC bifurcation deforms the state space and creates an area of locally reduced attraction to the fixed point. This area essentially allows trajectories to dwell there before escaping to the stable steady state, thus creating rhythmic transients. In the full thalamo-cortical model, we find a similar FoC bifurcation structure. Based on the analysis, we propose an explanation of why stimulation induced epileptiform activity may vary between trials, and predict how the variability could be related to ongoing oscillatory background activity. We compare our dynamic mechanism with other mechanisms (such as a slow parameter change) to generate excitable transients, and we discuss the proposed excitability mechanism in the context of stimulation responses in the epileptic cortex.

Validation of the PMD100TM and its NOLTM Index to detect nociception at different infusion regimen of remifentanil in patients under general anaesthesia.

PubMed

Stöckle, Pierre-André; Julien, Marco; Issa, Rami; Décary, Elizabeth; Brulotte, Véronique; Drolet, Pierre; Henri, Margaret; Poirier, Madeleine; Latulippe, Jean-François; Dorais, Marc; Verdonck, Olivier; Fortier, Louis-Philippe; Richebé, Philippe

2018-05-14

The NOL index is based on multiparametric analysis of heart rate (HR), skin conductance, wave plethysmography, and their time derivative. Our objective was to evaluate the NOL to detect standardized nociceptive stimuli with various remifentanil dosages under general anaesthesia. A prospective, observational study at a single center (NCT02602379) included 40 ASA I to III patients undergoing laparotomy under remifentanil-desflurane anaesthesia with epidural analgesia. A tetanic stimulation was applied (forearm) at remifentanil intravenous (IV) infusion of 0.005, 0.05, 0.1 and 0.15 mcg.kg-1.min-1. NOL and its variations were compared with other parameters namely HR, mean arterial pressure, Bispectral index and Analgesia nociception index (ANI). Receiver operating characteristic (ROC) curves were plotted to assess the response to both intubation and standardized stimulus under remifentanil infusion of 0.005 mcg.kg-1.min-1. The post-stimulation NOL values at remifentanil doses of 0.005, 0.05, 0.1 and 0.15 mcg.kg-1.min-1 (39 [23-55], 15 [7-30], 8 [4-14] and 8.5 [4-15]) were significantly higher than pre-stimulation counterparts (p<0.0001). For all other parameters, there was also significant difference between pre- and post-stimulation values at all remifentanil dosages (p<0.0001). Area under the ROC curve (AUC) for the NOL during standardized stimulation was larger than for all other parameters at the exception of ANI (p=0.94). The AUC of NOL for nociception during tracheal intubation was greater (0.93 vs. 0.84 and 0.64 for ANI and HR, respectively). NOL monitoring is a promising index to assess the level of nociception in patients under general anaesthesia.

Selecting Trade Books for Elementary Science Units.

ERIC Educational Resources Information Center

Rop, Charles J.; Rop, Sheri K.

2001-01-01

Explains the importance of using well-chosen trade books for stimulating student interest and motivation in the natural world. Discusses how to assess and select trade books. Lists selected trade books on the life cycles of plants. (YDS)

A wireless wearable surface functional electrical stimulator

NASA Astrophysics Data System (ADS)

Wang, Hai-Peng; Guo, Ai-Wen; Zhou, Yu-Xuan; Xia, Yang; Huang, Jia; Xu, Chong-Yao; Huang, Zong-Hao; Lü, Xiao-Ying; Wang, Zhi-Gong

2017-09-01

In this paper, a wireless wearable functional electrical stimulator controlled by Android phone with real-time-varying stimulation parameters for multichannel surface functional electrical stimulation application has been developed. It can help post-stroke patients using more conveniently. This study focuses on the prototype design, including the specific wristband concept, circuits and stimulation pulse-generation algorithm. A novel stimulator circuit with a driving stage using a complementary current source technique is proposed to achieve a high-voltage compliance, a large output impedance and an accurate linear voltage-to-current conversion. The size of the prototype has been significantly decreased to 17 × 7.5 × 1 cm3. The performance of the prototype has been tested with a loaded resistor and wrist extension/flexion movement of three hemiplegic patients. According to the experiments, the stimulator can generate four-channel charge-balanced biphasic stimulation with a voltage amplitude up to 60 V, and the pulse frequency and width can be adjusted in real time with a range of 100-600 μs and 20-80 Hz, respectively.

A Systematic Approach to Sensor Selection for Aircraft Engine Health Estimation

NASA Technical Reports Server (NTRS)

Simon, Donald L.; Garg, Sanjay

2009-01-01

A systematic approach for selecting an optimal suite of sensors for on-board aircraft gas turbine engine health estimation is presented. The methodology optimally chooses the engine sensor suite and the model tuning parameter vector to minimize the Kalman filter mean squared estimation error in the engine s health parameters or other unmeasured engine outputs. This technique specifically addresses the underdetermined estimation problem where there are more unknown system health parameters representing degradation than available sensor measurements. This paper presents the theoretical estimation error equations, and describes the optimization approach that is applied to select the sensors and model tuning parameters to minimize these errors. Two different model tuning parameter vector selection approaches are evaluated: the conventional approach of selecting a subset of health parameters to serve as the tuning parameters, and an alternative approach that selects tuning parameters as a linear combination of all health parameters. Results from the application of the technique to an aircraft engine simulation are presented, and compared to those from an alternative sensor selection strategy.

Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure

PubMed Central

Sowa, Jan-Peter; Manka, Paul; Katsounas, Antonios; Syn, Wing-Kin; Führer, Dagmar; Gieseler, Robert K.; Bechmann, Lars P.; Gerken, Guido; Moeller, Lars C.; Canbay, Ali

2015-01-01

Introduction Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. Methods 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. Results More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. Conclusions In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity. PMID:26147961

Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure.

PubMed

Anastasiou, Olympia; Sydor, Svenja; Sowa, Jan-Peter; Manka, Paul; Katsounas, Antonios; Syn, Wing-Kin; Führer, Dagmar; Gieseler, Robert K; Bechmann, Lars P; Gerken, Guido; Moeller, Lars C; Canbay, Ali

2015-01-01

Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer's disease.

PubMed

Köfalvi, Attila; Lemos, Cristina; Martín-Moreno, Ana M; Pinheiro, Bárbara S; García-García, Luis; Pozo, Miguel A; Valério-Fernandes, Ângela; Beleza, Rui O; Agostinho, Paula; Rodrigues, Ricardo J; Pasquaré, Susana J; Cunha, Rodrigo A; de Ceballos, María L

2016-11-01

Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations. We here addressed the possible role of CB2Rs in the regulation of glucose uptake in the mouse brain. To that aim, we have undertaken 1) measurement of (3)H-deoxyglucose uptake in cultured cortical astrocytes and neurons and in acute hippocampal slices; 2) real-time visualization of fluorescently labeled deoxyglucose uptake in superfused hippocampal slices; and 3) in vivo PET imaging of cerebral (18)F-fluorodeoxyglucose uptake. We now show that both selective (JWH133 and GP1a) as well as non-selective (WIN55212-2) CB2R agonists, but not the CB1R-selective agonist, ACEA, stimulate glucose uptake, in a manner that is sensitive to the CB2R-selective antagonist, AM630. Glucose uptake is stimulated in astrocytes and neurons in culture, in acute hippocampal slices, in different brain areas of young adult male C57Bl/6j and CD-1 mice, as well as in middle-aged C57Bl/6j mice. Among the endocannabinoid metabolizing enzymes, the selective inhibition of COX-2, rather than that of FAAH, MAGL or α,βDH6/12, also stimulates the uptake of glucose in hippocampal slices of middle-aged mice, an effect that was again prevented by AM630. However, we found the levels of the endocannabinoid, anandamide reduced in the hippocampus of TgAPP-2576 mice (a model of β-amyloidosis), and likely as a consequence, COX-2 inhibition failed to stimulate glucose uptake in these mice. Together, these results reveal a novel general glucoregulatory role for CB2Rs in the brain, raising therapeutic interest in CB2R agonists as nootropic agents. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Modelling exploration of non-stationary hydrological system

NASA Astrophysics Data System (ADS)

Kim, Kue Bum; Kwon, Hyun-Han; Han, Dawei

2015-04-01

Traditional hydrological modelling assumes that the catchment does not change with time (i.e., stationary conditions) which means the model calibrated for the historical period is valid for the future period. However, in reality, due to change of climate and catchment conditions this stationarity assumption may not be valid in the future. It is a challenge to make the hydrological model adaptive to the future climate and catchment conditions that are not observable at the present time. In this study a lumped conceptual rainfall-runoff model called IHACRES was applied to a catchment in southwest England. Long observation data from 1961 to 2008 were used and seasonal calibration (in this study only summer period is further explored because it is more sensitive to climate and land cover change than the other three seasons) has been done since there are significant seasonal rainfall patterns. We expect that the model performance can be improved by calibrating the model based on individual seasons. The data is split into calibration and validation periods with the intention of using the validation period to represent the future unobserved situations. The success of the non-stationary model will depend not only on good performance during the calibration period but also the validation period. Initially, the calibration is based on changing the model parameters with time. Methodology is proposed to adapt the parameters using the step forward and backward selection schemes. However, in the validation both the forward and backward multiple parameter changing models failed. One problem is that the regression with time is not reliable since the trend may not be in a monotonic linear relationship with time. The second issue is that changing multiple parameters makes the selection process very complex which is time consuming and not effective in the validation period. As a result, two new concepts are explored. First, only one parameter is selected for adjustment while the other parameters are set as constant. Secondly, regression is made against climate condition instead of against time. It has been found that such a new approach is very effective and this non-stationary model worked very well both in the calibration and validation period. Although the catchment is specific in southwest England and the data are for only the summer period, the methodology proposed in this study is general and applicable to other catchments. We hope this study will stimulate the hydrological community to explore a variety of sites so that valuable experiences and knowledge could be gained to improve our understanding of such a complex modelling issue in climate change impact assessment.

Clinical and radiographic evaluation of nanocrystalline hydroxyapatite with or without platelet-rich fibrin membrane in the treatment of periodontal intrabony defects

PubMed Central

Elgendy, Enas Ahmed; Abo Shady, Tamer Elamer

2015-01-01

Background: Nano-sized ceramics may represent a promising class of bone graft substitutes due to their improved osseointegrative properties. Nanocrystalline hydroxyapatite (NcHA) binds to bone and stimulate bone healing by stimulation of osteoblast activity. Platelet-rich fibrin (PRF), an intimate assembly of cytokines, glycan chains, and structural glycoproteins enmeshed within a slowly polymerized fibrin network, has the potential to accelerate soft and hard tissue healing. The present study aims to explore the clinical and radiographical outcome of NcHA bone graft with or without PRF, in the treatment of intrabony periodontal defects. Materials and Methods: In a split-mouth study design, 20 patients having two almost identical intrabony defects with clinical probing depth of at least 6 mm were selected for the study. Selected sites were randomly divided into two groups. In Group I, mucoperiosteal flap elevation followed by the placement of NcHA was done. In Group II, mucoperiosteal flap elevation, followed by the placement of NcHA with PRF was done. Clinical and radiographic parameters were recorded at baseline and at 6-month postoperatively. Results: Both treatment groups showed a significant probing pocket depth (PPD) reduction, clinical attachment gain, increase bone density 6-month after surgery compared with baseline. However, there was a significantly greater PPD reduction and clinical attachment gain when PRF was added to NcHA. Conclusion: The NcHA bone graft in combination with PRF demonstrated clinical advantages beyond that achieved by the NcHA alone. PMID:25810595

Electrode Position and Current Amplitude Modulate Impulsivity after Subthalamic Stimulation in Parkinsons Disease—A Computational Study

PubMed Central

Mandali, Alekhya; Chakravarthy, V. Srinivasa; Rajan, Roopa; Sarma, Sankara; Kishore, Asha

2016-01-01

Background: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) is highly effective in alleviating motor symptoms of Parkinson's disease (PD) which are not optimally controlled by dopamine replacement therapy. Clinical studies and reports suggest that STN-DBS may result in increased impulsivity and de novo impulse control disorders (ICD). Objective/Hypothesis: We aimed to compare performance on a decision making task, the Iowa Gambling Task (IGT), in healthy conditions (HC), untreated and medically-treated PD conditions with and without STN stimulation. We hypothesized that the position of electrode and stimulation current modulate impulsivity after STN-DBS. Methods: We built a computational spiking network model of basal ganglia (BG) and compared the model's STN output with STN activity in PD. Reinforcement learning methodology was applied to simulate IGT performance under various conditions of dopaminergic and STN stimulation where IGT total and bin scores were compared among various conditions. Results: The computational model reproduced neural activity observed in normal and PD conditions. Untreated and medically-treated PD conditions had lower total IGT scores (higher impulsivity) compared to HC (P < 0.0001). The electrode position that happens to selectively stimulate the part of the STN corresponding to an advantageous panel on IGT resulted in de-selection of that panel and worsening of performance (P < 0.0001). Supratherapeutic stimulation amplitudes also worsened IGT performance (P < 0.001). Conclusion(s): In our computational model, STN stimulation led to impulsive decision making in IGT in PD condition. Electrode position and stimulation current influenced impulsivity which may explain the variable effects of STN-DBS reported in patients. PMID:27965590

Selective Stimulation of Penumbral Cones Reveals Perception in the Shadow of Retinal Blood Vessels

PubMed Central

Spitschan, Manuel; Aguirre, Geoffrey K.; Brainard, David H.

2015-01-01

In 1819, Johann Purkinje described how a moving light source that displaces the shadow of the retinal blood vessels to adjacent cones can produce the entopic percept of a branching tree. Here, we describe a novel method for producing a similar percept. We used a device that mixes 56 narrowband primaries under computer control, in conjunction with the method of silent substitution, to present observers with a spectral modulation that selectively targeted penumbral cones in the shadow of the retinal blood vessels. Such a modulation elicits a clear Purkinje-tree percept. We show that the percept is specific to penumbral L and M cone stimulation and is not produced by selective penumbral S cone stimulation. The Purkinje-tree percept was strongest at 16 Hz and fell off at lower (8 Hz) and higher (32 Hz) temporal frequencies. Selective stimulation of open-field cones that are not in shadow, with penumbral cones silenced, also produced the percept, but it was not seen when penumbral and open-field cones were modulated together. This indicates the need for spatial contrast between penumbral and open-field cones to create the Purkinje-tree percept. Our observation provides a new means for studying the response of retinally stabilized images and demonstrates that penumbral cones can support spatial vision. Further, the result illustrates a way in which silent substitution techniques can fail to be silent. We show that inadvertent penumbral cone stimulation can accompany melanopsin-directed modulations that are designed only to silence open-field cones. This in turn can result in visual responses that might be mistaken as melanopsin-driven. PMID:25897842

Agonist-stimulated cobalt uptake provides selective visualization of neurons expressing AMPA- or kainate-type glutamate receptors in the retina.

PubMed

Pourcho, Roberta G; Qin, Pu; Goebel, Dennis J; Fyk-Kolodziej, Bozena

2002-12-16

Fast-acting excitatory neurotransmission in the retina is mediated primarily by glutamate, acting at alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) -selective and kainate-selective receptors. To localize these sites of action, cat retinas were stimulated with either AMPA or kainate and processed for histochemical visualization of cobalt uptake through calcium-permeable channels. Treatment with both agonists resulted in staining of A- and B-type horizontal cells and several types of OFF cone bipolar cells; there was no evidence for staining of ON cone bipolar cells or rod bipolar cells. The subpopulations of OFF cone bipolar cells differed in their responses with two distinct types that stained heavily with cobalt after exposure to AMPA and three different types that were preferentially labeled after exposure to kainate. Although many amacrine and ganglion cells appeared to respond to both agonists, AII amacrine cells were stained after stimulation by AMPA but not by kainate. The OFF cone bipolar cells that exhibit AMPA-stimulated cobalt uptake were found to have a high level of correspondence with cells that show immunocytochemical staining for the AMPA-selective glutamate receptor subunits GluR1 and GluR2/3. Similarly, the cone bipolar cells exhibiting kainate-stimulated cobalt uptake resemble those that are immunoreactive for the kainate subunit GluR5. The results indicate that, whereas many retinal neurons express both AMPA and kainate receptors, AII amacrine cells and subpopulations of OFF cone bipolar cells are limited to the expression of either AMPA or kainate receptors. This differential expression may contribute to the unique character of transmission by these cell types. Copyright 2002 Wiley-Liss, Inc.

Surface-distributed low-frequency asynchronous stimulation delays fatigue of stimulated muscles.

PubMed

Maneski, Lana Z Popović; Malešević, Nebojša M; Savić, Andrej M; Keller, Thierry; Popović, Dejan B

2013-12-01

One important reason why functional electrical stimulation (FES) has not gained widespread clinical use is the limitation imposed by rapid muscle fatigue due to non-physiological activation of the stimulated muscles. We aimed to show that asynchronous low-pulse-rate (LPR) electrical stimulation applied by multipad surface electrodes greatly postpones the occurrence of muscle fatigue compared with conventional stimulation (high pulse rate, HPR). We compared the produced force vs. time of the forearm muscles responsible for finger flexion in 2 stimulation protocols, LPR (fL = 10 Hz) and HPR (fH = 40 Hz). Surface-distributed low-frequency asynchronous stimulation (sDLFAS) doubles the time interval before the onset of fatigue (104 ± 80%) compared with conventional synchronous stimulation. Combining the performance of multipad electrodes (increased selectivity and facilitated positioning) with sDLFAS (decreased fatigue) can improve many FES applications in both the lower and upper extremities. Copyright © 2013 Wiley Periodicals, Inc.

Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review

PubMed Central

2012-01-01

Background There is increasing concern that prescription stimulants may be associated with adverse cardiovascular events such as stroke, myocardial infarction, and sudden death. Public health concerns are amplified by increasing use of prescription stimulants among adults. Methods The objective of this study was to conduct a systematic review of the evidence of an association between prescription stimulant use and adverse cardiovascular outcomes. PUBMED, MEDLINE, EMBASE and Google Scholar searches were conducted using key words related to these topics (MESH): ADHD; Adults; Amphetamine; Amphetamines; Arrhythmias, Cardiac; Cardiovascular Diseases; Cardiovascular System; Central Nervous Stimulants; Cerebrovascular; Cohort Studies; Case–control Studies; Death; Death, Sudden, Cardiac; Dextroamphetamine; Drug Toxicity; Methamphetamine; Methylphenidate; Myocardial Infarction; Stimulant; Stroke; Safety. Eligible studies were population-based studies of children, adolescents, or adults using prescription stimulant use as the independent variable and a hard cardiovascular outcome as the dependent variable. Results Ten population-based observational studies which evaluated prescription stimulant use with cardiovascular outcomes were reviewed. Six out of seven studies in children and adolescents did not show an association between stimulant use and adverse cardiovascular outcomes. In contrast, two out of three studies in adults found an association. Conclusions Findings of an association between prescription stimulant use and adverse cardiovascular outcomes are mixed. Studies of children and adolescents suggest that statistical power is limited in available study populations, and the absolute risk of an event is low. More suggestive of a safety signal, studies of adults found an increased risk for transient ischemic attack and sudden death/ventricular arrhythmia. Interpretation was limited due to differences in population, cardiovascular outcome selection/ascertainment, and methodology. Accounting for confounding and selection biases in these studies is of particular concern. Future studies should address this and other methodological issues. PMID:22682429

Flow velocity measurements with stimulated Rayleigh-Brillouin-gain spectroscopy

NASA Technical Reports Server (NTRS)

Herring, G. C.; Moosmueller, H.; Lee, S. A.; She, C. Y.

1983-01-01

Using stimulated Rayleigh-Brillouin-gain spectroscopy, velocity measurements in an atmospheric-pressure subsonic nitrogen flow with 10 percent uncertainty have been conducted. It is shown that the accuracy of the velocity measurements increases with gas pressure, making this spectroscopic technique ideal for measuring velocity and other parameters of high-pressure (greater than 1-atm) atomic or molecular flows.

Effect of Bilateral Stimulation of the Subthalamic Nucleus on Different Speech Subsystems in Patients with Parkinson's Disease

ERIC Educational Resources Information Center

Putzer, Manfred; Barry, William J.; Moringlane, Jean Richard

2008-01-01

The effect of deep brain stimulation on the two speech-production subsystems, articulation and phonation, of nine Parkinsonian patients is examined. Production parameters (stop closure voicing; stop closure, VOT, vowel) in fast syllable-repetitions were defined and measured and quantitative, objective metrics of vocal fold function were obtained…

Temporal Tuning of Word- and Face-selective Cortex.

PubMed

Yeatman, Jason D; Norcia, Anthony M

2016-11-01

Sensitivity to temporal change places fundamental limits on object processing in the visual system. An emerging consensus from the behavioral and neuroimaging literature suggests that temporal resolution differs substantially for stimuli of different complexity and for brain areas at different levels of the cortical hierarchy. Here, we used steady-state visually evoked potentials to directly measure three fundamental parameters that characterize the underlying neural response to text and face images: temporal resolution, peak temporal frequency, and response latency. We presented full-screen images of text or a human face, alternated with a scrambled image, at temporal frequencies between 1 and 12 Hz. These images elicited a robust response at the first harmonic that showed differential tuning, scalp topography, and delay for the text and face images. Face-selective responses were maximal at 4 Hz, but text-selective responses, by contrast, were maximal at 1 Hz. The topography of the text image response was strongly left-lateralized at higher stimulation rates, whereas the response to the face image was slightly right-lateralized but nearly bilateral at all frequencies. Both text and face images elicited steady-state activity at more than one apparent latency; we observed early (141-160 msec) and late (>250 msec) text- and face-selective responses. These differences in temporal tuning profiles are likely to reflect differences in the nature of the computations performed by word- and face-selective cortex. Despite the close proximity of word- and face-selective regions on the cortical surface, our measurements demonstrate substantial differences in the temporal dynamics of word- versus face-selective responses.

Combined sub-threshold dosages of phenobarbital and low-frequency stimulation effectively reduce seizures in amygdala-kindled rats.

PubMed

Asgari, Azam; Semnanian, Saeed; Atapour, Nafiseh; Shojaei, Amir; Moradi, Homeira; Mirnajafi-Zadeh, Javad

2014-08-01

Low-frequency stimulation (LFS) is a potential therapy utilized in patients who do not achieve satisfactory control of seizures with pharmacological treatments. Here, we investigated the interaction between anticonvulsant effects of LFS and phenobarbital (a commonly used medicine) on amygdala-kindled seizures in rats. Animals were kindled by electrical stimulation of basolateral amygdala in a rapid manner (12 stimulations/day). Fully kindled animals randomly received one of the three treatment choices: phenobarbital (1, 2, 3, 4 and 8 mg/kg; i.p.; 30 min before kindling stimulation), LFS (one or 4 packages contained 100 or 200 monophasic square wave pulses, 0.1-ms pulse duration at 1 Hz, immediately before kindling stimulation) or a combination of both (phenobarbital at 3 mg/kg and LFS). Phenobarbital alone at the doses of 1, 2 and 3 mg/kg had no significant effect on the main seizure parameters. LFS application always produced anticonvulsant effects unless applied with the pattern of one package of 100 pulses, which is considered as non-effective. All the seizure parameters were significantly reduced when phenobarbital (3 mg/kg) was administered prior to the application of the non-effective pattern of LFS. Phenobarbital (3 mg/kg) also increased the anticonvulsant actions of the effective LFS pattern. Our results provide an evidence of a positive cumulative anticonvulsant effect of LFS and phenobarbital, suggesting a potential combination therapy at sub-threshold dosages of phenobarbital and LFS to achieve a satisfactory clinical effect.

Retinal ganglion cell responses to voltage and current stimulation in wild-type and rd1 mouse retinas

NASA Astrophysics Data System (ADS)

Goo, Yong Sook; Ye, Jang Hee; Lee, Seokyoung; Nam, Yoonkey; Ryu, Sang Baek; Kim, Kyung Hwan

2011-06-01

Retinal prostheses are being developed to restore vision for those with retinal diseases such as retinitis pigmentosa or age-related macular degeneration. Since neural prostheses depend upon electrical stimulation to control neural activity, optimal stimulation parameters for successful encoding of visual information are one of the most important requirements to enable visual perception. In this paper, we focused on retinal ganglion cell (RGC) responses to different stimulation parameters and compared threshold charge densities in wild-type and rd1 mice. For this purpose, we used in vitro retinal preparations of wild-type and rd1 mice. When the neural network was stimulated with voltage- and current-controlled pulses, RGCs from both wild-type and rd1 mice responded; however the temporal pattern of RGC response is very different. In wild-type RGCs, a single peak within 100 ms appears, while multiple peaks (approximately four peaks) with ~10 Hz rhythm within 400 ms appear in RGCs in the degenerated retina of rd1 mice. We find that an anodic phase-first biphasic voltage-controlled pulse is more efficient for stimulation than a biphasic current-controlled pulse based on lower threshold charge density. The threshold charge densities for activation of RGCs both with voltage- and current-controlled pulses are overall more elevated for the rd1 mouse than the wild-type mouse. Here, we propose the stimulus range for wild-type and rd1 retinas when the optimal modulation of a RGC response is possible.

The effect of right ventricle pacemaker lead position on diastolic function in patients with preserved left ventricle ejection fraction.

PubMed

Mitov, Vladimir; Perisić, Zoran; Jolić, Aleksandar; Adamović, Dragana; Zastranović, Lale; Aleksić, Aleksandar; Kostić, Tomislav; Božinović, Nenad; Aleksić, Zeljka; Soldatović, Ivan

2013-01-01

Our aim was to analyze any changes during diastole in patients with normal left ventricular ejection fraction (LVEF), after pacemaker stimulation from the right ventricular outflow tract (RVOT) and right ventricular apex (RVA) lead position. This was a prospective, randomized, follow up study, which lasted for 12 months. Our research included 132 consecutive patients who were implanted with a permanent antibradycardiac pacemaker. Regarding the right ventricle lead position the patients were divided into two groups: The RVOT group--71 patients, with right ventricle outflow tract lead position and the RVA group--61 patients, with right ventricle apex lead position. We measured LVEF and diastolic parameters: peak filling ratio and time to peak filling ratio obtained by radionuclide ventriculography (RNV). The LVEF and various diastolic parameters and left atrial diameter were obtained by echocardiography. Based on the values of deceleration time of early diastolic filling (DTE), and other diastolic parameters like left atrial diameter, all the patients were classified into three degrees of diastolic dysfunction. Our results showed that there was no group difference in distribution of gender, age, body mass index (BMI), VVI to DDD pacemakers implantation ratio, RNV parameters (LVEF, peak filling rate (PFR), time to PFR (TPFR)) and echocardiography parameters: LVEF and parameters of diastolic dysfunction. After 12 months of pacemaker stimulation, LVEF by RNV remained the same in the RVOT group 51.31±15.80% (P=0.75), and also in the RVA group 53.83±6.57%, (P=0.19). In the RVOT group the PFR was highly lower and this finding was significant (P=0.01), while TPFR was also significantly lower (P=0.03). By dividing the patients according to the degree of diastolic dysfunction we found that most patients in both groups at enrollment had a second degree diastolic dysfunction. In both groups diastolic dysfunction increased, the number of patients with third degree diastolic dysfunction increased, and the number of patients with second degree diastolic dysfunction decreased, however, the worsening of diastolic function was significant only in the RVOT group. In conclusion, pacemaker stimulation from RVOT, but not in RVA, leads to progression of diastolic dysfunction in patients with preserved LVEF. This negative effect of pacemaker stimulation from RVOT on diastolic parameters was confirmed by two independent methods, RNV and echocardiography.

A frequency and pulse-width co-modulation strategy for transcutaneous neuromuscular electrical stimulation based on sEMG time-domain features

NASA Astrophysics Data System (ADS)

Zhou, Yu-Xuan; Wang, Hai-Peng; Bao, Xue-Liang; Lü, Xiao-Ying; Wang, Zhi-Gong

2016-02-01

Objective. Surface electromyography (sEMG) is often used as a control signal in neuromuscular electrical stimulation (NMES) systems to enhance the voluntary control and proprioceptive sensory feedback of paralyzed patients. Most sEMG-controlled NMES systems use the envelope of the sEMG signal to modulate the stimulation intensity (current amplitude or pulse width) with a constant frequency. The aims of this study were to develop a strategy that co-modulates frequency and pulse width based on features of the sEMG signal and to investigate the torque-reproduction performance and the level of fatigue resistance achieved with our strategy. Approach. We examined the relationships between wrist torque and two stimulation parameters (frequency and pulse width) and between wrist torque and two sEMG time-domain features (mean absolute value (MAV) and number of slope sign changes (NSS)) in eight healthy volunteers. By using wrist torque as an intermediate variable, customized and generalized transfer functions were constructed to convert the two features of the sEMG signal into the two stimulation parameters, thereby establishing a MAV/NSS dual-coding (MNDC) algorithm. Wrist torque reproduction performance was assessed by comparing the torque generated by the algorithms with that originally recorded during voluntary contractions. Muscle fatigue was assessed by measuring the decline percentage of the peak torque and by comparing the torque time integral of the response to test stimulation trains before and after fatigue sessions. Main Results. The MNDC approach could produce a wrist torque that closely matched the voluntary wrist torque. In addition, a smaller decay in the wrist torque was observed after the MNDC-coded fatigue stimulation was applied than after stimulation using pulse-width modulation alone. Significance. Compared with pulse-width modulation stimulation strategies that are based on sEMG detection, the MNDC strategy is more effective for both voluntary muscle force reproduction and muscle fatigue reduction.

Relative importance of physical and economic factors in Appalachian coalbed gas assessment

USGS Publications Warehouse

Attanasi, E.D.

1998-01-01

In the 1995 National Assessment of Oil and Gas Resources prepared by the U.S. Geological Survey, only 20% of the assessed technically recoverable Appalachian Province coalbed gas resources were economic. Physical and economic variables are examined to explain the disparity between economic and technically recoverable coalbed gas. The Anticline and Syncline plays of the Northern Appalachian Basin, which account for 77% of the assessed technically recoverable coalbed gas, are not economic. Analysis shows marginal reductions in costs or rate of return will not turn these plays into commercial successes. Physical parameters that determine ultimate well recoverability and the rate of gas recovery are primary reasons the Northern Appalachian Basin plays are non-commercial. If the application of new well stimulation technology could offset slow gas desorption rates, Appalachian Province economic gas could increase to more then 70% of the technically recoverable gas. Similarly, if operators are able to develop strategies to selectively drill plays by avoiding dry holes and non-commercial occurrences, the economic fraction of technically recoverable gas could increase to over half.In the 1995 National Assessment of Oil and Gas Resources prepared by the U.S. Geological Survey, only 20% of the assessed technically recoverable Appalachian Province coalbed gas resources were economic. Physical and economic variables are examined to explain the disparity between economic and technically recoverable coalbed gas. The Anticline and Syncline plays of the Northern Appalachian Basin, which account for 77% of the assessed technically recoverable coalbed gas, are not economic. Analysis shows marginal reductions in costs or rate of return will not turn these plays into commercial successes. Physical parameters that determine ultimate well recoverability and the rate of gas recovery are primary reasons the Northern Appalachian Basin plays are non-commercial. If the application of new well stimulation technology could offset slow gas desorption rates, Appalachian Province economic gas could increase to more then 70% of the technically recoverable gas. Similarly, if operators are able to develop strategies to selectively drill plays by avoiding dry holes and non-commercial occurrences, the economic fraction of technically recoverable gas could increase to over half.

Automatic parameter selection for feature-based multi-sensor image registration

NASA Astrophysics Data System (ADS)

DelMarco, Stephen; Tom, Victor; Webb, Helen; Chao, Alan

2006-05-01

Accurate image registration is critical for applications such as precision targeting, geo-location, change-detection, surveillance, and remote sensing. However, the increasing volume of image data is exceeding the current capacity of human analysts to perform manual registration. This image data glut necessitates the development of automated approaches to image registration, including algorithm parameter value selection. Proper parameter value selection is crucial to the success of registration techniques. The appropriate algorithm parameters can be highly scene and sensor dependent. Therefore, robust algorithm parameter value selection approaches are a critical component of an end-to-end image registration algorithm. In previous work, we developed a general framework for multisensor image registration which includes feature-based registration approaches. In this work we examine the problem of automated parameter selection. We apply the automated parameter selection approach of Yitzhaky and Peli to select parameters for feature-based registration of multisensor image data. The approach consists of generating multiple feature-detected images by sweeping over parameter combinations and using these images to generate estimated ground truth. The feature-detected images are compared to the estimated ground truth images to generate ROC points associated with each parameter combination. We develop a strategy for selecting the optimal parameter set by choosing the parameter combination corresponding to the optimal ROC point. We present numerical results showing the effectiveness of the approach using registration of collected SAR data to reference EO data.

[Alpha but not beta-adrenergic stimulation has a positive inotropic effect associated with alkalinization of intracellular pH].

PubMed

Gambassi, G; Lakatta, E G; Capogrossi, M C

1991-01-01

There is increasing evidence that alpha-adrenoceptors also exist in the myocardium and that an increase in force of contraction may be produced by stimulation of these sites. This positive inotropism seems to be dependent either on an increased amount of Ca++ released into the cytosol with each action potential or on increased myofilament responsiveness. In contrast, beta-adrenergic stimulation reduces the sensitivity of the contractile proteins and the positive inotropic effect is due to the activation of L-type calcium channels on the sarcolemma. We used single, isolated, enzymatically dissociated, adult rat ventricular myocytes. Cells were loaded either with the ester derivative of the Ca++ probe Indo-1 or with the intracellular pH probe Snarf-1 and at the same time we measured the contractile parameters and monitored the fluorescence as an index of intracellular calcium concentration or pH value. The single cells (bicarbonate buffer continuously gassed with O2 95%, CO2 5%, Ca++ 1.5 mM, field stimulation 0.5 Hz) were exposed to phenylephrine (50 microM) and nadolol (1 microM). Alpha-adrenergic stimulation increased twitch amplitude (delta ES = 1.93 +/- 0.77, n = 8; p less than 0.05) and showed only a slight increase in Ca++ transient. On the other end, the positive inotropic effect (delta ES = 2.84 +/- 0.86, n = 4; p less than 0.02) obtained with beta-adrenergic stimulation (isoproterenol 50 nM, bicarbonate buffer, Ca++ 0.5 mM, field stimulation 0.2 Hz) was always associated with a large increase in intracellular Ca++ concentration. Isoproterenol did not change intracellular pH (delta pH = 0.006 +/- 0.006, n = 4; NS) while phenylephrine increased it significantly (delta pH = 0.055 +/- 0.011, n = 8; p less than 0.002). Moreover, there was a statistically significant correlation between delta ES and delta pH (R2 = 0.532; p less than 0.05) when phenylephrine was present. This alkalinization as well as the increased contractility was antagonized by treatment with ethyl isopropyl-amiloride (10 microM), a selective Na+/H+ inhibitor (delta ES = 0.09 +/- 0.07, n = 6; NS and delta pH = -0.001 +/- 0.011, n = 6; NS). Thus, alpha-adrenergic stimulation in isolated cardiac cells exerts a positive inotropic effect and this is associated with a significant intracellular pH alkalinization. In contrast, the marked inotropic action of beta-stimulation does not involve any intracellular pH modulation. Therefore, it seems likely that, in myocardial cells, an increased myofilament responsiveness due to the alkalinization could represent a possible mechanism for the positive inotropic effect mediated by alpha-adrenergic stimulation.

Acute effect of Vagus nerve stimulation parameters on cardiac chronotropic, inotropic, and dromotropic responses

NASA Astrophysics Data System (ADS)

Ojeda, David; Le Rolle, Virginie; Romero-Ugalde, Hector M.; Gallet, Clément; Bonnet, Jean-Luc; Henry, Christine; Bel, Alain; Mabo, Philippe; Carrault, Guy; Hernández, Alfredo I.

2017-11-01

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy and depression, and is considered as a potential therapy for other pathologies, including Heart Failure (HF) or inflammatory diseases. In the case of HF, several experimental studies on animals have shown an improvement in the cardiac function and a reverse remodeling of the cardiac cavity when VNS is applied. However, recent clinical trials have not been able to reproduce the same response in humans. One of the hypothesis to explain this lack of response is related to the way in which stimulation parameters are defined. The combined effect of VNS parameters is still poorly-known, especially in the case of VNS synchronously delivered with cardiac activity. In this paper, we propose a methodology to analyze the acute cardiovascular effects of VNS parameters individually, as well as their interactive effects. A Latin hypercube sampling method was applied to design a uniform experimental plan. Data gathered from this experimental plan was used to produce a Gaussian process regression (GPR) model in order to estimate unobserved VNS sequences. Finally, a Morris screening sensitivity analysis method was applied to each obtained GPR model. Results highlight dominant effects of pulse current, pulse width and number of pulses over frequency and delay and, more importantly, the degree of interactions between these parameters on the most important acute cardiovascular responses. In particular, high interacting effects between current and pulse width were found. Similar sensitivity profiles were observed for chronotropic, dromotropic and inotropic effects. These findings are of primary importance for the future development of closed-loop, personalized neuromodulator technologies.

Enological Qualities and Interactions Between Native Yeast and Lactic Acid Bacteria from Queretaro, Mexico.

PubMed

Miranda-Castilleja, Dalia E; Martínez-Peniche, Ramón Á; Nadal Roquet-Jalmar, Montserrat; Aldrete-Tapia, J Alejandro; Arvizu-Medrano, Sofía M

2018-06-15

Despite the importance of strain compatibility, most of the enological strain selection studies are carried out separately on yeasts and lactic acid bacteria (LAB). In this study, the enological traits and interactions between native yeasts and LAB were studied. The H 2 S and acetic acid production, growth rates at 8 °C, killer phenotypes, flocculation, and tolerance to must and wine inhibitors were determined for 25 Saccharomyces yeasts. The ability to grow under two wine-like conditions was also determined in 37 LAB (Oenococcus oeni and Lactobacillus plantarum). The yeast-LAB compatibility of selected strains was tested in a sequential scheme. Finally, microvinification trials were performed using two strains from each group to determine the efficiencies and quality parameters. The phenotypic characterization by the K-means and hierarchical clusters indicated a correlation between flocculation and optical density increase in simulated must and wine medium (r = -0.415) and grouped the prominent yeasts SR19, SR26, and N05 as moderately flocculent, killer, acid producing, and highly tolerant strains. Among the LAB, L. plantarum FU39 grew 230% more than the rest. With regard to interactions, LAB growth stimulation (14-fold on average) due to the previous action of yeasts, particularly of SR19, was observed. The final quality of all wines was similar, but yeast SR19 performed a faster and more efficient fermentation than did N05, Also L. plantarum FU39 fermented faster than did O. oeni VC32. The use of quantitative data, and multivariate analyses allowed an integrative approach to the selection of a compatible and efficient pair of enological yeast-LAB strains. An alternative scheme is proposed for the joint selection of yeast and lactic acid bacteria strains, which allows us to foresee the interactions that may occur between them during winemaking. The kinetic parameters, turbidimetrically measured and analyzed by multivariate methods, simplify the detection of outstanding selectable microorganisms. This methodology can be implemented at any cellar or even any fermentative industry that aims to select compatible yeast and lactic acid bacteria. © 2018 Institute of Food Technologists®.

Broadband stimulated Raman spectroscopy in the deep ultraviolet region

NASA Astrophysics Data System (ADS)

Kuramochi, Hikaru; Fujisawa, Tomotsumi; Takeuchi, Satoshi; Tahara, Tahei

2017-09-01

We report broadband stimulated Raman measurements in the deep ultraviolet (DUV) region, which enables selective probing of the aromatic amino acid residues inside proteins through the resonance enhancement. We combine the narrowband DUV Raman pump pulse (<10 cm-1) at wavelengths as short as 240 nm and the broadband DUV probe pulse (>1000 cm-1) to realize stimulated Raman measurements covering a >1500 cm-1 spectral window. The stimulated Raman measurements for neat solvents, tryptophan, tyrosine, and glucose oxidase are performed using 240- and 290-nm Raman pump, highlighting the high potential of the DUV stimulated Raman probe for femtosecond time-resolved study of proteins.

M1/M2 muscarinic receptor selectivity using potassium (K/sup +/)-stimulated release of (/sup 3/H)-dopamine (DA) and (/sup 14/C)-acetyl-choline (ACH) in striatum

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

DeHaven, D.L.; Steranka, L.R.

Raiteri et al have suggested that muscarinic receptor subtypes can be differentiated in striatal synaptosomes by the release of DA (M1) or ACh (M2). The authors attempted to replicate this finding and to characterize responses of selective and non-selective cholinergic agonists and antagonists using K+-stimulated release of transmitters from rat striatal slices. The non-selective agonists ACh, carbachol and oxotremorine stimulated release of (/sup 3/H)-DA and inhibited release of (/sup 14/C)-ACh with EC50 values of 10.6, 9.2 and 4.2 ..mu..M (DA) and 1.2, 0.77 and 0.43 ..mu..M (ACh), respectively. The M1 agonist McN-A-343-11 selectively inhibited release of DA with an EC50more » value of 4.8 ..mu..M. Pilocarpine was ineffective in this system. The M1 antagonist pirenzepine reversed the effects of 10/sup -4/ M carbachol on release with an eight-fold selectivity for release of (/sup 3/H)-DA (IC50 = 0.77 ..mu..M) vs (/sup 14/C)-ACh (IC50 = 6.3 ..mu..M). These results suggest that although this system can determine relative subtype selectivities, the results obtained in this assay do not always correlate with those obtained from phosphatidyl inositol turnover or adenylate cyclase activity.« less

Optimization of Electrical Stimulation Parameters for Cardiac Tissue Engineering

PubMed Central

Tandon, Nina; Marsano, Anna; Maidhof, Robert; Wan, Leo; Park, Hyoungshin; Vunjak-Novakovic, Gordana

2010-01-01

In vitro application of pulsatile electrical stimulation to neonatal rat cardiomyocytes cultured on polymer scaffolds has been shown to improve the functional assembly of cells into contractile cardiac tissue constrcuts. However, to date, the conditions of electrical stimulation have not been optimized. We have systematically varied the electrode material, amplitude and frequency of stimulation, to determine the conditions that are optimal for cardiac tissue engineering. Carbon electrodes, exhibiting the highest charge-injection capacity and producing cardiac tissues with the best structural and contractile properties, and were thus used in tissue engineering studies. Cardiac tissues stimulated at 3V/cm amplitude and 3Hz frequency had the highest tissue density, the highest concentrations of cardiac troponin-I and connexin-43, and the best developed contractile behavior. These findings contribute to defining bioreactor design specifications and electrical stimulation regime for cardiac tissue engineering. PMID:21604379

Thalamic modulation of aggression.

PubMed

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

1975-01-01

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

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

PubMed

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

2012-07-01

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

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

PubMed Central

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

2013-01-01

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

Thermally stimulated processes in samarium-modified lead titanate ferroelectric ceramics

NASA Astrophysics Data System (ADS)

Peláiz-Barranco, A.; García-Wong, A. C.; González-Abreu, Y.; Gagou, Y.; Saint-Grégoire, P.

2013-08-01

The thermally stimulated processes in a samarium-modified lead titanate ferroelectric system are analyzed from the thermally stimulated depolarization discharge current. The discharge due to the space charge injected during the poling process, the pyroelectric response and a conduction process related to oxygen vacancies are evaluated considering a theoretical decomposition by using a numerical method. The pyroelectric response is separated from other components to evaluate the polarization behavior and some pyroelectric parameters. High remanent polarization, pyroelectric coefficient and merit figure values are obtained at room temperature.

Fracture Evolution Following a Hydraulic Stimulation within an EGS Reservoir

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

Mella, Michael

The objective of this project was to develop and demonstrate an approach for tracking the evolution of circulation immediately following a hydraulic stimulation in an EGS reservoir. Series of high-resolution tracer tests using conservative and thermally reactive tracers were designed at recently created EGS reservoirs in order to track changes in fluid flow parameters such as reservoir pore volume, flow capacity, and effective reservoir temperature over time. Data obtained from the project would be available for the calibration of reservoir models that could serve to predict EGS performance following a hydraulic stimulation.

[Clinical applications of transcranial magnetic stimulation for the treatment of various neurological diseases].

PubMed

Tsuji, Sadatoshi

2005-11-01

Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in various neurological and psychiatric diseases including depression, Parkinson disease, spinocerebellar degeneration, epilepsy, urinary incontinence, movement disorders, chronic pain, migraine and chronic tinnitus, etc. Several reports showed the therapeutic effects of rTMS as a treatment of depression and Parkinson disease (PD), whereas others found no significant effects. It is by now not yet fully understood whether rTMS has a therapeutic effect on those diseases. The controversy arises from the differences of the stimulation parameters and evaluation methods of the effects in those studies. The Japanese multi-center, double blinded, sham stimulation controlled trial in 85 patients with PD showed an efficacy in both the rTMS-treated and sham stimulated patients. This result does not prove the efficacy of the rTMS in PD; on the other hand, it does not rule out the efficacy. Possible mechanism of favorable effects of rTMS is related to increasing the release of dopamine in the mesolimbic and mesostriatal system. The other Japanese multi-center, double blinded, sham stimulation controlled trial in 99 patients with spinocerebellar degeneration revealed significant therapeutic effects of rTMS in 51 patients with SCA6. We studied the effects of rTMS on seizure susceptibility in rats which prevented the development of status epilepticus of pentylenetetrazol-induced convulsions. This finding suggests the possibility of therapeutic use of rTMS in epilepsy. Further studies should be performed aiming to reveal the optimal stimulation parameters, and are necessary to reveal the therapeutic role of the rTMS in neurological and psychiatric diseases.

Maintenance percutaneous posterior nerve stimulation for refractory lower urinary tract symptoms in patients with multiple sclerosis: an open label, multicenter, prospective study.

PubMed

Zecca, C; Digesu, G A; Robshaw, P; Singh, A; Elneil, S; Gobbi, C

2014-03-01

Percutaneous tibial nerve stimulation is an effective second line therapy for lower urinary tract symptoms. Data on percutaneous tibial nerve stimulation maintenance treatment are scarce. In this study we evaluate its effectiveness and propose an algorithm of percutaneous tibial nerve stimulation maintenance treatment in patients with multiple sclerosis. In this prospective, multicenter, open label trial consecutive patients with multiple sclerosis and lower urinary tract symptoms unresponsive to medical therapy were treated with 12 weekly sessions of percutaneous tibial nerve stimulation. Responder patients (50% or greater improvement of lower urinary tract symptoms as measured by the patient perception of bladder condition questionnaire) entered a maintenance phase with individualized treatment frequency based on patient response. Lower urinary tract symptoms were assessed using a 3-day frequency volume chart, urodynamics and patient perception of bladder condition questionnaire. Treatment satisfaction was evaluated using a global response assessment scale and a treatment satisfaction visual analog scale. A total of 83 patients were included in the study and 74 (89%) responded to initial treatment. Persistent efficacy occurred in all initial responders after a mean treatment of 24 months. The greatest frequency of maintenance percutaneous tibial nerve stimulation was every 2 weeks. Lower urinary tract symptoms and patient treatment satisfaction improved with time compared to initial treatment (p <0.05). Bladder diary parameters and voiding parameters improved compared to baseline (p <0.05). Prolonged percutaneous tibial nerve stimulation treatment leads to a persistent improvement of lower urinary tract symptoms in patients with multiple sclerosis. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Stimulation of the human medial temporal lobe between learning and recall selectively enhances forgetting

PubMed Central

Merkow, Maxwell B.; Burke, John F.; Ramayya, Ashwin G.; Sharan, Ashwini D.; Sperling, Michael R.; Kahana, Michael J.

2017-01-01

Background Direct electrical stimulation applied to the human medial temporal lobe (MTL) typically disrupts performance on memory tasks, however, the mechanism underlying this effect is not known. Objective To study the effects of MTL stimulation on memory performance Methods We studied the effects of MTL stimulation on memory in five patients undergoing invasive electrocorticographic monitoring during various phases of a memory task (encoding, distractor, recall). Results We found that MTL stimulation disrupted memory performance in a timing-dependent manner; we observed greater forgetting when applying stimulation during the delay between encoding and recall, compared to when it was applied during encoding or recall. Conclusions The results suggest that recall is most dependent on the MTL between learning and retrieval. PMID:28073638

A Power-Efficient Wireless System With Adaptive Supply Control for Deep Brain Stimulation.

PubMed

Lee, Hyung-Min; Park, Hangue; Ghovanloo, Maysam

2013-09-01

A power-efficient wireless stimulating system for a head-mounted deep brain stimulator (DBS) is presented. A new adaptive rectifier generates a variable DC supply voltage from a constant AC power carrier utilizing phase control feedback, while achieving high AC-DC power conversion efficiency (PCE) through active synchronous switching. A current-controlled stimulator adopts closed-loop supply control to automatically adjust the stimulation compliance voltage by detecting stimulation site potentials through a voltage readout channel, and improve the stimulation efficiency. The stimulator also utilizes closed-loop active charge balancing to maintain the residual charge at each site within a safe limit, while receiving the stimulation parameters wirelessly from the amplitude-shift-keyed power carrier. A 4-ch wireless stimulating system prototype was fabricated in a 0.5-μm 3M2P standard CMOS process, occupying 2.25 mm². With 5 V peak AC input at 2 MHz, the adaptive rectifier provides an adjustable DC output between 2.5 V and 4.6 V at 2.8 mA loading, resulting in measured PCE of 72 ~ 87%. The adaptive supply control increases the stimulation efficiency up to 30% higher than a fixed supply voltage to 58 ~ 68%. The prototype wireless stimulating system was verified in vitro .

A Power-Efficient Wireless System With Adaptive Supply Control for Deep Brain Stimulation

PubMed Central

Lee, Hyung-Min; Park, Hangue; Ghovanloo, Maysam

2014-01-01

A power-efficient wireless stimulating system for a head-mounted deep brain stimulator (DBS) is presented. A new adaptive rectifier generates a variable DC supply voltage from a constant AC power carrier utilizing phase control feedback, while achieving high AC-DC power conversion efficiency (PCE) through active synchronous switching. A current-controlled stimulator adopts closed-loop supply control to automatically adjust the stimulation compliance voltage by detecting stimulation site potentials through a voltage readout channel, and improve the stimulation efficiency. The stimulator also utilizes closed-loop active charge balancing to maintain the residual charge at each site within a safe limit, while receiving the stimulation parameters wirelessly from the amplitude-shift-keyed power carrier. A 4-ch wireless stimulating system prototype was fabricated in a 0.5-μm 3M2P standard CMOS process, occupying 2.25 mm². With 5 V peak AC input at 2 MHz, the adaptive rectifier provides an adjustable DC output between 2.5 V and 4.6 V at 2.8 mA loading, resulting in measured PCE of 72 ~ 87%. The adaptive supply control increases the stimulation efficiency up to 30% higher than a fixed supply voltage to 58 ~ 68%. The prototype wireless stimulating system was verified in vitro. PMID:24678126

Infrared neural stimulation in the cochlea

PubMed Central

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

2014-01-01

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

Infrared neural stimulation in the cochlea

NASA Astrophysics Data System (ADS)

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

2013-03-01

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

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

NASA Astrophysics Data System (ADS)

Sotiropoulos, Stamatios N.; Steinmetz, Peter N.

2007-06-01

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

[Repetitive transcranial magnetic stimulation: A potential therapy for cognitive disorders?

PubMed

Nouhaud, C; Sherrard, R M; Belmin, J

2017-03-01

Considering the limited effectiveness of drugs treatments in cognitive disorders, the emergence of noninvasive techniques to modify brain function is very interesting. Among these techniques, repetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability and have potential therapeutic effects on cognition and behaviour. These effects are due to physiological modifications in the stimulated cortical tissue and their associated circuits, which depend on the parameters of stimulation. The objective of this article is to specify current knowledge and efficacy of rTMS in cognitive disorders. Previous studies found very encouraging results with significant improvement of higher brain functions. Nevertheless, these few studies have limits: a few patients were enrolled, the lack of control of the mechanisms of action by brain imaging, insufficiently formalized technique and variability of cognitive tests. It is therefore necessary to perform more studies, which identify statistical significant improvement and to specify underlying mechanisms of action and the parameters of use of the rTMS to offer rTMS as a routine therapy for cognitive dysfunction. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Comparison of Coil Designs for Transcranial Magnetic Stimulation on Mice

NASA Astrophysics Data System (ADS)

Rastogi, Priyam; Hadimani, Ravi; Jiles, David

2015-03-01

Transcranial magnetic stimulation (TMS) is a non-invasive treatment for neurological disorders using time varying magnetic field. The electric field generated by the time varying magnetic field is used to depolarize the brain neurons which can lead to measurable effects. TMS provides a surgical free method for the treatment of neurological brain disorders like depression, post-traumatic stress disorder, traumatic brain injury and Parkinson's disease. Before using TMS on human subjects, it is appropriate that its effects are verified on animals such as mice. The magnetic field intensity and stimulated region of the brain can be controlled by the shape, position and current in the coils. There are few reports on the designs of the coils for mice. In this paper, different types of coils are developed and compared using an anatomically realistic mouse model derived from MRI images. Parameters such as focality, depth of the stimulation, electric field strength on the scalp and in the deep brain regions, are taken into account. These parameters will help researchers to determine the most suitable coil design according to their need. This should result in improvements in treatment of specific disorders. Carver Charitable Trust.

Model for economic evaluation of high energy gas fracturing

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

Engi, D.

1984-05-01

The HEGF/NPV model has been developed and adapted for interactive microcomputer calculations of the economic consequences of reservoir stimulation by high energy gas fracturing (HEGF) in naturally fractured formations. This model makes use of three individual models: a model of the stimulated reservoir, a model of the gas flow in this reservoir, and a model of the discounted expected net cash flow (net present value, or NPV) associated with the enhanced gas production. Nominal values of the input parameters, based on observed data and reasonable estimates, are used to calculate the initial expected increase in the average daily rate ofmore » production resulting from the Meigs County HEGF stimulation experiment. Agreement with the observed initial increase in rate is good. On the basis of this calculation, production from the Meigs County Well is not expected to be profitable, but the HEGF/NPV model probably provides conservative results. Furthermore, analyses of the sensitivity of the expected NPV to variations in the values of certain reservoir parameters suggest that the use of HEGF stimulation in somewhat more favorable formations is potentially profitable. 6 references, 4 figures, 3 tables.« less

Application of a rat hindlimb model: a prediction of force spaces reachable through stimulation of nerve fascicles.

PubMed

Johnson, Will L; Jindrich, Devin L; Zhong, Hui; Roy, Roland R; Edgerton, V Reggie

2011-12-01

A device to generate standing or locomotion through chronically placed electrodes has not been fully developed due in part to limitations of clinical experimentation and the high number of muscle activation inputs of the leg. We investigated the feasibility of functional electrical stimulation paradigms that minimize the input dimensions for controlling the limbs by stimulating at nerve fascicles, utilizing a model of the rat hindlimb, which combined previously collected morphological data with muscle physiological parameters presented herein. As validation of the model, we investigated the suitability of a lumped-parameter model for the prediction of muscle activation during dynamic tasks. Using the validated model, we found that the space of forces producible through activation of muscle groups sharing common nerve fascicles was nonlinearly dependent on the number of discrete muscle groups that could be individually activated (equivalently, the neuroanatomical level of activation). Seven commonly innervated muscle groups were sufficient to produce 78% of the force space producible through individual activation of the 42 modeled hindlimb muscles. This novel, neuroanatomically derived reduction in input dimension emphasizes the potential to simplify controllers for functional electrical stimulation to improve functional recovery after a neuromuscular injury.

Application of a Rat Hindlimb Model: A Prediction of Force Spaces Reachable Through Stimulation of Nerve Fascicles

PubMed Central

Johnson, Will L.; Jindrich, Devin L.; Zhong, Hui; Roy, Roland R.

2011-01-01

A device to generate standing or locomotion through chronically placed electrodes has not been fully developed due in part to limitations of clinical experimentation and the high number of muscle activation inputs of the leg. We investigated the feasibility of functional electrical stimulation paradigms that minimize the input dimensions for controlling the limbs by stimulating at nerve fascicles, utilizing a model of the rat hindlimb which combined previously collected morphological data with muscle physiological parameters presented herein. As validation of the model we investigated the suitability of a lumped-parameter model for prediction of muscle activation during dynamic tasks. Using the validated model we found that the space of forces producible through activation of muscle groups sharing common nerve fascicles was nonlinearly dependent on the number of discrete muscle groups that could be individually activated (equivalently, the neuroanatomical level of activation). Seven commonly innervated muscle groups were sufficient to produce 78% of the force space producible through individual activation of the 42 modeled hindlimb muscles. This novel, neuroanatomically derived reduction in input dimension emphasizes the potential to simplify controllers for functional electrical stimulation to improve functional recovery after a neuromuscular injury. PMID:21244999

Nisin production of Lactococcus lactis N8 with hemin-stimulated cell respiration in fed-batch fermentation system.

PubMed

Kördikanlıoğlu, Burcu; Şimşek, Ömer; Saris, Per E J

2015-01-01

In this study, nisin production of Lactococcus lactis N8 was optimized by independent variables of glucose, hemin and oxygen concentrations in fed-batch fermentation in which respiration of cells was stimulated with hemin. Response surface model was able to explain the changes of the nisin production of L. lactis N8 in fed-batch fermentation system with high fidelity (R(2) 98%) and insignificant lack of fit. Accordingly, the equation developed indicated the optimum parameters for glucose, hemin, and dissolved oxygen were 8 g L(-1) h(-1) , 3 μg mL(-1) and 40%, respectively. While 1711 IU mL(-1) nisin was produced by L. lactis N8 in control fed-batch fermentation, 5410 IU mL(-1) nisin production was achieved within the relevant optimum parameters where the respiration of cell was stimulated with hemin. Accordingly, nisin production was enhanced 3.1 fold in fed-batch fermentation using hemin. In conclusion the nisin production of L. lactis N8 was enhanced extensively as a result of increasing the biomass by stimulating the cell respiration with adding the hemin in the fed-batch fermentation. © 2015 American Institute of Chemical Engineers.

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

PubMed Central

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

2013-01-01

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

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

PubMed Central

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

2005-01-01

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

Non-Scanning Fiber-Optic Near-Infrared Beam Led to Two-Photon Optogenetic Stimulation In-Vivo

PubMed Central

Shivalingaiah, Shivaranjani; Dennis, Torry S.; Morris-Bobzean, Samara A.; Li, Ting; Perrotti, Linda I.; Mohanty, Samarendra K.

2014-01-01

Stimulation of specific neurons expressing opsins in a targeted region to manipulate brain function has proved to be a powerful tool in neuroscience. However, the use of visible light for optogenetic stimulation is invasive due to low penetration depth and tissue damage owing to larger absorption and scattering. Here, we report, for the first time, in-depth non-scanning fiber-optic two-photon optogenetic stimulation (FO-TPOS) of neurons in-vivo in transgenic mouse models. In order to optimize the deep-brain stimulation strategy, we characterized two-photon activation efficacy at different near-infrared laser parameters. The significantly-enhanced in-depth stimulation efficiency of FO-TPOS as compared to conventional single-photon beam was demonstrated both by experiments and Monte Carlo simulation. The non-scanning FO-TPOS technology will lead to better understanding of the in-vivo neural circuitry because this technology permits more precise and less invasive anatomical delivery of stimulation. PMID:25383687

Correspondence between visual and electrical input filters of ON and OFF mouse retinal ganglion cells

NASA Astrophysics Data System (ADS)

Sekhar, S.; Jalligampala, A.; Zrenner, E.; Rathbun, D. L.

2017-08-01

Objective. Over the past two decades retinal prostheses have made major strides in restoring functional vision to patients blinded by diseases such as retinitis pigmentosa. Presently, implants use single pulses to activate the retina. Though this stimulation paradigm has proved beneficial to patients, an unresolved problem is the inability to selectively stimulate the on and off visual pathways. To this end our goal was to test, using white noise, voltage-controlled, cathodic, monophasic pulse stimulation, whether different retinal ganglion cell (RGC) types in the wild type retina have different electrical input filters. This is an important precursor to addressing pathway-selective stimulation. Approach. Using full-field visual flash and electrical and visual Gaussian noise stimulation, combined with the technique of spike-triggered averaging (STA), we calculate the electrical and visual input filters for different types of RGCs (classified as on, off or on-off based on their response to the flash stimuli). Main results. Examining the STAs, we found that the spiking activity of on cells during electrical stimulation correlates with a decrease in the voltage magnitude preceding a spike, while the spiking activity of off cells correlates with an increase in the voltage preceding a spike. No electrical preference was found for on-off cells. Comparing STAs of wild type and rd10 mice revealed narrower electrical STA deflections with shorter latencies in rd10. Significance. This study is the first comparison of visual cell types and their corresponding temporal electrical input filters in the retina. The altered input filters in degenerated rd10 retinas are consistent with photoreceptor stimulation underlying visual type-specific electrical STA shapes in wild type retina. It is therefore conceivable that existing implants could target partially degenerated photoreceptors that have only lost their outer segments, but not somas, to selectively activate the on and off visual pathways.

Whole blood flow cytometric analysis of Ureaplasma-stimulated monocytes from pregnant women.

PubMed

Friedland, Yael D; Lee-Pullen, Tracey F; Nathan, Elizabeth; Watts, Rory; Keelan, Jeffrey A; Payne, Matthew S; Ireland, Demelza J

2015-06-01

We hypothesised that circulating monocytes of women with vaginal colonisation with Ureaplasma spp., genital microorganisms known to cause inflammation-driven preterm birth, would elicit a tolerised cytokine response to subsequent in vitro Ureaplasma parvum serovar 3 (UpSV3) stimulation. Using multi-parameter flow cytometry, we found no differences with regard to maternal colonisation status in the frequency of TNF-α-, IL-6-, IL-8- and IL-1β-expressing monocytes in response to subsequent UpSV3 stimulation (P > 0.10 for all cytokines). We conclude that vaginal Ureaplasma spp. colonisation does not specifically tolerise monocytes of pregnant women towards decreased responses to subsequent stimulation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pore pressure migration during hydraulic stimulation due to permeability enhancement by low-pressure subcritical fracture slip

NASA Astrophysics Data System (ADS)

Mukuhira, Yusuke; Moriya, Hirokazu; Ito, Takatoshi; Asanuma, Hiroshi; Häring, Markus

2017-04-01

Understanding the details of pressure migration during hydraulic stimulation is important for the design of an energy extraction system and reservoir management, as well as for the mitigation of hazardous-induced seismicity. Based on microseismic and regional stress information, we estimated the pore pressure increase required to generate shear slip on an existing fracture during stimulation. Spatiotemporal analysis of pore pressure migration revealed that lower pore pressure migrates farther and faster and that higher pore pressure migrates more slowly. These phenomena can be explained by the relationship between fracture permeability and stress state criticality. Subcritical fractures experience shear slip following smaller increases of pore pressure and promote migration of pore pressure because of their enhanced permeability. The difference in migration rates between lower and higher pore pressures suggests that the optimum wellhead pressure is the one that can stimulate relatively permeable fractures, selectively. Its selection optimizes economic benefits and minimizes seismic risk.

Development of wireless, chipless neural stimulator by using one-port surface acoustic wave delay line and diode-capacitor interface

NASA Astrophysics Data System (ADS)

Kim, Jisung; Kim, Saehan; Lee, Keekeun

2017-06-01

For the first time, a wireless and chipless neuron stimulator was developed by utilizing a surface acoustic wave (SAW) delay line, a diode-capacitor interface, a sharp metal tip, and antennas for the stimulation of neurons in the brain. The SAW delay line supersedes presently existing complex wireless transmission systems composed of a few thousands of transistors, enabling the fabrication of wireless and chipless transceiver systems. The diode-capacitor interface was used to convert AC signals to DC signals and induce stimulus pulses at a sharp metal probe. A 400 MHz RF energy was wirelessly radiated from antennas and then stimulation pulses were observed at a sharp gold probe. A ˜5 m reading distance was obtained using a 1 mW power from a network analyzer. The cycles of electromagnetic (EM) radiation from an antenna were controlled by shielding the antenna with an EM absorber. Stimulation pulses with different amplitudes and durations were successfully observed at the probe. The obtained pulses were ˜0.08 mV in amplitude and 3-10 Hz in frequency. Coupling-of-mode (COM) and SPICE modeling simulations were also used to determine the optimal structural parameters for SAW delay line and the values of passive elements. On the basis of the extracted parameters, the entire system was experimentally implemented and characterized.

Effects of intermittent theta burst stimulation on spasticity after stroke.

PubMed

Kim, Dae Hyun; Shin, Ji Cheol; Jung, Seungsoo; Jung, Tae-Min; Kim, Deog Young

2015-07-08

Spasticity is a common cause of long-term disability in poststroke hemiplegic patients. We investigated whether intermittent theta burst stimulation (iTBS) could reduce upper-limb spasticity after a stroke. Fifteen hemiplegic stroke patients were recruited for a double-blind sham-controlled cross-over design study. A single session of iTBS or sham stimulation was delivered on the motor hotspot of the affected flexor carpi radialis muscle in a random and counterbalanced order with a 1-week interval. Modified Ashworth scale (MAS), modified Tardieu scale (MTS), H-wave/M-wave amplitude ratio, peak torque (PT), peak torque angle (PTA), work of affected wrist flexor, and rectified integrated electromyographic activity of the flexor carpi radialis muscle were measured before, immediately after, 30 min after, and 1 week after iTBS or sham stimulation. Repeated-measures analysis of variance showed a significant interaction between time and intervention for the MAS, MTS, PT, PTA, and rectified integrated electromyographic activity (P<0.05), indicating that these parameters were significantly improved by iTBS compared with sham stimulation. However, the H-wave/M-wave amplitude ratio and work were not affected. MAS and MTS significantly improved for at least 30 min after iTBS, but the other parameters only improved immediately after iTBS (P<0.05). In conclusion, iTBS on the affected hemisphere may help to reduce poststroke spasticity transiently.

Spectral characteristics of light sources for S-cone stimulation.

PubMed

Schlegelmilch, F; Nolte, R; Schellhorn, K; Husar, P; Henning, G; Tornow, R P

2002-11-01

Electrophysiological investigations of the short-wavelength sensitive pathway of the human eye require the use of a suitable light source as a S-cone stimulator. Different light sources with their spectral distribution properties were investigated and compared with the ideal S-cone stimulator. First, the theoretical background of the calculation of relative cone energy absorption from the spectral distribution function of the light source is summarized. From the results of the calculation, the photometric properties of the ideal S-cone stimulator will be derived. The calculation procedure was applied to virtual light sources (computer generated spectral distribution functions with different medium wavelengths and spectrum widths) and to real light sources (blue and green light emitting diodes, blue phosphor of CRT-monitor, multimedia projector, LCD monitor and notebook display). The calculated relative cone absorbencies are compared to the conditions of an ideal S-cone stimulator. Monochromatic light sources with wavelengths of less than 456 nm are close to the conditions of an ideal S-cone stimulator. Spectrum widths up to 21 nm do not affect the S-cone activation significantly (S-cone activation change < 0.2%). Blue light emitting diodes with peak wavelength at 448 nm and spectrum bandwidth of 25 nm are very useful for S-cone stimulation (S-cone activation approximately 95%). A suitable display for S-cone stimulation is the Trinitron computer monitor (S-cone activation approximately 87%). The multimedia projector has a S-cone activation up to 91%, but their spectral distribution properties depends on the selected intensity. LCD monitor and notebook displays have a lower S-cone activation (< or = 74%). Carefully selecting the blue light source for S-cone stimulation can reduce the unwanted L-and M-cone activation down to 4% for M-cones and 1.5% for L-cones.

Optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens reveals local modulation of presynaptic release

PubMed Central

Melchior, James R.; Ferris, Mark J.; Stuber, Garret D.; Riddle, David R.; Jones, Sara R.

2015-01-01

The nucleus accumbens is highly heterogeneous, integrating regionally distinct afferent projections and accumbal interneurons, resulting in diverse local microenvironments. Dopamine (DA) neuron terminals similarly express a heterogeneous collection of terminal receptors that modulate DA signaling. Cyclic voltammetry is often used to probe DA terminal dynamics in brain slice preparations; however, this method traditionally requires electrical stimulation to induce DA release. Electrical stimulation excites all of the neuronal processes in the stimulation field, potentially introducing simultaneous, multi-synaptic modulation of DA terminal release. We used optogenetics to selectively stimulate DA terminals and used voltammetry to compare DA responses from electrical and optical stimulation of the same area of tissue around a recording electrode. We found that with multiple pulse stimulation trains, optically stimulated DA release increasingly exceeded that of electrical stimulation. Furthermore, electrical stimulation produced inhibition of DA release across longer duration stimulations. The GABAB antagonist, CGP 55845, increased electrically stimulated DA release significantly more than light stimulated release. The nicotinic acetylcholine receptor antagonist, dihydro-β-erythroidine hydrobromide, inhibited single pulse electrically stimulated DA release while having no effect on optically stimulated DA release. Our results demonstrate that electrical stimulation introduces local multi-synaptic modulation of DA release that is absent with optogenetically targeted stimulation. PMID:26011081

Absolute Quantification of Selected Proteins in the Human Osteoarthritic Secretome

PubMed Central

Peffers, Mandy J.; Beynon, Robert J.; Clegg, Peter D.

2013-01-01

Osteoarthritis (OA) is characterized by a loss of extracellular matrix which is driven by catabolic cytokines. Proteomic analysis of the OA cartilage secretome enables the global study of secreted proteins. These are an important class of molecules with roles in numerous pathological mechanisms. Although cartilage studies have identified profiles of secreted proteins, quantitative proteomics techniques have been implemented that would enable further biological questions to be addressed. To overcome this limitation, we used the secretome from human OA cartilage explants stimulated with IL-1β and compared proteins released into the media using a label-free LC-MS/MS-based strategy. We employed QconCAT technology to quantify specific proteins using selected reaction monitoring. A total of 252 proteins were identified, nine were differentially expressed by IL-1 β stimulation. Selected protein candidates were quantified in absolute amounts using QconCAT. These findings confirmed a significant reduction in TIMP-1 in the secretome following IL-1β stimulation. Label-free and QconCAT analysis produced equivocal results indicating no effect of cytokine stimulation on aggrecan, cartilage oligomeric matrix protein, fibromodulin, matrix metalloproteinases 1 and 3 or plasminogen release. This study enabled comparative protein profiling and absolute quantification of proteins involved in molecular pathways pertinent to understanding the pathogenesis of OA. PMID:24132152

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

PubMed

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

2017-09-01

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

In Vivo Magnetic Stimulation of Rat Sciatic Nerve With Centimeter- and Millimeter-Scale Solenoid Coils.

PubMed

Kagan, Zachary B; RamRakhyani, Anil Kumar; Lazzi, Gianluca; Normann, Richard A; Warren, David J

2016-11-01

Previous reports of magnetic stimulation of the peripheral nervous system (PNS) used various coil geometries, all with outer diameters larger than 35 mm, and stimulation energies in the 50 J range to evoke neural excitation. Recent reports of central nervous system (CNS) activation used sub-mm-scale solenoid coils with mJ energy levels. The goal of this study was to translate the lower energy levels from the CNS to the PNS via using smaller coils placed in closer proximity to the neural tissue. Such a performance improvement would advance the state of the art of magnetic stimulation and provide a path towards new neuroprosthetic devices. Primarily, we investigated the range of coil outer diameters from 25 mm down to 5 mm to better understand the dependence of coil diameter on energy required for PNS activation. Nine cm- and mm-scale copper solenoid coils, with various resistances, inductances, inner and outer diameters, and heights were compared by quantizing neuromuscular responses to magnetic stimulation via capacitive discharge excitation of rat sciatic nerves in vivo. Additionally, the effects of stimulus duration and coil position were investigated. As opposed to prior work, this study compares a subset of stimulation parameters in an intact nerve preparation, and shows that magnetic stimulation with coils that abut the nerve is a reliable, effective method of neuromuscular stimulation. Although we observed different energies required for neuromuscular activation depending on the coil and excitation parameters used, for the experimental configuration, devices, and stimulus waveform shapes presented in this manuscript, no systematic dependence of PNS activation on coil diameter was found, even for the mm-scale coils investigated herein. However, there was a clear relationship between discharge circuit capacitance and energy required to evoke a neuromuscular response. Coils approximately 12 mm in outer diameter and larger consistently evoked responses, whereas coils 5 mm in outer diameter did not. Furthermore, we observed meaningful neuromuscular excitation when stimulating with energies as low as 20 J. Although this is an improvement over prior work, it is still orders of magnitude greater than the energy required for conventional electrical stimulation, suggesting that these devices are presently not suitable for use in an application requiring continued pulsed stimulation. Nevertheless, these devices are suitable for basic research and as clinical tools that infrequently stimulate, such as in diagnostic applications.

Psychophysical correspondence between vibrotactile intensity and intracortical microstimulation for tactile neuroprostheses in rats

NASA Astrophysics Data System (ADS)

Devecioğlu, İsmail; Güçlü, Burak

2017-02-01

Objective. Recent studies showed that intracortical microstimulation (ICMS) generates artificial sensations which can be utilized as somatosensory feedback in cortical neuroprostheses. To mimic the natural psychophysical response, ICMS parameters are modulated according to psychometric equivalence functions (PEFs). PEFs match the intensity levels of ICMS and mechanical stimuli, which elicit equal detection probabilities, but they typically do not include the frequency as a control variable. We aimed to establish frequency-dependent PEFs for vibrotactile stimulation of the glabrous skin and ICMS in the primary somatosensory cortex of awake freely behaving rats. Approach. We collected psychometric data for vibrotactile and ICMS detection at three stimulation frequencies (40, 60 and 80 Hz). The psychometric data were fitted with a model equation of two independent variables (stimulus intensity and frequency) and four subject-dependent parameters. For each rat, we constructed a separate PEF which was used to estimate the ICMS current amplitude for a given displacement amplitude and frequency. The ICMS frequency was set equal to the vibrotactile frequency. We validated the PEFs in a modified task which included randomly selected probe trials presented either with a vibrotactile or an ICMS stimulus, and also at frequencies and intensity levels not tested before. Main results. The PEFs were generally successful in estimating the ICMS current intensities (no significant differences between vibrotactile and ICMS trials in Kolmogorov-Smirnov tests). Specifically, hit rates from both trial conditions were significantly correlated in 86% of the cases, and 52% of all data had perfect match in linear regression. Significance. The psychometric correspondence model presented in this study was constructed based on surface functions which define psychophysical detection probability as a function of stimulus intensity and frequency. Therefore, it may be used for the real-time modulation of the frequency and intensity of ICMS pulses in somatosensory neuroprostheses.

Psychophysical correspondence between vibrotactile intensity and intracortical microstimulation for tactile neuroprostheses in rats.

PubMed

Devecioğlu, İsmail; Güçlü, Burak

2017-02-01

Recent studies showed that intracortical microstimulation (ICMS) generates artificial sensations which can be utilized as somatosensory feedback in cortical neuroprostheses. To mimic the natural psychophysical response, ICMS parameters are modulated according to psychometric equivalence functions (PEFs). PEFs match the intensity levels of ICMS and mechanical stimuli, which elicit equal detection probabilities, but they typically do not include the frequency as a control variable. We aimed to establish frequency-dependent PEFs for vibrotactile stimulation of the glabrous skin and ICMS in the primary somatosensory cortex of awake freely behaving rats. We collected psychometric data for vibrotactile and ICMS detection at three stimulation frequencies (40, 60 and 80 Hz). The psychometric data were fitted with a model equation of two independent variables (stimulus intensity and frequency) and four subject-dependent parameters. For each rat, we constructed a separate PEF which was used to estimate the ICMS current amplitude for a given displacement amplitude and frequency. The ICMS frequency was set equal to the vibrotactile frequency. We validated the PEFs in a modified task which included randomly selected probe trials presented either with a vibrotactile or an ICMS stimulus, and also at frequencies and intensity levels not tested before. The PEFs were generally successful in estimating the ICMS current intensities (no significant differences between vibrotactile and ICMS trials in Kolmogorov-Smirnov tests). Specifically, hit rates from both trial conditions were significantly correlated in 86% of the cases, and 52% of all data had perfect match in linear regression. The psychometric correspondence model presented in this study was constructed based on surface functions which define psychophysical detection probability as a function of stimulus intensity and frequency. Therefore, it may be used for the real-time modulation of the frequency and intensity of ICMS pulses in somatosensory neuroprostheses.

Exploratory Movement Generates Higher-Order Information That Is Sufficient for Accurate Perception of Scaled Egocentric Distance

PubMed Central

Mantel, Bruno; Stoffregen, Thomas A.; Campbell, Alain; Bardy, Benoît G.

2015-01-01

Body movement influences the structure of multiple forms of ambient energy, including optics and gravito-inertial force. Some researchers have argued that egocentric distance is derived from inferential integration of visual and non-visual stimulation. We suggest that accurate information about egocentric distance exists in perceptual stimulation as higher-order patterns that extend across optics and inertia. We formalize a pattern that specifies the egocentric distance of a stationary object across higher-order relations between optics and inertia. This higher-order parameter is created by self-generated movement of the perceiver in inertial space relative to the illuminated environment. For this reason, we placed minimal restrictions on the exploratory movements of our participants. We asked whether humans can detect and use the information available in this higher-order pattern. Participants judged whether a virtual object was within reach. We manipulated relations between body movement and the ambient structure of optics and inertia. Judgments were precise and accurate when the higher-order optical-inertial parameter was available. When only optic flow was available, judgments were poor. Our results reveal that participants perceived egocentric distance from the higher-order, optical-inertial consequences of their own exploratory activity. Analysis of participants’ movement trajectories revealed that self-selected movements were complex, and tended to optimize availability of the optical-inertial pattern that specifies egocentric distance. We argue that accurate information about egocentric distance exists in higher-order patterns of ambient energy, that self-generated movement can generate these higher-order patterns, and that these patterns can be detected and used to support perception of egocentric distance that is precise and accurate. PMID:25856410

Upper-limb muscle responses to epidural, subdural and intraspinal stimulation of the cervical spinal cord

NASA Astrophysics Data System (ADS)

Sharpe, Abigail N.; Jackson, Andrew

2014-02-01

Objective. Electrical stimulation of the spinal cord has potential applications following spinal cord injury for reanimating paralysed limbs and promoting neuroplastic changes that may facilitate motor rehabilitation. Here we systematically compare the efficacy, selectivity and frequency-dependence of different stimulation methods in the cervical enlargement of anaesthetized monkeys. Approach. Stimulating electrodes were positioned at multiple epidural and subdural sites on both dorsal and ventral surfaces, as well as at different depths within the spinal cord. Motor responses were recorded from arm, forearm and hand muscles. Main results. Stimulation efficacy increased from dorsal to ventral stimulation sites, with the exception of ventral epidural electrodes which had the highest recruitment thresholds. Compared to epidural and intraspinal methods, responses to subdural stimulation were more selective but also more similar between adjacent sites. Trains of stimuli delivered to ventral sites elicited consistent responses at all frequencies whereas from dorsal sites we observed a mixture of short-latency facilitation and long-latency suppression. Finally, paired stimuli delivered to dorsal surface and intraspinal sites exhibited symmetric facilitatory interactions at interstimulus intervals between 2-5 ms whereas on the ventral side interactions tended to be suppressive for near-simultaneous stimuli. Significance. We interpret these results in the context of differential activation of afferent and efferent roots and intraspinal circuit elements. In particular, we propose that distinct direct and indirect actions of spinal cord stimulation on motoneurons may be advantageous for different applications, and this should be taken into consideration when designing neuroprostheses for upper-limb function.

Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants.

PubMed

Garcia-Knight, Miguel A; Nduati, Eunice; Hassan, Amin S; Gambo, Faith; Odera, Dennis; Etyang, Timothy J; Hajj, Nassim J; Berkley, James Alexander; Urban, Britta C; Rowland-Jones, Sarah L

2015-01-01

Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-α responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy and T-cell immunity in this vulnerable population is warranted.

Research on the Conductivity-Based Detection Principles of Bubbles in Two-Phase Flows and the Design of a Bubble Sensor for CBM Wells.

PubMed

Wu, Chuan; Wen, Guojun; Han, Lei; Wu, Xiaoming

2016-09-17

The parameters of gas-liquid two-phase flow bubbles in field coalbed methane (CBM) wells are of great significance for analyzing coalbed methane output, judging faults in CBM wells, and developing gas drainage and extraction processes, which stimulates an urgent need for detecting bubble parameters for CBM wells in the field. However, existing bubble detectors cannot meet the requirements of the working environments of CBM wells. Therefore, this paper reports findings on the principles of measuring the flow pattern, velocity, and volume of two-phase flow bubbles based on conductivity, from which a new bubble sensor was designed. The structural parameters and other parameters of the sensor were then computed, the "water film phenomenon" produced by the sensor was analyzed, and the appropriate materials for making the sensor were tested and selected. After the sensor was successfully devised, laboratory tests and field tests were performed, and the test results indicated that the sensor was highly reliable and could detect the flow patterns of two-phase flows, as well as the quantities, velocities, and volumes of bubbles. With a velocity measurement error of ±5% and a volume measurement error of ±7%, the sensor can meet the requirements of field use. Finally, the characteristics and deficiencies of the bubble sensor are summarized based on an analysis of the measurement errors and a comparison of existing bubble-measuring devices and the designed sensor.

Research on the Conductivity-Based Detection Principles of Bubbles in Two-Phase Flows and the Design of a Bubble Sensor for CBM Wells

PubMed Central

Wu, Chuan; Wen, Guojun; Han, Lei; Wu, Xiaoming

2016-01-01

The parameters of gas-liquid two-phase flow bubbles in field coalbed methane (CBM) wells are of great significance for analyzing coalbed methane output, judging faults in CBM wells, and developing gas drainage and extraction processes, which stimulates an urgent need for detecting bubble parameters for CBM wells in the field. However, existing bubble detectors cannot meet the requirements of the working environments of CBM wells. Therefore, this paper reports findings on the principles of measuring the flow pattern, velocity, and volume of two-phase flow bubbles based on conductivity, from which a new bubble sensor was designed. The structural parameters and other parameters of the sensor were then computed, the “water film phenomenon” produced by the sensor was analyzed, and the appropriate materials for making the sensor were tested and selected. After the sensor was successfully devised, laboratory tests and field tests were performed, and the test results indicated that the sensor was highly reliable and could detect the flow patterns of two-phase flows, as well as the quantities, velocities, and volumes of bubbles. With a velocity measurement error of ±5% and a volume measurement error of ±7%, the sensor can meet the requirements of field use. Finally, the characteristics and deficiencies of the bubble sensor are summarized based on an analysis of the measurement errors and a comparison of existing bubble-measuring devices and the designed sensor. PMID:27649206

Soft Encapsulation of Flexible Electrical Stimulation Implant: Challenges and Innovations

PubMed Central

Debelle, Adrien; Hermans, Laura; Bosquet, Maxime; Dehaeck, Sam; Lonys, Laurent; Scheid, Benoit; Nonclercq, Antoine; Vanhoestenberghe, Anne

2016-01-01

In this document we discuss the main challenges encountered when producing flexible electrical stimulation implants, and present our approach to solving them for prototype production. We include a study of the optimization of the flexible PCB design, the selection of additive manufacturing materials for the mold, and the chemical compatibility of the different materials. Our approach was tested on a flexible gastro-stimulator as part of the ENDOGES research program. PMID:28078073

Long-term evaluation of impedance levels and clinical development in subthalamic deep brain stimulation for Parkinson's disease.

PubMed

Hartmann, C J; Wojtecki, L; Vesper, J; Volkmann, J; Groiss, S J; Schnitzler, A; Südmeyer, M

2015-10-01

This study was conducted to better understand the development of clinical efficacy and impedance levels in the long-term course of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD). In this retrospective study of twenty PD patients, the motor part of the Unified Parkinson's Disease Rating Scale was periodically assessed i) after withdrawal of medication and inactivated stimulation, ii) after withdrawal of medication with activated stimulation and iii) after challenge with l-Dopa during activated stimulation up to 13 years after surgery. STN-DBS with or without medication significantly improved motor function up to 13 years after surgery. The contribution of axial symptoms increased over time. While the stimulation parameters were kept constant, the therapeutic impedances progressively declined. STN-DBS in PD remains effective in the long-term course of the disease. Constant current stimulation might be preferable over voltage-controlled stimulation, as it would alleviate the impact of impedance changes on the volume of tissue activated. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

Malezic, M; Hesse, S

1995-03-01

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

Conditioning stimulation techniques for enhancement of transcranially elicited evoked motor responses.

PubMed

Journée, H-L; Polak, H E; De Kleuver, M

2007-12-01

In spite of the use of multipulse, transcranial electrical stimulation (TES) is still insufficient in a subgroup of patients to elicit motor-evoked potentials during intraoperative neurophysiological monitoring (IONM). Classic facilitation methods used in awake patients are precluded under general anaesthesia. Conditioning techniques can be used in this situation. To present clinical experimental data and models of motor-neuron (MN) excitability for homonymous and heteronymous conditioning and discuss their applications in IONM. Data were obtained in a prospective study on multipulse TES-conditioning of the monosynaptic H-reflex and double multipulse TES. The principle of facilitation by conditioning stimulation is to apply a test stimulus when motor neurons (MNs) have been made maximally excitable by a conditioning stimulus. Both conditioning and test stimuli recruit separate populations of MNs. The overlapping fraction of MNs controls the efficacy of facilitation. Heteronymous conditioning stimulation, which is performed at a different site from the test stimulus, is illustrated by the TES-conditioned H-reflex (HR). Autonomous conditioning stimulation, which is performed at the same stimulation site, is illustrated by double-train TES (dt-TES). The facilitating curves obtained by conditioning stimulation are often 3-modal and show peaks of facilitation at short intertrain intervals (S-ITIs) of 10ms and between 15 and 20ms and at longer intertrain intervals (L-ITI) of over 100ms. The facilitation curves from HR and dt-TES are not always identical since different alphaMN pools are involved. Dt-TES is often successful in neurologically impaired patients whereas facilitation of the HR can be used when conditioned by TES at subthreshold levels allowing continuous IONM without movement in the surgical field. Alternatively, facilitation by conditioning from peripheral-nerve stimulation can be used for selective transmission of subthreshold TES motor responses to peripheral muscles, permitting motor-monitoring by a so-called selective motor-gating technique. Facilitation techniques offer many possibilities in IONM by enhancing low-amplitude TES-MEP responses. They can also selectively enhance responses in a few muscle groups for the reduction of movement.

Laser cooling of molecules by zero-velocity selection and single spontaneous emission

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

Ooi, C. H. Raymond

2010-11-15

A laser-cooling scheme for molecules is presented based on repeated cycle of zero-velocity selection, deceleration, and irreversible accumulation. Although this scheme also employs a single spontaneous emission as in [Raymond Ooi, Marzlin, and Audretsch, Eur. Phys. J. D 22, 259 (2003)], in order to circumvent the difficulty of maintaining closed pumping cycles in molecules, there are two distinct features which make the cooling process of this scheme faster and more practical. First, the zero-velocity selection creates a narrow velocity-width population with zero mean velocity, such that no further deceleration (with many stimulated Raman adiabatic passage (STIRAP) pulses) is required. Second,more » only two STIRAP processes are required to decelerate the remaining hot molecular ensemble to create a finite population around zero velocity for the next cycle. We present a setup to realize the cooling process in one dimension with trapping in the other two dimensions using a Stark barrel. Numerical estimates of the cooling parameters and simulations with density matrix equations using OH molecules show the applicability of the cooling scheme. For a gas at temperature T=1 K, the estimated cooling time is only 2 ms, with phase-space density increased by about 30 times. The possibility of extension to three-dimensional cooling via thermalization is also discussed.« less

Quantitative methods for evaluating the efficacy of thalamic deep brain stimulation in patients with essential tremor.

PubMed

Wastensson, Gunilla; Holmberg, Björn; Johnels, Bo; Barregard, Lars

2013-01-01

Deep brain stimulation (DBS) of the thalamus is a safe and efficient method for treatment of disabling tremor in patient with essential tremor (ET). However, successful tremor suppression after surgery requires careful selection of stimulus parameters. Our aim was to examine the possible use of certain quantitative methods for evaluating the efficacy of thalamic DBS in ET patients in clinical practice, and to compare these methods with traditional clinical tests. We examined 22 patients using the Essential Tremor Rating Scale (ETRS) and quantitative assessment of tremor with the stimulator both activated and deactivated. We used an accelerometer (CATSYS tremor Pen) for quantitative measurement of postural tremor, and a eurythmokinesimeter (EKM) to evaluate kinetic tremor in a rapid pointing task. The efficacy of DBS on tremor suppression was prominent irrespective of the method used. The agreement between clinical rating of postural tremor and tremor intensity as measured by the CATSYS tremor pen was relatively high (rs = 0.74). The agreement between kinetic tremor as assessed by the ETRS and the main outcome variable from the EKM test was low (rs = 0.34). The lack of agreement indicates that the EKM test is not comparable with the clinical test. Quantitative methods, such as the CATSYS tremor pen, could be a useful complement to clinical tremor assessment in evaluating the efficacy of DBS in clinical practice. Future studies should evaluate the precision of these methods and long-term impact on tremor suppression, activities of daily living (ADL) function and quality of life.

Deep brain stimulation for Parkinson's disease: recent trends and future direction.

PubMed

Fukaya, Chikashi; Yamamoto, Takamitsu

2015-01-01

To date, deep brain stimulation (DBS) has already been performed on more than 120,000 patients worldwide and in more than 7,000 patients in Japan. However, fundamental understanding of DBS effects on the pathological neural circuitry remains insufficient. Recent studies have specifically shown the importance of cortico-striato-thalamo-cortical (CSTC) loops, which were identified as functionally and anatomically discrete units. Three main circuits exist in the CSTC loops, namely, the motor, associative, and limbic circuits. From these theoretical backgrounds, it is determined that DBS sometimes influences not only motor functions but also the cognitive and affective functions of Parkinson's disease (PD) patients. The main targets of DBS for PD are subthalamic nucleus (STN) and globus pallidus interna (GPi). Ventralis intermedius (Vim)-DBS was found to be effective in improving tremor. However, Vim-DBS cannot sufficiently improve akinesia and rigidity. Therefore, Vim-DBS is seldom carried out for the treatment of PD. In this article, we review the present state of DBS, mainly STN-DBS and GPi-DBS, for PD. In the first part of the article, appropriate indications and practical effects established in previous studies are discussed. The findings of previous investigations on the complications caused by the surgical procedure and on the adverse events induced by DBS itself are reviewed. In the second part, we discuss target selection (GPi vs. STN) and the effect of DBS on nonmotor symptoms. In the final part, as issues that should be resolved, the suitable timing of surgery, symptoms unresponsive to DBS such as on-period axial symptoms, and the related postoperative programing of stimulation parameters, are discussed.

Computational Modeling and Neuroimaging Techniques for Targeting during Deep Brain Stimulation

PubMed Central

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

2016-01-01

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

Electrical stimulation modulates injury potentials in rats after spinal cord injury

PubMed Central

Zhang, Guanghao; Huo, Xiaolin; Wang, Aihua; Wu, Changzhe; Zhang, Cheng; Bai, Jinzhu

2013-01-01

An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as well as injury current, can be modulated by direct current field stimulation; however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV (as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around –70 mV, which is resting membrane potential (as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon illustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cell membrane and the reduction of cation influx. PMID:25206563

Visual training paired with electrical stimulation of the basal forebrain improves orientation-selective visual acuity in the rat.

PubMed

Kang, Jun Il; Groleau, Marianne; Dotigny, Florence; Giguère, Hugo; Vaucher, Elvire

2014-07-01

The cholinergic afferents from the basal forebrain to the primary visual cortex play a key role in visual attention and cortical plasticity. These afferent fibers modulate acute and long-term responses of visual neurons to specific stimuli. The present study evaluates whether this cholinergic modulation of visual neurons results in cortical activity and visual perception changes. Awake adult rats were exposed repeatedly for 2 weeks to an orientation-specific grating with or without coupling this visual stimulation to an electrical stimulation of the basal forebrain. The visual acuity, as measured using a visual water maze before and after the exposure to the orientation-specific grating, was increased in the group of trained rats with simultaneous basal forebrain/visual stimulation. The increase in visual acuity was not observed when visual training or basal forebrain stimulation was performed separately or when cholinergic fibers were selectively lesioned prior to the visual stimulation. The visual evoked potentials show a long-lasting increase in cortical reactivity of the primary visual cortex after coupled visual/cholinergic stimulation, as well as c-Fos immunoreactivity of both pyramidal and GABAergic interneuron. These findings demonstrate that when coupled with visual training, the cholinergic system improves visual performance for the trained orientation probably through enhancement of attentional processes and cortical plasticity in V1 related to the ratio of excitatory/inhibitory inputs. This study opens the possibility of establishing efficient rehabilitation strategies for facilitating visual capacity.

Antinociception induced by epidural motor cortex stimulation in naive conscious rats is mediated by the opioid system.

PubMed

Fonoff, Erich Talamoni; Dale, Camila Squarzoni; Pagano, Rosana Lima; Paccola, Carina Cicconi; Ballester, Gerson; Teixeira, Manoel Jacobsen; Giorgi, Renata

2009-01-03

Epidural motor cortex stimulation (MCS) has been used for treating patients with neuropathic pain resistant to other therapeutic approaches. Experimental evidence suggests that the motor cortex is also involved in the modulation of normal nociceptive response, but the underlying mechanisms of pain control have not been clarified yet. The aim of this study was to investigate the effects of epidural electrical MCS on the nociceptive threshold of naive rats. Electrodes were placed on epidural motor cortex, over the hind paw area, according to the functional mapping accomplished in this study. Nociceptive threshold and general activity were evaluated under 15-min electrical stimulating sessions. When rats were evaluated by the paw pressure test, MCS induced selective antinociception in the paw contralateral to the stimulated cortex, but no changes were noticed in the ipsilateral paw. When the nociceptive test was repeated 15 min after cessation of electrical stimulation, the nociceptive threshold returned to basal levels. On the other hand, no changes in the nociceptive threshold were observed in rats evaluated by the tail-flick test. Additionally, no behavioral or motor impairment were noticed in the course of stimulation session at the open-field test. Stimulation of posterior parietal or somatosensory cortices did not elicit any changes in the general activity or nociceptive response. Opioid receptors blockade by naloxone abolished the increase in nociceptive threshold induced by MCS. Data shown herein demonstrate that epidural electrical MCS elicits a substantial and selective antinociceptive effect, which is mediated by opioids.

Current Topics in Deep Brain Stimulation for Parkinson Disease

PubMed Central

UMEMURA, Atsushi; OYAMA, Genko; SHIMO, Yasushi; NAKAJIMA, Madoka; NAKAJIMA, Asuka; JO, Takayuki; SEKIMOTO, Satoko; ITO, Masanobu; MITSUHASHI, Takumi; HATTORI, Nobutaka; ARAI, Hajime

2016-01-01

There is a long history of surgical treatment for Parkinson disease (PD). After pioneering trials and errors, the current primary surgical treatment for PD is deep brain stimulation (DBS). DBS is a promising treatment option for patients with medically refractory PD. However, there are still many problems and controversies associated with DBS. In this review, we discuss current issues in DBS for PD, including patient selection, clinical outcomes, complications, target selection, long-term outcomes, management of axial symptoms, timing of surgery, surgical procedures, cost-effectiveness, and new technology. PMID:27349658

Electronic design of a multichannel programmable implant for neuromuscular electrical stimulation.

PubMed

Arabi, K; Sawan, M A

1999-06-01

An advanced stimulator for neuromuscular stimulation of spinal cord injured patients has been developed. The stimulator is externally controlled and powered by a single encoded radio frequency carrier and has four independently controlled bipolar stimulation channels. It offers a wide range of reprogrammability and flexibility, and can be used in many neuromuscular electrical stimulation applications. The implant system is adaptable to patient's needs and to future developments in stimulation algorithms by reprogramming the stimulator. The stimulator is capable of generating a wide range of stimulation waveforms and stimulation patterns and therefore is very suitable for selective nerve stimulation techniques. The reliability of the implant has been increased by using a forward error detection and correction communication protocol and by designing the chip for structural testability based on scan test approach. Implemented testability scheme makes it possible to verify the complete functionality of the implant before and after implantation. The stimulators architecture is designed to be modular and therefore its different blocks can be reused as standard building blocks in the design and implementation of other neuromuscular prostheses. Design for low-power techniques have also been employed to reduce power consumption of the electronic circuitry.

Interindividual differences in motor network connectivity and behavioral response to iTBS in stroke patients.

PubMed

Diekhoff-Krebs, Svenja; Pool, Eva-Maria; Sarfeld, Anna-Sophia; Rehme, Anne K; Eickhoff, Simon B; Fink, Gereon R; Grefkes, Christian

2017-01-01

Cerebral plasticity-inducing approaches like repetitive transcranial magnetic stimulation (rTMS) are of high interest in situations where reorganization of neural networks can be observed, e.g., after stroke. However, an increasing number of studies suggest that improvements in motor performance of the stroke-affected hand following modulation of primary motor cortex (M1) excitability by rTMS shows a high interindividual variability. We here tested the hypothesis that in stroke patients the interindividual variability of behavioral response to excitatory rTMS is related to interindividual differences in network connectivity of the stimulated region. Chronic stroke patients ( n  = 14) and healthy controls ( n  = 12) were scanned with functional magnetic resonance imaging (fMRI) while performing a simple hand motor task. Dynamic causal modeling (DCM) was used to investigate effective connectivity of key motor regions. On two different days after the fMRI experiment, patients received either intermittent theta-burst stimulation (iTBS) over ipsilesional M1 or control stimulation over the parieto-occipital cortex. Motor performance and TMS parameters of cortical excitability were measured before and after iTBS. Our results revealed that patients with better motor performance of the affected hand showed stronger endogenous coupling between supplemental motor area (SMA) and M1 before starting the iTBS intervention. Applying iTBS to ipsilesional M1 significantly increased ipsilesional M1 excitability and decreased contralesional M1 excitability as compared to control stimulation. Individual behavioral improvements following iTBS specifically correlated with neural coupling strengths in the stimulated hemisphere prior to stimulation, especially for connections targeting the stimulated M1. Combining endogenous connectivity and behavioral parameters explained 82% of the variance in hand motor performance observed after iTBS. In conclusion, the data suggest that the individual susceptibility to iTBS after stroke is influenced by interindividual differences in motor network connectivity of the lesioned hemisphere.

An automatic identification procedure to promote the use of FES-cycling training for hemiparetic patients.

PubMed

Ambrosini, Emilia; Ferrante, Simona; Schauer, Thomas; Ferrigno, Giancarlo; Molteni, Franco; Pedrocchi, Alessandra

2014-01-01

Cycling induced by Functional Electrical Stimulation (FES) training currently requires a manual setting of different parameters, which is a time-consuming and scarcely repeatable procedure. We proposed an automatic procedure for setting session-specific parameters optimized for hemiparetic patients. This procedure consisted of the identification of the stimulation strategy as the angular ranges during which FES drove the motion, the comparison between the identified strategy and the physiological muscular activation strategy, and the setting of the pulse amplitude and duration of each stimulated muscle. Preliminary trials on 10 healthy volunteers helped define the procedure. Feasibility tests on 8 hemiparetic patients (5 stroke, 3 traumatic brain injury) were performed. The procedure maximized the motor output within the tolerance constraint, identified a biomimetic strategy in 6 patients, and always lasted less than 5 minutes. Its reasonable duration and automatic nature make the procedure usable at the beginning of every training session, potentially enhancing the performance of FES-cycling training.

Left caloric vestibular stimulation as a tool to reveal implicit and explicit parameters of body representation.

PubMed

Sedda, A; Tonin, D; Salvato, G; Gandola, M; Bottini, G

2016-04-01

Homeostatic parameters, such as temperature, are related to body representation. In this study, we measured whether caloric vestibular stimulation (CVS) alters body temperature and tactile processing, and if in the direction predicted by a holistic body matrix representation. Skin temperature and tactile two-point discrimination (TPD) acuity were measured for both arms before, immediately after and with a delay from CVS. Participants were also administered a personality questionnaire and an anxiety inventory to rule out confounding factors. Two control experiments were planned to exclude casual variations. Our results show that temperature drops significantly in both arms after CVS. CVS also induces a bilateral improvement in tactile acuity (even though not immediately after but in the delayed condition). Finally, these effects are not due to learning, as demonstrated by the control experiment. In summary, our results suggest that vestibular stimulation updates body representation, supporting the evidence in favor of a body matrix. Copyright © 2016 Elsevier Inc. All rights reserved.

Electrical stimulation of anal sphincter or pudendal nerve improves anal sphincter pressure.

PubMed

Damaser, Margot S; Salcedo, Levilester; Wang, Guangjian; Zaszczurynski, Paul; Cruz, Michelle A; Butler, Robert S; Jiang, Hai-Hong; Zutshi, Massarat

2012-12-01

Stimulation of the pudendal nerve or the anal sphincter could provide therapeutic options for fecal incontinence with little involvement of other organs. The goal of this project was to assess the effects of pudendal nerve and anal sphincter stimulation on bladder and anal pressures. Ten virgin female Sprague Dawley rats were randomly allocated to control (n = 2), perianal stimulation (n = 4), and pudendal nerve stimulation (n = 4) groups. A monopolar electrode was hooked to the pudendal nerve or placed on the anal sphincter. Aballoon catheter was inserted into the anus to measure anal pressure, and a catheter was inserted into the bladder via the urethra to measure bladder pressure. Bladder and anal pressures were measured with different electrical stimulation parameters and different timing of electrical stimulation relative to spontaneous anal sphincter contractions. Increasing stimulation current had the most dramatic effect on both anal and bladder pressures. An immediate increase in anal pressure was observed when stimulating either the anal sphincter or the pudendal nerve at stimulation values of 1 mA or 2 mA. No increase in anal pressure was observed for lower current values. Bladder pressure increased at high current during anal sphincter stimulation, but not as much as during pudendal nerve stimulation. Increased bladder pressure during anal sphincter stimulation was due to contraction of the abdominal muscles. Electrical stimulation caused an increase in anal pressures with bladder involvement only at high current. These initial results suggest that electrical stimulation can increase anal sphincter pressure, enhancing continence control.

Laser biostimulation effects on invertebral disks: histological evidence on intra-observer samples. Retrospective double-blind study.

PubMed

Tramontana, Alfonso; Sorge, Roberto; Page, Juan Carlos Miangolarra

2016-12-30

Background and aims: The intervertebral disk degeneration is a pathological process determined by a decrease of mucopolysaccharides in the nucleus pulposus with the consequent dehydration and degeneration of the elastic fibers in the annulus fibrosus of the disk. The laser is a therapeutic tool that has, on the treated tissues, biostimulation effects with an increase of oxidative phosphorylation and production of ATP with an acceleration of the mucopolysaccharides synthesis with a consequent rehydration, biostimulation and production of new elastic fibers. The goal of this project is studying whether the laser stimulation may treat degenerated intervertebral disks. Materials and methods: 60 subjects with the same anthropometric parameters were selected and divided into two randomized groups. 30 subjects underwent laser stimulation, whereas 30 underwent placebo. All 60 subjects underwent a discectomy surgery and the intraoperative findings were examined in a lab, studying the positivity of the PAS reaction and the presence of potential newly formed elastic fibers. Results: It has been shown a higher number of mucopolysaccharides and young newly formed elastic fibers in the group that was treated with laser irradiation with a statistically significant difference, compared to the placebo group (p< 0.0001). Conclusions: Laser biostimulation can be an effective strategy in the therapy of the invertebral disks.

The Emerging Role for rTMS in Optimizing the Treatment of Adolescent Depression

PubMed Central

Croarkin, Paul E.; Wall, Christopher A.; McClintock, Shawn M.; Kozel, F. Andrew; Husain, Mustafa M.; Sampson, Shirlene M.

2010-01-01

Major depressive disorder (MDD) in adolescents is a common illness and significant public health problem. Treatment is challenging due to recurrences and limited modalities. Selective serotonin reuptake inhibitors (SSRIs) and Cognitive Behavioral Therapy (CBT) are considered the standard of care in severe or treatment resistant MDD in this age group. However, responses to these interventions are often suboptimal. A growing body of research supports the efficacy of repetitive transcranial magnetic stimulation for the treatment of MDD in adults. Induced seizures are a primary safety concern, although this is rare with appropriate precautions. There is, however, limited experience with rTMS as a therapeutic intervention for adolescent psychiatric disturbances. This review will summarize the rTMS efficacy and safety data in adults and describe all published experience with adolescent MDD. Applications in other adolescent psychiatric illnesses such as schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are reviewed. Safety and ethical issues are paramount with investigational treatments in adolescent psychiatric illnesses. However, further research with rTMS in adolescent MDD is imperative to establish standards for optimal stimulation site, treatment parameters, and its role in treatment algorithms. These may diverge from adult data. Early intervention with neuromodulation could also hold the promise of addressing the developmental course of dysfunctional neurocircuitry. PMID:20418774