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.

A study on stimulation of DC high voltage power of LCC series parallel resonant in projectile velocity measurement system

NASA Astrophysics Data System (ADS)

Lu, Dong-dong; Gu, Jin-liang; Luo, Hong-e.; Xia, Yan

2017-10-01

According to specific requirements of the X-ray machine system for measuring velocity of outfield projectile, a DC high voltage power supply system is designed for the high voltage or the smaller current. The system comprises: a series resonant circuit is selected as a full-bridge inverter circuit; a high-frequency zero-current soft switching of a high-voltage power supply is realized by PWM output by STM32; a nanocrystalline alloy transformer is chosen as a high-frequency booster transformer; and the related parameters of an LCC series-parallel resonant are determined according to the preset parameters of the transformer. The concrete method includes: a LCC series parallel resonant circuit and a voltage doubling circuit are stimulated by using MULTISM and MATLAB; selecting an optimal solution and an optimal parameter of all parts after stimulation analysis; and finally verifying the correctness of the parameter by stimulation of the whole system. Through stimulation analysis, the output voltage of the series-parallel resonant circuit gets to 10KV in 28s: then passing through the voltage doubling circuit, the output voltage gets to 120KV in one hour. According to the system, the wave range of the output voltage is so small as to provide the stable X-ray supply for the X-ray machine for measuring velocity of outfield projectile. It is fast in charging and high in efficiency.

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.

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.

Moving-window dynamic optimization: design of stimulation profiles for walking.

PubMed

Dosen, Strahinja; Popović, Dejan B

2009-05-01

The overall goal of the research is to improve control for electrical stimulation-based assistance of walking in hemiplegic individuals. We present the simulation for generating offline input (sensors)-output (intensity of muscle stimulation) representation of walking that serves in synthesizing a rule-base for control of electrical stimulation for restoration of walking. The simulation uses new algorithm termed moving-window dynamic optimization (MWDO). The optimization criterion was to minimize the sum of the squares of tracking errors from desired trajectories with the penalty function on the total muscle efforts. The MWDO was developed in the MATLAB environment and tested using target trajectories characteristic for slow-to-normal walking recorded in healthy individual and a model with the parameters characterizing the potential hemiplegic user. The outputs of the simulation are piecewise constant intensities of electrical stimulation and trajectories generated when the calculated stimulation is applied to the model. We demonstrated the importance of this simulation by showing the outputs for healthy and hemiplegic individuals, using the same target trajectories. Results of the simulation show that the MWDO is an efficient tool for analyzing achievable trajectories and for determining the stimulation profiles that need to be delivered for good tracking.

Analysis and Optimization of Pulse Dynamics for Magnetic Stimulation

PubMed Central

Goetz, Stefan M.; Truong, Cong Nam; Gerhofer, Manuel G.; Peterchev, Angel V.; Herzog, Hans-Georg; Weyh, Thomas

2013-01-01

Magnetic stimulation is a standard tool in brain research and has found important clinical applications in neurology, psychiatry, and rehabilitation. Whereas coil designs and the spatial field properties have been intensively studied in the literature, the temporal dynamics of the field has received less attention. Typically, the magnetic field waveform is determined by available device circuit topologies rather than by consideration of what is optimal for neural stimulation. This paper analyzes and optimizes the waveform dynamics using a nonlinear model of a mammalian axon. The optimization objective was to minimize the pulse energy loss. The energy loss drives power consumption and heating, which are the dominating limitations of magnetic stimulation. The optimization approach is based on a hybrid global-local method. Different coordinate systems for describing the continuous waveforms in a limited parameter space are defined for numerical stability. The optimization results suggest that there are waveforms with substantially higher efficiency than that of traditional pulse shapes. One class of optimal pulses is analyzed further. Although the coil voltage profile of these waveforms is almost rectangular, the corresponding current shape presents distinctive characteristics, such as a slow low-amplitude first phase which precedes the main pulse and reduces the losses. Representatives of this class of waveforms corresponding to different maximum voltages are linked by a nonlinear transformation. The main phase, however, scales with time only. As with conventional magnetic stimulation pulses, briefer pulses result in lower energy loss but require higher coil voltage than longer pulses. PMID:23469168

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.

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

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.

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.

[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.

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 left, right and bilateral stimulation of subthalamic nuclei in Parkinson's disease: differential effects on motor, speech and language function.

PubMed

Schulz, Geralyn M; Hosey, Lara A; Bradberry, Trent J; Stager, Sheila V; Lee, Li-Ching; Pawha, Rajesh; Lyons, Kelly E; Metman, Leo Verhagen; Braun, Allen R

2012-01-01

Deep brain stimulation (DBS) of the subthalamic nucleus improves the motor symptoms of Parkinson's disease, but may produce a worsening of speech and language performance at rates and amplitudes typically selected in clinical practice. The possibility that these dissociated effects might be modulated by selective stimulation of left and right STN has never been systematically investigated. To address this issue, we analyzed motor, speech and language functions of 12 patients implanted with bilateral stimulators configured for optimal motor responses. Behavioral responses were quantified under four stimulator conditions: bilateral DBS, right-only DBS, left-only DBS and no DBS. Under bilateral and left-only DBS conditions, our results exhibited a significant improvement in motor symptoms but worsening of speech and language. These findings contribute to the growing body of literature demonstrating that bilateral STN DBS compromises speech and language function and suggests that these negative effects may be principally due to left-sided stimulation. These findings may have practical clinical consequences, suggesting that clinicians might optimize motor, speech and language functions by carefully adjusting left- and right-sided stimulation parameters.

Optimizing microstimulation using a reinforcement learning framework.

PubMed

Brockmeier, Austin J; Choi, John S; Distasio, Marcello M; Francis, Joseph T; Príncipe, José C

2011-01-01

The ability to provide sensory feedback is desired to enhance the functionality of neuroprosthetics. Somatosensory feedback provides closed-loop control to the motor system, which is lacking in feedforward neuroprosthetics. In the case of existing somatosensory function, a template of the natural response can be used as a template of desired response elicited by electrical microstimulation. In the case of no initial training data, microstimulation parameters that produce responses close to the template must be selected in an online manner. We propose using reinforcement learning as a framework to balance the exploration of the parameter space and the continued selection of promising parameters for further stimulation. This approach avoids an explicit model of the neural response from stimulation. We explore a preliminary architecture--treating the task as a k-armed bandit--using offline data recorded for natural touch and thalamic microstimulation, and we examine the methods efficiency in exploring the parameter space while concentrating on promising parameter forms. The best matching stimulation parameters, from k = 68 different forms, are selected by the reinforcement learning algorithm consistently after 334 realizations.

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.

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.

Commentary: physical approaches for the treatment of epilepsy: electrical and magnetic stimulation and cooling.

PubMed

Löscher, Wolfgang; Cole, Andrew J; McLean, Michael J

2009-04-01

Physical approaches for the treatment of epilepsy currently under study or development include electrical or magnetic brain stimulators and cooling devices, each of which may be implanted or applied externally. Some devices may stimulate peripheral structures, whereas others may be implanted directly into the brain. Stimulation may be delivered chronically, intermittently, or in response to either manual activation or computer-based detection of events of interest. Physical approaches may therefore ultimately be appropriate for seizure prophylaxis by causing a modification of the underlying substrate, presumably with a reduction in the intrinsic excitability of cerebral structures, or for seizure termination, by interfering with the spontaneous discharge of pathological neuronal networks. Clinical trials of device-based therapies are difficult due to ethical issues surrounding device implantation, problems with blinding, potential carryover effects that may occur in crossover designs if substrate modification occurs, and subject heterogeneity. Unresolved issues in the development of physical treatments include optimization of stimulation parameters, identification of the optimal volume of brain to be stimulated, development of adequate power supplies to stimulate the necessary areas, and a determination that stimulation itself does not promote epileptogenesis or adverse long-term effects on normal brain function.

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.

Optimal voltage stimulation parameters for network-mediated responses in wild type and rd10 mouse retinal ganglion cells

NASA Astrophysics Data System (ADS)

Jalligampala, Archana; Sekhar, Sudarshan; Zrenner, Eberhart; Rathbun, Daniel L.

2017-04-01

To further improve the quality of visual percepts elicited by microelectronic retinal prosthetics, substantial efforts have been made to understand how retinal neurons respond to electrical stimulation. It is generally assumed that a sufficiently strong stimulus will recruit most retinal neurons. However, recent evidence has shown that the responses of some retinal neurons decrease with excessively strong stimuli (a non-monotonic response function). Therefore, it is necessary to identify stimuli that can be used to activate the majority of retinal neurons even when such non-monotonic cells are part of the neuronal population. Taking these non-monotonic responses into consideration, we establish the optimal voltage stimulation parameters (amplitude, duration, and polarity) for epiretinal stimulation of network-mediated (indirect) ganglion cell responses. We recorded responses from 3958 mouse retinal ganglion cells (RGCs) in both healthy (wild type, WT) and a degenerating (rd10) mouse model of retinitis pigmentosa—using flat-mounted retina on a microelectrode array. Rectangular monophasic voltage-controlled pulses were presented with varying voltage, duration, and polarity. We found that in 4-5 weeks old rd10 mice the RGC thresholds were comparable to those of WT. There was a marked response variability among mouse RGCs. To account for this variability, we interpolated the percentage of RGCs activated at each point in the voltage-polarity-duration stimulus space, thus identifying the optimal voltage-controlled pulse (-2.4 V, 0.88 ms). The identified optimal voltage pulse can activate at least 65% of potentially responsive RGCs in both mouse strains. Furthermore, this pulse is well within the range of stimuli demonstrated to be safe and effective for retinal implant patients. Such optimized stimuli and the underlying method used to identify them support a high yield of responsive RGCs and will serve as an effective guideline for future in vitro investigations of retinal electrostimulation by establishing standard stimuli for each unique experimental condition.

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.

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.

Desynchronization boost by non-uniform coordinated reset stimulation in ensembles of pulse-coupled neurons

PubMed Central

Lücken, Leonhard; Yanchuk, Serhiy; Popovych, Oleksandr V.; Tass, Peter A.

2013-01-01

Several brain diseases are characterized by abnormal neuronal synchronization. Desynchronization of abnormal neural synchrony is theoretically compelling because of the complex dynamical mechanisms involved. We here present a novel type of coordinated reset (CR) stimulation. CR means to deliver phase resetting stimuli at different neuronal sub-populations sequentially, i.e., at times equidistantly distributed in a stimulation cycle. This uniform timing pattern seems to be intuitive and actually applies to the neural network models used for the study of CR so far. CR resets the population to an unstable cluster state from where it passes through a desynchronized transient, eventually resynchronizing if left unperturbed. In contrast, we show that the optimal stimulation times are non-uniform. Using the model of weakly pulse-coupled neurons with phase response curves, we provide an approach that enables to determine optimal stimulation timing patterns that substantially maximize the desynchronized transient time following the application of CR stimulation. This approach includes an optimization search for clusters in a low-dimensional pulse coupled map. As a consequence, model-specific non-uniformly spaced cluster states cause considerably longer desynchronization transients. Intriguingly, such a desynchronization boost with non-uniform CR stimulation can already be achieved by only slight modifications of the uniform CR timing pattern. Our results suggest that the non-uniformness of the stimulation times can be a medically valuable parameter in the calibration procedure for CR stimulation, where the latter has successfully been used in clinical and pre-clinical studies for the treatment of Parkinson's disease and tinnitus. PMID:23750134

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

NASA Astrophysics Data System (ADS)

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

2005-03-01

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

Electrical Stimulation of Afferent Pathways for the Suppression of Pathological Tremor

PubMed Central

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

2017-01-01

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

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.

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.

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

PubMed

Fitzgerald, Paul B

2013-09-16

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

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

Optimization of interaction conditions for efficient short laser pulse amplification by stimulated Brillouin scattering in the strongly coupled regime

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

Chiaramello, M.; Riconda, C.; Amiranoff, F.

Plasma amplification of low energy, a short (∼100–500 fs) laser pulse by an energetic long (∼10 ps) pulse via strong coupling Stimulated Brillouin Backscattering is investigated with an extensive analysis of one-dimensional particle-in-cell simulations. Parameters relevant to nowadays experimental conditions are investigated. The obtained seed pulse spectra are analyzed as a function of the interaction conditions such as plasma profile, pulses delay, and seed or pulse duration. The factors affecting the amount of energy transferred are determined, and the competition between Brillouin-based amplification and parasitic Raman backscattering is analyzed, leading to the optimization of the interaction conditions.

Surrogate-based optimization of hydraulic fracturing in pre-existing fracture networks

NASA Astrophysics Data System (ADS)

Chen, Mingjie; Sun, Yunwei; Fu, Pengcheng; Carrigan, Charles R.; Lu, Zhiming; Tong, Charles H.; Buscheck, Thomas A.

2013-08-01

Hydraulic fracturing has been used widely to stimulate production of oil, natural gas, and geothermal energy in formations with low natural permeability. Numerical optimization of fracture stimulation often requires a large number of evaluations of objective functions and constraints from forward hydraulic fracturing models, which are computationally expensive and even prohibitive in some situations. Moreover, there are a variety of uncertainties associated with the pre-existing fracture distributions and rock mechanical properties, which affect the optimized decisions for hydraulic fracturing. In this study, a surrogate-based approach is developed for efficient optimization of hydraulic fracturing well design in the presence of natural-system uncertainties. The fractal dimension is derived from the simulated fracturing network as the objective for maximizing energy recovery sweep efficiency. The surrogate model, which is constructed using training data from high-fidelity fracturing models for mapping the relationship between uncertain input parameters and the fractal dimension, provides fast approximation of the objective functions and constraints. A suite of surrogate models constructed using different fitting methods is evaluated and validated for fast predictions. Global sensitivity analysis is conducted to gain insights into the impact of the input variables on the output of interest, and further used for parameter screening. The high efficiency of the surrogate-based approach is demonstrated for three optimization scenarios with different and uncertain ambient conditions. Our results suggest the critical importance of considering uncertain pre-existing fracture networks in optimization studies of hydraulic fracturing.

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.

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.

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.

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

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

Optimization of Neuromodulation for Bladder Control in a Rat Cystitis Model.

PubMed

Su, Xin; Nickles, Angela; Nelson, Dwight E

2016-01-01

In a bladder overactivity model of cystitis induced by intravesical infusion of acetic acid (a.a.), several parameters of spinal nerve stimulation (SNS) were optimized using continuous infusion cystometry. The optimal stimulation was further characterized through measurements of urodynamic function using single-fill cystometry. In anesthetized male rats, a cannula was placed into the bladder dome for saline or 0.3% a.a. infusion and intravesical pressure monitoring. For SNS, two teflon-coated stainless steel electrodes were placed bilaterally under each of the L6 spinal nerves, and current stimulation was controlled independently using two Grass stimulators. Stimulation of 1 Hz or 50 Hz at motor threshold (Tmot ) was ineffective for altering bladder activities, but 10-Hz SNS increased the infused volume (IV) in a stimulation intensity-dependent fashion (P < 0.01, mixed model repeated analysis). Pairwise comparisons of IV differences to each stimulation intensity show that IV during 1 × Tmot stimulation was significantly larger than 0 × Tmot (no stim, P = 0.001), while the IV during 2 × Tmot stimulation was significantly larger than other intensities tested (P < 0.01). The mean IV (±SEM) during 0 × Tmot (no stim), 0.5 × Tmot , 1 × Tmot , and 2 × Tmot were 0.23 ± 0.04 mL, 0.25 ± 0.03 mL, 0.26 ± 0.03 mL, and 0.40 ± 0.04 mL, respectively. In single-fill cystometry, 10-Hz SNS at 1 × Tmot and 2 × Tmot stimulation increased the IV, or voiding duration and threshold pressure. SNS did not produce significant effects on basal pressure and micturition pressure. SNS significantly attenuates hypersensitive micturition reflex; 10 Hz and high-intensity stimulation are mostly effective. Acute peripheral nerve activation increases the functional bladder capacity, which may be via mechanisms on the afferent arm of the bladder micturition reflex. © 2015 International Neuromodulation Society.

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.

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.

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.

Apparatus and Methods for Manipulation and Optimization of Biological Systems

NASA Technical Reports Server (NTRS)

Sun, Ren (Inventor); Ho, Chih-Ming (Inventor); Wong, Pak Kin (Inventor); Yu, Fuqu (Inventor)

2014-01-01

The invention provides systems and methods for manipulating biological systems, for example to elicit a more desired biological response from a biological sample, such as a tissue, organ, and/or a cell. In one aspect, the invention operates by efficiently searching through a large parametric space of stimuli and system parameters to manipulate, control, and optimize the response of biological samples sustained in the system. In one aspect, the systems and methods of the invention use at least one optimization algorithm to modify the actuator's control inputs for stimulation, responsive to the sensor's output of response signals. The invention can be used, e.g., to optimize any biological system, e.g., bioreactors for proteins, and the like, small molecules, polysaccharides, lipids, and the like. Another use of the apparatus and methods includes is for the discovery of key parameters in complex biological systems.

Methods for parameter identification in oscillatory networks and application to cortical and thalamic 600 Hz activity.

PubMed

Leistritz, L; Suesse, T; Haueisen, J; Hilgenfeld, B; Witte, H

2006-01-01

Directed information transfer in the human brain occurs presumably by oscillations. As of yet, most approaches for the analysis of these oscillations are based on time-frequency or coherence analysis. The present work concerns the modeling of cortical 600 Hz oscillations, localized within the Brodmann Areas 3b and 1 after stimulation of the nervus medianus, by means of coupled differential equations. This approach leads to the so-called parameter identification problem, where based on a given data set, a set of unknown parameters of a system of ordinary differential equations is determined by special optimization procedures. Some suitable algorithms for this task are presented in this paper. Finally an oscillatory network model is optimally fitted to the data taken from ten volunteers.

Reducing the uncertainty of parameters controlling seasonal carbon and water fluxes in Chinese forests and its implication for simulated climate sensitivities

NASA Astrophysics Data System (ADS)

Li, Yue; Yang, Hui; Wang, Tao; MacBean, Natasha; Bacour, Cédric; Ciais, Philippe; Zhang, Yiping; Zhou, Guangsheng; Piao, Shilong

2017-08-01

Reducing parameter uncertainty of process-based terrestrial ecosystem models (TEMs) is one of the primary targets for accurately estimating carbon budgets and predicting ecosystem responses to climate change. However, parameters in TEMs are rarely constrained by observations from Chinese forest ecosystems, which are important carbon sink over the northern hemispheric land. In this study, eddy covariance data from six forest sites in China are used to optimize parameters of the ORganizing Carbon and Hydrology In Dynamics EcosystEms TEM. The model-data assimilation through parameter optimization largely reduces the prior model errors and improves the simulated seasonal cycle and summer diurnal cycle of net ecosystem exchange, latent heat fluxes, and gross primary production and ecosystem respiration. Climate change experiments based on the optimized model are deployed to indicate that forest net primary production (NPP) is suppressed in response to warming in the southern China but stimulated in the northeastern China. Altered precipitation has an asymmetric impact on forest NPP at sites in water-limited regions, with the optimization-induced reduction in response of NPP to precipitation decline being as large as 61% at a deciduous broadleaf forest site. We find that seasonal optimization alters forest carbon cycle responses to environmental change, with the parameter optimization consistently reducing the simulated positive response of heterotrophic respiration to warming. Evaluations from independent observations suggest that improving model structure still matters most for long-term carbon stock and its changes, in particular, nutrient- and age-related changes of photosynthetic rates, carbon allocation, and tree mortality.

Spinal Cord Stimulation (SCS) and Functional Magnetic Resonance Imaging (fMRI): Modulation of Cortical Connectivity With Therapeutic SCS.

PubMed

Deogaonkar, Milind; Sharma, Mayur; Oluigbo, Chima; Nielson, Dylan M; Yang, Xiangyu; Vera-Portocarrero, Louis; Molnar, Gregory F; Abduljalil, Amir; Sederberg, Per B; Knopp, Michael; Rezai, Ali R

2016-02-01

The neurophysiological basis of pain relief due to spinal cord stimulation (SCS) and the related cortical processing of sensory information are not completely understood. The aim of this study was to use resting state functional magnetic resonance imaging (rs-fMRI) to detect changes in cortical networks and cortical processing related to the stimulator-induced pain relief. Ten patients with complex regional pain syndrome (CRPS) or neuropathic leg pain underwent thoracic epidural spinal cord stimulator implantation. Stimulation parameters associated with "optimal" pain reduction were evaluated prior to imaging studies. Rs-fMRI was obtained on a 3 Tesla, Philips Achieva MRI. Rs-fMRI was performed with stimulator off (300TRs) and stimulator at optimum (Opt, 300 TRs) pain relief settings. Seed-based analysis of the resting state functional connectivity was conducted using seeds in regions established as participating in pain networks or in the default mode network (DMN) in addition to the network analysis. NCUT (normalized cut) parcellation was used to generate 98 cortical and subcortical regions of interest in order to expand our analysis of changes in functional connections to the entire brain. We corrected for multiple comparisons by limiting the false discovery rate to 5%. Significant differences in resting state connectivity between SCS off and optimal state were seen between several regions related to pain perception, including the left frontal insula, right primary and secondary somatosensory cortices, as well as in regions involved in the DMN, such as the precuneus. In examining changes in connectivity across the entire brain, we found decreased connection strength between somatosensory and limbic areas and increased connection strength between somatosensory and DMN with optimal SCS resulting in pain relief. This suggests that pain relief from SCS may be reducing negative emotional processing associated with pain, allowing somatosensory areas to become more integrated into default mode activity. SCS reduces the affective component of pain resulting in optimal pain relief. Study shows a decreased connectivity between somatosensory and limbic areas associated with optimal pain relief due to SCS. © 2015 International Neuromodulation Society.

A translational platform for prototyping closed-loop neuromodulation systems

PubMed Central

Afshar, Pedram; Khambhati, Ankit; Stanslaski, Scott; Carlson, David; Jensen, Randy; Linde, Dave; Dani, Siddharth; Lazarewicz, Maciej; Cong, Peng; Giftakis, Jon; Stypulkowski, Paul; Denison, Tim

2013-01-01

While modulating neural activity through stimulation is an effective treatment for neurological diseases such as Parkinson's disease and essential tremor, an opportunity for improving neuromodulation therapy remains in automatically adjusting therapy to continuously optimize patient outcomes. Practical issues associated with achieving this include the paucity of human data related to disease states, poorly validated estimators of patient state, and unknown dynamic mappings of optimal stimulation parameters based on estimated states. To overcome these challenges, we present an investigational platform including: an implanted sensing and stimulation device to collect data and run automated closed-loop algorithms; an external tool to prototype classifier and control-policy algorithms; and real-time telemetry to update the implanted device firmware and monitor its state. The prototyping system was demonstrated in a chronic large animal model studying hippocampal dynamics. We used the platform to find biomarkers of the observed states and transfer functions of different stimulation amplitudes. Data showed that moderate levels of stimulation suppress hippocampal beta activity, while high levels of stimulation produce seizure-like after-discharge activity. The biomarker and transfer function observations were mapped into classifier and control-policy algorithms, which were downloaded to the implanted device to continuously titrate stimulation amplitude for the desired network effect. The platform is designed to be a flexible prototyping tool and could be used to develop improved mechanistic models and automated closed-loop systems for a variety of neurological disorders. PMID:23346048

A translational platform for prototyping closed-loop neuromodulation systems.

PubMed

Afshar, Pedram; Khambhati, Ankit; Stanslaski, Scott; Carlson, David; Jensen, Randy; Linde, Dave; Dani, Siddharth; Lazarewicz, Maciej; Cong, Peng; Giftakis, Jon; Stypulkowski, Paul; Denison, Tim

2012-01-01

While modulating neural activity through stimulation is an effective treatment for neurological diseases such as Parkinson's disease and essential tremor, an opportunity for improving neuromodulation therapy remains in automatically adjusting therapy to continuously optimize patient outcomes. Practical issues associated with achieving this include the paucity of human data related to disease states, poorly validated estimators of patient state, and unknown dynamic mappings of optimal stimulation parameters based on estimated states. To overcome these challenges, we present an investigational platform including: an implanted sensing and stimulation device to collect data and run automated closed-loop algorithms; an external tool to prototype classifier and control-policy algorithms; and real-time telemetry to update the implanted device firmware and monitor its state. The prototyping system was demonstrated in a chronic large animal model studying hippocampal dynamics. We used the platform to find biomarkers of the observed states and transfer functions of different stimulation amplitudes. Data showed that moderate levels of stimulation suppress hippocampal beta activity, while high levels of stimulation produce seizure-like after-discharge activity. The biomarker and transfer function observations were mapped into classifier and control-policy algorithms, which were downloaded to the implanted device to continuously titrate stimulation amplitude for the desired network effect. The platform is designed to be a flexible prototyping tool and could be used to develop improved mechanistic models and automated closed-loop systems for a variety of neurological disorders.

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

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

Particle Swarm Optimization for Programming Deep Brain Stimulation Arrays

PubMed Central

Peña, Edgar; Zhang, Simeng; Deyo, Steve; Xiao, YiZi; Johnson, Matthew D.

2017-01-01

Objective Deep brain stimulation (DBS) therapy relies on both precise neurosurgical targeting and systematic optimization of stimulation settings to achieve beneficial clinical outcomes. One recent advance to improve targeting is the development of DBS arrays (DBSAs) with electrodes segmented both along and around the DBS lead. However, increasing the number of independent electrodes creates the logistical challenge of optimizing stimulation parameters efficiently. Approach Solving such complex problems with multiple solutions and objectives is well known to occur in biology, in which complex collective behaviors emerge out of swarms of individual organisms engaged in learning through social interactions. Here, we developed a particle swarm optimization (PSO) algorithm to program DBSAs using a swarm of individual particles representing electrode configurations and stimulation amplitudes. Using a finite element model of motor thalamic DBS, we demonstrate how the PSO algorithm can efficiently optimize a multi-objective function that maximizes predictions of axonal activation in regions of interest (ROI, cerebellar-receiving area of motor thalamus), minimizes predictions of axonal activation in regions of avoidance (ROA, somatosensory thalamus), and minimizes power consumption. Main Results The algorithm solved the multi-objective problem by producing a Pareto front. ROI and ROA activation predictions were consistent across swarms (<1% median discrepancy in axon activation). The algorithm was able to accommodate for (1) lead displacement (1 mm) with relatively small ROI (≤9.2%) and ROA (≤1%) activation changes, irrespective of shift direction; (2) reduction in maximum per-electrode current (by 50% and 80%) with ROI activation decreasing by 5.6% and 16%, respectively; and (3) disabling electrodes (n=3 and 12) with ROI activation reduction by 1.8% and 14%, respectively. Additionally, comparison between PSO predictions and multi-compartment axon model simulations showed discrepancies of <1% between approaches. Significance The PSO algorithm provides a computationally efficient way to program DBS systems especially those with higher electrode counts. PMID:28068291

Particle swarm optimization for programming deep brain stimulation arrays

NASA Astrophysics Data System (ADS)

Peña, Edgar; Zhang, Simeng; Deyo, Steve; Xiao, YiZi; Johnson, Matthew D.

2017-02-01

Objective. Deep brain stimulation (DBS) therapy relies on both precise neurosurgical targeting and systematic optimization of stimulation settings to achieve beneficial clinical outcomes. One recent advance to improve targeting is the development of DBS arrays (DBSAs) with electrodes segmented both along and around the DBS lead. However, increasing the number of independent electrodes creates the logistical challenge of optimizing stimulation parameters efficiently. Approach. Solving such complex problems with multiple solutions and objectives is well known to occur in biology, in which complex collective behaviors emerge out of swarms of individual organisms engaged in learning through social interactions. Here, we developed a particle swarm optimization (PSO) algorithm to program DBSAs using a swarm of individual particles representing electrode configurations and stimulation amplitudes. Using a finite element model of motor thalamic DBS, we demonstrate how the PSO algorithm can efficiently optimize a multi-objective function that maximizes predictions of axonal activation in regions of interest (ROI, cerebellar-receiving area of motor thalamus), minimizes predictions of axonal activation in regions of avoidance (ROA, somatosensory thalamus), and minimizes power consumption. Main results. The algorithm solved the multi-objective problem by producing a Pareto front. ROI and ROA activation predictions were consistent across swarms (<1% median discrepancy in axon activation). The algorithm was able to accommodate for (1) lead displacement (1 mm) with relatively small ROI (⩽9.2%) and ROA (⩽1%) activation changes, irrespective of shift direction; (2) reduction in maximum per-electrode current (by 50% and 80%) with ROI activation decreasing by 5.6% and 16%, respectively; and (3) disabling electrodes (n  =  3 and 12) with ROI activation reduction by 1.8% and 14%, respectively. Additionally, comparison between PSO predictions and multi-compartment axon model simulations showed discrepancies of  <1% between approaches. Significance. The PSO algorithm provides a computationally efficient way to program DBS systems especially those with higher electrode counts.

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

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.

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.

Optimal stimulus scheduling for active estimation of evoked brain networks.

PubMed

Kafashan, MohammadMehdi; Ching, ShiNung

2015-12-01

We consider the problem of optimal probing to learn connections in an evoked dynamic network. Such a network, in which each edge measures an input-output relationship between sites in sensor/actuator-space, is relevant to emerging applications in neural mapping and neural connectivity estimation. We show that the problem of scheduling nodes to a probe (i.e., stimulate) amounts to a problem of optimal sensor scheduling. By formulating the evoked network in state-space, we show that the solution to the greedy probing strategy has a convenient form and, under certain conditions, is optimal over a finite horizon. We adopt an expectation maximization technique to update the state-space parameters in an online fashion and demonstrate the efficacy of the overall approach in a series of detailed numerical examples. The proposed method provides a principled means to actively probe time-varying connections in neuronal networks. The overall method can be implemented in real time and is particularly well-suited to applications in stimulation-based cortical mapping in which the underlying network dynamics are changing over time.

Optimal stimulus scheduling for active estimation of evoked brain networks

NASA Astrophysics Data System (ADS)

Kafashan, MohammadMehdi; Ching, ShiNung

2015-12-01

Objective. We consider the problem of optimal probing to learn connections in an evoked dynamic network. Such a network, in which each edge measures an input-output relationship between sites in sensor/actuator-space, is relevant to emerging applications in neural mapping and neural connectivity estimation. Approach. We show that the problem of scheduling nodes to a probe (i.e., stimulate) amounts to a problem of optimal sensor scheduling. Main results. By formulating the evoked network in state-space, we show that the solution to the greedy probing strategy has a convenient form and, under certain conditions, is optimal over a finite horizon. We adopt an expectation maximization technique to update the state-space parameters in an online fashion and demonstrate the efficacy of the overall approach in a series of detailed numerical examples. Significance. The proposed method provides a principled means to actively probe time-varying connections in neuronal networks. The overall method can be implemented in real time and is particularly well-suited to applications in stimulation-based cortical mapping in which the underlying network dynamics are changing over time.

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.

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.

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.

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.

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

Optimal number of stimulation contacts for coordinated reset neuromodulation

PubMed Central

Lysyansky, Borys; Popovych, Oleksandr V.; Tass, Peter A.

2013-01-01

In this computational study we investigate coordinated reset (CR) neuromodulation designed for an effective control of synchronization by multi-site stimulation of neuronal target populations. This method was suggested to effectively counteract pathological neuronal synchrony characteristic for several neurological disorders. We study how many stimulation sites are required for optimal CR-induced desynchronization. We found that a moderate increase of the number of stimulation sites may significantly prolong the post-stimulation desynchronized transient after the stimulation is completely switched off. This can, in turn, reduce the amount of the administered stimulation current for the intermittent ON–OFF CR stimulation protocol, where time intervals with stimulation ON are recurrently followed by time intervals with stimulation OFF. In addition, we found that the optimal number of stimulation sites essentially depends on how strongly the administered current decays within the neuronal tissue with increasing distance from the stimulation site. In particular, for a broad spatial stimulation profile, i.e., for a weak spatial decay rate of the stimulation current, CR stimulation can optimally be delivered via a small number of stimulation sites. Our findings may contribute to an optimization of therapeutic applications of CR neuromodulation. PMID:23885239

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.

Designing optimal stimuli to control neuronal spike timing

PubMed Central

Packer, Adam M.; Yuste, Rafael; Paninski, Liam

2011-01-01

Recent advances in experimental stimulation methods have raised the following important computational question: how can we choose a stimulus that will drive a neuron to output a target spike train with optimal precision, given physiological constraints? Here we adopt an approach based on models that describe how a stimulating agent (such as an injected electrical current or a laser light interacting with caged neurotransmitters or photosensitive ion channels) affects the spiking activity of neurons. Based on these models, we solve the reverse problem of finding the best time-dependent modulation of the input, subject to hardware limitations as well as physiologically inspired safety measures, that causes the neuron to emit a spike train that with highest probability will be close to a target spike train. We adopt fast convex constrained optimization methods to solve this problem. Our methods can potentially be implemented in real time and may also be generalized to the case of many cells, suitable for neural prosthesis applications. With the use of biologically sensible parameters and constraints, our method finds stimulation patterns that generate very precise spike trains in simulated experiments. We also tested the intracellular current injection method on pyramidal cells in mouse cortical slices, quantifying the dependence of spiking reliability and timing precision on constraints imposed on the applied currents. PMID:21511704

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

PubMed Central

Kent, A R; Grill, W M

2012-01-01

Deep brain stimulation (DBS) is an effective treatment for movement disorders, but the selection of stimulus parameters is a clinical burden and often yields sub-optimal outcomes for patients. Measurement of electrically evoked compound action potentials (ECAPs) during DBS could offer insight into the type and spatial extent of neural element activation and provide a potential feedback signal for the rational selection of stimulus 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 1,000 to 5,000 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. PMID:22510375

A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties.

PubMed

Salinas, Evelia Y; Hu, Jerry C; Athanasiou, Kyriacos

2018-04-26

The use of tissue-engineered articular cartilage (TEAC) constructs has the potential to become a powerful treatment option for cartilage lesions resulting from trauma or early stages of pathology. Although fundamental tissue-engineering strategies based on the use of scaffolds, cells, and signals have been developed, techniques that lead to biomimetic AC constructs that can be translated to in vivo use are yet to be fully confirmed. Mechanical stimulation during tissue culture can be an effective strategy to enhance the mechanical, structural, and cellular properties of tissue-engineered constructs toward mimicking those of native AC. This review focuses on the use of mechanical stimulation to attain and enhance the properties of AC constructs needed to translate these implants to the clinic. In vivo, mechanical loading at maximal and supramaximal physiological levels has been shown to be detrimental to AC through the development of degenerative changes. In contrast, multiple studies have revealed that during culture, mechanical stimulation within narrow ranges of magnitude and duration can produce anisotropic, mechanically robust AC constructs with high cellular viability. Significant progress has been made in evaluating a variety of mechanical stimulation techniques on TEAC, either alone or in combination with other stimuli. These advancements include determining and optimizing efficacious loading parameters (e.g., duration and frequency) to yield improvements in construct design criteria, such as collagen II content, compressive stiffness, cell viability, and fiber organization. With the advancement of mechanical stimulation as a potent strategy in AC tissue engineering, a compendium detailing the results achievable by various stimulus regimens would be of great use for researchers in academia and industry. The objective is to list the qualitative and quantitative effects that can be attained when direct compression, hydrostatic pressure, shear, and tensile loading are used to tissue-engineer AC. Our goal is to provide a practical guide to their use and optimization of loading parameters. For each loading condition, we will also present and discuss benefits and limitations of bioreactor configurations that have been used. The intent is for this review to serve as a reference for including mechanical stimulation strategies as part of AC construct culture regimens.

[Stimulation parameters for automatic examination of color vision].

PubMed

Sommerhalder, J; Pelizzone, M; Roth, A

1997-05-01

We have developed a polyvalent computer controlled instrument, which uses the "two equation method" (Rayleigh and Moreland equations) to measure human colour vision. This "colorimeter" (or anomaloscope) was used to determine the influence of some important stimulation parameters. The influence of stimulus exposure time, observation field size, absolute stimulus luminance, saturation and luminance mismatches between mixture and reference stimuli were measured on our computer controlled colorimeter. All subjects were normal observers. 1) An exposure time of 2s was found to be optimal for clinical work. 2) The Moreland equation on a 7 degrees observation field yields results in which population variability is comparable to a Rayleigh equation on a 2 degrees field. 3) A retinal illuminance between 40 and 1000 trolands can be used for automated Moreland matches. 4) The saturation of the reference field for the Moreland match can be preset to a fixed value. 5) It is important to vary automatically the radiance of the reference field to provide an approximate luminance match as the ratio of primaries in the mixture field is changed. These measurements allows us to determine optimal conditions for automated colour vision examinations and to make recommendations for an international standard.

A numerically optimized active shield for improved transcranial magnetic stimulation targeting.

PubMed

Hernandez-Garcia, Luis; Hall, Timothy; Gomez, Luis; Michielssen, Eric

2010-10-01

Transcranial magnetic stimulation (TMS) devices suffer of poor targeting and penetration depth. A new approach to designing TMS coils is introduced in order to improve the focus of the stimulation region through the use of actively shielded probes. Iterative optimization techniques were used to design different active shielding coils for TMS probes. The new approach aims to increase the amount of energy deposited in a thin cylindrical region below the probe relative to the energy deposited elsewhere in the region ("sharpness"), whereas, simultaneously increase the induced electric field deep in the target region relative to the surface ("penetration"). After convergence, the resulting designs showed that there is a clear tradeoff between sharpness and penetration that can be controlled by the choice of a tuning parameter. The resulting designs were tested on a realistic human head conductivity model, taking the contribution from surface charges into account. The design of choice reduced penetration depths by 16.7%. The activated surface area was reduced by 24.1% and the volume of the activation was reduced from 42.6% by the shield. Restoring the lost penetration could be achieved by increasing the total power to the coil by 16.3%, but in that case, the stimulated volume reduction was only 13.1% and there was a slight increase in the stimulated surface area (2.9%). Copyright © 2010 Elsevier Inc. All rights reserved.

Stimulation of the human auditory nerve with optical radiation

NASA Astrophysics Data System (ADS)

Fishman, Andrew; Winkler, Piotr; Mierzwinski, Jozef; Beuth, Wojciech; Izzo Matic, Agnella; Siedlecki, Zygmunt; Teudt, Ingo; Maier, Hannes; Richter, Claus-Peter

2009-02-01

A novel, spatially selective method to stimulate cranial nerves has been proposed: contact free stimulation with optical radiation. The radiation source is an infrared pulsed laser. The Case Report is the first report ever that shows that optical stimulation of the auditory nerve is possible in the human. The ethical approach to conduct any measurements or tests in humans requires efficacy and safety studies in animals, which have been conducted in gerbils. This report represents the first step in a translational research project to initiate a paradigm shift in neural interfaces. A patient was selected who required surgical removal of a large meningioma angiomatum WHO I by a planned transcochlear approach. Prior to cochlear ablation by drilling and subsequent tumor resection, the cochlear nerve was stimulated with a pulsed infrared laser at low radiation energies. Stimulation with optical radiation evoked compound action potentials from the human auditory nerve. Stimulation of the auditory nerve with infrared laser pulses is possible in the human inner ear. The finding is an important step for translating results from animal experiments to human and furthers the development of a novel interface that uses optical radiation to stimulate neurons. Additional measurements are required to optimize the stimulation parameters.

Eliciting naturalistic cortical responses with a sensory prosthesis via optimized microstimulation

NASA Astrophysics Data System (ADS)

Choi, John S.; Brockmeier, Austin J.; McNiel, David B.; von Kraus, Lee M.; Príncipe, José C.; Francis, Joseph T.

2016-10-01

Objective. Lost sensations, such as touch, could one day be restored by electrical stimulation along the sensory neural pathways. Such stimulation, when informed by electronic sensors, could provide naturalistic cutaneous and proprioceptive feedback to the user. Perceptually, microstimulation of somatosensory brain regions produces localized, modality-specific sensations, and several spatiotemporal parameters have been studied for their discernibility. However, systematic methods for encoding a wide array of naturally occurring stimuli into biomimetic percepts via multi-channel microstimulation are lacking. More specifically, generating spatiotemporal patterns for explicitly evoking naturalistic neural activation has not yet been explored. Approach. We address this problem by first modeling the dynamical input-output relationship between multichannel microstimulation and downstream neural responses, and then optimizing the input pattern to reproduce naturally occurring touch responses as closely as possible. Main results. Here we show that such optimization produces responses in the S1 cortex of the anesthetized rat that are highly similar to natural, tactile-stimulus-evoked counterparts. Furthermore, information on both pressure and location of the touch stimulus was found to be highly preserved. Significance. Our results suggest that the currently presented stimulus optimization approach holds great promise for restoring naturalistic levels of sensation.

In vivo production of a novel glycoconjugate vaccine against Shigella flexneri 2a in recombinant Escherichia coli: identification of stimulating factors for in vivo glycosylation.

PubMed

Kämpf, Michael M; Braun, Martin; Sirena, Dominique; Ihssen, Julian; Thöny-Meyer, Linda; Ren, Qun

2015-01-23

Glycoconjugated vaccines composed of polysaccharide antigens covalently linked to immunogenic carrier proteins have proved to belong to the most effective and safest vaccines for combating bacterial pathogens. The functional transfer of the N-glycosylation machinery from Campylobacter jejuni to the standard prokaryotic host Escherichia coli established a novel bioconjugation methodology termed bacterial glycoengineering. In this study, we report on the production of a new recombinant glycoconjugate vaccine against Shigella flexneri 2a representing the major serotype for global outbreaks of shigellosis. We demonstrate that S. flexneri 2a O-polysaccharides can be transferred to a detoxified variant of Pseudomonas aeruginosa carrier protein exotoxin A (EPA) by the C. jejuni oligosaccharyltransferase PglB, resulting in glycosylated EPA-2a. Moreover, we optimized the in vivo production of this novel vaccine by identification and quantitative analysis of critical process parameters for glycoprotein synthesis. It was found that sequential induction of oligosaccharyltransferase PglB and carrier protein EPA increased the specific productivity of EPA-2a by a factor of 1.6. Furthermore, by the addition of 10 g/L of the monosaccharide N-acetylglucosamine during induction, glycoconjugate vaccine yield was boosted up to 3.1-fold. The optimum concentration of Mg2+ ions for N-glycan transfer was determined to be 10 mM. Finally, optimized parameters were transferred to high cell density cultures with a 46-fold increase of overall yield of glycoconjugate compared to the one in initial shake flask production. The present study is the first attempt to identify stimulating parameters for improved productivity of S. flexneri 2a bioconjugates. Optimization of glycosylation efficiency will ultimately foster the transfer of lab-scale expression to a cost-effective in vivo production process for a glycoconjugate vaccine against S. flexneri 2a in E. coli. This study is an important step towards this goal and provides a starting point for further optimization studies.

Optimal coordination and control of posture and movements.

PubMed

Johansson, Rolf; Fransson, Per-Anders; Magnusson, Måns

2009-01-01

This paper presents a theoretical model of stability and coordination of posture and locomotion, together with algorithms for continuous-time quadratic optimization of motion control. Explicit solutions to the Hamilton-Jacobi equation for optimal control of rigid-body motion are obtained by solving an algebraic matrix equation. The stability is investigated with Lyapunov function theory and it is shown that global asymptotic stability holds. It is also shown how optimal control and adaptive control may act in concert in the case of unknown or uncertain system parameters. The solution describes motion strategies of minimum effort and variance. The proposed optimal control is formulated to be suitable as a posture and movement model for experimental validation and verification. The combination of adaptive and optimal control makes this algorithm a candidate for coordination and control of functional neuromuscular stimulation as well as of prostheses. Validation examples with experimental data are provided.

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

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.

Orthogonal design to sift the optimal parameter of Neiguan acupuncture for cerebral infarction

PubMed Central

Zhang, Yanan; Yang, Sha; Fan, Xiaonong; Wang, Shu; He, Nina; Li, Lingxin; Luo, Ding; Shi, Xuemin

2013-01-01

The individual difference and non-repeatability in acupuncture have not only restricted the development of acupuncture, but have also affected the specificity of acupoints. The present study used instruments to control needle depth, lifting and thrusting frequency, and the duration of acupuncture. Effects of the quantified acupuncture were observed at Neiguan (PC6) with different stimulation parameters. A frequency of 1, 2, or 3 Hz and duration of 5, 60, or 180 seconds were used to observe cerebral blood flow and ratio of infarct volume recovery. Results showed that stimulation at Neiguan with a frequency of 1 Hz and long duration of 180 seconds or 2/3 Hz and long duration of 5/60 seconds significantly increased cerebral blood flow and decreased the ratio of infarct volume. Interactions between frequency and duration play a critical role in quantified acupuncture therapy. PMID:25206575

Optimization and comparison of three spatial interpolation methods for electromagnetic levels in the AM band within an urban area.

PubMed

Rufo, Montaña; Antolín, Alicia; Paniagua, Jesús M; Jiménez, Antonio

2018-04-01

A comparative study was made of three methods of interpolation - inverse distance weighting (IDW), spline and ordinary kriging - after optimization of their characteristic parameters. These interpolation methods were used to represent the electric field levels for three emission frequencies (774kHz, 900kHz, and 1107kHz) and for the electrical stimulation quotient, Q E , characteristic of complex electromagnetic environments. Measurements were made with a spectrum analyser in a village in the vicinity of medium-wave radio broadcasting antennas. The accuracy of the models was quantified by comparing their predictions with levels measured at the control points not used to generate the models. The results showed that optimizing the characteristic parameters of each interpolation method allows any of them to be used. However, the best results in terms of the regression coefficient between each model's predictions and the actual control point field measurements were for the IDW method. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Neural signal processing and closed-loop control algorithm design for an implanted neural recording and stimulation system.

PubMed

Hamilton, Lei; McConley, Marc; Angermueller, Kai; Goldberg, David; Corba, Massimiliano; Kim, Louis; Moran, James; Parks, Philip D; Sang Chin; Widge, Alik S; Dougherty, Darin D; Eskandar, Emad N

2015-08-01

A fully autonomous intracranial device is built to continually record neural activities in different parts of the brain, process these sampled signals, decode features that correlate to behaviors and neuropsychiatric states, and use these features to deliver brain stimulation in a closed-loop fashion. In this paper, we describe the sampling and stimulation aspects of such a device. We first describe the signal processing algorithms of two unsupervised spike sorting methods. Next, we describe the LFP time-frequency analysis and feature derivation from the two spike sorting methods. Spike sorting includes a novel approach to constructing a dictionary learning algorithm in a Compressed Sensing (CS) framework. We present a joint prediction scheme to determine the class of neural spikes in the dictionary learning framework; and, the second approach is a modified OSort algorithm which is implemented in a distributed system optimized for power efficiency. Furthermore, sorted spikes and time-frequency analysis of LFP signals can be used to generate derived features (including cross-frequency coupling, spike-field coupling). We then show how these derived features can be used in the design and development of novel decode and closed-loop control algorithms that are optimized to apply deep brain stimulation based on a patient's neuropsychiatric state. For the control algorithm, we define the state vector as representative of a patient's impulsivity, avoidance, inhibition, etc. Controller parameters are optimized to apply stimulation based on the state vector's current state as well as its historical values. The overall algorithm and software design for our implantable neural recording and stimulation system uses an innovative, adaptable, and reprogrammable architecture that enables advancement of the state-of-the-art in closed-loop neural control while also meeting the challenges of system power constraints and concurrent development with ongoing scientific research designed to define brain network connectivity and neural network dynamics that vary at the individual patient level and vary over time.

Computationally optimized ECoG stimulation with local safety constraints.

PubMed

Guler, Seyhmus; Dannhauer, Moritz; Roig-Solvas, Biel; Gkogkidis, Alexis; Macleod, Rob; Ball, Tonio; Ojemann, Jeffrey G; Brooks, Dana H

2018-06-01

Direct stimulation of the cortical surface is used clinically for cortical mapping and modulation of local activity. Future applications of cortical modulation and brain-computer interfaces may also use cortical stimulation methods. One common method to deliver current is through electrocorticography (ECoG) stimulation in which a dense array of electrodes are placed subdurally or epidurally to stimulate the cortex. However, proximity to cortical tissue limits the amount of current that can be delivered safely. It may be desirable to deliver higher current to a specific local region of interest (ROI) while limiting current to other local areas more stringently than is guaranteed by global safety limits. Two commonly used global safety constraints bound the total injected current and individual electrode currents. However, these two sets of constraints may not be sufficient to prevent high current density locally (hot-spots). In this work, we propose an efficient approach that prevents current density hot-spots in the entire brain while optimizing ECoG stimulus patterns for targeted stimulation. Specifically, we maximize the current along a particular desired directional field in the ROI while respecting three safety constraints: one on the total injected current, one on individual electrode currents, and the third on the local current density magnitude in the brain. This third set of constraints creates a computational barrier due to the huge number of constraints needed to bound the current density at every point in the entire brain. We overcome this barrier by adopting an efficient two-step approach. In the first step, the proposed method identifies the safe brain region, which cannot contain any hot-spots solely based on the global bounds on total injected current and individual electrode currents. In the second step, the proposed algorithm iteratively adjusts the stimulus pattern to arrive at a solution that exhibits no hot-spots in the remaining brain. We report on simulations on a realistic finite element (FE) head model with five anatomical ROIs and two desired directional fields. We also report on the effect of ROI depth and desired directional field on the focality of the stimulation. Finally, we provide an analysis of optimization runtime as a function of different safety and modeling parameters. Our results suggest that optimized stimulus patterns tend to differ from those used in clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

Energy-optimal electrical excitation of nerve fibers.

PubMed

Jezernik, Saso; Morari, Manfred

2005-04-01

We derive, based on an analytical nerve membrane model and optimal control theory of dynamical systems, an energy-optimal stimulation current waveform for electrical excitation of nerve fibers. Optimal stimulation waveforms for nonleaky and leaky membranes are calculated. The case with a leaky membrane is a realistic case. Finally, we compare the waveforms and energies necessary for excitation of a leaky membrane in the case where the stimulation waveform is a square-wave current pulse, and in the case of energy-optimal stimulation. The optimal stimulation waveform is an exponentially rising waveform and necessitates considerably less energy to excite the nerve than a square-wave pulse (especially true for larger pulse durations). The described theoretical results can lead to drastically increased battery lifetime and/or decreased energy transmission requirements for implanted biomedical systems.

An optimized IFN-γ ELISpot assay for the sensitive and standardized monitoring of CMV protein-reactive effector cells of cell-mediated immunity.

PubMed

Barabas, Sascha; Spindler, Theresa; Kiener, Richard; Tonar, Charlotte; Lugner, Tamara; Batzilla, Julia; Bendfeldt, Hanna; Rascle, Anne; Asbach, Benedikt; Wagner, Ralf; Deml, Ludwig

2017-03-07

In healthy individuals, Cytomegalovirus (CMV) infection is efficiently controlled by CMV-specific cell-mediated immunity (CMI). Functional impairment of CMI in immunocompromized individuals however can lead to uncontrolled CMV replication and severe clinical complications. Close monitoring of CMV-specific CMI is therefore clinically relevant and might allow a reliable prognosis of CMV disease as well as assist personalized therapeutic decisions. Objective of this work was the optimization and technical validation of an IFN-γ ELISpot assay for a standardized, sensitive and reliable quantification of CMV-reactive effector cells. T-activated® immunodominant CMV IE-1 and pp65 proteins were used as stimulants. All basic assay parameters and reagents were tested and optimized to establish a user-friendly protocol and maximize the signal-to-noise ratio of the ELISpot assay. Optimized and standardized ELISpot revealed low intra-assay, inter-assay and inter-operator variability (coefficient of variation CV below 22%) and CV inter-site was lower than 40%. Good assay linearity was obtained between 6 × 10 4 and 2 × 10 5 PBMC per well upon stimulation with T-activated® IE-1 (R 2  = 0.97) and pp65 (R 2  = 0.99) antigens. Remarkably, stimulation of peripheral blood mononuclear cells (PBMC) with T-activated® IE-1 and pp65 proteins resulted in the activation of a broad range of CMV-reactive effector cells, including CD3 + CD4 + (Th), CD3 + CD8 + (CTL), CD3 - CD56 + (NK) and CD3 + CD56 + (NKT-like) cells. Accordingly, the optimized IFN-γ ELISpot assay revealed very high sensitivity (97%) in a cohort of 45 healthy donors, of which 32 were CMV IgG-seropositive. The combined use of T-activated® IE-1 and pp65 proteins for the stimulation of PBMC with the optimized IFN-γ ELISpot assay represents a highly standardized, valuable tool to monitor the functionality of CMV-specific CMI with great sensitivity and reliability.

Modeling seismic stimulation: Enhanced non-aqueous fluid extraction from saturated porous media under pore-pressure pulsing at low frequencies

NASA Astrophysics Data System (ADS)

Lo, Wei-Cheng; Sposito, Garrison; Huang, Yu-Han

2012-03-01

Seismic stimulation, the application of low-frequency stress-pulsing to the boundary of a porous medium containing water and a non-aqueous fluid to enhance the removal of the latter, shows great promise for both contaminated groundwater remediation and enhanced oil recovery, but theory to elucidate the underlying mechanisms lag significantly behind the progress achieved in experimental research. We address this conceptual lacuna by formulating a boundary-value problem to describe pore-pressure pulsing at seismic frequencies that is based on the continuum theory of poroelasticity for an elastic porous medium permeated by two immiscible fluids. An exact analytical solution is presented that is applied numerically using elasticity parameters and hydraulic data relevant to recent proof-of-principle laboratory experiments investigating the stimulation-induced mobilization of trichloroethene (TCE) in water flowing through a compressed sand core. The numerical results indicated that significant stimulation-induced increases of the TCE concentration in effluent can be expected from pore-pressure pulsing in the frequency range of 25-100 Hz, which is in good agreement with what was observed in the laboratory experiments. Sensitivity analysis of our numerical results revealed that the TCE concentration in the effluent increases with the porous medium framework compressibility and the pulsing pressure. Increasing compressibility also leads to an optimal stimulation response at lower frequencies, whereas changing the pulsing pressure does not affect the optimal stimulation frequency. Within the context of our model, the dominant physical cause for enhancement of non-aqueous fluid mobility by seismic stimulation is the dilatory motion of the porous medium in which the solid and fluid phases undergo opposite displacements, resulting in stress-induced changes of the pore volume.

Controversy: Noninvasive and invasive cortical stimulation show efficacy in treating stroke patients.

PubMed

Hummel, Friedhelm C; Celnik, Pablo; Pascual-Leone, Alvero; Fregni, Felipe; Byblow, Winston D; Buetefisch, Cathrin M; Rothwell, John; Cohen, Leonardo G; Gerloff, Christian

2008-10-01

Stroke is the leading cause of disability in the adult population of western industrialized countries. Despite significant improvements of acute stroke care, two thirds of stroke survivors have to cope with persisting neurologic deficits. Adjuvant brain stimulation is a novel approach to improving the treatment of residual deficits after stroke. Transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and epidural electrical stimulation have been used in first trials on small cohorts of stroke patients. Effect sizes in the order of 8% to 30% of functional improvement have been reported, but a publication bias toward presenting "promising" but not negative results is likely. Many questions regarding underlying mechanisms, optimal stimulation parameters, combination with other types of interventions, among others, are open. This review addresses six controversies related to the experimental application of brain stimulation techniques to stroke patients. Cortical stimulation after stroke will need to be individually tailored and a thorough patient stratification according to type and extent of clinical deficit, lesion location, lesion size, comorbidities, time in the recovery process, and perhaps also age and gender will be necessary. There is consensus that cortical stimulation in stroke patients is still experimental and should only be applied in the frame of scientific studies.

A numerically optimized active shield for improved TMS targeting

PubMed Central

Hernandez-Garcia, Luis; Hall, Timothy; Gomez, Luis; Michielssen, Eric

2010-01-01

Transcranial magnetic stimulation (TMS) devices suffer of poor targeting and penetration depth. A new approach to designing TMS coils is introduced in order to improve the focus of the stimulation region through the use of actively shielded probes. Iterative optimization techniques were used to design different active shielding coils for TMS probes. The new approach aims to increase the amount of energy deposited in a thin cylindrical region below the probe relative to the energy deposited elsewhere in the region (“sharpness”), while simultaneously increase the induced electric field deep in the target region relative to the surface (“penetration”). After convergence, the resulting designs showed that there is a clear tradeoff between sharpness and penetration that can be controlled by the choice of a tuning parameter. The resulting designs were tested on a realistic human head conductivity model, taking the contribution from surface charges into account. The design of choice reduced penetration depths by 16.7%. The activated surface area was reduced by 24.1 % and the volume of the activation was reduced from 42.6% by the shield. Restoring the lost penetration could be achieved by increasing the total power to the coil by 16.3%, but in that case, the stimulated volume reduction was only 13.1% and there was a slight increase in the stimulated surface area (2.9 %) PMID:20965451

[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.

Optimal control of multiphoton ionization dynamics of small alkali aggregates

NASA Astrophysics Data System (ADS)

Lindinger, A.; Bartelt, A.; Lupulescu, C.; Vajda, S.; Woste, Ludger

2003-11-01

We have performed transient multi-photon ionization experiments on small alkali clusters of different size in order to probe their wave packet dynamics, structural reorientations, charge transfers and dissociative events in different vibrationally excited electronic states including their ground state. The observed processes were highly dependent on the irradiated pulse parameters like wavelength range or its phase and amplitude; an emphasis to employ a feedback control system for generating the optimum pulse shapes. Their spectral and temporal behavior reflects interesting properties about the investigated system and the irradiated photo-chemical process. First, we present the vibrational dynamics of bound electronically excited states of alkali dimers and trimers. The scheme for observing the wave packet dynamics in the electronic ground state using stimulated Raman-pumping is shown. Since the employed pulse parameters significantly influence the efficiency of the irradiated dynamic pathways photo-induced ioniziation experiments were carried out. The controllability of 3-photon ionization pathways is investigated on the model-like systems NaK and K2. A closed learning loop for adaptive feedback control is used to find the optimal fs pulse shape. Sinusoidal parameterizations of the spectral phase modulation are investigated in regard to the obtained optimal field. By reducing the number of parameters and thereby the complexity of the phase moduation, optimal pulse shapes can be generated that carry fingerprints of the molecule's dynamical properties. This enables to find "understandable" optimal pulse forms and offers the possiblity to gain insight into the photo-induced control process. Characteristic motions of the involved wave packets are proposed to explain the optimized dynamic dissociation pathways.

Predicting human chronically paralyzed muscle force: a comparison of three mathematical models.

PubMed

Frey Law, Laura A; Shields, Richard K

2006-03-01

Chronic spinal cord injury (SCI) induces detrimental musculoskeletal adaptations that adversely affect health status, ranging from muscle paralysis and skin ulcerations to osteoporosis. SCI rehabilitative efforts may increasingly focus on preserving the integrity of paralyzed extremities to maximize health quality using electrical stimulation for isometric training and/or functional activities. Subject-specific mathematical muscle models could prove valuable for predicting the forces necessary to achieve therapeutic loading conditions in individuals with paralyzed limbs. Although numerous muscle models are available, three modeling approaches were chosen that can accommodate a variety of stimulation input patterns. To our knowledge, no direct comparisons between models using paralyzed muscle have been reported. The three models include 1) a simple second-order linear model with three parameters and 2) two six-parameter nonlinear models (a second-order nonlinear model and a Hill-derived nonlinear model). Soleus muscle forces from four individuals with complete, chronic SCI were used to optimize each model's parameters (using an increasing and decreasing frequency ramp) and to assess the models' predictive accuracies for constant and variable (doublet) stimulation trains at 5, 10, and 20 Hz in each individual. Despite the large differences in modeling approaches, the mean predicted force errors differed only moderately (8-15% error; P=0.0042), suggesting physiological force can be adequately represented by multiple mathematical constructs. The two nonlinear models predicted specific force characteristics better than the linear model in nearly all stimulation conditions, with minimal differences between the two nonlinear models. Either nonlinear mathematical model can provide reasonable force estimates; individual application needs may dictate the preferred modeling strategy.

How stimulation speed affects Event-Related Potentials and BCI performance.

PubMed

Höhne, Johannes; Tangermann, Michael

2012-01-01

In most paradigms for Brain-Computer Interfaces (BCIs) that are based on Event-Related Potentials (ERPs), stimuli are presented with a pre-defined and constant speed. In order to boost BCI performance by optimizing the parameters of stimulation, this offline study investigates the impact of the stimulus onset asynchrony (SOA) on ERPs and the resulting classification accuracy. The SOA is defined as the time between the onsets of two consecutive stimuli, which represents a measure for stimulation speed. A simple auditory oddball paradigm was tested in 14 SOA conditions with a SOA between 50 ms and 1000 ms. Based on an offline ERP analysis, the BCI performance (quantified by the Information Transfer Rate, ITR in bits/min) was simulated. A great variability in the simulated BCI performance was observed within subjects (N=11). This indicates a potential increase in BCI performance (≥ 1.6 bits/min) for ERP-based paradigms, if the stimulation speed is specified for each user individually.

Measurement of cytoplasmic Ca2+ concentration in Saccharomyces cerevisiae induced by air cold plasma

NASA Astrophysics Data System (ADS)

Xiaoyu, DONG

2018-03-01

In this study, a novel approach to measure the absolute cytoplasmic Ca2+ concentration ([Ca2+]cyt) using the Ca2+ indicator fluo-3 AM was established. The parameters associated with the probe fluo-3 AM were optimized to accurately determine fluorescence intensity from the Ca2+-bound probe. Using three optimized parameters (final concentration of 6 mM probe, incubation time of 135 min, loading probe before plasma treatment), the maximum fluorescence intensity (F max = 527.8 a.u.) and the minimum fluorescence intensity (F min = 63.8 a.u.) were obtained in a saturated Ca2+ solution or a solution of lacking Ca2+. Correspondingly, the maximum [Ca2+]cyt induced by cold plasma was 1232.5 nM. Therefore, the Ca2+ indicator fluo-3 AM was successfully applied to measure the absolute [Ca2+]cyt in Saccharomyces cerevisiae stimulated by cold plasma at atmospheric air pressure.

Impact of uncertain head tissue conductivity in the optimization of transcranial direct current stimulation for an auditory target

NASA Astrophysics Data System (ADS)

Schmidt, Christian; Wagner, Sven; Burger, Martin; van Rienen, Ursula; Wolters, Carsten H.

2015-08-01

Objective. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique to modify neural excitability. Using multi-array tDCS, we investigate the influence of inter-individually varying head tissue conductivity profiles on optimal electrode configurations for an auditory cortex stimulation. Approach. In order to quantify the uncertainty of the optimal electrode configurations, multi-variate generalized polynomial chaos expansions of the model solutions are used based on uncertain conductivity profiles of the compartments skin, skull, gray matter, and white matter. Stochastic measures, probability density functions, and sensitivity of the quantities of interest are investigated for each electrode and the current density at the target with the resulting stimulation protocols visualized on the head surface. Main results. We demonstrate that the optimized stimulation protocols are only comprised of a few active electrodes, with tolerable deviations in the stimulation amplitude of the anode. However, large deviations in the order of the uncertainty in the conductivity profiles could be noted in the stimulation protocol of the compensating cathodes. Regarding these main stimulation electrodes, the stimulation protocol was most sensitive to uncertainty in skull conductivity. Finally, the probability that the current density amplitude in the auditory cortex target region is supra-threshold was below 50%. Significance. The results suggest that an uncertain conductivity profile in computational models of tDCS can have a substantial influence on the prediction of optimal stimulation protocols for stimulation of the auditory cortex. The investigations carried out in this study present a possibility to predict the probability of providing a therapeutic effect with an optimized electrode system for future auditory clinical and experimental procedures of tDCS applications.

A review of the efficacy of transcranial magnetic stimulation (TMS) treatment for depression, and current and future strategies to optimize efficacy.

PubMed

Loo, Colleen K; Mitchell, Philip B

2005-11-01

There is a growing interest in extending the use of repetitive transcranial magnetic stimulation (rTMS) beyond research centres to the widespread clinical treatment of depression. Thus it is timely to critically review the evidence for the efficacy of rTMS as an antidepressant treatment. Factors relevant to the efficacy of rTMS are discussed along with the implications of these for the further optimization of rTMS. Clinical trials of the efficacy of rTMS in depressed subjects are summarized and reviewed, focusing mainly on sham-controlled studies and meta-analyses published to date. There is a fairly consistent statistical evidence for the superiority of rTMS over a sham control, though the degree of clinical improvement is not large. However, this data is derived mainly from two-week comparisons of rTMS versus sham, and evidence suggests greater efficacy with longer treatment courses. Studies so far have also varied greatly in approaches to rTMS stimulation (with respect to stimulation site, stimulus parameters etc) with little empirical evidence to inform on the relative merits of these approaches. Only studies published in English were reviewed. Many of the studies in the literature had small sample sizes and different methodologies, making comparisons between studies difficult. Current published studies and meta-analyses have evaluated the efficacy of rTMS as given in treatment paradigms that are almost certainly suboptimal (e.g of two weeks' duration). While the data nevertheless supports positive outcomes for rTMS, there is much scope for the further refinement and development of rTMS as an antidepressant treatment. Ongoing research is critical for optimizing the efficacy of rTMS.

An optimal beam alignment method for large-scale distributed space surveillance radar system

NASA Astrophysics Data System (ADS)

Huang, Jian; Wang, Dongya; Xia, Shuangzhi

2018-06-01

Large-scale distributed space surveillance radar is a very important ground-based equipment to maintain a complete catalogue for Low Earth Orbit (LEO) space debris. However, due to the thousands of kilometers distance between each sites of the distributed radar system, how to optimally implement the Transmitting/Receiving (T/R) beams alignment in a great space using the narrow beam, which proposed a special and considerable technical challenge in the space surveillance area. According to the common coordinate transformation model and the radar beam space model, we presented a two dimensional projection algorithm for T/R beam using the direction angles, which could visually describe and assess the beam alignment performance. Subsequently, the optimal mathematical models for the orientation angle of the antenna array, the site location and the T/R beam coverage are constructed, and also the beam alignment parameters are precisely solved. At last, we conducted the optimal beam alignment experiments base on the site parameters of Air Force Space Surveillance System (AFSSS). The simulation results demonstrate the correctness and effectiveness of our novel method, which can significantly stimulate the construction for the LEO space debris surveillance equipment.

Pursuing Polymer Dielectric Interfacial Effect in Organic Transistors for Photosensing Performance Optimization.

PubMed

Wu, Xiaohan; Chu, Yingli; Liu, Rui; Katz, Howard E; Huang, Jia

2017-12-01

Polymer dielectrics in organic field-effect transistors (OFETs) are essential to provide the devices with overall flexibility, stretchability, and printability and simultaneously introduce charge interaction on the interface with organic semiconductors (OSCs). The interfacial effect between various polymer dielectrics and OSCs significantly and intricately influences device performance. However, understanding of this effect is limited because the interface is buried and the interfacial charge interaction is difficult to stimulate and characterize. Here, this challenge is overcome by utilizing illumination to stimulate the interfacial effect in various OFETs and to characterize the responses of the effect by measuring photoinduced changes of the OFETs performances. This systemic investigation reveals the mechanism of the intricate interfacial effect in detail, and mathematically explains how the photosensitive OFETs characteristics are determined by parameters including polar group of the polymer dielectric and the OSC side chain. By utilizing this mechanism, performance of organic electronics can be precisely controlled and optimized. OFETs with strong interfacial effect can also show a signal additivity caused by repeated light pulses, which is applicable for photostimulated synapse emulator. Therefore, this work enlightens a detailed understanding on the interface effect and provides novel strategies for optimizing OFET photosensory performances.

Optimal arrangement of magnetic coils for functional magnetic stimulation of the inspiratory muscles in dogs.

PubMed

Lin, Vernon Weh-Hau; Zhu, Ercheng; Sasse, Scott A; Sassoon, Catherine; Hsiao, Ian N

2005-12-01

In an attempt to maximize inspiratory pressure and volume, the optimal position of a single or of dual magnetic coils during functional magnetic stimulation (FMS) of the inspiratory muscles was evaluated in twenty-three dogs. Unilateral phrenic magnetic stimulation (UPMS) or bilateral phrenic magnetic stimulation (BPMS), posterior cervical magnetic stimulation (PCMS), anterior cervical magnetic stimulation (ACMS) as well as a combination of PCMS and ACMS were performed. Trans-diaphragmatic pressure (Pdi), flow, and lung volume changes with an open airway were measured. Transdiaphragmatic pressure was also measured with an occluded airway. Changes in inspiratory parameters during FMS were compared with 1) electrical stimulation of surgically exposed bilateral phrenic nerves (BPES) and 2) ventral root electrical stimulation at C5-C7 (VRES C5-C7). Relative to the Pdi generated by BPES of 36.3 +/- 4.5 cm H2O (Mean +/- SEM), occluded Pdi(s) produced by UPMS, BPMS, PCMS, ACMS, and a combined PCMS + ACMS were 51.7%, 61.5%, 22.4%, 100.3%, and 104.5% of the maximal Pdi, respectively. Pdi(s) produced by UPMS, BPMS, PCMS, ACMS, and combined ACMS + PCMS were 38.0%, 45.2%, 16.5%, 73.8%, and 76.8%, respectively, of the Pdi induced by VRES (C5-C7) (48.0 +/- 3.9 cm H2O). The maximal Pdi(s) generated during ACMS and combined PCMS + ACMS were higher than the maximal Pdi(s) generated during UPMS, BPMS, or PCMS (p < 0.05). ACMS alone induced 129.8% of the inspiratory flow (73.0 +/- 9.4 L/ min) and 77.5% of the volume (626 +/- 556 ml) induced by BPES. ACMS and combined PCMS + ACMS produce a greater inspiratory pressure than UPMS, BPMS or PCMS. ACMS can be used to generate sufficient inspiratory pressure, flow, and volume for activation of the inspiratory muscles.

Verification of an optimized stimulation point on the abdominal wall for transcutaneous neuromuscular electrical stimulation for activation of deep lumbar stabilizing muscles.

PubMed

Baek, Seung Ok; Cho, Hee Kyung; Jung, Gil Su; Son, Su Min; Cho, Yun Woo; Ahn, Sang Ho

2014-09-01

Transcutaneous neuromuscular electrical stimulation (NMES) can stimulate contractions in deep lumbar stabilizing muscles. An optimal protocol has not been devised for the activation of these muscles by NMES, and information is lacking regarding an optimal stimulation point on the abdominal wall. The goal was to determine a single optimized stimulation point on the abdominal wall for transcutaneous NMES for the activation of deep lumbar stabilizing muscles. Ultrasound images of the spinal stabilizing muscles were captured during NMES at three sites on the lateral abdominal wall. After an optimal location for the placement of the electrodes was determined, changes in the thickness of the lumbar multifidus (LM) were measured during NMES. Three stimulation points were investigated using 20 healthy physically active male volunteers. A reference point R, 1 cm superior to the iliac crest along the midaxillary line, was used. Three study points were used: stimulation point S1 was located 2 cm superior and 2 cm medial to the anterior superior iliac spine, stimulation point S3 was 2 cm below the lowest rib along the same sagittal plane as S1, and stimulation point S2 was midway between S1 and S3. Sessions were conducted stimulating at S1, S2, or S3 using R for reference. Real-time ultrasound imaging (RUSI) of the abdominal muscles was captured during each stimulation session. In addition, RUSI images were captured of the LM during stimulation at S1. Thickness, as measured by RUSI, of the transverse abdominis (TrA), obliquus internus, and obliquus externus was greater during NMES than at rest for all three study points (p<.05). Transverse abdominis was significantly stimulated more by NMES at S1 than at the other points (p<.05). The LM thickness was also significantly greater during NMES at S1 than at rest (p<.05). Neuromuscular electrical stimulation at S1 optimally activated deep spinal stabilizing muscles, TrA and LM, as evidenced by RUSI. The authors recommend this optimal stimulation point be used for NMES in the course of lumbar spine stabilization training in patients having difficulty initiating contraction of these muscles. Copyright © 2014 Elsevier Inc. All rights reserved.

Frequency dependence of behavioral modulation by hippocampal electrical stimulation

PubMed Central

La Corte, Giorgio; Wei, Yina; Chernyy, Nick; Gluckman, Bruce J.

2013-01-01

Electrical stimulation offers the potential to develop novel strategies for the treatment of refractory medial temporal lobe epilepsy. In particular, direct electrical stimulation of the hippocampus presents the opportunity to modulate pathological dynamics at the ictal focus, although the neuroanatomical substrate of this region renders it susceptible to altering cognition and affective processing as a side effect. We investigated the effects of three electrical stimulation paradigms on separate groups of freely moving rats (sham, 8-Hz and 40-Hz sine-wave stimulation of the ventral/intermediate hippocampus, where 8- and 40-Hz stimulation were chosen to mimic naturally occurring hippocampal oscillations). Animals exhibited attenuated locomotor and exploratory activity upon stimulation at 40 Hz, but not at sham or 8-Hz stimulation. Such behavioral modifications were characterized by a significant reduction in rearing frequency, together with increased freezing behavior. Logistic regression analysis linked the observed changes in animal locomotion to 40-Hz electrical stimulation independently of time-related variables occurring during testing. Spectral analysis, conducted to monitor the electrophysiological profile in the CA1 area of the dorsal hippocampus, showed a significant reduction in peak theta frequency, together with reduced theta power in the 40-Hz vs. the sham stimulation animal group, independent of locomotion speed (theta range: 4–12 Hz). These findings contribute to the development of novel and safe medical protocols by indicating a strategy to constrain or optimize parameters in direct hippocampal electrical stimulation. PMID:24198322

Increasing spatial resolution and comparison of MR imaging sequences for the inner ear

NASA Astrophysics Data System (ADS)

Snyder, Carl J.; Bolinger, Lizann; Rubinstein, Jay T.; Wang, Ge

2002-04-01

The size and location of the cochlea and cochlear nerve are needed to assess the feasibility of cochlea implantation, provide information for surgical planning, and aid in construction of cochlear models. Models of implant stimulation incorporating anatomical and physiological information are likely to provide a better understanding of the biophysics of information transferred with cochlear implants and aid in electrode design and arrangement on cochlear implants. Until recently MR did not provide the necessary image resolution and suffered from long acquisition times. The purpose of this study was to optimize both Fast Spin Echo (FSE) and Steady State Free Precession (FIESTA) imaging scan parameters for the inner ear and comparatively examine both for improved image quality and increased spatial resolution. Image quality was determined by two primary measurements, signal to noise ratio (SNR), and image sharpness. Optimized parameters for FSE were 120ms, 3000ms, 64, and 32.25kHz for the TE, TR, echo train length, and bandwidth, respectively. FIESTA parameters were optimized to 2.7, 5.5ms, 70 degree(s), and 62.5kHz, for TE, TR, flip angle, and bandwidth, respectively. While both had the same in-plane spatial resolution, 0.625mm, FIESTA data shows higher SNR per acquisition time and better edge sharpness.

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.

Optimization of SSVEP brain responses with application to eight-command Brain-Computer Interface.

PubMed

Bakardjian, Hovagim; Tanaka, Toshihisa; Cichocki, Andrzej

2010-01-18

This study pursues the optimization of the brain responses to small reversing patterns in a Steady-State Visual Evoked Potentials (SSVEP) paradigm, which could be used to maximize the efficiency of applications such as Brain-Computer Interfaces (BCI). We investigated the SSVEP frequency response for 32 frequencies (5-84 Hz), and the time dynamics of the brain response at 8, 14 and 28 Hz, to aid the definition of the optimal neurophysiological parameters and to outline the onset-delay and other limitations of SSVEP stimuli in applications such as our previously described four-command BCI system. Our results showed that the 5.6-15.3 Hz pattern reversal stimulation evoked the strongest responses, peaking at 12 Hz, and exhibiting weaker local maxima at 28 and 42 Hz. After stimulation onset, the long-term SSVEP response was highly non-stationary and the dynamics, including the first peak, was frequency-dependent. The evaluation of the performance of a frequency-optimized eight-command BCI system with dynamic neurofeedback showed a mean success rate of 98%, and a time delay of 3.4s. Robust BCI performance was achieved by all subjects even when using numerous small patterns clustered very close to each other and moving rapidly in 2D space. These results emphasize the need for SSVEP applications to optimize not only the analysis algorithms but also the stimuli in order to maximize the brain responses they rely on. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

A novel combinational approach of microstimulation and bioluminescence imaging to study the mechanisms of action of cerebral electrical stimulation in mice

PubMed Central

Arsenault, Dany; Drouin-Ouellet, Janelle; Saint-Pierre, Martine; Petrou, Petros; Dubois, Marilyn; Kriz, Jasna; Barker, Roger A; Cicchetti, Antonio; Cicchetti, Francesca

2015-01-01

Key points We have developed a unique prototype to perform brain stimulation in mice. This system presents a number of advantages and new developments: 1) all stimulation parameters can be adjusted, 2) both positive and negative current pulses can be generated, guaranteeing electrically balanced stimulation regimen, 3) which can be produced with both low and high impedance electrodes, 4) the developed electrodes ensure localized stimulation and 5) can be used to stimulate and/or record brain potential and 6) in vivo recording of electric pulses allows the detection of defective electrodes (wire breakage or short circuits). This new micro-stimulator device further allows simultaneous live bioluminescence imaging of the mouse brain, enabling real time assessment of the impact of stimulation on cerebral tissue. The use of this novel tool in various transgenic mouse models of disease opens up a whole new range of possibilities in better understanding brain stimulation. Abstract Deep brain stimulation (DBS) is used to treat a number of neurological conditions and is currently being tested to intervene in neuropsychiatric conditions. However, a better understanding of how it works would ensure that side effects could be minimized and benefits optimized. We have thus developed a unique device to perform brain stimulation (BS) in mice and to address fundamental issues related to this methodology in the pre-clinical setting. This new microstimulator prototype was specifically designed to allow simultaneous live bioluminescence imaging of the mouse brain, allowing real time assessment of the impact of stimulation on cerebral tissue. We validated the authenticity of this tool in vivo by analysing the expression of toll-like receptor 2 (TLR2), corresponding to the microglial response, in the stimulated brain regions of TLR2-fluc-GFP transgenic mice, which we further corroborated with post-mortem analyses in these animals as well as in human brains of patients who underwent DBS to treat their Parkinson's disease. In the present study, we report on the development of the first BS device that allows for simultaneous live in vivo imaging in mice. This tool opens up a whole new range of possibilities that allow a better understanding of BS and how to optimize its effects through its use in murine models of disease. PMID:25653107

Neuromuscular Electrical Stimulation for Treatment of Muscle Impairment: Critical Review and Recommendations for Clinical Practice

PubMed Central

Houghton, Pamela; Anthony, Joseph; Rennie, Sandy; Shay, Barbara L.; Hoens, Alison M.

2017-01-01

Purpose: In response to requests from physiotherapists for guidance on optimal stimulation of muscle using neuromuscular electrical stimulation (NMES), a review, synthesis, and extraction of key data from the literature was undertaken by six Canadian physical therapy (PT) educators, clinicians, and researchers in the field of electrophysical agents. The objective was to identify commonly treated conditions for which there was a substantial body of literature from which to draw conclusions regarding the effectiveness of NMES. Included studies had to apply NMES with visible and tetanic muscle contractions. Method: Four electronic databases (CINAHL, Embase, PUBMED, and SCOPUS) were searched for relevant literature published between database inceptions until May 2015. Additional articles were identified from bibliographies of the systematic reviews and from personal collections. Results: The extracted data were synthesized using a consensus process among the authors to provide recommendations for optimal stimulation parameters and application techniques to address muscle impairments associated with the following conditions: stroke (upper or lower extremity; both acute and chronic), anterior cruciate ligament reconstruction, patellofemoral pain syndrome, knee osteoarthritis, and total knee arthroplasty as well as critical illness and advanced disease states. Summaries of key details from each study incorporated into the review were also developed. The final sections of the article outline the recommended terminology for describing practice using electrical currents and provide tips for safe and effective clinical practice using NMES. Conclusion: This article provides physiotherapists with a resource to enable evidence-informed, effective use of NMES for PT practice. PMID:29162949

Music acupuncture stimulation method.

PubMed

Brătilă, F; Moldovan, C

2007-01-01

Harmonic Medicine is the model using the theory that the body rhythms synchronize to an outer rhythm applied for therapeutic purpose, can restores the energy balance in acupuncture channels and organs and the condition of well-being. The purpose of this scientific work was to demonstrate the role played by harmonic sounds in the stimulation of the Lung (LU) Meridian (Shoutaiyin Feijing) and of the Kidney (KI) Meridian (Zushaoyin Shenjing). It was used an original method that included: measurement and electronic sound stimulation of the Meridian Entry Point, measurement of Meridian Exit Point, computer data processing, bio feed-back adjustment of the music stimulation parameters. After data processing, it was found that the sound stimulation of the Lung Meridian Frequency is optimal between 122 Hz and 128 Hz, with an average of 124 Hz (87% of the subjects) and for Kidney Meridian from 118 Hz to 121 Hz, with an average of 120 Hz (67% of the subjects). The acupuncture stimulation was more intense for female subjects (> 7%) than for the male ones. We preliminarily consider that an informational resonance phenomenon can be developed between the acupuncture music stimulation frequency and the cellular dipole frequency, being a really "resonant frequency signature" of an acupoint. The harmonic generation and the electronic excitation or low-excitation status of an acupuncture point may be considered as a resonance mechanism. By this kind of acupunctural stimulation, a symphony may act and play a healer role.

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.

Black holes are almost optimal quantum cloners

NASA Astrophysics Data System (ADS)

Adami, Christoph; Ver Steeg, Greg

2015-06-01

If black holes were able to clone quantum states, a number of paradoxes in black hole physics would disappear. However, the linearity of quantum mechanics forbids exact cloning of quantum states. Here we show that black holes indeed clone incoming quantum states with a fidelity that depends on the black hole’s absorption coefficient, without violating the no-cloning theorem because the clones are only approximate. Perfectly reflecting black holes are optimal universal ‘quantum cloning machines’ and operate on the principle of stimulated emission, exactly as their quantum optical counterparts. In the limit of perfect absorption, the fidelity of clones is only equal to what can be obtained via quantum state estimation methods. But for any absorption probability less than one, the cloning fidelity is nearly optimal as long as ω /T≥slant 10, a common parameter for modest-sized black holes.

The development and modeling of devices and paradigms for transcranial magnetic stimulation

PubMed Central

Goetz, Stefan M.; Deng, Zhi-De

2017-01-01

Magnetic stimulation is a noninvasive neurostimulation technique that can evoke action potentials and modulate neural circuits through induced electric fields. Biophysical models of magnetic stimulation have become a major driver for technological developments and the understanding of the mechanisms of magnetic neurostimulation and neuromodulation. Major technological developments involve stimulation coils with different spatial characteristics and pulse sources to control the pulse waveform. While early technological developments were the result of manual design and invention processes, there is a trend in both stimulation coil and pulse source design to mathematically optimize parameters with the help of computational models. To date, macroscopically highly realistic spatial models of the brain as well as peripheral targets, and user-friendly software packages enable researchers and practitioners to simulate the treatment-specific and induced electric field distribution in the brains of individual subjects and patients. Neuron models further introduce the microscopic level of neural activation to understand the influence of activation dynamics in response to different pulse shapes. A number of models that were designed for online calibration to extract otherwise covert information and biomarkers from the neural system recently form a third branch of modeling. PMID:28443696

On the single sweep processing of auditory brainstem responses: click vs. chirp stimulations and active vs. passive electrodes.

PubMed

Corona-Strauss, Farah I; Delb, Wolfgang; Bloching, Marc; Strauss, Daniel J

2008-01-01

We have recently shown that click evoked auditory brainstem responses (ABRs) single sweeps can efficiently be processed by a hybrid novelty detection system. This approach allowed for the objective detection of hearing thresholds in a fraction of time of conventional schemes, making it appropriate for the efficient implementation of newborn hearing screening procedures. It is the objective of this study to evaluate whether this approach might further be improved by different stimulation paradigms and electrode settings. In particular, we evaluate chirp stimulations which compensate the basilar-membrane dispersion and active electrodes which are less sensitive to movements. This is the first study which is directed to a single sweep processing of chirp evoked ABRs. By concentrating on transparent features and a minimum number of adjustable parameters, we present an objective comparison of click vs.chirp stimulations and active vs. passive electrodes in the ultrafast ABR detection. We show that chirp evoked brainstem responses and active electrodes might improve the single sweeps analysis of ABRs.Consequently, we conclude that a single sweep processing of ABRs for the objective determination of hearing thresholds can further be improved by the use of optimized chirp stimulations and active electrodes.

The development and modelling of devices and paradigms for transcranial magnetic stimulation.

PubMed

Goetz, Stefan M; Deng, Zhi-De

2017-04-01

Magnetic stimulation is a non-invasive neurostimulation technique that can evoke action potentials and modulate neural circuits through induced electric fields. Biophysical models of magnetic stimulation have become a major driver for technological developments and the understanding of the mechanisms of magnetic neurostimulation and neuromodulation. Major technological developments involve stimulation coils with different spatial characteristics and pulse sources to control the pulse waveform. While early technological developments were the result of manual design and invention processes, there is a trend in both stimulation coil and pulse source design to mathematically optimize parameters with the help of computational models. To date, macroscopically highly realistic spatial models of the brain, as well as peripheral targets, and user-friendly software packages enable researchers and practitioners to simulate the treatment-specific and induced electric field distribution in the brains of individual subjects and patients. Neuron models further introduce the microscopic level of neural activation to understand the influence of activation dynamics in response to different pulse shapes. A number of models that were designed for online calibration to extract otherwise covert information and biomarkers from the neural system recently form a third branch of modelling.

Vagus Nerve Stimulation Applied with a Rapid Cycle Has More Profound Influence on Hippocampal Electrophysiology Than a Standard Cycle.

PubMed

Larsen, Lars E; Wadman, Wytse J; Marinazzo, Daniele; van Mierlo, Pieter; Delbeke, Jean; Daelemans, Sofie; Sprengers, Mathieu; Thyrion, Lisa; Van Lysebettens, Wouter; Carrette, Evelien; Boon, Paul; Vonck, Kristl; Raedt, Robrecht

2016-07-01

Although vagus nerve stimulation (VNS) is widely used, therapeutic mechanisms and optimal stimulation parameters remain elusive. In the present study, we investigated the effect of VNS on hippocampal field activity and compared the efficiency of different VNS paradigms. Hippocampal electroencephalography (EEG) and perforant path dentate field-evoked potentials were acquired before and during VNS in freely moving rats, using 2 VNS duty cycles: a rapid cycle (7 s on, 18 s off) and standard cycle (30 s on, 300 s off) and various output currents. VNS modulated the evoked potentials, reduced total power of the hippocampal EEG, and slowed the theta rhythm. In the hippocampal EEG, theta (4-8 Hz) and high gamma (75-150 Hz) activity displayed strong phase amplitude coupling that was reduced by VNS. Rapid-cycle VNS had a greater effect than standard-cycle VNS on all outcome measures. Using rapid cycle VNS, a maximal effect on EEG parameters was found at 300 μA, beyond which effects saturated. The findings suggest that rapid-cycle VNS produces a more robust outcome than standard cycle VNS and support already existing preclinical evidence that relatively low output currents are sufficient to produce changes in brain physiology and thus likely also therapeutic efficacy.

Pulse duration settings in subthalamic stimulation for Parkinson's disease

PubMed Central

Steigerwald, Frank; Timmermann, Lars; Kühn, Andrea; Schnitzler, Alfons; Reich, Martin M.; Kirsch, Anna Dalal; Barbe, Michael Thomas; Visser‐Vandewalle, Veerle; Hübl, Julius; van Riesen, Christoph; Groiss, Stefan Jun; Moldovan, Alexia‐Sabine; Lin, Sherry; Carcieri, Stephen; Manola, Ljubomir

2017-01-01

ABSTRACT Background Stimulation parameters in deep brain stimulation (DBS) of the subthalamic nucleus for Parkinson's disease (PD) are rarely tested in double‐blind conditions. Evidence‐based recommendations on optimal stimulator settings are needed. Results from the CUSTOM‐DBS study are reported, comparing 2 pulse durations. Methods A total of 15 patients were programmed using a pulse width of 30 µs (test) or 60 µs (control). Efficacy and side‐effect thresholds and unified PD rating scale (UPDRS) III were measured in meds‐off (primary outcome). The therapeutic window was the difference between patients’ efficacy and side effect thresholds. Results The therapeutic window was significantly larger at 30 µs than 60 µs (P = ·0009) and the efficacy (UPDRS III score) was noninferior (P = .00008). Interpretation Subthalamic neurostimulation at 30 µs versus 60 µs pulse width is equally effective on PD motor signs, is more energy efficient, and has less likelihood of stimulation‐related side effects. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. PMID:29165837

Real-time and wearable functional electrical stimulation system for volitional hand motor function control using the electromyography bridge method

PubMed Central

Wang, Hai-peng; Bi, Zheng-yang; Zhou, Yang; Zhou, Yu-xuan; Wang, Zhi-gong; Lv, Xiao-ying

2017-01-01

Voluntary participation of hemiplegic patients is crucial for functional electrical stimulation therapy. A wearable functional electrical stimulation system has been proposed for real-time volitional hand motor function control using the electromyography bridge method. Through a series of novel design concepts, including the integration of a detecting circuit and an analog-to-digital converter, a miniaturized functional electrical stimulation circuit technique, a low-power super-regeneration chip for wireless receiving, and two wearable armbands, a prototype system has been established with reduced size, power, and overall cost. Based on wrist joint torque reproduction and classification experiments performed on six healthy subjects, the optimized surface electromyography thresholds and trained logistic regression classifier parameters were statistically chosen to establish wrist and hand motion control with high accuracy. Test results showed that wrist flexion/extension, hand grasp, and finger extension could be reproduced with high accuracy and low latency. This system can build a bridge of information transmission between healthy limbs and paralyzed limbs, effectively improve voluntary participation of hemiplegic patients, and elevate efficiency of rehabilitation training. PMID:28250759

Correlation of spatial intensity distribution of light reaching the retina and restoration of vision by optogenetic stimulation

NASA Astrophysics Data System (ADS)

Shivalingaiah, Shivaranjani; Gu, Ling; Mohanty, Samarendra K.

2011-03-01

Stimulation of retinal neuronal cells using optogenetics via use of chanelrhodopsin-2 (ChR2) and blue light has opened up a new direction for restoration of vision with respect to treatment of Retinitis pigmentosa (RP). In addition to delivery of ChR2 to specific retinal layer using genetic engineering, threshold level of blue light needs to be delivered onto the retina for generating action potential and successful behavioral outcome. We report measurement of intensity distribution of light reaching the retina of Retinitis pigmentosa (RP) mouse models and compared those results with theoretical simulations of light propagation in eye. The parameters for the stimulating source positioning in front of eye was determined for optimal light delivery to the retina. In contrast to earlier viral method based delivery of ChR2 onto retinal ganglion cells, in-vivo electroporation method was employed for retina-transfection of RP mice. The behavioral improvement in mice with Thy1-ChR2-YFP transfected retina, expressing ChR2 in retinal ganglion cells, was found to correlate with stimulation intensity.

Hippocampal closed-loop modeling and implications for seizure stimulation design

NASA Astrophysics Data System (ADS)

Sandler, Roman A.; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.; Marmarelis, Vasilis Z.

2015-10-01

Objective. Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the entorhinal cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Approach. Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3 → CA1, via the schaffer-collateral synapse, and CA1 → CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (principal dynamic modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Main results. Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Significance. Deep-brain stimulation (DBS) is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy.

Hippocampal closed-loop modeling and implications for seizure stimulation design.

PubMed

Sandler, Roman A; Song, Dong; Hampson, Robert E; Deadwyler, Sam A; Berger, Theodore W; Marmarelis, Vasilis Z

2015-10-01

Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the entorhinal cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3 → CA1, via the schaffer-collateral synapse, and CA1 → CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (principal dynamic modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Deep-brain stimulation (DBS) is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy.

The effect of single and repeated prefrontal intermittent theta burst stimulation on cortical reactivity and working memory.

PubMed

Chung, Sung Wook; Rogasch, Nigel C; Hoy, Kate E; Fitzgerald, Paul B

With an increasing interest in the use of theta burst stimulation (TBS) as a cognitive enhancer and a potential therapeutic tool for psychiatric disorders, there is a need to identify optimal parameters of TBS in the prefrontal cortex. This study examined the effect of two blocks of prefrontal intermittent TBS (iTBS) on cortical reactivity and working memory performance, compared to one block of iTBS and sham stimulation. We hypothesized that greater cortical effects would be obtained with two blocks of iTBS. Eighteen healthy participants attended three experimental sessions and received either sham, one block or two blocks of iTBS with a 15-min interval. Concurrent transcranial magnetic stimulation with electroencephalography (TMS-EEG) was used to assess the change in cortical reactivity via TMS-evoked potentials. Working memory performance was assessed using the N-back task. Cluster-based permutation statistics and two-way ANOVAs were used for neurophysiological and behavioural data, respectively. Both single and two blocks of iTBS resulted in a significant increase in the amplitude of TMS-evoked N100 and P200. No significant differences were observed between active conditions in either neurophysiological changes or working memory performance, and both failed to improve working memory performance relative to sham. Two blocks of iTBS did not result in stronger measured effects as compared to one block of iTBS. Future studies are needed to identify the optimal stimulation pattern in order to achieve a desired effect. It is also important to establish the best approach in quantifying neuromodulatory effects targeting the prefrontal cortex. Copyright © 2018 Elsevier Inc. All rights reserved.

Controlled release of optimized electroporation enhances the transdermal efficiency of sinomenine hydrochloride for treating arthritis in vitro and in clinic

PubMed Central

Feng, Shun; Zhu, Lijun; Huang, Zhisheng; Wang, Haojia; Li, Hong; Zhou, Hua; Lu, Linlin; Wang, Ying; Liu, Zhongqiu; Liu, Liang

2017-01-01

Sinomenine hydrochloride (SH) is an ideal drug for the treatment of rheumatoid arthritis and osteoarthritis. However, high plasma concentration of systemically administered SH can release histamine, which can cause rash and gastrointestinal side effects. Topical delivery can increase SH concentration in the synovial fluid without high plasma level, thus minimizing systemic side effects. However, passive diffusion of SH was found to be inefficient because of the presence of the stratum corneum layer. Therefore, an effective method is required to compensate for the low efficiency of SH passive diffusion. In this study, transdermal experiments in vitro and clinical tests were utilized to explore the optimized parameters for electroporation of topical delivery for SH. Fluorescence experiment and hematoxylin and eosin staining analysis were performed to reveal the mechanism by which electroporation promoted permeation. In vitro, optimized electroporation parameters were 3 KHz, exponential waveform, and intensity 10. Using these parameters, transdermal permeation of SH was increased by 1.9–10.1 fold in mice skin and by 1.6–47.1 fold in miniature pig skin compared with passive diffusion. After the electroporation stimulation, the intercellular intervals and epidermal cracks in the skin increased. In clinical tests, SH concentration in synovial fluid was 20.84 ng/mL after treatment with electroporation. Therefore, electroporation with optimized parameters could significantly enhance transdermal permeation of SH. The mechanism by which electroporation promoted permeation was that the electronic pulses made the skin structure looser. To summarize, electroporation may be an effective complementary method for transdermal permeation of SH. The controlled release of electroporation may be a promising clinical method for transdermal drug administration. PMID:28670109

Locally optimal extracellular stimulation for chaotic desynchronization of neural populations.

PubMed

Wilson, Dan; Moehlis, Jeff

2014-10-01

We use optimal control theory to design a methodology to find locally optimal stimuli for desynchronization of a model of neurons with extracellular stimulation. This methodology yields stimuli which lead to positive Lyapunov exponents, and hence desynchronizes a neural population. We analyze this methodology in the presence of interneuron coupling to make predictions about the strength of stimulation required to overcome synchronizing effects of coupling. This methodology suggests a powerful alternative to pulsatile stimuli for deep brain stimulation as it uses less energy than pulsatile stimuli, and could eliminate the time consuming tuning process.

Stimulated Brillouin scattering materials, experimental design and applications: A review

NASA Astrophysics Data System (ADS)

Bai, Zhenxu; Yuan, Hang; Liu, Zhaohong; Xu, Pengbai; Gao, Qilin; Williams, Robert J.; Kitzler, Ondrej; Mildren, Richard P.; Wang, Yulei; Lu, Zhiwei

2018-01-01

Stimulated Brillouin scattering (SBS), as one type of third-order nonlinear optics effect, is extensively exploited and rapidly developed in the field of lasers and optoelectronics. A large number of theoretical and experimental studies on SBS have been carried out in the past decades. Especially, the exploration of new SBS materials and new types of SBS modulation methods have been engaged simultaneously, as the properties of different materials have great influence on the SBS performance such as generation threshold, Brillouin amplification efficiency, frequency shift, breakdown threshold, etc. This article provides a comprehensive review of the characteristics of different types of SBS materials, SBS applications, experimental design methods, as well as the parameter optimization method, which is expected to provide reference and guidance to SBS related experiments.

A PC-based shutter glasses controller for visual stimulation using multithreading in LabWindows/CVI.

PubMed

Gramatikov, Ivan; Simons, Kurt; Guyton, David; Gramatikov, Boris

2017-05-01

Amblyopia, commonly known as "lazy eye," is poor vision in an eye from prolonged neurologic suppression. It is a major public health problem, afflicting up to 3.6% of children, and will lead to lifelong visual impairment if not identified and treated in early childhood. Traditional treatment methods, such as occluding or penalizing the good eye with eye patches or blurring eye drops, do not always yield satisfactory results. Newer methods have emerged, based on liquid crystal shutter glasses that intermittently occlude the better eye, or alternately occlude the two eyes, thus stimulating vision in the "lazy" eye. As yet there is no technology that allows easy and efficient optimization of the shuttering characteristics for a given individual. The purpose of this study was to develop an inexpensive, computer-based system to perform liquid crystal shuttering in laboratory and clinical settings to help "wake up" the suppressed eye in amblyopic patients, and to help optimize the individual shuttering parameters such as wave shape, level of transparency/opacity, frequency, and duty cycle of the shuttering. We developed a liquid crystal glasses controller connected by USB cable to a PC computer. It generates the voltage waveforms going to the glasses, and has potentiometer knobs for interactive adjustments by the patient. In order to achieve good timing performance in this bidirectional system, we used multithreading programming techniques with data protection, implemented in LabWindows/CVI. The hardware and software developed were assessed experimentally. We achieved an accuracy of ±1Hz for the frequency, and ±2% for the duty cycle of the occlusion pulses. We consider these values to be satisfactory for the purpose of optimizing the visual stimulation by means of shutter glasses. The system can be used for individual optimization of shuttering attributes by clinicians, for training sessions in clinical settings, or even at home, aimed at stimulating vision in the "lazy" eye. Multithreading offers significant benefits for data acquisition and instrument control, making it possible to implement time-efficient algorithms in inexpensive yet versatile medical instrumentation with only minimum requirements on the hardware. Copyright © 2017 Elsevier B.V. All rights reserved.

Transcranial Electrical Neuromodulation Based on the Reciprocity Principle

PubMed Central

Fernández-Corazza, Mariano; Turovets, Sergei; Luu, Phan; Anderson, Erik; Tucker, Don

2016-01-01

A key challenge in multi-electrode transcranial electrical stimulation (TES) or transcranial direct current stimulation (tDCS) is to find a current injection pattern that delivers the necessary current density at a target and minimizes it in the rest of the head, which is mathematically modeled as an optimization problem. Such an optimization with the Least Squares (LS) or Linearly Constrained Minimum Variance (LCMV) algorithms is generally computationally expensive and requires multiple independent current sources. Based on the reciprocity principle in electroencephalography (EEG) and TES, it could be possible to find the optimal TES patterns quickly whenever the solution of the forward EEG problem is available for a brain region of interest. Here, we investigate the reciprocity principle as a guideline for finding optimal current injection patterns in TES that comply with safety constraints. We define four different trial cortical targets in a detailed seven-tissue finite element head model, and analyze the performance of the reciprocity family of TES methods in terms of electrode density, targeting error, focality, intensity, and directionality using the LS and LCMV solutions as the reference standards. It is found that the reciprocity algorithms show good performance comparable to the LCMV and LS solutions. Comparing the 128 and 256 electrode cases, we found that use of greater electrode density improves focality, directionality, and intensity parameters. The results show that reciprocity principle can be used to quickly determine optimal current injection patterns in TES and help to simplify TES protocols that are consistent with hardware and software availability and with safety constraints. PMID:27303311

Transcranial Electrical Neuromodulation Based on the Reciprocity Principle.

PubMed

Fernández-Corazza, Mariano; Turovets, Sergei; Luu, Phan; Anderson, Erik; Tucker, Don

2016-01-01

A key challenge in multi-electrode transcranial electrical stimulation (TES) or transcranial direct current stimulation (tDCS) is to find a current injection pattern that delivers the necessary current density at a target and minimizes it in the rest of the head, which is mathematically modeled as an optimization problem. Such an optimization with the Least Squares (LS) or Linearly Constrained Minimum Variance (LCMV) algorithms is generally computationally expensive and requires multiple independent current sources. Based on the reciprocity principle in electroencephalography (EEG) and TES, it could be possible to find the optimal TES patterns quickly whenever the solution of the forward EEG problem is available for a brain region of interest. Here, we investigate the reciprocity principle as a guideline for finding optimal current injection patterns in TES that comply with safety constraints. We define four different trial cortical targets in a detailed seven-tissue finite element head model, and analyze the performance of the reciprocity family of TES methods in terms of electrode density, targeting error, focality, intensity, and directionality using the LS and LCMV solutions as the reference standards. It is found that the reciprocity algorithms show good performance comparable to the LCMV and LS solutions. Comparing the 128 and 256 electrode cases, we found that use of greater electrode density improves focality, directionality, and intensity parameters. The results show that reciprocity principle can be used to quickly determine optimal current injection patterns in TES and help to simplify TES protocols that are consistent with hardware and software availability and with safety constraints.

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.

On the efficiency of FES cycling: a framework and systematic review.

PubMed

Hunt, K J; Fang, J; Saengsuwan, J; Grob, M; Laubacher, M

2012-01-01

Research and development in the art of cycling using functional electrical stimulation (FES) of the paralysed leg muscles has been going on for around thirty years. A range of physiological benefits has been observed in clinical studies but an outstanding problem with FES-cycling is that efficiency and power output are very low. The present work had the following aims: (i) to provide a tutorial introduction to a novel framework and methods of estimation of metabolic efficiency using example data sets, and to propose benchmark measures for evaluating FES-cycling performance; (ii) to systematically review the literature pertaining specifically to the metabolic efficiency of FES-cycling, to analyse the observations and possible explanations for the low efficiency, and to pose hypotheses for future studies which aim to improve performance. We recommend the following as benchmark measures for assessment of the performance of FES-cycling: (i) total work efficiency, delta efficiency and stimulation cost; (ii) we recommend, further, that these benchmark measures be complemented by mechanical measures of maximum power output, sustainable steady-state power output and endurance. Performance assessments should be carried out at a well-defined operating point, i.e. under conditions of well controlled work rate and cadence, because these variables have a strong effect on energy expenditure. Future work should focus on the two main factors which affect FES-cycling performance, namely: (i) unfavourable biomechanics, i.e. crude recruitment of muscle groups, non-optimal timing of muscle activation, and lack of synergistic and antagonistic joint control; (ii) non-physiological recruitment of muscle fibres, i.e. mixed recruitment of fibres of different type and deterministic constant-frequency stimulation. We hypothesise that the following areas may bring better FES-cycling performance: (i) study of alternative stimulation strategies for muscle activation including irregular stimulation patterns (e.g. doublets, triplets, stochastic patterns) and variable frequency stimulation trains, where it appears that increasing frequency over time may be profitable; (ii) study of better timing parameters for the stimulated muscle groups, and addition of more muscle groups: this path may be approached using EMG studies and constrained numerical optimisation employing dynamic models; (iii) development of optimal stimulation protocols for muscle reconditioning and FES-cycle training.

Application of Shuffled Frog Leaping Algorithm and Genetic Algorithm for the Optimization of Urban Stormwater Drainage

NASA Astrophysics Data System (ADS)

Kumar, S.; Kaushal, D. R.; Gosain, A. K.

2017-12-01

Urban hydrology will have an increasing role to play in the sustainability of human settlements. Expansion of urban areas brings significant changes in physical characteristics of landuse. Problems with administration of urban flooding have their roots in concentration of population within a relatively small area. As watersheds are urbanized, infiltration decreases, pattern of surface runoff is changed generating high peak flows, large runoff volumes from urban areas. Conceptual rainfall-runoff models have become a foremost tool for predicting surface runoff and flood forecasting. Manual calibration is often time consuming and tedious because of the involved subjectivity, which makes automatic approach more preferable. The calibration of parameters usually includes numerous criteria for evaluating the performances with respect to the observed data. Moreover, derivation of objective function assosciat6ed with the calibration of model parameters is quite challenging. Various studies dealing with optimization methods has steered the embracement of evolution based optimization algorithms. In this paper, a systematic comparison of two evolutionary approaches to multi-objective optimization namely shuffled frog leaping algorithm (SFLA) and genetic algorithms (GA) is done. SFLA is a cooperative search metaphor, stimulated by natural memetics based on the population while, GA is based on principle of survival of the fittest and natural evolution. SFLA and GA has been employed for optimizing the major parameters i.e. width, imperviousness, Manning's coefficient and depression storage for the highly urbanized catchment of Delhi, India. The study summarizes the auto-tuning of a widely used storm water management model (SWMM), by internal coupling of SWMM with SFLA and GA separately. The values of statistical parameters such as, Nash-Sutcliffe efficiency (NSE) and Percent Bias (PBIAS) were found to lie within the acceptable limit, indicating reasonably good model performance. Overall, this study proved promising for assessing risk in urban drainage systems and should prove useful to improve integrity of the urban system, its reliability and provides guidance for inundation preparedness.Keywords: Hydrologic model, SWMM, Urbanization, SFLA and GA.

Atlas-Independent, Electrophysiological Mapping of the Optimal Locus of Subthalamic Deep Brain Stimulation for the Motor Symptoms of Parkinson Disease.

PubMed

Conrad, Erin C; Mossner, James M; Chou, Kelvin L; Patil, Parag G

2018-05-23

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease (PD). However, motor outcomes can be variable, perhaps due to inconsistent positioning of the active contact relative to an unknown optimal locus of stimulation. Here, we determine the optimal locus of STN stimulation in a geometrically unconstrained, mathematically precise, and atlas-independent manner, using Unified Parkinson Disease Rating Scale (UPDRS) motor outcomes and an electrophysiological neuronal stimulation model. In 20 patients with PD, we mapped motor improvement to active electrode location, relative to the individual, directly MRI-visualized STN. Our analysis included a novel, unconstrained and computational electrical-field model of neuronal activation to estimate the optimal locus of DBS. We mapped the optimal locus to a tightly defined ovoid region 0.49 mm lateral, 0.88 mm posterior, and 2.63 mm dorsal to the anatomical midpoint of the STN. On average, this locus is 11.75 lateral, 1.84 mm posterior, and 1.08 mm ventral to the mid-commissural point. Our novel, atlas-independent method reveals a single, ovoid optimal locus of stimulation in STN DBS for PD. The methodology, here applied to UPDRS and PD, is generalizable to atlas-independent mapping of other motor and non-motor effects of DBS. © 2018 S. Karger AG, Basel.

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

PubMed

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

2016-01-01

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

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.

Autonomous Optimization of Targeted Stimulation of Neuronal Networks

PubMed Central

Kumar, Sreedhar S.; Wülfing, Jan; Okujeni, Samora; Boedecker, Joschka; Riedmiller, Martin

2016-01-01

Driven by clinical needs and progress in neurotechnology, targeted interaction with neuronal networks is of increasing importance. Yet, the dynamics of interaction between intrinsic ongoing activity in neuronal networks and their response to stimulation is unknown. Nonetheless, electrical stimulation of the brain is increasingly explored as a therapeutic strategy and as a means to artificially inject information into neural circuits. Strategies using regular or event-triggered fixed stimuli discount the influence of ongoing neuronal activity on the stimulation outcome and are therefore not optimal to induce specific responses reliably. Yet, without suitable mechanistic models, it is hardly possible to optimize such interactions, in particular when desired response features are network-dependent and are initially unknown. In this proof-of-principle study, we present an experimental paradigm using reinforcement-learning (RL) to optimize stimulus settings autonomously and evaluate the learned control strategy using phenomenological models. We asked how to (1) capture the interaction of ongoing network activity, electrical stimulation and evoked responses in a quantifiable ‘state’ to formulate a well-posed control problem, (2) find the optimal state for stimulation, and (3) evaluate the quality of the solution found. Electrical stimulation of generic neuronal networks grown from rat cortical tissue in vitro evoked bursts of action potentials (responses). We show that the dynamic interplay of their magnitudes and the probability to be intercepted by spontaneous events defines a trade-off scenario with a network-specific unique optimal latency maximizing stimulus efficacy. An RL controller was set to find this optimum autonomously. Across networks, stimulation efficacy increased in 90% of the sessions after learning and learned latencies strongly agreed with those predicted from open-loop experiments. Our results show that autonomous techniques can exploit quantitative relationships underlying activity-response interaction in biological neuronal networks to choose optimal actions. Simple phenomenological models can be useful to validate the quality of the resulting controllers. PMID:27509295

Autonomous Optimization of Targeted Stimulation of Neuronal Networks.

PubMed

Kumar, Sreedhar S; Wülfing, Jan; Okujeni, Samora; Boedecker, Joschka; Riedmiller, Martin; Egert, Ulrich

2016-08-01

Driven by clinical needs and progress in neurotechnology, targeted interaction with neuronal networks is of increasing importance. Yet, the dynamics of interaction between intrinsic ongoing activity in neuronal networks and their response to stimulation is unknown. Nonetheless, electrical stimulation of the brain is increasingly explored as a therapeutic strategy and as a means to artificially inject information into neural circuits. Strategies using regular or event-triggered fixed stimuli discount the influence of ongoing neuronal activity on the stimulation outcome and are therefore not optimal to induce specific responses reliably. Yet, without suitable mechanistic models, it is hardly possible to optimize such interactions, in particular when desired response features are network-dependent and are initially unknown. In this proof-of-principle study, we present an experimental paradigm using reinforcement-learning (RL) to optimize stimulus settings autonomously and evaluate the learned control strategy using phenomenological models. We asked how to (1) capture the interaction of ongoing network activity, electrical stimulation and evoked responses in a quantifiable 'state' to formulate a well-posed control problem, (2) find the optimal state for stimulation, and (3) evaluate the quality of the solution found. Electrical stimulation of generic neuronal networks grown from rat cortical tissue in vitro evoked bursts of action potentials (responses). We show that the dynamic interplay of their magnitudes and the probability to be intercepted by spontaneous events defines a trade-off scenario with a network-specific unique optimal latency maximizing stimulus efficacy. An RL controller was set to find this optimum autonomously. Across networks, stimulation efficacy increased in 90% of the sessions after learning and learned latencies strongly agreed with those predicted from open-loop experiments. Our results show that autonomous techniques can exploit quantitative relationships underlying activity-response interaction in biological neuronal networks to choose optimal actions. Simple phenomenological models can be useful to validate the quality of the resulting controllers.

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.

Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

PubMed Central

Hoang, Kimberly B.; Cassar, Isaac R.; Grill, Warren M.; Turner, Dennis A.

2017-01-01

The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures) or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs), and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs), and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI) changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms. PMID:29066947

A model of optimal voluntary muscular control.

PubMed

FitzHugh, R

1977-07-19

In the absence of detailed knowledge of how the CNS controls a muscle through its motor fibers, a reasonable hypothesis is that of optimal control. This hypothesis is studied using a simplified mathematical model of a single muscle, based on A.V. Hill's equations, with series elastic element omitted, and with the motor signal represented by a single input variable. Two cost functions were used. The first was total energy expended by the muscle (work plus heat). If the load is a constant force, with no inertia, Hill's optimal velocity of shortening results. If the load includes a mass, analysis by optimal control theory shows that the motor signal to the muscle consists of three phases: (1) maximal stimulation to accelerate the mass to the optimal velocity as quickly as possible, (2) an intermediate level of stimulation to hold the velocity at its optimal value, once reached, and (3) zero stimulation, to permit the mass to slow down, as quickly as possible, to zero velocity at the specified distance shortened. If the latter distance is too small, or the mass too large, the optimal velocity is not reached, and phase (2) is absent. For lengthening, there is no optimal velocity; there are only two phases, zero stimulation followed by maximal stimulation. The second cost function was total time. The optimal control for shortening consists of only phases (1) and (3) above, and is identical to the minimal energy control whenever phase (2) is absent from the latter. Generalization of this model to include viscous loads and a series elastic element are discussed.

Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation

NASA Astrophysics Data System (ADS)

Baumgarten, C.; Zhao, Y.; Sauleau, P.; Malrain, C.; Jannin, P.; Haegelen, C.

2016-03-01

Deep brain stimulation of the medial globus pallidus is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The lack of side-effect predictive model leads the neurologist to secure an optimal electrode placement by iterating clinical testing on an awake patient during the surgical procedure. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning based method called PyMAN (for Pyramidal tract side effect Model based on Artificial Neural network) that accounted for the current of the stimulation, the 3D electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the medial globus pallidus have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was .78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

Functional electrical stimulation controlled by artificial neural networks: pilot experiments with simple movements are promising for rehabilitation applications.

PubMed

Ferrante, Simona; Pedrocchi, Alessandra; Iannò, Marco; De Momi, Elena; Ferrarin, Maurizio; Ferrigno, Giancarlo

2004-01-01

This study falls within the ambit of research on functional electrical stimulation for the design of rehabilitation training for spinal cord injured patients. In this context, a crucial issue is the control of the stimulation parameters in order to optimize the patterns of muscle activation and to increase the duration of the exercises. An adaptive control system (NEURADAPT) based on artificial neural networks (ANNs) was developed to control the knee joint in accordance with desired trajectories by stimulating quadriceps muscles. This strategy includes an inverse neural model of the stimulated limb in the feedforward line and a neural network trained on-line in the feedback loop. NEURADAPT was compared with a linear closed-loop proportional integrative derivative (PID) controller and with a model-based neural controller (NEUROPID). Experiments on two subjects (one healthy and one paraplegic) show the good performance of NEURADAPT, which is able to reduce the time lag introduced by the PID controller. In addition, control systems based on ANN techniques do not require complicated calibration procedures at the beginning of each experimental session. After the initial learning phase, the ANN, thanks to its generalization capacity, is able to cope with a certain range of variability of skeletal muscle properties.

Development of an integrated surface stimulation device for systematic evaluation of wound electrotherapy.

PubMed

Howe, D S; Dunning, J; Zorman, C; Garverick, S L; Bogie, K M

2015-02-01

Ideally, all chronic wounds would be prevented as they can become life threatening complications. The concept that a wound produces a 'current of injury' due to the discontinuity in the electrical field of intact skin provides the basis for the concept that electrical stimulation (ES) may provide an effective treatment for chronic wounds. The optimal stimulation waveform parameters are unknown, limiting the reliability of achieving a successful clinical therapeutic outcome. In order to gain a more thorough understanding of ES for chronic wound therapy, systematic evaluation using a valid in vivo model is required. The focus of the current paper is development of the flexible modular surface stimulation (MSS) device by our group. This device can be programed to deliver a variety of clinically relevant stimulation paradigms and is essential to facilitate systematic in vivo studies. The MSS version 2.0 for small animal use provides all components of a single-channel, programmable current-controlled ES system within a lightweight, flexible, independently-powered portable device. Benchtop testing and validation indicates that custom electronics and control algorithms support the generation of high-voltage, low duty-cycle current pulses in a power-efficient manner, extending battery life and allowing ES therapy to be delivered for up to 7 days without needing to replace or disturb the wound dressing.

Programming for Stimulation-Induced Transient Nonmotor Psychiatric Symptoms after Bilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease

PubMed Central

Wu, Xi; Qiu, Yiqing; Simfukwe, Keith; Wang, Jiali; Chen, Jianchun

2017-01-01

Background Stimulation-induced transient nonmotor psychiatric symptoms (STPSs) are side effects following bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients. We designed algorithms which (1) determine the electrode contacts that induce STPSs and (2) provide a programming protocol to eliminate STPS and maintain the optimal motor functions. Our objective is to test the effectiveness of these algorithms. Materials and Methods 454 PD patients who underwent programming sessions after STN-DBS implantations were retrospectively analyzed. Only STPS patients were enrolled. In these patients, the contacts inducing STPS were found and the programming protocol algorithms used. Results Eleven patients were diagnosed with STPS. Of these patients, two had four episodes of crying, and two had four episodes of mirthful laughter. In one patient, two episodes of abnormal sense of spatial orientation were observed. Hallucination episodes were observed twice in one patient, while five patients recorded eight episodes of hypomania. There were no statistical differences between the UPDRS-III under the final stimulation parameter (without STPS) and previous optimum UPDRS-III under the STPSs (p = 1.000). Conclusion The flow diagram used for determining electrode contacts that induce STPS and the programming protocol employed in the treatment of these symptoms are effective. PMID:28894620

A high-voltage cardiac stimulator for field shocks of a whole heart in a bath

NASA Astrophysics Data System (ADS)

Mashburn, David N.; Hinkson, Stephen J.; Woods, Marcella C.; Gilligan, Jonathan M.; Holcomb, Mark R.; Wikswo, John P.

2007-10-01

Defibrillators are a critical tool for treating heart disease; however, the mechanisms by which they halt fibrillation are still not fully understood and are the subject of ongoing research. Clinical defibrillators do not provide the precise control of shock timing, duration, and voltage or other features needed for detailed scientific inquiry, and there are few, if any, commercially available units designed for research applications. For this reason, we have developed a high-voltage, programmable, capacitive-discharge stimulator optimized to deliver defibrillation shocks with precise timing and voltage control to an isolated animal heart, either in air or in a bath. This stimulator is capable of delivering voltages of up to 500V and energies of nearly 100J with timing accuracy of a few microseconds and with rise and fall times of 5μs or less and is controlled only by two external timing pulses and a control computer that sets the stimulation parameters via a LABVIEW interface. Most importantly, the stimulator has circuits to protect the high-voltage circuitry and the operator from programming and input-output errors. This device has been tested and used successfully in field shock experiments on rabbit hearts as well as other protocols requiring high voltage.

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.

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

SU-D-304-06: Measurement of LET in Patient-Specific Proton Therapy Treatment Fields Using Optically Stimulated Luminescence Detectors

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

Granville, DA; Sahoo, N; Sawakuchi, GO

Purpose: To investigate the use of optically stimulated luminescence (OSL) detectors (OSLDs) for measurements of dose-averaged linear energy transfer (LET) in patient-specific proton therapy treatment fields. Methods: We used Al{sub 2}O{sub 3}:C OSLDs made from the same material as commercially available nanoDot OSLDs from Landauer, Inc. We calibrated two parameters of the OSL signal as functions of LET in therapeutic proton beams: the ratio of the ultraviolet and blue emission intensities (UV/blue ratio) and the OSL curve shape. These calibration curves were created by irradiating OSLDs in passively scattered beams of known LET (0.96 to 3.91 keV/µm). The LET valuesmore » were determined using a validated Monte Carlo model of the beamline. We then irradiated new OSLDs with the prescription dose (16 to 74 cGy absorbed dose to water) at the center of the spread-out Bragg peak (SOBP) of four patient-specific treatment fields. From readouts of these OSLDs, we determined both the UV/blue ratio and OSL curve shape parameters. Combining these parameters with the calibration curves, we were able to measure LET using the OSLDs. The measurements were compared to the theoretical LET values obtained from Monte Carlo simulations of the patient-specific treatments fields. Results: Using the UV/blue ratio parameter, we were able to measure LET within 3.8%, 6.2%, 5.6% and 8.6% of the Monte Carlo value for each of the patient fields. Similarly, using the OSL curve shape parameter, LET measurements agreed within 0.5%, 11.0%, 2.5% and 7.6% for each of the four fields. Conclusion: We have demonstrated a method to verify LET in patient-specific proton therapy treatment fields using OSLDs. The possibility of enhancing biological effectiveness of proton therapy treatment plans by including LET in the optimization has been previously shown. The LET verification method we have demonstrated will be useful in the quality assurance of such LET optimized treatment plans. DA Granville received financial support from the Natural Sciences and Engineering Research Council of Canada.« less

Transcutaneous stimulation of the posterior tibial nerve for treating refractory urge incontinence of idiopathic and neurogenic origin.

PubMed

Valles-Antuña, C; Pérez-Haro, M L; González-Ruiz de L, C; Quintás-Blanco, A; Tamargo-Diaz, E M; García-Rodríguez, J; San Martín-Blanco, A; Fernandez-Gomez, J M

2017-09-01

To assess the efficacy of treatment with transcutaneous posterior tibial nerve stimulation (TPTNS) in patients with urge urinary incontinence, of neurogenic or nonneurogenic origin, refractory to first-line therapeutic options. We included 65 patients with urge urinary incontinence refractory to medical treatment. A case history review, a urodynamic study and a somatosensory evoked potentials (SEP) study were conducted before the TPTNS, studying the functional urological condition by means of a voiding diary. The treatment consisted of 10 weekly sessions of TPTNS lasting 30minutes. Some 57.7% of the patients showed abnormal tibial SEPs, and 42% showed abnormal pudendal SEPs. A statistically significant symptomatic improvement was observed in all clinical parameters after treatment with TPTNS, and 66% of the patients showed an overall improvement, regardless of sex, the presence of underlying neurological disorders, detrusor hyperactivity in the urodynamic study or SEP disorders. There were no adverse effects during the treatment. TPTNS is an effective and well tolerated treatment in patients with urge incontinence refractory to first-line therapies and should be offered early in the treatment strategy. New studies are needed to identify the optimal parameters of stimulation, the most effective treatment protocols and long-term efficacy, as well as its applicability to patients with a neurogenic substrate. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

A Mixed Integer Linear Programming Approach to Electrical Stimulation Optimization Problems.

PubMed

Abouelseoud, Gehan; Abouelseoud, Yasmine; Shoukry, Amin; Ismail, Nour; Mekky, Jaidaa

2018-02-01

Electrical stimulation optimization is a challenging problem. Even when a single region is targeted for excitation, the problem remains a constrained multi-objective optimization problem. The constrained nature of the problem results from safety concerns while its multi-objectives originate from the requirement that non-targeted regions should remain unaffected. In this paper, we propose a mixed integer linear programming formulation that can successfully address the challenges facing this problem. Moreover, the proposed framework can conclusively check the feasibility of the stimulation goals. This helps researchers to avoid wasting time trying to achieve goals that are impossible under a chosen stimulation setup. The superiority of the proposed framework over alternative methods is demonstrated through simulation examples.

Understanding and enhancing motor recovery after stroke using transcranial magnetic stimulation

PubMed Central

Hoyer, Erik H.; Celnik, Pablo A.

2013-01-01

Stroke is the leading cause of long-term disability. Understanding how people recover from stroke and other brain lesions remain one of the biggest conundrums in neuroscience. As a result, concerted efforts in recent years have focused on investigating the neurophysiological changes that occur in the brain after stroke, and in developing novel strategies to enhance motor recovery. In particular, transcranial magnetic stimulation (TMS) is a non-invasive tool that has been used to investigate the brain plasticity changes resulting from stroke and as a therapeutic modality to safely improve motor function. In this review, we discuss the contributions of TMS to understand how different motor areas, such as the ipsilesional hemisphere, secondary motor areas, and contralesional hemisphere are involved in motor recovery. We also consider recent studies using repetitive TMS (rTMS) in stroke patients to enhance upper extremity function. Although further studies are needed, these investigations provide an important starting point to understand the stimulation parameters and patient characteristics that may influence the optimal response to non-invasive brain stimulation. Future directions of rTMS are discussed in the context of post-stroke motor recovery. PMID:22124033

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.

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

PubMed Central

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

2011-01-01

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

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

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

PubMed

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

2012-10-01

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

Hemoglobin promotes somatic embryogenesis in peanut cultures.

PubMed

Jayabalan, N; Anthony, P; Davey, M R; Power, J B; Lowe, K C

2004-02-01

Critical parameters influencing somatic embryogenesis include growth regulators and oxygen supply. Consequently, the present investigation has focused on optimization of a somatic embryogenic system for peanut (Arachis hypogaea L.) through media supplementation with the auxin, picloram. The latter at 30 mg L(-1) was optimal for inducing regeneration of somatic embryos from cultured explants of zygotic embryos. In contrast, somatic embryogenesis did not occur in the absence of this growth regulator. An assessment has also been made of the beneficial effect on somatic embryogenesis and plant regeneration of the commercial hemoglobin (Hb) solution, Erythrogen. Hemoglobin at 1:50 and 1:100 (v:v) stimulated increases in mean fresh weight (up to a maximum of 57% over control), mean number of explants producing somatic embryos (15%) and mean number of somatic embryos per explant (29%).

An improved genetic algorithm for designing optimal temporal patterns of neural stimulation

NASA Astrophysics Data System (ADS)

Cassar, Isaac R.; Titus, Nathan D.; Grill, Warren M.

2017-12-01

Objective. Electrical neuromodulation therapies typically apply constant frequency stimulation, but non-regular temporal patterns of stimulation may be more effective and more efficient. However, the design space for temporal patterns is exceedingly large, and model-based optimization is required for pattern design. We designed and implemented a modified genetic algorithm (GA) intended for design optimal temporal patterns of electrical neuromodulation. Approach. We tested and modified standard GA methods for application to designing temporal patterns of neural stimulation. We evaluated each modification individually and all modifications collectively by comparing performance to the standard GA across three test functions and two biophysically-based models of neural stimulation. Main results. The proposed modifications of the GA significantly improved performance across the test functions and performed best when all were used collectively. The standard GA found patterns that outperformed fixed-frequency, clinically-standard patterns in biophysically-based models of neural stimulation, but the modified GA, in many fewer iterations, consistently converged to higher-scoring, non-regular patterns of stimulation. Significance. The proposed improvements to standard GA methodology reduced the number of iterations required for convergence and identified superior solutions.

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.

Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields

PubMed Central

Ruffini, Giulio; Fox, Michael D.; Ripolles, Oscar; Miranda, Pedro Cavaleiro; Pascual-Leone, Alvaro

2014-01-01

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint of the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). PMID:24345389

Atlas of optimal coil orientation and position for TMS: A computational study.

PubMed

Gomez-Tames, Jose; Hamasaka, Atsushi; Laakso, Ilkka; Hirata, Akimasa; Ugawa, Yoshikazu

2018-04-17

Transcranial magnetic stimulation (TMS) activates target brain structures in a non-invasive manner. The optimal orientation of the TMS coil for the motor cortex is well known and can be estimated using motor evoked potentials. However, there are no easily measurable responses for activation of other cortical areas and the optimal orientation for these areas is currently unknown. This study investigated the electric field strength, optimal coil orientation, and relative locations to optimally stimulate the target cortex based on computed electric field distributions. A total of 518,616 stimulation scenarios were studied using realistic head models (2401 coil locations × 12 coil angles × 18 head models). Inter-subject registration methods were used to generate an atlas of optimized TMS coil orientations on locations on the standard brain. We found that the maximum electric field strength is greater in primary somatosensory cortex and primary motor cortex than in other cortical areas. Additionally, a universal optimal coil orientation applicable to most subjects is more feasible at the primary somatosensory cortex and primary motor cortex. We confirmed that optimal coil angle follows the anatomical shape of the hand motor area to realize personalized optimization of TMS. Finally, on average, the optimal coil positions for TMS on the scalp deviated 5.5 mm from the scalp points with minimum cortex-scalp distance. This deviation was minimal at the premotor cortex and primary motor cortex. Personalized optimal coil orientation is preferable for obtaining the most effective stimulation. Copyright © 2018. Published by Elsevier Inc.

Physical activity modulates corticospinal excitability of the lower limb in young and old adults.

PubMed

Hassanlouei, Hamidollah; Sundberg, Christopher W; Smith, Ashleigh E; Kuplic, Andrew; Hunter, Sandra K

2017-08-01

Aging is associated with reduced neuromuscular function, which may be due in part to altered corticospinal excitability. Regular physical activity (PA) may ameliorate these age-related declines, but the influence of PA on corticospinal excitability is unknown. The purpose of this study was to determine the influence of age, sex, and PA on corticospinal excitability by comparing the stimulus-response curves of motor evoked potentials (MEP) in 28 young (22.4 ± 2.2 yr; 14 women and 14 men) and 50 old adults (70.2 ± 6.1 yr; 22 women and 28 men) who varied in activity levels. Transcranial magnetic stimulation was used to elicit MEPs in the active vastus lateralis muscle (10% maximal voluntary contraction) with 5% increments in stimulator intensity until the maximum MEP amplitude. Stimulus-response curves of MEP amplitudes were fit with a four-parameter sigmoidal curve and the maximal slope calculated (slope max ). Habitual PA was assessed with tri-axial accelerometry and participants categorized into either those meeting the recommended PA guidelines for optimal health benefits (>10,000 steps/day, high-PA; n = 21) or those not meeting the guidelines (<10,000 steps/day, low-PA; n = 41). The MEP amplitudes and slope max were greater in the low-PA compared with the high-PA group ( P < 0.05). Neither age nor sex influenced the stimulus-response curve parameters ( P > 0.05), suggesting that habitual PA influenced the excitability of the corticospinal tract projecting to the lower limb similarly in both young and old adults. These findings provide evidence that achieving the recommended PA guidelines for optimal health may mediate its effects on the nervous system by decreasing corticospinal excitability. NEW & NOTEWORTHY Transcranial magnetic stimulation was used to determine whether achieving the recommended 10,000 steps/day for optimal health influenced the excitability of the corticospinal tract projecting to the knee extensor muscles. Irrespective of age and sex, individuals who achieved >10,000 steps/day had lower corticospinal excitability than those who performed <10,000 steps/day, possibly representing greater control of inhibitory and excitatory networks. Physical activity involving >10,000 steps/day may mediate its effects on the nervous system by decreasing corticospinal excitability. Copyright © 2017 the American Physiological Society.

STUDIES OF A FREE ELECTRON LASER DRIVEN BY A LASER-PLASMA ACCELERATOR

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

Montgomery, A.; Schroeder, C.; Fawley, W.

A free electron laser (FEL) uses an undulator, a set of alternating magnets producing a periodic magnetic fi eld, to stimulate emission of coherent radiation from a relativistic electron beam. The Lasers, Optical Accelerator Systems Integrated Studies (LOASIS) group at Lawrence Berkeley National Laboratory (LBNL) will use an innovative laserplasma wakefi eld accelerator to produce an electron beam to drive a proposed FEL. In order to optimize the FEL performance, the dependence on electron beam and undulator parameters must be understood. Numerical modeling of the FEL using the simulation code GINGER predicts the experimental results for given input parameters. Amongmore » the parameters studied were electron beam energy spread, emittance, and mismatch with the undulator focusing. Vacuum-chamber wakefi elds were also simulated to study their effect on FEL performance. Energy spread was found to be the most infl uential factor, with output FEL radiation power sharply decreasing for relative energy spreads greater than 0.33%. Vacuum chamber wakefi elds and beam mismatch had little effect on the simulated LOASIS FEL at the currents considered. This study concludes that continued improvement of the laser-plasma wakefi eld accelerator electron beam will allow the LOASIS FEL to operate in an optimal regime, producing high-quality XUV and x-ray pulses.« less

Optimal stimulation as theoretical basis of hyperactivity.

PubMed

Zentall, Sydney

1975-07-01

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

Targeting of the Subthalamic Nucleus for Deep Brain Stimulation: A Survey Among Parkinson Disease Specialists.

PubMed

Hamel, Wolfgang; Köppen, Johannes A; Alesch, François; Antonini, Angelo; Barcia, Juan A; Bergman, Hagai; Chabardes, Stephan; Contarino, Maria Fiorella; Cornu, Philippe; Demmel, Walter; Deuschl, Günther; Fasano, Alfonso; Kühn, Andrea A; Limousin, Patricia; McIntyre, Cameron C; Mehdorn, H Maximilian; Pilleri, Manuela; Pollak, Pierre; Rodríguez-Oroz, Maria C; Rumià, Jordi; Samuel, Michael; Timmermann, Lars; Valldeoriola, Francesc; Vesper, Jan; Visser-Vandewalle, Veerle; Volkmann, Jens; Lozano, Andres M

2017-03-01

Deep brain stimulation within or adjacent to the subthalamic nucleus (STN) represents the most common stereotactic procedure performed for Parkinson disease. Better STN imaging is often regarded as a requirement for improving stereotactic targeting. However, it is unclear whether there is consensus about the optimal target. To obtain an expert opinion on the site regarded optimal for "STN stimulation," movement disorder specialists were asked to indicate their preferred position for an active contact on hard copies of the Schaltenbrand and Wahren atlas depicting the STN in all 3 planes. This represented an idealized setting, and it mimicked optimal imaging for direct target definition in a perfectly delineated STN. The suggested targets were heterogeneous, although some clustering was observed in the dorsolateral STN and subthalamic area. In particular, in the anteroposterior direction, the intended targets differed to a great extent. Most of the indicated targets are thought to also result in concomitant stimulation of structures adjacent to the STN, including the zona incerta, fields of Forel, and internal capsule. This survey illustrates that most sites regarded as optimal for STN stimulation are close to each other, but there appears to be no uniform perception of the optimal anatomic target, possibly influencing surgical results. The anatomic sweet zone for STN stimulation needs further specification, as this information is likely to make magnetic resonance imaging-based target definition less variable when applied to individual patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Oral dosing of chemical indicators for in vivo monitoring of Ca2+ dynamics in insect muscle.

PubMed

Ferdinandus; Arai, Satoshi; Ishiwata, Shin'ichi; Suzuki, Madoka; Sato, Hirotaka

2015-01-01

This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action) and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing). A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects.

Oral Dosing of Chemical Indicators for In Vivo Monitoring of Ca2+ Dynamics in Insect Muscle

PubMed Central

Ferdinandus; Arai, Satoshi; Ishiwata, Shin’ichi; Suzuki, Madoka; Sato, Hirotaka

2015-01-01

This paper proposes a remarkably facile staining protocol to visually investigate dynamic physiological events in insect tissues. We attempted to monitor Ca2+ dynamics during contraction of electrically stimulated living muscle. Advances in circuit miniaturization and insect neuromuscular physiology have enabled the hybridization of living insects and man-made electronic components, such as microcomputers, the result of which has been often referred as a Living Machine, Biohybrid, or Cyborg Insect. In order for Cyborg Insects to be of practical use, electrical stimulation parameters need to be optimized to induce desired muscle response (motor action) and minimize the damage in the muscle due to the electrical stimuli. Staining tissues and organs as well as measuring the dynamics of chemicals of interest in muscle should be conducted to quantitatively and systematically evaluate the effect of various stimulation parameters on the muscle response. However, existing staining processes require invasive surgery and/or arduous procedures using genetically encoded sensors. In this study, we developed a non-invasive and remarkably facile method for staining, in which chemical indicators can be orally administered (oral dosing). A chemical Ca2+ indicator was orally introduced into an insect of interest via food containing the chemical indicator and the indicator diffused from the insect digestion system to the target muscle tissue. We found that there was a positive relationship between the fluorescence intensity of the indicator and the frequency of electrical stimulation which indicates the orally dosed indicator successfully monitored Ca2+ dynamics in the muscle tissue. This oral dosing method has a potential to globally stain tissues including neurons, and investigating various physiological events in insects. PMID:25590329

A novel approach for automatic visualization and activation detection of evoked potentials induced by epidural spinal cord stimulation in individuals with spinal cord injury.

PubMed

Mesbah, Samineh; Angeli, Claudia A; Keynton, Robert S; El-Baz, Ayman; Harkema, Susan J

2017-01-01

Voluntary movements and the standing of spinal cord injured patients have been facilitated using lumbosacral spinal cord epidural stimulation (scES). Identifying the appropriate stimulation parameters (intensity, frequency and anode/cathode assignment) is an arduous task and requires extensive mapping of the spinal cord using evoked potentials. Effective visualization and detection of muscle evoked potentials induced by scES from the recorded electromyography (EMG) signals is critical to identify the optimal configurations and the effects of specific scES parameters on muscle activation. The purpose of this work was to develop a novel approach to automatically detect the occurrence of evoked potentials, quantify the attributes of the signal and visualize the effects across a high number of scES parameters. This new method is designed to automate the current process for performing this task, which has been accomplished manually by data analysts through observation of raw EMG signals, a process that is laborious and time-consuming as well as prone to human errors. The proposed method provides a fast and accurate five-step algorithms framework for activation detection and visualization of the results including: conversion of the EMG signal into its 2-D representation by overlaying the located signal building blocks; de-noising the 2-D image by applying the Generalized Gaussian Markov Random Field technique; detection of the occurrence of evoked potentials using a statistically optimal decision method through the comparison of the probability density functions of each segment to the background noise utilizing log-likelihood ratio; feature extraction of detected motor units such as peak-to-peak amplitude, latency, integrated EMG and Min-max time intervals; and finally visualization of the outputs as Colormap images. In comparing the automatic method vs. manual detection on 700 EMG signals from five individuals, the new approach decreased the processing time from several hours to less than 15 seconds for each set of data, and demonstrated an average accuracy of 98.28% based on the combined false positive and false negative error rates. The sensitivity of this method to the signal-to-noise ratio (SNR) was tested using simulated EMG signals and compared to two existing methods, where the novel technique showed much lower sensitivity to the SNR.

A novel approach for automatic visualization and activation detection of evoked potentials induced by epidural spinal cord stimulation in individuals with spinal cord injury

PubMed Central

Mesbah, Samineh; Angeli, Claudia A.; Keynton, Robert S.; Harkema, Susan J.

2017-01-01

Voluntary movements and the standing of spinal cord injured patients have been facilitated using lumbosacral spinal cord epidural stimulation (scES). Identifying the appropriate stimulation parameters (intensity, frequency and anode/cathode assignment) is an arduous task and requires extensive mapping of the spinal cord using evoked potentials. Effective visualization and detection of muscle evoked potentials induced by scES from the recorded electromyography (EMG) signals is critical to identify the optimal configurations and the effects of specific scES parameters on muscle activation. The purpose of this work was to develop a novel approach to automatically detect the occurrence of evoked potentials, quantify the attributes of the signal and visualize the effects across a high number of scES parameters. This new method is designed to automate the current process for performing this task, which has been accomplished manually by data analysts through observation of raw EMG signals, a process that is laborious and time-consuming as well as prone to human errors. The proposed method provides a fast and accurate five-step algorithms framework for activation detection and visualization of the results including: conversion of the EMG signal into its 2-D representation by overlaying the located signal building blocks; de-noising the 2-D image by applying the Generalized Gaussian Markov Random Field technique; detection of the occurrence of evoked potentials using a statistically optimal decision method through the comparison of the probability density functions of each segment to the background noise utilizing log-likelihood ratio; feature extraction of detected motor units such as peak-to-peak amplitude, latency, integrated EMG and Min-max time intervals; and finally visualization of the outputs as Colormap images. In comparing the automatic method vs. manual detection on 700 EMG signals from five individuals, the new approach decreased the processing time from several hours to less than 15 seconds for each set of data, and demonstrated an average accuracy of 98.28% based on the combined false positive and false negative error rates. The sensitivity of this method to the signal-to-noise ratio (SNR) was tested using simulated EMG signals and compared to two existing methods, where the novel technique showed much lower sensitivity to the SNR. PMID:29020054

Group-level variations in motor representation areas of thenar and anterior tibial muscles: Navigated Transcranial Magnetic Stimulation Study.

PubMed

Niskanen, Eini; Julkunen, Petro; Säisänen, Laura; Vanninen, Ritva; Karjalainen, Pasi; Könönen, Mervi

2010-08-01

Navigated transcranial magnetic stimulation (TMS) can be used to stimulate functional cortical areas at precise anatomical location to induce measurable responses. The stimulation has commonly been focused on anatomically predefined motor areas: TMS of that area elicits a measurable muscle response, the motor evoked potential. In clinical pathologies, however, the well-known homunculus somatotopy theory may not be straightforward, and the representation area of the muscle is not fixed. Traditionally, the anatomical locations of TMS stimulations have not been reported at the group level in standard space. This study describes a methodology for group-level analysis by investigating the normal representation areas of thenar and anterior tibial muscle in the primary motor cortex. The optimal representation area for these muscles was mapped in 59 healthy right-handed subjects using navigated TMS. The coordinates of the optimal stimulation sites were then normalized into standard space to determine the representation areas of these muscles at the group-level in healthy subjects. Furthermore, 95% confidence interval ellipsoids were fitted into the optimal stimulation site clusters to define the variation between subjects in optimal stimulation sites. The variation was found to be highest in the anteroposterior direction along the superior margin of the precentral gyrus. These results provide important normative information for clinical studies assessing changes in the functional cortical areas because of plasticity of the brain. Furthermore, it is proposed that the presented methodology to study TMS locations at the group level on standard space will be a suitable tool for research purposes in population studies. 2010 Wiley-Liss, Inc.

3D Monte Carlo simulation of light propagation for laser acupuncture and optimization of illumination parameters

NASA Astrophysics Data System (ADS)

Zhong, Fulin; Li, Ting; Pan, Boan; Wang, Pengbo

2017-02-01

Laser acupuncture is an effective photochemical and nonthermal stimulation of traditional acupuncture points with lowintensity laser irradiation, which is advantageous in painless, sterile, and safe compared to traditional acupuncture. Laser diode (LD) provides single wavelength and relatively-higher power light for phototherapy. The quantitative effect of illumination parameters of LD in use of laser acupuncture is crucial for practical operation of laser acupuncture. However, this issue is not fully demonstrated, especially since experimental methodologies with animals or human are pretty hard to address to this issue. For example, in order to protect viability of cells and tissue, and get better therapeutic effect, it's necessary to control the output power varied at 5mW 10mW range, while the optimized power is still not clear. This study aimed to quantitatively optimize the laser output power, wavelength, and irradiation direction with highly realistic modeling of light transport in acupunctured tissue. A Monte Carlo Simulation software for 3D vowelized media and the highest-precision human anatomical model Visible Chinese Human (VCH) were employed. Our 3D simulation results showed that longer wavelength/higher illumination power, larger absorption in laser acupuncture; the vertical direction emission of the acupuncture laser results in higher amount of light absorption in both the acupunctured voxel of tissue and muscle layer. Our 3D light distribution of laser acupuncture within VCH tissue model is potential to be used in optimization and real time guidance in clinical manipulation of laser acupuncture.

Optimal Pulse Configuration Design for Heart Stimulation. A Theoretical, Numerical and Experimental Study.

NASA Astrophysics Data System (ADS)

Hardy, Neil; Dvir, Hila; Fenton, Flavio

Existing pacemakers consider the rectangular pulse to be the optimal form of stimulation current. However, other waveforms for the use of pacemakers could save energy while still stimulating the heart. We aim to find the optimal waveform for pacemaker use, and to offer a theoretical explanation for its advantage. Since the pacemaker battery is a charge source, here we probe the stimulation current waveforms with respect to the total charge delivery. In this talk we present theoretical analysis and numerical simulations of myocyte ion-channel currents acting as an additional source of charge that adds to the external stimulating charge for stimulation purposes. Therefore, we find that as the action potential emerges, the external stimulating current can be reduced accordingly exponentially. We then performed experimental studies in rabbit and cat hearts and showed that indeed exponential truncated pulses with less total charge can still induce activation in the heart. From the experiments, we present curves showing the savings in charge as a function of exponential waveform and we calculated that the longevity of the pacemaker battery would be ten times higher for the exponential current compared to the rectangular waveforms. Thanks to Petit Undergraduate Research Scholars Program and NSF# 1413037.

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

PubMed Central

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

2010-01-01

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

Fractal analyses reveal independent complexity and predictability of gait

PubMed Central

Dierick, Frédéric; Nivard, Anne-Laure

2017-01-01

Locomotion is a natural task that has been assessed for decades and used as a proxy to highlight impairments of various origins. So far, most studies adopted classical linear analyses of spatio-temporal gait parameters. Here, we use more advanced, yet not less practical, non-linear techniques to analyse gait time series of healthy subjects. We aimed at finding more sensitive indexes related to spatio-temporal gait parameters than those previously used, with the hope to better identify abnormal locomotion. We analysed large-scale stride interval time series and mean step width in 34 participants while altering walking direction (forward vs. backward walking) and with or without galvanic vestibular stimulation. The Hurst exponent α and the Minkowski fractal dimension D were computed and interpreted as indexes expressing predictability and complexity of stride interval time series, respectively. These holistic indexes can easily be interpreted in the framework of optimal movement complexity. We show that α and D accurately capture stride interval changes in function of the experimental condition. Walking forward exhibited maximal complexity (D) and hence, adaptability. In contrast, walking backward and/or stimulation of the vestibular system decreased D. Furthermore, walking backward increased predictability (α) through a more stereotyped pattern of the stride interval and galvanic vestibular stimulation reduced predictability. The present study demonstrates the complementary power of the Hurst exponent and the fractal dimension to improve walking classification. Our developments may have immediate applications in rehabilitation, diagnosis, and classification procedures. PMID:29182659

Teat anatomy affects requirements for udder preparation in Mediterranean buffaloes.

PubMed

Ambord, Sarah; Stoffel, Michael H; Bruckmaier, Rupert M

2010-11-01

The present study was conducted to assess the interrelation between teat anatomy and machine milking in dairy buffaloes raised in Switzerland. A 3-min pre-stimulation induced milk ejection before cluster attachment in most cases and caused an optimal milk removal during machine milking. In an additional experiment, longitudinal cross-section ultrasound was obtained before and after a 3-min pre-stimulation. Teat wall thickness, teat diameter, cisternal diameter and teat canal length were evaluated. It was observed that 3-min pre-stimulation dramatically reduced teat canal length whereas all the other anatomical parameters remained unchanged. The vacuum needed to open the teat canal was also measured before and after a 3-min pre-stimulation by using a special teat cup with only the mouthpiece of the liner remaining on the top of the teat cup (no liner, no pulsation). Without pre-stimulation but after wetting the teat canal by stripping one squirt of milk out of the teat, no milk could be withdrawn with a vacuum up to 39 kPa. However, after pre-stimulation, milk flow occurred in all buffaloes at a vacuum between 16 and 38 kPa. In the last experiment, the teat tissue was examined in slaughtered buffaloes and compared with teat tissue of cows. No difference was noted in histological sections and teat canal length was similar in cows and buffaloes. Proximal to the teat canal, the teat did not pass into an open cistern but the lumen was collapsed. In conclusion, buffaloes need to be well pre-stimulated because the tissue above the teat canal provides additional teat closure before milk ejection. Therefore, milk can only be obtained after pre-stimulation.

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.

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

NASA Astrophysics Data System (ADS)

Fan, Denggui; Wang, Zhihui; Wang, Qingyun

2016-07-01

The effect of conventional deep brain stimulation (DBS) on debilitating symptoms of Parkinson's disease can be limited because it can only yield the spherical field. And, some side effects are clearly induced with influencing their adjacent ganglia. Recent experimental evidence for patients with Parkinson's disease has shown that a novel DBS electrode with 32 independent stimulation source contacts can effectively optimize the clinical therapy by enlarging the therapeutic windows, when it is applied on the subthalamic nucleus (STN). This is due to the selective activation in clusters of various stimulation contacts which can be steered directionally and accurately on the targeted regions of interest. In addition, because of the serious damage to the neural tissues, the charge-unbalanced stimulation is not typically indicated and the real DBS utilizes charge-balanced bi-phasic (CBBP) pulses. Inspired by this, we computationally investigate the optimal control of directional CBBP-DBS from the proposed parkinsonian neuronal network of basal ganglia-thalamocortical circuit. By appropriately tuning stimulation for different neuronal populations, it can be found that directional steering CBBP-DBS paradigms are superior to the spherical case in improving parkinsonian dynamical properties including the synchronization of neuronal populations and the reliability of thalamus relaying the information from cortex, which is in a good agreement with the physiological experiments. Furthermore, it can be found that directional steering stimulations can increase the optimal stimulation intensity of desynchronization by more than 1 mA compared to the spherical case. This is consistent with the experimental result with showing that there exists at least one steering direction that can allow increasing the threshold of side effects by 1 mA. In addition, we also simulate the local field potential (LFP) and dominant frequency (DF) of the STN neuronal population induced by the activation of 32 different contacts with optimal stimulation intensity and immediately after the stimulation, respectively. These can reveal regional differences in pathological activity within STN nucleus. It is shown that in line with the experimental results directional steering stimulation can induce the low-amplitude LFP which implies the occurrence of desynchronizing regime, as well as the distribution of DF can locate at the 13-40 Hz of beta frequency range. Hopefully, the obtained results can provide theoretical evidences in exploring pathophysiologic activity of brain.

Acoustically-Responsive Scaffolds: Control of Growth Factor Release for Tissue Regeneration Using Ultrasound

NASA Astrophysics Data System (ADS)

Moncion, Alexander

Administration of exogenous growth factors (GFs) is a proposed method of stimulating tissue regeneration. Conventional administration routes, such as at-site or systemic injections, have yielded problems with efficacy and/or safety, thus hindering the translation of GF-based regenerative techniques. Hydrogel scaffolds are commonly used as biocompatible delivery vehicles for GFs. Yet hydrogels do not afford spatial or temporal control of GF release - two critical parameters for tissue regeneration. Controlled delivery of GFs is critical for angiogenesis, which is a crucial process in tissue engineering that provides oxygen and nutrients to cells within an implanted hydrogel scaffold. Angiogenesis requires multiple GFs that are presented with distinct spatial and temporal profiles. Thus, controlled release of GFs with spatiotemporal modulation would significantly improve tissue regeneration by recapitulating endogenous GF presentation. In order to achieve this goal, we have developed acoustically-responsive scaffolds (ARSs), which are fibrin hydrogels doped with sonosensitive perfluorocarbon (PFC) emulsions capable of encapsulating various payloads. Focused, mega-Hertz range, ultrasound (US) can modulate the release of a payload non-invasively and in an on-demand manner from ARSs via physical mechanisms termed acoustic droplet vaporization (ADV) and inertial cavitation (IC). This work presents the relationship between the ADV/IC thresholds and various US and hydrogel parameters. These physical mechanisms were used for the controlled release of fluorescent dextran in vitro and in vivo to determine the ARS and US parameters that yielded optimal payload release. The optimal ARS and US parameters were used to demonstrate the controlled release of basic fibroblast growth factor from an in vivo subcutaneous implant model - leading to enhanced angiogenesis and perfusion. Additionally, different acoustic parameters and PFCs were tested and optimized to demonstrate the controlled release of two encapsulated payloads within an ARS. Overall, ARSs are a promising platform for GF delivery in tissue regeneration applications.

Uncertainty Analysis of Simulated Hydraulic Fracturing

NASA Astrophysics Data System (ADS)

Chen, M.; Sun, Y.; Fu, P.; Carrigan, C. R.; Lu, Z.

2012-12-01

Artificial hydraulic fracturing is being used widely to stimulate production of oil, natural gas, and geothermal reservoirs with low natural permeability. Optimization of field design and operation is limited by the incomplete characterization of the reservoir, as well as the complexity of hydrological and geomechanical processes that control the fracturing. Thus, there are a variety of uncertainties associated with the pre-existing fracture distribution, rock mechanics, and hydraulic-fracture engineering that require evaluation of their impact on the optimized design. In this study, a multiple-stage scheme was employed to evaluate the uncertainty. We first define the ranges and distributions of 11 input parameters that characterize the natural fracture topology, in situ stress, geomechanical behavior of the rock matrix and joint interfaces, and pumping operation, to cover a wide spectrum of potential conditions expected for a natural reservoir. These parameters were then sampled 1,000 times in an 11-dimensional parameter space constrained by the specified ranges using the Latin-hypercube method. These 1,000 parameter sets were fed into the fracture simulators, and the outputs were used to construct three designed objective functions, i.e. fracture density, opened fracture length and area density. Using PSUADE, three response surfaces (11-dimensional) of the objective functions were developed and global sensitivity was analyzed to identify the most sensitive parameters for the objective functions representing fracture connectivity, which are critical for sweep efficiency of the recovery process. The second-stage high resolution response surfaces were constructed with dimension reduced to the number of the most sensitive parameters. An additional response surface with respect to the objective function of the fractal dimension for fracture distributions was constructed in this stage. Based on these response surfaces, comprehensive uncertainty analyses were conducted among input parameters and objective functions. In addition, reduced-order emulation models resulting from this analysis can be used for optimal control of hydraulic fracturing. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

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.

Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields.

PubMed

Ruffini, Giulio; Fox, Michael D; Ripolles, Oscar; Miranda, Pedro Cavaleiro; Pascual-Leone, Alvaro

2014-04-01

Recently, multifocal transcranial current stimulation (tCS) devices using several relatively small electrodes have been used to achieve more focal stimulation of specific cortical targets. However, it is becoming increasingly recognized that many behavioral manifestations of neurological and psychiatric disease are not solely the result of abnormality in one isolated brain region but represent alterations in brain networks. In this paper we describe a method for optimizing the configuration of multifocal tCS for stimulation of brain networks, represented by spatially extended cortical targets. We show how, based on fMRI, PET, EEG or other data specifying a target map on the cortical surface for excitatory, inhibitory or neutral stimulation and a constraint on the maximal number of electrodes, a solution can be produced with the optimal currents and locations of the electrodes. The method described here relies on a fast calculation of multifocal tCS electric fields (including components normal and tangential to the cortical boundaries) using a five layer finite element model of a realistic head. Based on the hypothesis that the effects of current stimulation are to first order due to the interaction of electric fields with populations of elongated cortical neurons, it is argued that the optimization problem for tCS stimulation can be defined in terms of the component of the electric field normal to the cortical surface. Solutions are found using constrained least squares to optimize current intensities, while electrode number and their locations are selected using a genetic algorithm. For direct current tCS (tDCS) applications, we provide some examples of this technique using an available tCS system providing 8 small Ag/AgCl stimulation electrodes. We demonstrate the approach both for localized and spatially extended targets defined using rs-fcMRI and PET data, with clinical applications in stroke and depression. Finally, we extend these ideas to more general stimulation protocols, such as alternating current tCS (tACS). Copyright © 2013 Elsevier Inc. All rights reserved.

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

A Neuromonitoring Approach to Facial Nerve Preservation During Image-guided Robotic Cochlear Implantation.

PubMed

Ansó, Juan; Dür, Cilgia; Gavaghan, Kate; Rohrbach, Helene; Gerber, Nicolas; Williamson, Tom; Calvo, Enric M; Balmer, Thomas Wyss; Precht, Christina; Ferrario, Damien; Dettmer, Matthias S; Rösler, Kai M; Caversaccio, Marco D; Bell, Brett; Weber, Stefan

2016-01-01

A multielectrode probe in combination with an optimized stimulation protocol could provide sufficient sensitivity and specificity to act as an effective safety mechanism for preservation of the facial nerve in case of an unsafe drill distance during image-guided cochlear implantation. A minimally invasive cochlear implantation is enabled by image-guided and robotic-assisted drilling of an access tunnel to the middle ear cavity. The approach requires the drill to pass at distances below 1  mm from the facial nerve and thus safety mechanisms for protecting this critical structure are required. Neuromonitoring is currently used to determine facial nerve proximity in mastoidectomy but lacks sensitivity and specificity necessaries to effectively distinguish the close distance ranges experienced in the minimally invasive approach, possibly because of current shunting of uninsulated stimulating drilling tools in the drill tunnel and because of nonoptimized stimulation parameters. To this end, we propose an advanced neuromonitoring approach using varying levels of stimulation parameters together with an integrated bipolar and monopolar stimulating probe. An in vivo study (sheep model) was conducted in which measurements at specifically planned and navigated lateral distances from the facial nerve were performed to determine if specific sets of stimulation parameters in combination with the proposed neuromonitoring system could reliably detect an imminent collision with the facial nerve. For the accurate positioning of the neuromonitoring probe, a dedicated robotic system for image-guided cochlear implantation was used and drilling accuracy was corrected on postoperative microcomputed tomographic images. From 29 trajectories analyzed in five different subjects, a correlation between stimulus threshold and drill-to-facial nerve distance was found in trajectories colliding with the facial nerve (distance <0.1  mm). The shortest pulse duration that provided the highest linear correlation between stimulation intensity and drill-to-facial nerve distance was 250  μs. Only at low stimulus intensity values (≤0.3  mA) and with the bipolar configurations of the probe did the neuromonitoring system enable sufficient lateral specificity (>95%) at distances to the facial nerve below 0.5  mm. However, reduction in stimulus threshold to 0.3  mA or lower resulted in a decrease of facial nerve distance detection range below 0.1  mm (>95% sensitivity). Subsequent histopathology follow-up of three representative cases where the neuromonitoring system could reliably detect a collision with the facial nerve (distance <0.1  mm) revealed either mild or inexistent damage to the nerve fascicles. Our findings suggest that although no general correlation between facial nerve distance and stimulation threshold existed, possibly because of variances in patient-specific anatomy, correlations at very close distances to the facial nerve and high levels of specificity would enable a binary response warning system to be developed using the proposed probe at low stimulation currents.

Charge and energy minimization in electrical/magnetic stimulation of nervous tissue

NASA Astrophysics Data System (ADS)

Jezernik, Sašo; Sinkjaer, Thomas; Morari, Manfred

2010-08-01

In this work we address the problem of stimulating nervous tissue with the minimal necessary energy at reduced/minimal charge. Charge minimization is related to a valid safety concern (avoidance and reduction of stimulation-induced tissue and electrode damage). Energy minimization plays a role in battery-driven electrical or magnetic stimulation systems (increased lifetime, repetition rates, reduction of power requirements, thermal management). Extensive new theoretical results are derived by employing an optimal control theory framework. These results include derivation of the optimal electrical stimulation waveform for a mixed energy/charge minimization problem, derivation of the charge-balanced energy-minimal electrical stimulation waveform, solutions of a pure charge minimization problem with and without a constraint on the stimulation amplitude, and derivation of the energy-minimal magnetic stimulation waveform. Depending on the set stimulus pulse duration, energy and charge reductions of up to 80% are deemed possible. Results are verified in simulations with an active, mammalian-like nerve fiber model.

Charge and energy minimization in electrical/magnetic stimulation of nervous tissue.

PubMed

Jezernik, Saso; Sinkjaer, Thomas; Morari, Manfred

2010-08-01

In this work we address the problem of stimulating nervous tissue with the minimal necessary energy at reduced/minimal charge. Charge minimization is related to a valid safety concern (avoidance and reduction of stimulation-induced tissue and electrode damage). Energy minimization plays a role in battery-driven electrical or magnetic stimulation systems (increased lifetime, repetition rates, reduction of power requirements, thermal management). Extensive new theoretical results are derived by employing an optimal control theory framework. These results include derivation of the optimal electrical stimulation waveform for a mixed energy/charge minimization problem, derivation of the charge-balanced energy-minimal electrical stimulation waveform, solutions of a pure charge minimization problem with and without a constraint on the stimulation amplitude, and derivation of the energy-minimal magnetic stimulation waveform. Depending on the set stimulus pulse duration, energy and charge reductions of up to 80% are deemed possible. Results are verified in simulations with an active, mammalian-like nerve fiber model.

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.

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.

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.

Frequency steps and compositions determine properties of nee- dling sensation during electroacupuncture.

PubMed

Xuan, Chen; Xiaoran, Ye; Suying, Ge; Zhifang, Yao; Xiaoqing, Huang

2015-04-01

To investigate the relationship of electro-parameters and the electroacupuncture sensation (EAS), which is thought to be an important factor for optimal treatment. The frequency steps and compositions of three frequently used electrical stimulations were set when the switch of the electroacupuncture apparatus was turned to the second or third grade of the dense-disperse frequency wave (DD2 and DD3, respectively) or the second grade of the continuous wave (C2). Three groups of patients according to the three electroacupuncture stimulations were divided again into three sub-groups according to the stimulated acupoints: the face acupoint Quanliao (SI 18), the upper-limb acupoint Quchi (LI 11) and the back acupoint Dachangshu (BL 25). The EAS values were measured every 5 min during 30 min electroacupuncture treatments using a visual analogue scale. The frequency compositions of the three electroacupuncture stimulations were 3.3 and 33 Hz, 12.5 and 66.7 Hz, and 3.3 and 3.3 Hz; each frequency step was 30, 54 and 0 Hz, respectively. In each sub-group of the C2 group, the EAS values from 10 to 30 min were significantly weaker than at 0 min. The sensation fluctuations in the DD2 and DD3 groups were different during the 30 min. The greater the frequency step of the electroacupuncture stimulation, the longer the needling sensation lasted. The electroacupuncture stimulations of the DD3 group were unsuitable for the facial acupoint because of its painful and uncomfortable EAS, but more suitable for the back acupoint.

Mechanisms for pattern specificity of deep-brain stimulation in Parkinson’s disease

PubMed Central

Mato, Germán; Dellavale, Damián

2017-01-01

Deep brain stimulation (DBS) has become a widely used technique for treating advanced stages of neurological and psychiatric illness. In the case of motor disorders related to basal ganglia (BG) dysfunction, several mechanisms of action for the DBS therapy have been identified which might be involved simultaneously or in sequence. However, the identification of a common key mechanism underlying the clinical relevant DBS configurations has remained elusive due to the inherent complexity related to the interaction between the electrical stimulation and the neural tissue, and the intricate circuital structure of the BG-thalamocortical network. In this work, it is shown that the clinically relevant range for both, the frequency and intensity of the electrical stimulation pattern, is an emergent property of the BG anatomy at the system-level that can be addressed using mean-field descriptive models of the BG network. Moreover, it is shown that the activity resetting mechanism elicited by electrical stimulation provides a natural explanation to the ineffectiveness of irregular (i.e., aperiodic) stimulation patterns, which has been commonly observed in previously reported pathophysiology models of Parkinson’s disease. Using analytical and numerical techniques, these results have been reproduced in both cases: 1) a reduced mean-field model that can be thought as an elementary building block capable to capture the underlying fundamentals of the relevant loops constituting the BG-thalamocortical network, and 2) a detailed model constituted by the direct and hyperdirect loops including one-dimensional spatial structure of the BG nuclei. We found that the optimal ranges for the essential parameters of the stimulation patterns can be understood without taking into account biophysical details of the relevant structures. PMID:28813460

Production, characteristics and applications of phytase from a rhizosphere isolated Enterobacter sp. ACSS.

PubMed

Chanderman, Ashira; Puri, Adarsh Kumar; Permaul, Kugen; Singh, Suren

2016-10-01

Optimization of process parameters for phytase production by Enterobacter sp. ACSS led to a 4.6-fold improvement in submerged fermentation, which was enhanced further in fed-batch fermentation. The purified 62 kDa monomeric phytase was optimally active at pH 2.5 and 60 °C and retained activity over a wide range of temperature (40-80 °C) and pH (2.0-6.0) with a half-life of 11.3 min at 80 °C. The kinetic parameters K m, V max, K cat, and K cat/K m of the pure phytase were 0.21 mM, 131.58 nmol mg(-1) s(-1), 1.64 × 10(3) s(-1), and 7.81 × 10(6) M(-1) s(-1), respectively. The enzyme was fairly stable in the presence of pepsin under physiological conditions. It was stimulated by Ca(+2), Mg(+2) and Mn(+2), but inhibited by Zn(+2), Cu(+2), Fe(+2), Pb(+2), Ba(+2) and surfactants. The enzyme can be applied in dephytinizing animal feeds, and the baking industry.

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.

Individualized treatment with transcranial direct current stimulation in patients with chronic non-fluent aphasia due to stroke

PubMed Central

Shah-Basak, Priyanka P.; Norise, Catherine; Garcia, Gabriella; Torres, Jose; Faseyitan, Olufunsho; Hamilton, Roy H.

2015-01-01

While evidence suggests that transcranial direct current stimulation (tDCS) may facilitate language recovery in chronic post-stroke aphasia, individual variability in patient response to different patterns of stimulation remains largely unexplored. We sought to characterize this variability among chronic aphasic individuals, and to explore whether repeated stimulation with an individualized optimal montage could lead to persistent reduction of aphasia severity. In a two-phase study, we first stimulated patients with four active montages (left hemispheric anode or cathode; right hemispheric anode or cathode) and one sham montage (Phase 1). We examined changes in picture naming ability to address (1) variability in response to different montages among our patients, and (2) whether individual patients responded optimally to at least one montage. During Phase 2, subjects who responded in Phase 1 were randomized to receive either real-tDCS or to receive sham stimulation (10 days); patients who were randomized to receive sham stimulation first were then crossed over to receive real-tDCS (10 days). In both phases, 2 mA tDCS was administered for 20 min per real-tDCS sessions and patients performed a picture naming task during stimulation. Patients' language ability was re-tested after 2-weeks and 2-months following real and sham tDCS in Phase 2. In Phase 1, despite considerable individual variability, the greatest average improvement was observed after left-cathodal stimulation. Seven out of 12 subjects responded optimally to at least one montage as demonstrated by transient improvement in picture-naming. In Phase 2, aphasia severity improved at 2-weeks and 2-months following real-tDCS but not sham. Despite individual variability with respect to optimal tDCS approach, certain montages result in consistent transient improvement in persons with chronic post-stroke aphasia. This preliminary study supports the notion that individualized tDCS treatment may enhance aphasia recovery in a persistent manner. PMID:25954178

A patient-controlled functional electrical stimulation system for arm weight relief.

PubMed

Klauer, C; Ferrante, S; Ambrosini, E; Shiri, U; Dähne, F; Schmehl, I; Pedrocchi, A; Schauer, T

2016-11-01

A patient-driven control strategy for Functional Electrical Stimulation (FES), which amplifies volitionally-initiated shoulder abductions, is proposed to improve stroke patients' rehabilitation. Based on the measured abduction angle, a FES-induced muscle recruitment is generated that yields a pre-specified percentage of this angle - yielding arm weight relief. To guarantee the correct recruitment also under fatigue and uncertain muscle activation we employ feedback control of the recruitment level determined by filtering the FES-evoked electromyogram. Filter parameters are user-optimized to obtain a linear relation between filter output and angle with a good signal-to-noise ratio. The auto-tuned recruitment controller (RC) was tested on five healthy subjects and compared to direct stimulation (DS) while muscle fatigue progressively occurred. Results showed a more linear relation between recruitment level and angle than between non-controlled stimulation intensity and angle (R 2 =0.93 vs. R 2 =0.79, angular range of 54°). After 6 min of stimulation, abduction decreased by 42% ± 14 for DS and by 0% ± 12 for RC, showing an effective compensation of fatigue. RC yielded significant smaller errors than DS in generating desired angles (0.23% ± 5.9 vs. 14.6% ± 9.7). When FES-induced arm weight support was provided, a mean reduction of the volitional effort (determined by Electromyography) of 78% was achieved compared to angular tracking without FES. First experiments with one acute stroke patient are also reported. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Assessing the applicability of WRF optimal parameters under the different precipitation simulations in the Greater Beijing Area

NASA Astrophysics Data System (ADS)

Di, Zhenhua; Duan, Qingyun; Wang, Chen; Ye, Aizhong; Miao, Chiyuan; Gong, Wei

2018-03-01

Forecasting skills of the complex weather and climate models have been improved by tuning the sensitive parameters that exert the greatest impact on simulated results based on more effective optimization methods. However, whether the optimal parameter values are still work when the model simulation conditions vary, which is a scientific problem deserving of study. In this study, a highly-effective optimization method, adaptive surrogate model-based optimization (ASMO), was firstly used to tune nine sensitive parameters from four physical parameterization schemes of the Weather Research and Forecasting (WRF) model to obtain better summer precipitation forecasting over the Greater Beijing Area in China. Then, to assess the applicability of the optimal parameter values, simulation results from the WRF model with default and optimal parameter values were compared across precipitation events, boundary conditions, spatial scales, and physical processes in the Greater Beijing Area. The summer precipitation events from 6 years were used to calibrate and evaluate the optimal parameter values of WRF model. Three boundary data and two spatial resolutions were adopted to evaluate the superiority of the calibrated optimal parameters to default parameters under the WRF simulations with different boundary conditions and spatial resolutions, respectively. Physical interpretations of the optimal parameters indicating how to improve precipitation simulation results were also examined. All the results showed that the optimal parameters obtained by ASMO are superior to the default parameters for WRF simulations for predicting summer precipitation in the Greater Beijing Area because the optimal parameters are not constrained by specific precipitation events, boundary conditions, and spatial resolutions. The optimal values of the nine parameters were determined from 127 parameter samples using the ASMO method, which showed that the ASMO method is very highly-efficient for optimizing WRF model parameters.

Electromagnetic pulses bone healing booster

NASA Astrophysics Data System (ADS)

Sintea, S. R.; Pomazan, V. M.; Bica, D.; Grebenisan, D.; Bordea, N.

2015-11-01

Posttraumatic bone restoration triggered by the need to assist and stimulate compensatory bone growth in periodontal condition. Recent studies state that specific electromagnetic stimulation can boost the bone restoration, reaching up to 30% decrease in recovery time. Based on the existing data on the electromagnetic parameters, a digital electronic device is proposed for intra oral mounting and bone restoration stimulation in periodontal condition. The electrical signal is applied to an inductive mark that will create and impregnate magnetic field in diseased tissue. The device also monitors the status of the electromagnetic field. Controlled wave forms and pulse frequency signal at programmable intervals are obtained with optimized number of components and miniaturized using surface mounting devices (SMD) circuits and surface mounting technology (SMT), with enhanced protection against abnormal current growth, given the intra-oral environment. The system is powered by an autonomous power supply (battery), to limit the problems caused by powering medical equipment from the main power supply. Currently the device is used in clinical testing, in cycles of six up to twelve months. Basic principles for the electrical scheme and algorithms for pulse generation, pulse control, electromagnetic field control and automation of current monitoring are presented, together with the friendly user interface, suitable for medical data and patient monitoring.

rTMS in the treatment of drug addiction: an update about human studies.

PubMed

Bellamoli, Elisa; Manganotti, Paolo; Schwartz, Robert P; Rimondo, Claudia; Gomma, Maurizio; Serpelloni, Giovanni

2014-01-01

Drug addiction can be a devastating and chronic relapsing disorder with social, psychological, and physical consequences, and more effective treatment options are needed. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that has been assessed in a growing number of studies for its therapeutic potential in treating addiction. This review paper offers an overview on the current state of clinical research in treating drug addiction with rTMS. Because of the limited research in this area, all studies (including case reports) that evaluated the therapeutic use of rTMS in nicotine, alcohol, or illicit drug addiction were included in this review. Papers published prior to December 2012 were found through an NCBI PubMed search. A total of eleven studies were identified that met review criteria. There is nascent evidence that rTMS could be effective in reducing cocaine craving and nicotine and alcohol craving and consumption and might represent a potential therapeutic tool for treating addiction. Further studies are needed to identify the optimal parameters of stimulation for the most effective treatment of drug addiction, to improve our comprehension of the treatment neurophysiological effects, and to conduct rigorous, controlled efficacy studies with adequate power.

Determine Optimal Stimulus Amplitude for Using Vestibular Stochastic Stimulation to Improve Balance Function

NASA Technical Reports Server (NTRS)

Goel, R.; Kofman, I.; DeDios, Y. E.; Jeevarajan, J.; Stepanyan, V.; Nair, M.; Congdon, S.; Fregia, M.; Cohen, H.; Bloomberg, J.J.;

A compact planar multi-broad band monopole antenna for mobile devices

NASA Astrophysics Data System (ADS)

Zhong, Xiaoqing; Yao, Bin; Zheng, Qinhong; Yang, Jikong; Cao, Xiangqi

2015-10-01

A Multiple-frequency broadband planar monopole antenna is proposed in this Paper. The antenna is stimulated and numerically optimized by HFSS13.0 (High Frequency Structure Simulator). The size of it is 39mm×22mm×1.7mm. The antenna resonates at many frequencies. The parameter S11<=-6dB means the proposed antenna matches well with its feed-line and covers many useful operation frequency bands, including 2G(DCS1800 and PCS1900), 3G(UMTS), 4G(LTE2300 and LTE2500), ISM, WLAN. It is quiet appropriate for the present ultra-thin smart phones

Continuous 4-1BB co-stimulatory signals for the optimal expansion of tumor-infiltrating lymphocytes for adoptive T-cell therapy.

PubMed

Chacon, Jessica Ann; Pilon-Thomas, Shari; Sarnaik, Amod A; Radvanyi, Laszlo G

2013-09-01

Co-stimulation through members of the tumor necrosis factor receptor (TNFR) family appears to be critical for the generation of T cells with optimal effector-memory properties for adoptive cell therapy. Our work suggests that continuous 4-1BB/CD137 co-stimulation is required for the expansion of T cells with an optimal therapeutic profile and that the administration of 4-1BB agonists upon adoptive cell transfer further improves antitumor T-cell functions.

Computational modeling of transcranial direct current stimulation (tDCS) in obesity: Impact of head fat and dose guidelines☆

PubMed Central

Truong, Dennis Q.; Magerowski, Greta; Blackburn, George L.; Bikson, Marom; Alonso-Alonso, Miguel

2013-01-01

Recent studies show that acute neuromodulation of the prefrontal cortex with transcranial direct current stimulation (tDCS) can decrease food craving, attentional bias to food, and actual food intake. These data suggest potential clinical applications for tDCS in the field of obesity. However, optimal stimulation parameters in obese individuals are uncertain. One fundamental concern is whether a thick, low-conductivity layer of subcutaneous fat around the head can affect current density distribution and require dose adjustments during tDCS administration. The aim of this study was to investigate the role of head fat on the distribution of current during tDCS and evaluate whether dosing standards for tDCS developed for adult individuals in general are adequate for the obese population. We used MRI-derived high-resolution computational models that delineated fat layers in five human heads from subjects with body mass index (BMI) ranging from “normal-lean” to “super-obese” (20.9 to 53.5 kg/m2). Data derived from these simulations suggest that head fat influences tDCS current density across the brain, but its relative contribution is small when other components of head anatomy are added. Current density variability between subjects does not appear to have a direct and/or simple link to BMI. These results indicate that guidelines for the use of tDCS can be extrapolated to obese subjects without sacrificing efficacy and/or treatment safety; the recommended standard parameters can lead to the delivery of adequate current flow to induce neuromodulation of brain activity in the obese population. PMID:24159560

A Numerical Study of Factors Affecting Fracture-Fluid Cleanup and Produced Gas/Water in Marcellus Shale: Part II

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

Seales, Maxian B.; Dilmore, Robert; Ertekin, Turgay

Horizontal wells combined with successful multistage-hydraulic-fracture treatments are currently the most-established method for effectively stimulating and enabling economic development of gas-bearing organic-rich shale formations. Fracture cleanup in the stimulated reservoir volume (SRV) is critical to stimulation effectiveness and long-term well performance. But, fluid cleanup is often hampered by formation damage, and post-fracture well performance frequently falls to less than expectations. A systematic study of the factors that hinder fracture-fluid cleanup in shale formations can help optimize fracture treatments and better quantify long-term volumes of produced water and gas. Fracture-fluid cleanup is a complex process influenced by mutliphase flow through porousmore » media (relative permeability hysteresis, capillary pressure), reservoir-rock and -fluid properties, fracture-fluid properties, proppant placement, fracture-treatment parameters, and subsequent flowback and field operations. Changing SRV and fracture conductivity as production progresses further adds to the complexity of this problem. Numerical simulation is the best and most-practical approach to investigate such a complicated blend of mechanisms, parameters, their interactions, and subsequent effect on fracture-fluid cleanup and well deliverability. Here, a 3D, two-phase, dual-porosity model was used to investigate the effect of mutliphase flow, proppant crushing, proppant diagenesis, shut-in time, reservoir-rock compaction, gas slippage, and gas desorption on fracture-fluid cleanup and well performance in Marcellus Shale. Our findings have shed light on the factors that substantially constrain efficient fracture-fluid cleanup in gas shales, and we have provided guidelines for improved fracture-treatment designs and water management.« less

A Numerical Study of Factors Affecting Fracture-Fluid Cleanup and Produced Gas/Water in Marcellus Shale: Part II

DOE PAGES

Seales, Maxian B.; Dilmore, Robert; Ertekin, Turgay; ...

2017-04-01

Horizontal wells combined with successful multistage-hydraulic-fracture treatments are currently the most-established method for effectively stimulating and enabling economic development of gas-bearing organic-rich shale formations. Fracture cleanup in the stimulated reservoir volume (SRV) is critical to stimulation effectiveness and long-term well performance. But, fluid cleanup is often hampered by formation damage, and post-fracture well performance frequently falls to less than expectations. A systematic study of the factors that hinder fracture-fluid cleanup in shale formations can help optimize fracture treatments and better quantify long-term volumes of produced water and gas. Fracture-fluid cleanup is a complex process influenced by mutliphase flow through porousmore » media (relative permeability hysteresis, capillary pressure), reservoir-rock and -fluid properties, fracture-fluid properties, proppant placement, fracture-treatment parameters, and subsequent flowback and field operations. Changing SRV and fracture conductivity as production progresses further adds to the complexity of this problem. Numerical simulation is the best and most-practical approach to investigate such a complicated blend of mechanisms, parameters, their interactions, and subsequent effect on fracture-fluid cleanup and well deliverability. Here, a 3D, two-phase, dual-porosity model was used to investigate the effect of mutliphase flow, proppant crushing, proppant diagenesis, shut-in time, reservoir-rock compaction, gas slippage, and gas desorption on fracture-fluid cleanup and well performance in Marcellus Shale. Our findings have shed light on the factors that substantially constrain efficient fracture-fluid cleanup in gas shales, and we have provided guidelines for improved fracture-treatment designs and water management.« less

Optimized Extraction, Preliminary Characterization, and In Vitro Antioxidant Activity of Polysaccharides from Glycyrrhiza Uralensis Fisch

PubMed Central

Chen, Jie; Li, Wan-chen; Gu, Xin-li

2017-01-01

Background This study performed optimized extraction, preliminary characterization, and in vitro antioxidant activities of polysaccharides from Glycyrrhiza uralensis Fisch. Material/Methods Three parameters (extraction temperature, ratio of water to raw material, and extraction time) were optimized for yields of G. uralensis polysaccharides (GUP) using response surface methodology with Box-Behnken design (BBD). The GUP was purified using DEAE cellulose 32-column chromatography. The main fraction obtained from G. uralensis Fisch was GUP-II, which was composed of rhamnose, arabinose, galactose, and glucose monosaccharide, was screened for antioxidant properties using DP Hand hydroxyl radical scavenging assays. In addition, immunological activity of GUP-II was determined by nitric oxide and lymphocyte proliferation assays. Results Optimization revealed maximum GUP yields with an extraction temperature of 99°C, water: raw material ratio of 15: 1, and extraction duration of 2 h. GUP-II purified from G. uralensis Fisch had good in vitro DPPH and hydroxyl radical scavenging abilities. Immunologically, GUP-II significantly stimulated NO production in RAW 264.7 macrophages, and significantly enhanced LPS-induced lymphocyte proliferation. Conclusions Extraction of GUP from G. uralensis Fisch can be optimized with respect to temperature, extraction period, and ratio of water to material, using response surface methodology. The purified product (GUP-II) possesses excellent antioxidant and immunological activities. PMID:28404983

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.

Deep Brain Stimulation for Essential Tremor: Aligning Thalamic and Posterior Subthalamic Targets in 1 Surgical Trajectory.

PubMed

Bot, Maarten; van Rootselaar, Fleur; Contarino, Maria Fiorella; Odekerken, Vincent; Dijk, Joke; de Bie, Rob; Schuurman, Richard; van den Munckhof, Pepijn

2017-12-21

Ventral intermediate nucleus (VIM) deep brain stimulation (DBS) and posterior subthalamic area (PSA) DBS suppress tremor in essential tremor (ET) patients, but it is not clear which target is optimal. Aligning both targets in 1 surgical trajectory would facilitate exploring stimulation of either target in a single patient. To evaluate aligning VIM and PSA in 1 surgical trajectory for DBS in ET. Technical aspects of trajectories, intraoperative stimulation findings, final electrode placement, target used for chronic stimulation, and adverse and beneficial effects were evaluated. In 17 patients representing 33 trajectories, we successfully aligned VIM and PSA targets in 26 trajectories. Trajectory distance between targets averaged 7.2 (range 6-10) mm. In all but 4 aligned trajectories, optimal intraoperative tremor suppression was obtained in the PSA. During follow-up, active electrode contacts were located in PSA in the majority of cases. Overall, successful tremor control was achieved in 69% of patients. Stimulation-induced dysarthria or gait ataxia occurred in, respectively, 56% and 44% of patients. Neither difference in tremor suppression or side effects was noted between aligned and nonaligned leads nor between the different locations of chronic stimulation. Alignment of VIM and PSA for DBS in ET is feasible and enables intraoperative exploration of both targets in 1 trajectory. This facilitates positioning of electrode contacts in both areas, where multiple effective points of stimulation can be found. In the majority of aligned leads, optimal intraoperative and chronic stimulation were located in the PSA. Copyright © 2017 by the Congress of Neurological Surgeons

Optimized multi-electrode stimulation increases focality and intensity at target

NASA Astrophysics Data System (ADS)

Dmochowski, Jacek P.; Datta, Abhishek; Bikson, Marom; Su, Yuzhuo; Parra, Lucas C.

2011-08-01

Transcranial direct current stimulation (tDCS) provides a non-invasive tool to elicit neuromodulation by delivering current through electrodes placed on the scalp. The present clinical paradigm uses two relatively large electrodes to inject current through the head resulting in electric fields that are broadly distributed over large regions of the brain. In this paper, we present a method that uses multiple small electrodes (i.e. 1.2 cm diameter) and systematically optimize the applied currents to achieve effective and targeted stimulation while ensuring safety of stimulation. We found a fundamental trade-off between achievable intensity (at the target) and focality, and algorithms to optimize both measures are presented. When compared with large pad-electrodes (approximated here by a set of small electrodes covering 25cm2), the proposed approach achieves electric fields which exhibit simultaneously greater focality (80% improvement) and higher target intensity (98% improvement) at cortical targets using the same total current applied. These improvements illustrate the previously unrecognized and non-trivial dependence of the optimal electrode configuration on the desired electric field orientation and the maximum total current (due to safety). Similarly, by exploiting idiosyncratic details of brain anatomy, the optimization approach significantly improves upon prior un-optimized approaches using small electrodes. The analysis also reveals the optimal use of conventional bipolar montages: maximally intense tangential fields are attained with the two electrodes placed at a considerable distance from the target along the direction of the desired field; when radial fields are desired, the maximum-intensity configuration consists of an electrode placed directly over the target with a distant return electrode. To summarize, if a target location and stimulation orientation can be defined by the clinician, then the proposed technique is superior in terms of both focality and intensity as compared to previous solutions and is thus expected to translate into improved patient safety and increased clinical efficacy.

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury.

PubMed

Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H

2016-03-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 min after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 min. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS+c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 min/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 min of daily stimulation compared with 6h, as in our prior study, making it a potential therapy for humans with spinal cord injury. Copyright © 2015 Elsevier Inc. All rights reserved.

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury

PubMed Central

Song, Weiguo; Amer, Alzahraa; Ryan, Daniel; Martin, John H.

2016-01-01

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 minutes after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 minutes. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS + c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 minutes/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 minutes of daily stimulation compared with 6 hours, as in our prior study, making it a potential therapy for humans with spinal cord injury. PMID:26708732

High vs. Low Frequency Stimulation Effects on Fine Motor Control in Chronic Hemiplegia: A Pilot Study

PubMed Central

Doucet, Barbara M.; Griffin, Lisa

2014-01-01

Introduction The optimal parameters of neuromuscular electrical stimulation (NMES) for recovery of hand function following stroke are not known. This clinical pilot study examined whether higher or lower frequencies are more effective for improving fine motor control of the hand in a chronic post-stroke population. Methods A one-month, 4x/week in-home regimen of either a high frequency (40Hz) or low frequency (20Hz) NMES program was applied to the hemiplegic thenar muscles of 16 persons with chronic stroke. Participants were identified a priori as having a low level of function (LF) or a high level of function (HF). Outcome measures of strength, dexterity, and endurance were measured before and after participation in the regimen. Results LF subjects showed no significant changes with either the high or the low frequency NMES regimen. HF subjects showed significant changes in strength, dexterity and endurance. Within this group, higher frequencies of stimulation yielded strength gains and increased motor activation; lower frequencies impacted dexterity and endurance. Conclusions The results suggest that higher frequencies of stimulation could be more effective in improving strength and motor activation properties and that lower frequencies may impact coordination and endurance changes; results also indicate that persons with a higher functional level of recovery may respond more favorably to NMES regimens, but further study with larger patient groups is warranted. PMID:23893829

Immunization Route Dictates Cross-Priming Efficiency and Impacts the Optimal Timing of Adjuvant Delivery

PubMed Central

Bouvier, Isabelle; Jusforgues-Saklani, Hélène; Lim, Annick; Lemaître, Fabrice; Lemercier, Brigitte; Auriau, Charlotte; Nicola, Marie-Anne; Leroy, Sandrine; Law, Helen K.; Bandeira, Antonio; Moon, James J.; Bousso, Philippe; Albert, Matthew L.

2011-01-01

Delivery of cell-associated antigen represents an important strategy for vaccination. While many experimental models have been developed in order to define the critical parameters for efficient cross-priming, few have utilized quantitative methods that permit the study of the endogenous repertoire. Comparing different strategies of immunization, we report that local delivery of cell-associated antigen results in delayed T cell cross-priming due to the increased time required for antigen capture and presentation. In comparison, delivery of disseminated antigen resulted in rapid T cell priming. Surprisingly, local injection of cell-associated antigen, while slower, resulted in the differentiation of a more robust, polyfunctional, effector response. We also evaluated the combination of cell-associated antigen with poly I:C delivery and observed an immunization route-specific effect regarding the optimal timing of innate immune stimulation. These studies highlight the importance of considering the timing and persistence of antigen presentation, and suggest that intradermal injection with delayed adjuvant delivery is the optimal strategy for achieving CD8+ T cell cross-priming. PMID:22566860

Super-resolution for scanning light stimulation systems

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

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

Super-resolution (SR) is a technique used in digital image processing to overcome the resolution limitation of imaging systems. In this process, a single high resolution image is reconstructed from multiple low resolution images. SR is commonly used for CCD and CMOS (Complementary Metal-Oxide-Semiconductor) sensor images, as well as for medical applications, e.g., magnetic resonance imaging. Here, we demonstrate that super-resolution can be applied with scanning light stimulation (LS) systems, which are common to obtain space-resolved electro-optical parameters of a sample. For our purposes, the Projection Onto Convex Sets (POCS) was chosen and modified to suit the needs of LS systems.more » To demonstrate the SR adaption, an Optical Beam Induced Current (OBIC) LS system was used. The POCS algorithm was optimized by means of OBIC short circuit current measurements on a multicrystalline solar cell, resulting in a mean square error reduction of up to 61% and improved image quality.« less

An experimental vestibular neural prosthesis: design and preliminary results with rhesus monkeys stimulated with modulated pulses.

PubMed

Nie, Kaibao; Ling, Leo; Bierer, Steven M; Kaneko, Chris R S; Fuchs, Albert F; Oxford, Trey; Rubinstein, Jay T; Phillips, James O

2013-06-01

A vestibular neural prosthesis was designed on the basis of a cochlear implant for treatment of Meniere's disease and other vestibular disorders. Computer control software was developed to generate patterned pulse stimuli for exploring optimal parameters to activate the vestibular nerve. Two rhesus monkeys were implanted with the prototype vestibular prosthesis and they were behaviorally evaluated post implantation surgery. Horizontal and vertical eye movement responses to patterned electrical pulse stimulations were collected on both monkeys. Pulse amplitude modulated (PAM) and pulse rate modulated (PRM) trains were applied to the lateral canal of each implanted animal. Robust slow-phase nystagmus responses following the PAM or PRM modulation pattern were observed in both implanted monkeys in the direction consistent with the activation of the implanted canal. Both PAM and PRM pulse trains can elicit a significant amount of in-phase modulated eye velocity changes and they could potentially be used for efficiently coding head rotational signals in future vestibular neural prostheses.

Stroking and tapping the skin: behavioral and electrodermal effects.

PubMed

Etzi, Roberta; Carta, Carlotta; Gallace, Alberto

2018-02-01

Being caressed represents one of the most typical expressions of affection conveyed by touch. Converging evidence suggests that the pleasant perception of gentle and slow stroking delivered to the hairy skin is mediated by C-Tactile afferents (CTs). While behavioral and neural responses to CT-optimal touch have been moderately explored so far, less is known about the autonomic reaction to different kinds of touch (both CT-optimal and not). Here, we investigated whether physiological arousal varies as a function of the specific tactile stimulation provided. Stroking (slow: 3 cm/s 'CT-optimal'; or fast: 30 cm/s) and tapping (random or fixed spatial order) stimulations were delivered to the participants' forearm with a brush, for durations of 9 or 60 s. Participants' skin conductance response (SCR) and level (SCL), as well as subjective evaluations, were recorded. The results revealed that being stroked (at both the velocities) induced higher SCR and SCL than being tapped. Moreover, while higher SCR was elicited by CT-suboptimal stroking compared to CT-optimal stroking, SCL was not affected differently by CT-optimal touch. No differences were found between the effects of 9 and 60 s stimulations. Slow stroking was evaluated as the most pleasant, relaxing and 'social' type of touch compared to the other tactile stimulations. Taken together, these findings shed light on the psychophysiological responses to stroking (including CT-optimal touch) and tapping, and contribute to elucidate the mechanisms underlying hedonic tactile perception.

Optimal Stimulus Amplitude for Vestibular Stochastic Stimulation to Improve Sensorimotor Function

NASA Technical Reports Server (NTRS)

Goel, R.; Kofman, I.; DeDios, Y. E.; Jeevarajan, J.; Stepanyan, V.; Nair, M.; Congdon, S.; Fregia, M.; Cohen, H.; Bloomberg, J. J.;

A pharmacokinetic model of filgrastim and pegfilgrastim application in normal mice and those with cyclophosphamide-induced granulocytopaenia.

PubMed

Scholz, M; Ackermann, M; Engel, C; Emmrich, F; Loeffler, M; Kamprad, M

2009-12-01

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used as treatment for granulocytopaenia during cytotoxic chemotherapy; however, optimal scheduling of this pharmaceutical is unknown. Biomathematical models can help to pre-select optimal application schedules but precise pharmacokinetic properties of the pharmaceuticals are required at first. In this study, we have aimed to construct a pharmacokinetic model of G-CSF derivatives filgrastim and pegfilgrastim in mice. Healthy CD-1 mice and those with cyclophosphamide-induced granulocytopaenia were studied after administration of filgrastim and pegfilgrastim in different dosing and timing schedules. Close meshed time series of granulocytes and G-CSF plasma concentrations were determined. An ordinary differential equations model of pharmacokinetics was constructed on the basis of known mechanisms of drug distribution and degradation. Predictions of the model fit well with all experimental data for both filgrastim and pegfilgrastim. We obtained a unique parameter setting for all experimental scenarios. Differences in pharmacokinetics between filgrastim and pegfilgrastim can be explained by different estimates of model parameters rather than by different model mechanisms. Parameter estimates with respect to distribution and clearance of the drug derivatives are in agreement with qualitative experimental results. Dynamics of filgrastim and pegfilgrastim plasma levels can be explained by the same pharmacokinetic model but different model parameters. Beause of a strong clearance mechanism mediated by granulocytes, granulocytotic and granulocytopaenic conditions must be studied simultaneously to construct a reliable model. The pharmacokinetic model will be extended to a murine model of granulopoiesis under chemotherapy and G-CSF application.

Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases

PubMed Central

Fox, Michael D.; Buckner, Randy L.; Liu, Hesheng; Chakravarty, M. Mallar; Lozano, Andres M.; Pascual-Leone, Alvaro

2014-01-01

Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mechanisms remain unclear, and the ideal stimulation site for a given technique is often ambiguous, limiting optimization of the stimulation and its application in further disorders. In this article, we identify diseases treated with both types of stimulation, list the stimulation sites thought to be most effective in each disease, and test the hypothesis that these sites are different nodes within the same brain network as defined by resting-state functional-connectivity MRI. Sites where DBS was effective were functionally connected to sites where noninvasive brain stimulation was effective across diseases including depression, Parkinson's disease, obsessive-compulsive disorder, essential tremor, addiction, pain, minimally conscious states, and Alzheimer’s disease. A lack of functional connectivity identified sites where stimulation was ineffective, and the sign of the correlation related to whether excitatory or inhibitory noninvasive stimulation was found clinically effective. These results suggest that resting-state functional connectivity may be useful for translating therapy between stimulation modalities, optimizing treatment, and identifying new stimulation targets. More broadly, this work supports a network perspective toward understanding and treating neuropsychiatric disease, highlighting the therapeutic potential of targeted brain network modulation. PMID:25267639

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.

Flavonoids released by carrot (Daucus carota) seedlings stimulate hyphal development of vesicular-arbuscular mycorrhizal fungi in the presence of optimal CO2 enrichment.

PubMed

Poulin, M J; Bel-Rhlid, R; Piché, Y; Chênevert, R

1993-10-01

Carbon dioxide has been previously identified as a critical volatile factor that stimulates hyphal growth ofGigaspora margarita, a vesiculararbuscular mycorrhizal fungus, and we determined the optimal concentration at 2.0%. The beneficial effect of CO2 on fungal development is also visible in the presence of stimulatory (quercetin, myricetin) or inhibitory (naringenin) flavonoids. Sterile root exudates from carrot seedlings stimulate the hyphal development ofG. margarita in the presence of optimal CO2 enrichment. Three flavonols (quercetin, kaempferol, rutin or quercetin 3-rutinoside) and two flavones (apigenin, luteolin) were identified in carrot root exudates by means of HPLC retention time. Flavonols like quercetin and kaempferol are known to have stimulatory effects on hyphal growth ofG. margarita.

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.

Determination of the optimal mesh parameters for Iguassu centrifuge flow and separation calculations

NASA Astrophysics Data System (ADS)

Romanihin, S. M.; Tronin, I. V.

2016-09-01

We present the method and the results of the determination for optimal computational mesh parameters for axisymmetric modeling of flow and separation in the Iguasu gas centrifuge. The aim of this work was to determine the mesh parameters which provide relatively low computational cost whithout loss of accuracy. We use direct search optimization algorithm to calculate optimal mesh parameters. Obtained parameters were tested by the calculation of the optimal working regime of the Iguasu GC. Separative power calculated using the optimal mesh parameters differs less than 0.5% from the result obtained on the detailed mesh. Presented method can be used to determine optimal mesh parameters of the Iguasu GC with different rotor speeds.

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.

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.

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

PubMed

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

2016-02-01

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

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.

Transcranial direct current stimulation in obsessive-compulsive disorder: emerging clinical evidence and considerations for optimal montage of electrodes.

PubMed

Senço, Natasha M; Huang, Yu; D'Urso, Giordano; Parra, Lucas C; Bikson, Marom; Mantovani, Antonio; Shavitt, Roseli G; Hoexter, Marcelo Q; Miguel, Eurípedes C; Brunoni, André R

2015-07-01

Neuromodulation techniques for obsessive-compulsive disorder (OCD) treatment have expanded with greater understanding of the brain circuits involved. Transcranial direct current stimulation (tDCS) might be a potential new treatment for OCD, although the optimal montage is unclear. To perform a systematic review on meta-analyses of repetitive transcranianal magnetic stimulation (rTMS) and deep brain stimulation (DBS) trials for OCD, aiming to identify brain stimulation targets for future tDCS trials and to support the empirical evidence with computer head modeling analysis. Systematic reviews of rTMS and DBS trials on OCD in Pubmed/MEDLINE were searched. For the tDCS computational analysis, we employed head models with the goal of optimally targeting current delivery to structures of interest. Only three references matched our eligibility criteria. We simulated four different electrodes montages and analyzed current direction and intensity. Although DBS, rTMS and tDCS are not directly comparable and our theoretical model, based on DBS and rTMS targets, needs empirical validation, we found that the tDCS montage with the cathode over the pre-supplementary motor area and extra-cephalic anode seems to activate most of the areas related to OCD.

Impacts of selected stimulation patterns on the perception threshold in electrocutaneous stimulation

PubMed Central

2011-01-01

Background Consistency is one of the most important concerns to convey stable artificially induced sensory feedback. However, the constancy of perceived sensations cannot be guaranteed, as the artificially evoked sensation is a function of the interaction of stimulation parameters. The hypothesis of this study is that the selected stimulation parameters in multi-electrode cutaneous stimulation have significant impacts on the perception threshold. Methods The investigated parameters included the stimulated location, the number of active electrodes, the number of pulses, and the interleaved time between a pair of electrodes. Biphasic, rectangular pulses were applied via five surface electrodes placed on the forearm of 12 healthy subjects. Results Our main findings were: 1) the perception thresholds at the five stimulated locations were significantly different (p < 0.0001), 2) dual-channel simultaneous stimulation lowered the perception thresholds and led to smaller variance in perception thresholds compared to single-channel stimulation, 3) the perception threshold was inversely related to the number of pulses, and 4) the perception threshold increased with increasing interleaved time when the interleaved time between two electrodes was below 500 μs. Conclusions To maintain a consistent perception threshold, our findings indicate that dual-channel simultaneous stimulation with at least five pulses should be used, and that the interleaved time between two electrodes should be longer than 500 μs. We believe that these findings have implications for design of reliable sensory feedback codes. PMID:21306616

Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

PubMed

Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

2012-01-01

Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

PubMed Central

Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.

2014-01-01

Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229

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

PubMed

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

2015-10-01

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

Modulation of long-term potentiation-like cortical plasticity in the healthy brain with low frequency-pulsed electromagnetic fields.

PubMed

Premi, Enrico; Benussi, Alberto; La Gatta, Antonio; Visconti, Stefano; Costa, Angelo; Gilberti, Nicola; Cantoni, Valentina; Padovani, Alessandro; Borroni, Barbara; Magoni, Mauro

2018-06-13

Non-depolarizing magnetic fields, like low frequency-pulsed electromagnetic fields (LF-PEMFs) have shown the ability to modulate living structures, principally by influencing synaptic activity and ion channels on cellular membranes. Recently, the CTU Mega 20 device was presented as a molecular accelerator, using energy up to 200 J and providing high-power (2 Tesla) pulsating fields with a water-repulsive (diamagnetic) action and tissue biostimulation. We tested the hypothesis that LF-PEMFs could modulate long-term corticospinal excitability in healthy brains by applying CTU Mega 20 ® . Ten healthy subjects without known neurological and/or psychiatric diseases entered the study. A randomized double-blind sham-controlled crossover design was employed, recording TMS parameters (amplitude variation of the motor evoked potential as index of cortical excitability perturbations of the motor system) before (pre) and after (post + 0, + 15, + 30 min) a single CTU Mega 20 session on the corresponding primary right-hand motor area, using a real (magnetic field = 2 Tesla; intensity = 90 J; impulse frequency = 7 Hz; duration = 15 min) or sham device. A two-way repeated measures ANOVA with TIME (pre, post + 0, + 15, + 30 min) and TREATMENT (real vs. sham stimulation) as within-subjects factor was applied. A significant TIME × TREATMENT interaction was found (p < 0.001). Post hoc comparisons showed a significant effect of TIME, with significant differences at + 0, + 15 and + 30 min compared to baseline after real stimulation (all p < 0.05) but not after sham stimulation (all p < 0.05) and significant effects of TREATMENT, with significant differences at + 0, + 15 and + 30 min for real stimulation compared to sham stimulation (all p < 0.005). No significant depolarizing effects were detected throughout the (real) stimulation. Our proof-of-concept study in healthy subjects supports the idea that non-ionizing LF-PEMFs induced by the CTU Mega 20 diamagnetic acceleration system could represent a new approach for brain neuromodulation. Further studies to optimize protocol parameters for different neurological and psychiatric conditions are warranted. Trial Registration The present work has been retrospectively registered as clinical trial on ClinicalTrials.gov NCT03537469 and publicly released on May 24, 2018.

[Negative symptoms of schizophrenia: from electrophysiology to electrotherapy].

PubMed

Micoulaud Franchi, J-A; Quiles, C; Belzeaux, R; Adida, M; Azorin, J-M

2015-12-01

The aim of this review of the literature is to summarize the state of the knowledge concerning the relationship between negative symptoms in schizophrenia, electrophysiology and electrotherapy. The scientific literature search of international articles was performed during August and September 2015 using the PubMed electronic database. We used the following MeSH terms: "Negative symptoms", "Schizophrenia", "Electrophysiology", "Neurophysiology", "EEG power", "Alpha rhythm", "Transcranial magnetic stimulation", "Transcranial direct current stimulation", "Electroconvulsive therapy", "Neurofeedback", "Vagus Nerve Stimulation", "Deep Brain Stimulation", and "State dependent". Negative symptoms in schizophrenia are associated with altered activity in prefrontal cortex in functional neuroimaging studies. This is in line with electrophysiological measurements that found a change in EEG spectral power in the alpha frequency band over prefrontal brain regions. The notion of functional hypofrontality has led to hypotheses that electrotherapy applied to the prefrontal cortex may be an effective treatment of negative symptoms in schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) were used to increase cortical activity in schizophrenia and achieve a clinical effect on negative symptoms. Three meta-analyses confirmed, with a moderate effect size, that rTMS is an effective treatment option for negative symptoms in schizophrenia. The two subsequently published prospective multicenter studies, however, found opposite results from each other. Two randomized controlled studies suggested that tDCS is an effective treatment option for negative symptoms. There is no study on the efficacy of neurofeedback, vagal nerve stimulation or deep brain stimulation on negative symptoms in schizophrenia. Additional studies are needed to confirm the efficacy of rTMS and tDCS on negative symptoms in schizophrenia. Influencing factors, related to clinical and stimulation parameters, of rTMS and tDCS on negative symptoms should be better investigated. Effects related to electrophysiological brain activity of the patient, especially in the alpha band, during the stimulation should also be better investigated. The action of electrotherapy may be state dependent, and a better understanding of electrophysiological effects of electrotherapy techniques could enable their optimization. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

C-tactile afferent stimulating touch carries a positive affective value.

PubMed

Pawling, Ralph; Cannon, Peter R; McGlone, Francis P; Walker, Susannah C

2017-01-01

The rewarding sensation of touch in affiliative interactions is hypothesized to be underpinned by a specialized system of nerve fibers called C-Tactile afferents (CTs), which respond optimally to slowly moving, gentle touch, typical of a caress. However, empirical evidence to support the theory that CTs encode socially relevant, rewarding tactile information in humans is currently limited. While in healthy participants, touch applied at CT optimal velocities (1-10cm/sec) is reliably rated as subjectively pleasant, neuronopathy patients lacking large myelinated afferents, but with intact C-fibres, report that the conscious sensation elicited by stimulation of CTs is rather vague. Given this weak perceptual impact the value of self-report measures for assessing the specific affective value of CT activating touch appears limited. Therefore, we combined subjective ratings of touch pleasantness with implicit measures of affective state (facial electromyography) and autonomic arousal (heart rate) to determine whether CT activation carries a positive affective value. We recorded the activity of two key emotion-relevant facial muscle sites (zygomaticus major-smile muscle, positive affect & corrugator supercilii-frown muscle, negative affect) while participants evaluated the pleasantness of experimenter administered stroking touch, delivered using a soft brush, at two velocities (CT optimal 3cm/sec & CT non-optimal 30cm/sec), on two skin sites (CT innervated forearm & non-CT innervated palm). On both sites, 3cm/sec stroking touch was rated as more pleasant and produced greater heart rate deceleration than 30cm/sec stimulation. However, neither self-report ratings nor heart rate responses discriminated stimulation on the CT innervated arm from stroking of the non-CT innervated palm. In contrast, significantly greater activation of the zygomaticus major (smiling muscle) was seen specifically to CT optimal, 3cm/sec, stroking on the forearm in comparison to all other stimuli. These results offer the first empirical evidence in humans that tactile stimulation that optimally activates CTs carries a positive affective valence that can be measured implicitly.

Raman Amplification and Tunable Pulse Delays in Silicon Waveguides

NASA Astrophysics Data System (ADS)

Rukhlenko, Ivan D.; Garanovich, Ivan L.; Premaratne, Malin; Sukhorukov, Andrey A.; Agrawal, Govind P.

2010-10-01

The nonlinear process of stimulated Raman scattering is important for silicon photonics as it enables optical amplification and lasing. However, generally employed numerical approaches provide very little insight into the contribution of different silicon Raman amplifier (SRA) parameters. In this paper, we solve the coupled pump-signal equations analytically and derive an exact formula for the envelope of a signal pulse when picosecond optical pulses are amplified inside a SRA pumped by a continuous-wave laser beam. Our solution is valid for an arbitrary pulse shape and fully accounts for the Raman gain-dispersion effects, including temporal broadening and group-velocity reduction. Our results are useful for optimizing the performance of SRAs and for engineering controllable signal delays.

Speeding up adiabatic population transfer in a Josephson qutrit via counter-diabatic driving

NASA Astrophysics Data System (ADS)

Feng, Zhi-Bo; Lu, Xiao-Jing; Li, M.; Yan, Run-Ying; Zhou, Yun-Qing

2017-12-01

We propose a theoretical scheme to speed up adiabatic population transfer in a Josephson artificial qutrit by transitionless quantum driving. At a magic working point, an effective three-level subsystem can be chosen to constitute our qutrit. With Stokes and pump driving, adiabatic population transfer can be achieved in the qutrit by means of stimulated Raman adiabatic passage. Assisted by a counter-diabatic driving, the adiabatic population transfer can be sped up drastically with accessible parameters. Moreover, the accelerated operation is flexibly reversible and highly robust against decoherence effects. Thanks to these distinctive advantages, the present protocol could offer a promising avenue for optimal coherent operations in Josephson quantum circuits.

SRS in the single molecule limit (Conference Presentation)

NASA Astrophysics Data System (ADS)

Potma, Eric O.; Crampton, Kevin T.; Fast, Alexander; Apkarian, Vartkess A.

2017-02-01

We present combined surface-enhanced stimulated Raman scattering (SE-SRS) and surface-enhanced coherent anti-Stokes Raman scattering (SE-CARS) measurements on individual plasmonic antennas dressed with bipyridyl-ethylene molecules. By carefully optimizing the conditions for performing SE-SRS experiments, we have obtained stable and reproducible molecular surface-enhanced SRS spectra from single nano-antennas. Using surface-enhanced Raman scattering (SERS) and transmission electron microscopy of the same antennas, we confirm that the observed SE-SRS signals originate from only one or a few molecules. We highlight the physics of surface enhancement in the context of coherent Raman scattering and derive sensitivity parameters under the relevant conditions. The implications of single molecule SRS measurements are discussed.

Multiwave low-laser therapy in the pain treatment

NASA Astrophysics Data System (ADS)

Moldovan, Corneliu I.; Antipa, Ciprian; Bratila, Florin; Brukner, Ion; Vasiliu, Virgil V.

1995-03-01

Sixteen patients with knee pain, 17 patients with low back pain and 23 patients with vertebral pain were randomly allocated to multiwave laser therapy (MWL). The MWL was performed through an original method by a special designed laser system. The stimulation parameters adaptably optimized in a closed loop by measuring the reflected laser radiation. A control group of 11 patients was conventionally treated with a single infrared laser system. All patients were assessed by single observer using a visual analogue scale in a controlled trial. Our results indicate that the treatment with different laser wavelengths, different output power and frequencies, simultaneously applied through optic-fibers, has significant effects on the pain when compared with the common low laser therapy.

Electrical stimulation of mechanoreceptors

NASA Astrophysics Data System (ADS)

Echenique, A. M.; Graffigna, J. P.

2011-12-01

Within the field of Rehabilitation Engineering, this work is aimed at identifying the optimal parameters of electric current stimulus which activate the nervous axons of mecanoreceptors found in the fingertip, allowing, this way, to resemble tactile senses. These sensorial feelings can be used by aiding technological means, namely, the sensorial substitution technology, in an attempt to render information to blind people through the tactile sense. The physical pressure on sensorial areas (fingertips) used for reading activities through the Braille System is the main effect that is imitated and studied in this research work. An experimental aiding prototype for Braille reading research has been developed and tested with blinds and reduced vision people, with highly satisfactory results.

A Numerical Study of Factors Affecting Fracture-Fluid Cleanup and Produced Gas/Water in Marcellus Shale: Part II

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

Seales, Maxian B.; Dilmore, Robert; Ertekin, Turgay

Horizontal wells combined with successful multi-stage hydraulic fracture treatments are currently the most established method for effectively stimulating and enabling economic development of gas bearing organic-rich shale formations. Fracture cleanup in the Stimulated Reservoir Volume (SRV) is critical to stimulation effectiveness and long-term well performance. However, fluid cleanup is often hampered by formation damage, and post-fracture well performance frequently falls below expectations. A systematic study of the factors that hinder fracture fluid cleanup in shale formations can help optimize fracture treatments and better quantify long term volumes of produced water and gas. Fracture fluid cleanup is a complex process influencedmore » by multi-phase flow through porous media (relative permeability hysteresis, capillary pressure etc.), reservoir rock and fluid properties, fracture fluid properties, proppant placement, fracture treatment parameters, and subsequent flowback and field operations. Changing SRV and fracture conductivity as production progresses further adds to the complexity of this problem. Numerical simulation is the best, and most practical approach to investigate such a complicated blend of mechanisms, parameters, their interactions, and subsequent impact on fracture fluid cleanup and well deliverability. In this paper, a 3-dimensional, 2-phase, dual-porosity model was used to investigate the impact of multiphase flow, proppant crushing, proppant diagenesis, shut-in time, reservoir rock compaction, gas slippage, and gas desorption on fracture fluid cleanup, and well performance in Marcellus shale. The research findings have shed light on the factors that substantially constrains efficient fracture fluid cleanup in gas shales, and provided guidelines for improved fracture treatment designs and water management.« less

Transcranial direct current stimulation improves isometric time to exhaustion of the knee extensors.

PubMed

Angius, L; Pageaux, B; Hopker, J; Marcora, S M; Mauger, A R

2016-12-17

Transcranial direct current stimulation (tDCS) can increase cortical excitability of a targeted brain area, which may affect endurance exercise performance. However, optimal electrode placement for tDCS remains unclear. We tested the effect of two different tDCS electrode montages for improving exercise performance. Nine subjects underwent a control (CON), placebo (SHAM) and two different tDCS montage sessions in a randomized design. In one tDCS session, the anodal electrode was placed over the left motor cortex and the cathodal on contralateral forehead (HEAD), while for the other montage the anodal electrode was placed over the left motor cortex and cathodal electrode above the shoulder (SHOULDER). tDCS was delivered for 10min at 2.0mA, after which participants performed an isometric time to exhaustion (TTE) test of the right knee extensors. Peripheral and central neuromuscular parameters were assessed at baseline, after tDCS application and after TTE. Heart rate (HR), ratings of perceived exertion (RPE), and leg muscle exercise-induced muscle pain (PAIN) were monitored during the TTE. TTE was longer and RPE lower in the SHOULDER condition (P<0.05). Central and peripheral parameters, and HR and PAIN did not present any differences between conditions after tDCS stimulation (P>0.05). In all conditions maximal voluntary contraction (MVC) significantly decreased after the TTE (P<0.05) while motor-evoked potential area (MEP) increased after TTE (P<0.05). These findings demonstrate that SHOULDER montage is more effective than HEAD montage to improve endurance performance, likely through avoiding the negative effects of the cathode on excitability. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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.

Structure of Immune Stimulating Complex Matrices and Immune Stimulating Complexes in Suspension Determined by Small-Angle X-Ray Scattering

PubMed Central

Pedersen, Jan Skov; Oliveira, Cristiano L.P.; Hübschmann, Henriette Baun; Arleth, Lise; Manniche, Søren; Kirkby, Nicolai; Nielsen, Hanne Mørck

2012-01-01

Immune stimulating complex (ISCOM) particles consisting of a mixture of Quil-A, cholesterol, and phospholipids were structurally characterized by small-angle x-ray scattering (SAXS). The ISCOM particles are perforated vesicles of very well-defined structures. We developed and implemented a novel (to our knowledge) modeling method based on Monte Carlo simulation integrations to describe the SAXS data. This approach is similar to the traditional modeling of SAXS data, in which a structure is assumed, the scattering intensity is calculated, and structural parameters are optimized by weighted least-squares methods when the model scattering intensity is fitted to the experimental data. SAXS data from plain ISCOM matrix particles in aqueous suspension, as well as those from complete ISCOMs (i.e., with an antigen (tetanus toxoid) incorporated) can be modeled as a polydisperse distribution of perforated bilayer vesicles with icosahedral, football, or tennis ball structures. The dominating structure is the tennis ball structure, with an outer diameter of 40 nm and with 20 holes 5–6 nm in diameter. The lipid bilayer membrane is 4.6 nm thick, with a low-electron-density, 2.0-nm-thick hydrocarbon core. Surprisingly, in the ISCOMs, the tetanus toxoid is located just below the membrane inside the particles. PMID:22677391

Effect of Anatomically Realistic Full-Head Model on Activation of Cortical Neurons in Subdural Cortical Stimulation—A Computational Study

NASA Astrophysics Data System (ADS)

Seo, Hyeon; Kim, Donghyeon; Jun, Sung Chan

2016-06-01

Electrical brain stimulation (EBS) is an emerging therapy for the treatment of neurological disorders, and computational modeling studies of EBS have been used to determine the optimal parameters for highly cost-effective electrotherapy. Recent notable growth in computing capability has enabled researchers to consider an anatomically realistic head model that represents the full head and complex geometry of the brain rather than the previous simplified partial head model (extruded slab) that represents only the precentral gyrus. In this work, subdural cortical stimulation (SuCS) was found to offer a better understanding of the differential activation of cortical neurons in the anatomically realistic full-head model than in the simplified partial-head models. We observed that layer 3 pyramidal neurons had comparable stimulation thresholds in both head models, while layer 5 pyramidal neurons showed a notable discrepancy between the models; in particular, layer 5 pyramidal neurons demonstrated asymmetry in the thresholds and action potential initiation sites in the anatomically realistic full-head model. Overall, the anatomically realistic full-head model may offer a better understanding of layer 5 pyramidal neuronal responses. Accordingly, the effects of using the realistic full-head model in SuCS are compelling in computational modeling studies, even though this modeling requires substantially more effort.

Electrical Stimulation as a Means for Improving Vision.

PubMed

Sehic, Amer; Guo, Shuai; Cho, Kin-Sang; Corraya, Rima M; Chen, Dong F; Utheim, Tor P

2016-11-01

Evolving research has provided evidence that noninvasive electrical stimulation (ES) of the eye may be a promising therapy for either preserving or restoring vision in several retinal and optic nerve diseases. In this review, we focus on minimally invasive strategies for the delivery of ES and accordingly summarize the current literature on transcorneal, transorbital, and transpalpebral ES in both animal experiments and clinical studies. Various mechanisms are believed to underlie the effects of ES, including increased production of neurotrophic agents, improved chorioretinal blood circulation, and inhibition of proinflammatory cytokines. Different animal models have demonstrated favorable effects of ES on both the retina and the optic nerve. Promising effects of ES have also been demonstrated in clinical studies; however, all current studies have a lack of randomization and/or a control group (sham). There is thus a pressing need for a deeper understanding of the underlying mechanisms that govern clinical success and optimization of stimulation parameters in animal studies. In addition, such research should be followed by large, prospective, clinical studies to explore the full potential of ES. Through this review, we aim to provide insight to guide future research on ES as a potential therapy for improving vision. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Electrical Stimulation and Cutaneous Wound Healing: A Review of Clinical Evidence

PubMed Central

Ud-Din, Sara; Bayat, Ardeshir

2014-01-01

Electrical stimulation (ES) has been shown to have beneficial effects in wound healing. It is important to assess the effects of ES on cutaneous wound healing in order to ensure optimization for clinical practice. Several different applications as well as modalities of ES have been described, including direct current (DC), alternating current (AC), high-voltage pulsed current (HVPC), low-intensity direct current (LIDC) and electrobiofeedback ES. However, no one method has been advocated as the most optimal for the treatment of cutaneous wound healing. Therefore, this review aims to examine the level of evidence (LOE) for the application of different types of ES to enhance cutaneous wound healing in the skin. An extensive search was conducted to identify relevant clinical studies utilising ES for cutaneous wound healing since 1980 using PubMed, Medline and EMBASE. A total of 48 studies were evaluated and assigned LOE. All types of ES demonstrated positive effects on cutaneous wound healing in the majority of studies. However, the reported studies demonstrate contrasting differences in the parameters and types of ES application, leading to an inability to generate sufficient evidence to support any one standard therapeutic approach. Despite variations in the type of current, duration, and dosing of ES, the majority of studies showed a significant improvement in wound area reduction or accelerated wound healing compared to the standard of care or sham therapy as well as improved local perfusion. The limited number of LOE-1 trials for investigating the effects of ES in wound healing make critical evaluation and assessment somewhat difficult. Further, better-designed clinical trials are needed to improve our understanding of the optimal dosing, timing and type of ES to be used. PMID:27429287

Transient stimulation expands superior antitumor T cells for adoptive therapy

PubMed Central

Kagoya, Yuki; Nakatsugawa, Munehide; Ochi, Toshiki; Guo, Tingxi; Anczurowski, Mark; Saso, Kayoko; Butler, Marcus O.

2017-01-01

Adoptive cell therapy is a potentially curative therapeutic approach for patients with cancer. In this treatment modality, antitumor T cells are exponentially expanded in vitro prior to infusion. Importantly, the results of recent clinical trials suggest that the quality of expanded T cells critically affects their therapeutic efficacy. Although anti-CD3 mAb-based stimulation is widely used to expand T cells in vitro, a protocol to generate T cell grafts for optimal adoptive therapy has yet to be established. In this study, we investigated the differences between T cell stimulation mediated by anti–CD3/CD28 mAb–coated beads and cell-based artificial antigen-presenting cells (aAPCs) expressing CD3/CD28 counter-receptors. We found that transient stimulation with cell-based aAPCs, but not prolonged stimulation with beads, resulted in the superior expansion of CD8+ T cells. Transiently stimulated CD8+ T cells maintained a stem cell–like memory phenotype and were capable of secreting multiple cytokines significantly more efficiently than chronically stimulated T cells. Importantly, the chimeric antigen receptor–engineered antitumor CD8+ T cells expanded via transient stimulation demonstrated superior persistence and antitumor responses in adoptive immunotherapy mouse models. These results suggest that restrained stimulation is critical for generating T cell grafts for optimal adoptive immunotherapy for cancer. PMID:28138559

What is the optimal anodal electrode position for inducing corticomotor excitability changes in transcranial direct current stimulation?

PubMed

Lee, Minji; Kim, Yun-Hee; Im, Chang-Hwan; Kim, Jung-Hoon; Park, Chang-hyun; Chang, Won Hyuk; Lee, Ahee

2015-01-01

Transcranial direct current stimulation (tDCS) non-invasively modulates brain function by inducing neuronal excitability. The conventional hot spot for inducing the highest current density in the hand motor area may not be the optimal site for effective stimulation. In this study, we investigated the influence of the center position of the anodal electrode on changes in motor cortical excitability. We considered three tDCS conditions in 16 healthy subjects: (i) real stimulation with the anodal electrode located at the conventional hand motor hot spot determined by motor evoked potentials (MEPs); (ii) real stimulation with the anodal electrode located at the point with the highest current density in the hand motor area as determined by electric current simulation; and (iii) sham stimulation. Motor cortical excitability as measured by MEP amplitude increased after both real stimulation conditions, but not after sham stimulation. Stimulation using the simulation-derived anodal electrode position, which was found to be posterior to the MEP hot spot for all subjects, induced higher motor cortical excitability. Individual positioning of the anodal electrode, based on the consideration of anatomical differences between subjects, appears to be important for maximizing the effects of tDCS. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Transient stimulation expands superior antitumor T cells for adoptive therapy.

PubMed

Kagoya, Yuki; Nakatsugawa, Munehide; Ochi, Toshiki; Cen, Yuchen; Guo, Tingxi; Anczurowski, Mark; Saso, Kayoko; Butler, Marcus O; Hirano, Naoto

2017-01-26

Adoptive cell therapy is a potentially curative therapeutic approach for patients with cancer. In this treatment modality, antitumor T cells are exponentially expanded in vitro prior to infusion. Importantly, the results of recent clinical trials suggest that the quality of expanded T cells critically affects their therapeutic efficacy. Although anti-CD3 mAb-based stimulation is widely used to expand T cells in vitro, a protocol to generate T cell grafts for optimal adoptive therapy has yet to be established. In this study, we investigated the differences between T cell stimulation mediated by anti-CD3/CD28 mAb-coated beads and cell-based artificial antigen-presenting cells (aAPCs) expressing CD3/CD28 counter-receptors. We found that transient stimulation with cell-based aAPCs, but not prolonged stimulation with beads, resulted in the superior expansion of CD8 + T cells. Transiently stimulated CD8 + T cells maintained a stem cell-like memory phenotype and were capable of secreting multiple cytokines significantly more efficiently than chronically stimulated T cells. Importantly, the chimeric antigen receptor-engineered antitumor CD8 + T cells expanded via transient stimulation demonstrated superior persistence and antitumor responses in adoptive immunotherapy mouse models. These results suggest that restrained stimulation is critical for generating T cell grafts for optimal adoptive immunotherapy for cancer.

Increasing platelet concentration in platelet-rich plasma inhibits anterior cruciate ligament cell function in three-dimensional culture.

PubMed

Yoshida, Ryu; Cheng, Mingyu; Murray, Martha M

2014-02-01

Tissue engineering is one new strategy being developed to treat ACL ruptures. One such approach is bio-enhanced ACL repair, where a suture repair is supplemented with a bio-active scaffold containing platelets. However, the optimal concentration of platelets to stimulate ACL healing is not known. We hypothesized that increasing platelet concentrations in the scaffold would enhance critical cell behaviors. Porcine ACL fibroblasts were obtained from explant culture and suspended in platelet poor plasma (PPP), 1× platelet-rich plasma (PRP), 3× PRP, 5× PRP, or phosphate buffered saline (PBS). The cell suspensions were cultured in a 3D collagen scaffold. Cellular metabolism (MTT assay), apoptosis (TUNEL assay), and gene expression for type I and type III collagen were measured. 1× PRP significantly outperformed 5× PRP in all parameters studied: Type I and III collagen gene expression, apoptosis prevention, and cell metabolism stimulation. ACL fibroblasts cultured with 1× PRP had the highest type I and type III collagen gene expression. 1× PRP and PPP groups had the highest cell metabolism and lowest apoptosis rates. Concentration of platelets had significant effects on the behavior of ACL fibroblasts; thus, it is an important parameter that should be specified in clinical or basic science studies. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Microscale to Manufacturing Scale-up of Cell-Free Cytokine Production—A New Approach for Shortening Protein Production Development Timelines

PubMed Central

Zawada, James F; Yin, Gang; Steiner, Alexander R; Yang, Junhao; Naresh, Alpana; Roy, Sushmita M; Gold, Daniel S; Heinsohn, Henry G; Murray, Christopher J

2011-01-01

Engineering robust protein production and purification of correctly folded biotherapeutic proteins in cell-based systems is often challenging due to the requirements for maintaining complex cellular networks for cell viability and the need to develop associated downstream processes that reproducibly yield biopharmaceutical products with high product quality. Here, we present an alternative Escherichia coli-based open cell-free synthesis (OCFS) system that is optimized for predictable high-yield protein synthesis and folding at any scale with straightforward downstream purification processes. We describe how the linear scalability of OCFS allows rapid process optimization of parameters affecting extract activation, gene sequence optimization, and redox folding conditions for disulfide bond formation at microliter scales. Efficient and predictable high-level protein production can then be achieved using batch processes in standard bioreactors. We show how a fully bioactive protein produced by OCFS from optimized frozen extract can be purified directly using a streamlined purification process that yields a biologically active cytokine, human granulocyte-macrophage colony-stimulating factor, produced at titers of 700 mg/L in 10 h. These results represent a milestone for in vitro protein synthesis, with potential for the cGMP production of disulfide-bonded biotherapeutic proteins. Biotechnol. Bioeng. 2011; 108:1570–1578. © 2011 Wiley Periodicals, Inc. PMID:21337337

Control and optimization system

DOEpatents

Xinsheng, Lou

2013-02-12

A system for optimizing a power plant includes a chemical loop having an input for receiving an input parameter (270) and an output for outputting an output parameter (280), a control system operably connected to the chemical loop and having a multiple controller part (230) comprising a model-free controller. The control system receives the output parameter (280), optimizes the input parameter (270) based on the received output parameter (280), and outputs an optimized input parameter (270) to the input of the chemical loop to control a process of the chemical loop in an optimized manner.

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.

Development and Validation of a Novel Dual Luciferase Reporter Gene Assay to Quantify Ebola Virus VP24 Inhibition of IFN Signaling

PubMed Central

Frau, Aldo; Sgarbanti, Marco; Orsatti, Roberto

2018-01-01

The interferon (IFN) system is the first line of defense against viral infections. Evasion of IFN signaling by Ebola viral protein 24 (VP24) is a critical event in the pathogenesis of the infection and, hence, VP24 is a potential target for drug development. Since no drugs target VP24, the identification of molecules able to inhibit VP24, restoring and possibly enhancing the IFN response, is a goal of concern. Accordingly, we developed a dual signal firefly and Renilla luciferase cell-based drug screening assay able to quantify IFN-mediated induction of Interferon Stimulated Genes (ISGs) and its inhibition by VP24. Human Embryonic Kidney 293T (HEK293T) cells were transiently transfected with a luciferase reporter gene construct driven by the promoter of ISGs, Interferon-Stimulated Response Element (ISRE). Stimulation of cells with IFN-α activated the IFN cascade leading to the expression of ISRE. Cotransfection of cells with a plasmid expressing VP24 cloned from a virus isolated during the last 2014 outbreak led to the inhibition of ISRE transcription, quantified by a luminescent signal. To adapt this system to test a large number of compounds, we performed it in 96-well plates; optimized the assay analyzing different parameters; and validated the system by calculating the Z′- and Z-factor, which showed values of 0.62 and 0.53 for IFN-α stimulation assay and VP24 inhibition assay, respectively, indicative of robust assay performance. PMID:29495311

Development and Validation of a Novel Dual Luciferase Reporter Gene Assay to Quantify Ebola Virus VP24 Inhibition of IFN Signaling.

PubMed

Fanunza, Elisa; Frau, Aldo; Sgarbanti, Marco; Orsatti, Roberto; Corona, Angela; Tramontano, Enzo

2018-02-24

The interferon (IFN) system is the first line of defense against viral infections. Evasion of IFN signaling by Ebola viral protein 24 (VP24) is a critical event in the pathogenesis of the infection and, hence, VP24 is a potential target for drug development. Since no drugs target VP24, the identification of molecules able to inhibit VP24, restoring and possibly enhancing the IFN response, is a goal of concern. Accordingly, we developed a dual signal firefly and Renilla luciferase cell-based drug screening assay able to quantify IFN-mediated induction of Interferon Stimulated Genes (ISGs) and its inhibition by VP24. Human Embryonic Kidney 293T (HEK293T) cells were transiently transfected with a luciferase reporter gene construct driven by the promoter of ISGs, Interferon-Stimulated Response Element (ISRE). Stimulation of cells with IFN-α activated the IFN cascade leading to the expression of ISRE. Cotransfection of cells with a plasmid expressing VP24 cloned from a virus isolated during the last 2014 outbreak led to the inhibition of ISRE transcription, quantified by a luminescent signal. To adapt this system to test a large number of compounds, we performed it in 96-well plates; optimized the assay analyzing different parameters; and validated the system by calculating the Z'- and Z-factor, which showed values of 0.62 and 0.53 for IFN-α stimulation assay and VP24 inhibition assay, respectively, indicative of robust assay performance.

Optimization of pressure settings during adaptive servo-ventilation support using real-time heart rate variability assessment: initial case report.

PubMed

Imamura, Teruhiko; Nitta, Daisuke; Kinugawa, Koichiro

2017-01-05

Adaptive servo-ventilation (ASV) therapy is a recent non-invasive positive pressure ventilation therapy that was developed for patients with heart failure (HF) refractory to optimal medical therapy. However, it is likely that ASV therapy at relatively higher pressure setting worsens some of the patients' prognosis compared with optimal medical therapy. Therefore, identification of optimal pressure settings of ASV therapy is warranted. We present the case of a 42-year-old male with HF, which was caused by dilated cardiomyopathy, who was admitted to our institution for evaluating his eligibility for heart transplantation. To identify the optimal pressure setting [peak end-expiratory pressure (PEEP) ramp test], we performed an ASV support test, during which the PEEP settings were set at levels ranging from 4 to 8 mmHg, and a heart rate variability (HRV) analysis using the MemCalc power spectral density method. Clinical parameters varied dramatically during the PEEP ramp test. Over incremental PEEP levels, pulmonary capillary wedge pressure, cardiac index and high-frequency level (reflecting parasympathetic activity) decreased; however, the low-frequency level increased along with increase in plasma noradrenaline concentrations. An inappropriately high PEEP setting may stimulate sympathetic nerve activity accompanied by decreased cardiac output. This was the first report on the PEEP ramp test during ASV therapy. Further research is warranted to determine whether use of optimal pressure settings using HRV analyses may improve the long-term prognosis of such patients.

Extreme Learning Machine and Particle Swarm Optimization in optimizing CNC turning operation

NASA Astrophysics Data System (ADS)

Janahiraman, Tiagrajah V.; Ahmad, Nooraziah; Hani Nordin, Farah

2018-04-01

The CNC machine is controlled by manipulating cutting parameters that could directly influence the process performance. Many optimization methods has been applied to obtain the optimal cutting parameters for the desired performance function. Nonetheless, the industry still uses the traditional technique to obtain those values. Lack of knowledge on optimization techniques is the main reason for this issue to be prolonged. Therefore, the simple yet easy to implement, Optimal Cutting Parameters Selection System is introduced to help the manufacturer to easily understand and determine the best optimal parameters for their turning operation. This new system consists of two stages which are modelling and optimization. In modelling of input-output and in-process parameters, the hybrid of Extreme Learning Machine and Particle Swarm Optimization is applied. This modelling technique tend to converge faster than other artificial intelligent technique and give accurate result. For the optimization stage, again the Particle Swarm Optimization is used to get the optimal cutting parameters based on the performance function preferred by the manufacturer. Overall, the system can reduce the gap between academic world and the industry by introducing a simple yet easy to implement optimization technique. This novel optimization technique can give accurate result besides being the fastest technique.

3D Monte Carlo model with direct photon flux recording for optimal optogenetic light delivery

NASA Astrophysics Data System (ADS)

Shin, Younghoon; Kim, Dongmok; Lee, Jihoon; Kwon, Hyuk-Sang

2017-02-01

Configuring the light power emitted from the optical fiber is an essential first step in planning in-vivo optogenetic experiments. However, diffusion theory, which was adopted for optogenetic research, precluded accurate estimates of light intensity in the semi-diffusive region where the primary locus of the stimulation is located. We present a 3D Monte Carlo model that provides an accurate and direct solution for light distribution in this region. Our method directly records the photon trajectory in the separate volumetric grid planes for the near-source recording efficiency gain, and it incorporates a 3D brain mesh to support both homogeneous and heterogeneous brain tissue. We investigated the light emitted from optical fibers in brain tissue in 3D, and we applied the results to design optimal light delivery parameters for precise optogenetic manipulation by considering the fiber output power, wavelength, fiber-to-target distance, and the area of neural tissue activation.

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

Onset of Action of Sacral Neuromodulation in Lower Urinary Tract Dysfunction-What is the Optimal Duration of Test Stimulation?

PubMed

Jairam, Ranjana; Drossaerts, Jamie; Marcelissen, Tom; van Koeveringe, Gommert; van Kerrebroeck, Philip

2018-06-01

Since the development of sacral neuromodulation, a large number of patients with lower urinary tract symptoms have been treated with this procedure. A test stimulation is performed prior to implantation. At centers worldwide the duration of this test stimulation varies considerably since it is not certain when the onset of the therapy effect can be expected. The objective of this prospective study was to evaluate the average onset time of sacral neuromodulation in patients with lower urinary tract symptoms. All patients who were eligible for treatment with sacral neuromodulation were asked to participate in this study. A voiding diary was filled out prior to and during test stimulation using an implanted tined lead. Success was defined as a 50% or greater improvement compared to baseline in any of the main complaint parameters. The Mann-Whitney U test was used to compare the mean time to success between patients with overactive bladder syndrome and patients with nonobstructive urinary retention. Of the 45 patients 24 with nonobstructive urinary retention and 21 with overactive bladder syndrome agreed to participate and were included in study. Test stimulation was successful in 29 patients (64%). Mean time to success in all patients was 3.3 days (range 1 to 9). There was no significant difference in mean time to success between cases of overactive bladder syndrome and nonobstructive urinary retention (3.25 and 3.5 days, respectively, p = 0.76). The results imply that a test stimulation of more than 2 weeks is not necessary if a cutoff of 50% or greater improvement is adopted. However, further improvement can be expected with prolonged test stimulation. This might be important since it might have implications for long-term results. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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.

A Modified Penalty Parameter Approach for Optimal Estimation of UH with Simultaneous Estimation of Infiltration Parameters

NASA Astrophysics Data System (ADS)

Bhattacharjya, Rajib Kumar

2018-05-01

The unit hydrograph and the infiltration parameters of a watershed can be obtained from observed rainfall-runoff data by using inverse optimization technique. This is a two-stage optimization problem. In the first stage, the infiltration parameters are obtained and the unit hydrograph ordinates are estimated in the second stage. In order to combine this two-stage method into a single stage one, a modified penalty parameter approach is proposed for converting the constrained optimization problem to an unconstrained one. The proposed approach is designed in such a way that the model initially obtains the infiltration parameters and then searches the optimal unit hydrograph ordinates. The optimization model is solved using Genetic Algorithms. A reduction factor is used in the penalty parameter approach so that the obtained optimal infiltration parameters are not destroyed during subsequent generation of genetic algorithms, required for searching optimal unit hydrograph ordinates. The performance of the proposed methodology is evaluated by using two example problems. The evaluation shows that the model is superior, simple in concept and also has the potential for field application.

Biophysical basis of low-power-laser effects

NASA Astrophysics Data System (ADS)

Karu, Tiina I.

1996-06-01

Biological responses of cells to visible and near IR (laser) radiation occur due to physical and/or chemical changes in photoacceptor molecules, components of respiratory chains (cyt a/a3 in mitochondria). As a result of the photoexcitation of electronic states, the following physical and/or chemical changes can occur: alteration of redox properties and acceleration of electron transfer, changes in biochemical activity due to local transient heating of chromophores, one-electron auto-oxidation and O2- production, and photodynamic action and 1O2 production. Different reaction channels can be activated to achieve the photobiological macroeffect. The primary physical and/or chemical changes induced by light in photoacceptor molecules are followed by a cascade of biochemical reactions in the cell that do not need further light activation and occur in the dark (photosignal transduction and amplification chains). These actions are connected with changes in cellular homeostasis parameters. The crucial step here is thought to be an alteration of the cellular redox state: a shift towards oxidation is associated with stimulation of cellular vitality, and a shift towards reduction is linked to inhibition. Cells with a lower than normal pH, where the redox state is shifted in the reduced direction, are considered to be more sensitive to the stimulative action of light than those with the respective parameters being optimal or near optimal. This circumstance explains the possible variations in observed magnitudes of low-power laser effects. Light action on the redox state of a cell via the respiratory chain also explains the diversity of low-power laser effects. Beside explaining many controversies in the field of low-power laser effects (i.e., the diversity of effects, the variable magnitude or absence of effects in certain studies), the proposed redox-regulation mechanism may be a fundamental explanation for some clinical effects of irradiation, for example the positive results achieved in treating wounds, chronic inflammation, and ischemia, all characterized by acidosis and hypoxia.

Interactions of monochromatic visible light and near-IR radiation with cells: currently discussed mechanisms

NASA Astrophysics Data System (ADS)

Karu, Tiina I.

1995-05-01

Biological responses of cells to visible and near IR (laser) radiation occur due to physical and/or chemical changes in photoacceptor molecules, components of respiratory chains (cyt a/a3 in mitochondria, and cyt d in E. coli). As a result of the photoexcitation of electronic states, the following physical and/or chemical changes can occur: alteration of redox properties and acceleration of electron transfer, changes in biochemical activity due to local transient heating of chromophores, one-electron auto-oxidation and O2- production, and photodynamic action and 1O2 production. Different reaction channels can be activated to achieve the photobiological macroeffect. The primary physical and/or chemical changes induced by light in photoacceptor molecules are followed by a cascade of biochemical reactions in the cell that do not need further light activation and occur in the dark (photosignal transduction and amplification chains). These reactions are connected with changes in cellular homeostasis parameters. The crucial step here is thought to be an alteration of the cellular redox state: a shift towards oxidation is associated with stimulation of cellular vitality, and a shift towards reduction is linked to inhibition. Cells with a lower than normal pH, where the redox state is shifted in the reduced direction, are considered to be more sensitive to the stimulative action of light than those with the respective parameters being optimal or near optimal. This circumstance explains the possible variations in observed magnitudes of low-power laser effects. Light action on the redox state of a cell via the respiratory chain also explains the diversity of low-power laser effects. Beside explaining many controversies in the field of low-power laser effects (i.e., the diversity of effects, the variable magnitude or absence of effects in certain studies), the proposed redox-regulation mechanism may be a fundamental explanation of some clinical effects of irradiation, for example the positive results achieved in treating wounds, chronic inflammation, and ischemia, all characterized by acidosis and hypoxia.

Mechanisms of interaction of monochromatic visible light with cells

NASA Astrophysics Data System (ADS)

Karu, Tiina I.

1996-01-01

Biological responses of cells to visible and near IR (laser) radiation occur due to physical and/or chemical changes in photoacceptor molecules, components of respiratory chains (cyt a/a3 in mitochondria). As a result of the photoexcitation of electronic states, the following physical and/or chemical changes can occur: alteration of redox properties and acceleration of electron transfer, changes in biochemical activity due to local transient heating of chromophores, one-electron auto-oxidation and O'2- production, and photodynamic action and 1O2 production. Different reaction channels can be activated to achieve the photobiological macroeffect. The primary physical and/or chemical changes induced by light in photoacceptor molecules are followed by a cascade of biochemical reactions in the cell that do not need further light activation and occur in the dark (photosignal transduction and amplification chains). These reactions are connected with changes in cellular homeostasis parameters. The crucial step here is thought to be an alteration of the cellular redox state: a shift towards oxidation is associated with stimulation of cellular vitality, and a shift towards reduction is linked to inhibition. Cells with a lower than normal pH, where the redox state is shifted in the reduced direction, are considered to be more sensitive to the stimulative action of light than those with the respective parameters being optimal or near optimal. This circumstance explains the possible variations in observed magnitudes of low- power laser effects. Light action on the redox state of a cell via the respiratory chain also explains the diversity of low-power laser effects. Besides explaining many controversies in the field of low-power laser effects (i.e., the diversity of effects, the variable magnitude or absence of effects in certain studies), the proposed redox-regulation mechanism may be a fundamental explanation for some clinical effects of irradiation, for example the positive results achieved in treating wounds, chronic inflammation, and ischemia, all characterized by acidosis and hypoxia.

Experimental parameter identification of a multi-scale musculoskeletal model controlled by electrical stimulation: application to patients with spinal cord injury.

PubMed

Benoussaad, Mourad; Poignet, Philippe; Hayashibe, Mitsuhiro; Azevedo-Coste, Christine; Fattal, Charles; Guiraud, David

2013-06-01

We investigated the parameter identification of a multi-scale physiological model of skeletal muscle, based on Huxley's formulation. We focused particularly on the knee joint controlled by quadriceps muscles under electrical stimulation (ES) in subjects with a complete spinal cord injury. A noninvasive and in vivo identification protocol was thus applied through surface stimulation in nine subjects and through neural stimulation in one ES-implanted subject. The identification protocol included initial identification steps, which are adaptations of existing identification techniques to estimate most of the parameters of our model. Then we applied an original and safer identification protocol in dynamic conditions, which required resolution of a nonlinear programming (NLP) problem to identify the serial element stiffness of quadriceps. Each identification step and cross validation of the estimated model in dynamic condition were evaluated through a quadratic error criterion. The results highlighted good accuracy, the efficiency of the identification protocol and the ability of the estimated model to predict the subject-specific behavior of the musculoskeletal system. From the comparison of parameter values between subjects, we discussed and explored the inter-subject variability of parameters in order to select parameters that have to be identified in each patient.

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

PubMed

Malavera, Alejandra; Vasquez, Alejandra; Fregni, Felipe

2015-01-01

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

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.

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

Photovoltaic Pixels for Neural Stimulation: Circuit Models and Performance.

PubMed

Boinagrov, David; Lei, Xin; Goetz, Georges; Kamins, Theodore I; Mathieson, Keith; Galambos, Ludwig; Harris, James S; Palanker, Daniel

2016-02-01

Photovoltaic conversion of pulsed light into pulsed electric current enables optically-activated neural stimulation with miniature wireless implants. In photovoltaic retinal prostheses, patterns of near-infrared light projected from video goggles onto subretinal arrays of photovoltaic pixels are converted into patterns of current to stimulate the inner retinal neurons. We describe a model of these devices and evaluate the performance of photovoltaic circuits, including the electrode-electrolyte interface. Characteristics of the electrodes measured in saline with various voltages, pulse durations, and polarities were modeled as voltage-dependent capacitances and Faradaic resistances. The resulting mathematical model of the circuit yielded dynamics of the electric current generated by the photovoltaic pixels illuminated by pulsed light. Voltages measured in saline with a pipette electrode above the pixel closely matched results of the model. Using the circuit model, our pixel design was optimized for maximum charge injection under various lighting conditions and for different stimulation thresholds. To speed discharge of the electrodes between the pulses of light, a shunt resistor was introduced and optimized for high frequency stimulation.

Simultaneous versus sequential optimal experiment design for the identification of multi-parameter microbial growth kinetics as a function of temperature.

PubMed

Van Derlinden, E; Bernaerts, K; Van Impe, J F

2010-05-21

Optimal experiment design for parameter estimation (OED/PE) has become a popular tool for efficient and accurate estimation of kinetic model parameters. When the kinetic model under study encloses multiple parameters, different optimization strategies can be constructed. The most straightforward approach is to estimate all parameters simultaneously from one optimal experiment (single OED/PE strategy). However, due to the complexity of the optimization problem or the stringent limitations on the system's dynamics, the experimental information can be limited and parameter estimation convergence problems can arise. As an alternative, we propose to reduce the optimization problem to a series of two-parameter estimation problems, i.e., an optimal experiment is designed for a combination of two parameters while presuming the other parameters known. Two different approaches can be followed: (i) all two-parameter optimal experiments are designed based on identical initial parameter estimates and parameters are estimated simultaneously from all resulting experimental data (global OED/PE strategy), and (ii) optimal experiments are calculated and implemented sequentially whereby the parameter values are updated intermediately (sequential OED/PE strategy). This work exploits OED/PE for the identification of the Cardinal Temperature Model with Inflection (CTMI) (Rosso et al., 1993). This kinetic model describes the effect of temperature on the microbial growth rate and encloses four parameters. The three OED/PE strategies are considered and the impact of the OED/PE design strategy on the accuracy of the CTMI parameter estimation is evaluated. Based on a simulation study, it is observed that the parameter values derived from the sequential approach deviate more from the true parameters than the single and global strategy estimates. The single and global OED/PE strategies are further compared based on experimental data obtained from design implementation in a bioreactor. Comparable estimates are obtained, but global OED/PE estimates are, in general, more accurate and reliable. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Multi-parameter optimization of piezoelectric actuators for multi-mode active vibration control of cylindrical shells

NASA Astrophysics Data System (ADS)

Hu, K. M.; Li, Hua

2018-07-01

A novel technique for the multi-parameter optimization of distributed piezoelectric actuators is presented in this paper. The proposed method is designed to improve the performance of multi-mode vibration control in cylindrical shells. The optimization parameters of actuator patch configuration include position, size, and tilt angle. The modal control force of tilted orthotropic piezoelectric actuators is derived and the multi-parameter cylindrical shell optimization model is established. The linear quadratic energy index is employed as the optimization criterion. A geometric constraint is proposed to prevent overlap between tilted actuators, which is plugged into a genetic algorithm to search the optimal configuration parameters. A simply-supported closed cylindrical shell with two actuators serves as a case study. The vibration control efficiencies of various parameter sets are evaluated via frequency response and transient response simulations. The results show that the linear quadratic energy indexes of position and size optimization decreased by 14.0% compared to position optimization; those of position and tilt angle optimization decreased by 16.8%; and those of position, size, and tilt angle optimization decreased by 25.9%. It indicates that, adding configuration optimization parameters is an efficient approach to improving the vibration control performance of piezoelectric actuators on shells.

β-(1→6)-D-glucan secreted during the optimised production of exopolysaccharides by Paecilomyces variotii has immunostimulatory activity.

PubMed

Osaku, Erica F; Menolli, Rafael A; de M Costa, Claudia R L; Tessaro, Fernando Henrique G; de Melo, Renan H; do Amaral, Alex E; Duarte, Péricles A D; de Santana Filho, Arquimedes Paixão; Ruthes, Andrea Caroline; da C Silva, José Luis; Mello, Rosiane G

2018-06-01

Paecilomyces variotii is a filamentous fungus that occurs worldwide in soil and decaying vegetation. Optimization of the fermentation process for exopolysaccharide (EPS) production from the fungus P. variotii, structure determination and immuno-stimulating activity of EPS were performed. Response surface methodology (RSM) coupled with central composite design (CCD) was used to optimize the physical and chemical factors required to produce EPS in submerged fermentation. Preliminary investigations to choose the three factors for the present work were made using a factorial experimental design. Glucose, ammonium nitrate (NH 4 NO 3 ) and pH were used as variables for which, with constant temperature of 28 °C and agitation of 90 rpm, the optimal process parameters were determined as glucose values of 0.96%, NH 4 NO 3 0.26% and pH 8.0. The three parameters presented significant effects. In this condition of culture, the main composition of the isolated EPS was a linear β-(1 → 6)-linked-D-glucan, as determined by Nuclear Magnetic Resonance (NMR) and methylation analysis. This polysaccharide is a very unusual as an EPS from fungi, especially a filamentous fungus such as P. variotii. Murine peritoneal macrophages cultivated with β-glucan for 6 and 48 h showed an increase in TNF-α, IL-6 and nitric oxide release with increased polysaccharide concentrations. Therefore, we conclude that the β-(1 → 6)-linked-D-glucan produced in optimised conditions of P. variotii cultivation has an immune-stimulatory activity on murine macrophages.

A conceptual demonstration of freeze desalination-membrane distillation (FD-MD) hybrid desalination process utilizing liquefied natural gas (LNG) cold energy.

PubMed

Wang, Peng; Chung, Tai-Shung

2012-09-01

The severe global water scarcity and record-high fossil oil price have greatly stimulated the research interests on new desalination technologies which can be driven by renewable energy or waste energy. In this study, a hybrid desalination process comprising freeze desalination and membrane distillation (FD-MD) processes was developed and explored in an attempt to utilize the waste cold energy released from re-gasification of liquefied natural gas (LNG). The concept of this technology was demonstrated using indirect-contact freeze desalination (ICFD) and direct-contact membrane distillation (DCMD) configurations. By optimizing the ICFD operation parameters, namely, the usage of nucleate seeds, operation duration and feed concentration, high quality drinkable water with a low salinity ∼0.144 g/L was produced in the ICFD process. At the same time, using the optimized hollow fiber module length and packing density in the DCMD process, ultra pure water with a low salinity of 0.062 g/L was attained at a condition of high energy efficiency (EE). Overall, by combining FD and MD processes and adopting the optimized operation parameters, the hybrid FD-MD system has been successfully demonstrated. A high total water recovery of 71.5% was achieved, and the water quality obtained met the standard for drinkable water. In addition, with results from specific energy calculation, it was proven that the hybrid process is an energy-saving process and utilization of LNG cold energy could greatly reduce the total energy consumption. Copyright © 2012 Elsevier Ltd. All rights reserved.

Optimization of epilepsy treatment with vagus nerve stimulation

NASA Astrophysics Data System (ADS)

Uthman, Basim; Bewernitz, Michael; Liu, Chang-Chia; Ghacibeh, Georges

2007-11-01

Epilepsy is one of the most common chronic neurological disorders that affects close to 50 million people worldwide. Antiepilepsy drugs (AEDs), the main stay of epilepsy treatment, control seizures in two thirds of patients only. Other therapies include the ketogenic diet, ablative surgery, hormonal treatments and neurostimulation. While other approaches to stimulation of the brain are currently in the experimental phase vagus nerve stimulation (VNS) has been approved by the FDA since July 1997 for the adjunctive treatment of intractable partial onset epilepsy with and without secondary generalization in patients twelve years of age or older. The safety and efficacy of VNS have been proven and duplicated in two subsequent double-blinded controlled studies after two pilot studies demonstrated the feasibility of VNS in man. Long term observational studies confirmed the safety of VNS and that its effectiveness is sustained over time. While AEDs influence seizure thresholds via blockade or modulation of ionic channels, inhibit excitatory neurotransmitters or enhance inhibitory neurotransmitters the exact mechanism of action of VNS is not known. Neuroimaging studies revealed that VNS increases blood flow in certain regions of the brain such as the thalamus. Chemical lesions in the rat brains showed that norepinephrine is an important link in the anticonvulsant effect of VNS. Analysis of cerebrospinal fluid obtained from patients before and after treatment with VNS showed modest decreases in excitatory neurotransmitters. Although Hammond et al. reported no effect of VNS on scalp EEG by visual analysis and Salinsky et al. found no effect of VNS on scalp EEG by spectral analysis, Kuba et al. suggested that VNS reduces interictal epileptiform activity. Further, nonlinear dynamical analysis of the electroencephalogram in the rat and man have reportedly shown predictable changes (decrease in the short term Lyapunov exponent STLmax and T-index) more than an hour prior to the clinical or electroencephalographic seizure onset. It is possible that intermittent VNS maintains chaoticity of brain activity in patients with epilepsy that respond to this therapy. The most optimal stimulation parameters of VNS are not known and further study of nonlinear dynamics of brain activity may shed some light on more effective interception or prevention of seizures. Online real time analysis may allow on-demand stimulation rather than hit-or-miss approach

Comprehensive joint feedback control for standing by functional neuromuscular stimulation-a simulation study.

PubMed

Nataraj, Raviraj; Audu, Musa L; Kirsch, Robert F; Triolo, Ronald J

2010-12-01

Previous investigations of feedback control of standing after spinal cord injury (SCI) using functional neuromuscular stimulation (FNS) have primarily targeted individual joints. This study assesses the potential efficacy of comprehensive (trunk, hips, knees, and ankles) joint feedback control against postural disturbances using a bipedal, 3-D computer model of SCI stance. Proportional-derivative feedback drove an artificial neural network trained to produce muscle excitation patterns consistent with maximal joint stiffness values achievable about neutral stance given typical SCI muscle properties. Feedback gains were optimized to minimize upper extremity (UE) loading required to stabilize against disturbances. Compared to the baseline case of maximum constant muscle excitations used clinically, the controller reduced UE loading by 55% in resisting external force perturbations and by 84% during simulated one-arm functional tasks. Performance was most sensitive to inaccurate measurements of ankle plantar/dorsiflexion position and hip ab/adduction velocity feedback. In conclusion, comprehensive joint feedback demonstrates potential to markedly improve FNS standing function. However, alternative control structures capable of effective performance with fewer sensor-based feedback parameters may better facilitate clinical usage.

Comprehensive Joint Feedback Control for Standing by Functional Neuromuscular Stimulation – a Simulation Study

PubMed Central

Nataraj, Raviraj; Audu, Musa L.; Kirsch, Robert F.; Triolo, Ronald J.

2013-01-01

Previous investigations of feedback control of standing after spinal cord injury (SCI) using functional neuromuscular stimulation (FNS) have primarily targeted individual joints. This study assesses the potential efficacy of comprehensive (trunk, hips, knees, and ankles) joint-feedback control against postural disturbances using a bipedal, three-dimensional computer model of SCI stance. Proportional-derivative feedback drove an artificial neural network trained to produce muscle excitation patterns consistent with maximal joint stiffness values achievable about neutral stance given typical SCI muscle properties. Feedback gains were optimized to minimize upper extremity (UE) loading required to stabilize against disturbances. Compared to the baseline case of maximum constant muscle excitations used clinically, the controller reduced UE loading by 55% in resisting external force perturbations and by 84% during simulated one-arm functional tasks. Performance was most sensitive to inaccurate measurements of ankle plantar/dorsiflexion position and hip ab/adduction velocity feedback. In conclusion, comprehensive joint-feedback demonstrates potential to markedly improve FNS standing function. However, alternative control structures capable of effective performance with fewer sensor-based feedback parameters may better facilitate clinical usage. PMID:20923741

Influence of reabsorption and reemission on stimulated Raman scattering of polymethine dyes in multiple scattering media

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

Yashchuk, V P; Komyshan, A O; Smaliuk, A P

2013-12-31

It is shown that reabsorption of the luminescence radiation in the range of its overlapping with the absorption spectrum and the following reemission to a long-wavelength range may noticeably affect the process of stimulated Raman scattering (SRS) in polymethine dyes in multiple scattering media (MSM). This is related to the fact that SRS in such media occurs jointly with the random lasing (RL), which favors SRS and makes up with it a united nonlinear process. Reemission into the long-wavelength spectrum range amplified in MSM causes the RL spectrum to shift to longer wavelengths and initiates the long-wavelength band of RL,more » in which a main part of the lasing energy is concentrated. This weakens or completely stops the SRS if the band is beyond the range of possible spectral localisation of Stokes lines. This process depends on the efficiency of light scattering, dye concentration, temperature and pump intensity; hence, there exist optimal values of these parameters for obtaining SRS in MSM. (nonlinear optical phenomena)« less

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.

The point spread function of the human head and its implications for transcranial current stimulation

NASA Astrophysics Data System (ADS)

Dmochowski, Jacek P.; Bikson, Marom; Parra, Lucas C.

2012-10-01

Rational development of transcranial current stimulation (tCS) requires solving the ‘forward problem’: the computation of the electric field distribution in the head resulting from the application of scalp currents. Derivation of forward models has represented a major effort in brain stimulation research, with model complexity ranging from spherical shells to individualized head models based on magnetic resonance imagery. Despite such effort, an easily accessible benchmark head model is greatly needed when individualized modeling is either undesired (to observe general population trends as opposed to individual differences) or unfeasible. Here, we derive a closed-form linear system which relates the applied current to the induced electric potential. It is shown that in the spherical harmonic (Fourier) domain, a simple scalar multiplication relates the current density on the scalp to the electric potential in the brain. Equivalently, the current density in the head follows as the spherical convolution between the scalp current distribution and the point spread function of the head, which we derive. Thus, if one knows the spherical harmonic representation of the scalp current (i.e. the electrode locations and current intensity to be employed), one can easily compute the resulting electric field at any point inside the head. Conversely, one may also readily determine the scalp current distribution required to generate an arbitrary electric field in the brain (the ‘backward problem’ in tCS). We demonstrate the simplicity and utility of the model with a series of characteristic curves which sweep across a variety of stimulation parameters: electrode size, depth of stimulation, head size and anode-cathode separation. Finally, theoretically optimal montages for targeting an infinitesimal point in the brain are shown.

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.

Design and Validation of a Compressive Tissue Stimulator with High-Throughput Capacity and Real-Time Modulus Measurement Capability

PubMed Central

Salvetti, David J.; Pino, Christopher J.; Manuel, Steven G.; Dallmeyer, Ian; Rangarajan, Sanjeet V.; Meyer, Tobias; Kotov, Misha

2012-01-01

Mechanical stimulation has been shown to impact the properties of engineered hyaline cartilage constructs and is relevant for engineering of cartilage and osteochondral tissues. Most mechanical stimulators developed to date emphasize precision over adaptability to standard tissue culture equipment and protocols. The realization of mechanical characteristics in engineered constructs approaching native cartilage requires the optimization of complex variables (type of stimulus, regimen, and bimolecular signals). We have proposed and validated a stimulator design that focuses on high construct capacity, compatibility with tissue culture plastic ware, and regimen adaptability to maximize throughput. This design utilizes thin force sensors in lieu of a load cell and a linear encoder to verify position. The implementation of an individual force sensor for each sample enables the measurement of Young's modulus while stimulating the sample. Removable and interchangeable Teflon plungers mounted using neodymium magnets contact each sample. Variations in plunger height and design can vary the strain and force type on individual samples. This allows for the evaluation of a myriad of culture conditions and regimens simultaneously. The system was validated using contact accuracy, and Young's modulus measurements range as key parameters. Contact accuracy for the system was excellent within 1.16% error of the construct height in comparison to measurements made with a micrometer. Biomaterials ranging from bioceramics (cancellous bone, 123 MPa) to soft gels (1% agarose, 20 KPa) can be measured without any modification to the device. The accuracy of measurements in conjunction with the wide range of moduli tested demonstrate the unique characteristics of the device and the feasibility of using this device in mapping real-time changes to Young's modulus of tissue constructs (cartilage, bone) through the developmental phases in ex vivo culture conditions. PMID:21988089

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

Purity assessment of recombinant human granulocyte colony-stimulating factor in finished drug product by capillary zone electrophoresis.

PubMed

Benković, Goran; Skrlin, Ana; Madić, Tomislav; Debeljak, Zeljko; Medić-Šarić, Marica

2014-09-01

Current methods for determination of impurities with different charge-to-volume ratio are limited especially in terms of sensitivity and precision. The main goal of this research was to establish a quantitative method for determination of impurities with charges differing from that of recombinant human granulocyte colony-stimulating factor (rhG-CSF, filgrastim) with superior precision and sensitivity compared to existing methods. A CZE method has been developed, optimized, and validated for a purity assessment of filgrastim in liquid pharmaceutical formulations. Optimal separation of filgrastim from the related impurities with different charges was achieved on a 50 μm id fused-silica capillary of a total length of 80.5 cm. A BGE that contains 100 mM phosphoric acid adjusted to pH 7.0 with triethanolamine was used. The applied voltage was 20 kV while the temperature was maintained at 25°C. UV detection was set to 200 nm. Method was validated in terms of selectivity/specificity, linearity, precision, LOD, LOQ, stability, and robustness. Linearity was observed in the concentration range of 6-600 μg/mL and the LOQ was determined to be 0.3% relative to the concentration of filgrastim of 0.6 mg/mL. Other validation parameters were also found to be acceptable; thus the method was successfully applied for a quantitative purity assessment of filgrastim in a finished drug product. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Environmental Stimulation Model

ERIC Educational Resources Information Center

Zentall, Sydney S.

1977-01-01

An approach to treatment of hyperactive children is suggested which is based on the assumption that the hyperactive child is actually understimulated and hyperactive behaviors function to increase the external stimulation to approach a more optimal level. (Author/GW)

[The role of the basophil activation test (BAT) in qualification for specific immunotherapy with inhalant allergens].

PubMed

Bulanda, Małgorzata; Dyga, Wojciech; Rusinek, Barbara; Czarnobilska, Ewa

Qualification for specific immunotherapy (SIT) according to the guidelines of the European Academy of Allergy and Clinical Immunology (EAACI) includes medical history, skin prik tests (SPT) and/or measuring the concentration of sIgE. It is necessary to perform additional diagnostic tests in case of discrepancies between the history and the results of SPT/sIgE or differences between SPT and sIgE. Basophil activation test (BAT) assesses the expression of activation markers of these cells, eg. CD63 and CD203c after stimulation. The aim of our study was to evaluate the usefulness of BAT in the qualification for the SIT in comparison to the SPT and sIgE and in case of discrepancies between the results of SPT and sIgE. The study included 30 patients with allergic rhinitis (AR) caused by allergy to house dust mite (Dermatophagoides pteronyssinus, Dp) or birch pollen qualified for SIT. All patients had SPT, sIgE and BAT determination. The group of patients with allergy to birch was a control group for Dp allergic and vice versa. BAT with CD63 antigen expression was performed using a Flow2CAST test. Basophils were stimulated with allergen preparation (50, 500, and 5000 SBU/ml concentrations). BAT results were expressed as a stimulation index (SI). For optimal concentrations of 50 and 500 SBU/ml parameters comparing BAT to SPT and sIgE as the gold standards were consecutively: sensitivity 82-100% and 93-100%, specificity 50-94% and 47-89%, positive predictive value 65- 94% and 61-87%, negative predictive value 86-100% and 93-100%. Correlation BAT - SPT and BAT - sIgE ranged within 0.59 to 0.84 and 0.51 to 0.72. BAT was helpful in 2 of 30 patients with incompatible results of SPT and sIgE. Optimal concentrations for basophil stimulation are 50 and 500 SBU/ ml. BAT may be useful diagnostic tool in the qualification for the SIT in case of discrepancies between the results of SPT and sIgE.

Optimization of a centrifugal compressor impeller using CFD: the choice of simulation model parameters

NASA Astrophysics Data System (ADS)

Neverov, V. V.; Kozhukhov, Y. V.; Yablokov, A. M.; Lebedev, A. A.

2017-08-01

Nowadays the optimization using computational fluid dynamics (CFD) plays an important role in the design process of turbomachines. However, for the successful and productive optimization it is necessary to define a simulation model correctly and rationally. The article deals with the choice of a grid and computational domain parameters for optimization of centrifugal compressor impellers using computational fluid dynamics. Searching and applying optimal parameters of the grid model, the computational domain and solver settings allows engineers to carry out a high-accuracy modelling and to use computational capability effectively. The presented research was conducted using Numeca Fine/Turbo package with Spalart-Allmaras and Shear Stress Transport turbulence models. Two radial impellers was investigated: the high-pressure at ψT=0.71 and the low-pressure at ψT=0.43. The following parameters of the computational model were considered: the location of inlet and outlet boundaries, type of mesh topology, size of mesh and mesh parameter y+. Results of the investigation demonstrate that the choice of optimal parameters leads to the significant reduction of the computational time. Optimal parameters in comparison with non-optimal but visually similar parameters can reduce the calculation time up to 4 times. Besides, it is established that some parameters have a major impact on the result of modelling.

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.

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.

Bio-heat transfer model of deep brain stimulation-induced temperature changes

NASA Astrophysics Data System (ADS)

Elwassif, Maged M.; Kong, Qingjun; Vazquez, Maribel; Bikson, Marom

2006-12-01

There is a growing interest in the use of chronic deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. Fundamental questions remain about the physiologic effects of DBS. Previous basic research studies have focused on the direct polarization of neuronal membranes by electrical stimulation. The goal of this paper is to provide information on the thermal effects of DBS using finite element models to investigate the magnitude and spatial distribution of DBS-induced temperature changes. The parameters investigated include stimulation waveform, lead selection, brain tissue electrical and thermal conductivities, blood perfusion, metabolic heat generation during the stimulation and lead thermal conductivity/heat dissipation through the electrode. Our results show that clinical DBS protocols will increase the temperature of surrounding tissue by up to 0.8 °C depending on stimulation/tissue parameters.

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

Blood Pressure Responses to Endovascular Stimulation: A Potential Therapy for Autonomic Disorders With Vasodilatation.

PubMed

Naksuk, Niyada; Killu, Ammar M; Yogeswaran, Vidhushei; Desimone, Christopher V; Suddendorf, Scott H; Ladewig, Dorothy J; Powers, Joanne M; Weber, Sarah; Madhavan, Malini; Cha, Yong-Mei; Kapa, Suraj; Asirvatham, Samuel J

2016-09-01

We have previously shown that sympathetic ganglia stimulation via the renal vein rapidly increases blood pressure. This study further investigated the optimal target sites and effective energy levels for stimulation of the renal vasculatures and nearby sympathetic ganglia for rapid increase in blood pressure. The pre-study protocol for endovascular stimulations included 2 minutes of stimulation (1-150 V and 10 pulses per second) and at least 2 minutes of rest during poststimulation. If blood pressure and/or heart rate were changed during the stimulation, time to return to baseline was allowed prior to the next stimulation. In 11 acute canine studies, we performed 85 renal artery, 30 renal vein, and 8 hepatic vasculature stimulations. The mean arterial pressure (MAP) rapidly increased during stimulation of renal artery (95 ± 18 mmHg vs. 103 ± 15 mmHg; P < 0.0001), renal vein (90 ± 16 mmHg vs. 102 ± 20 mmHg; P = 0.001), and hepatic vasculatures (74 ± 8 mmHg vs. 82 ± 11 mmHg; P = 0.04). Predictors of a significant increase in MAP were energy >10 V focused on the left renal artery, bilateral renal arteries, and bilateral renal veins (especially the mid segment). Overall, heart rate was unchanged, but muscle fasciculation was observed in 22.0% with an output >10 V (range 15-150 V). Analysis after excluding the stimulations that resulted in fasciculation yielded similar results to the main findings. Stimulation of intra-abdominal vasculatures promptly increased the MAP and thus may be a potential treatment option for hypotension in autonomic disorders. Predictors of optimal stimulation include energy delivery and the site of stimulation (for the renal vasculatures), which informs the design of subsequent research. © 2016 Wiley Periodicals, Inc.

Mathematical models of human paralyzed muscle after long-term training.

PubMed

Law, L A Frey; Shields, R K

2007-01-01

Spinal cord injury (SCI) results in major musculoskeletal adaptations, including muscle atrophy, faster contractile properties, increased fatigability, and bone loss. The use of functional electrical stimulation (FES) provides a method to prevent paralyzed muscle adaptations in order to sustain force-generating capacity. Mathematical muscle models may be able to predict optimal activation strategies during FES, however muscle properties further adapt with long-term training. The purpose of this study was to compare the accuracy of three muscle models, one linear and two nonlinear, for predicting paralyzed soleus muscle force after exposure to long-term FES training. Further, we contrasted the findings between the trained and untrained limbs. The three models' parameters were best fit to a single force train in the trained soleus muscle (N=4). Nine additional force trains (test trains) were predicted for each subject using the developed models. Model errors between predicted and experimental force trains were determined, including specific muscle force properties. The mean overall error was greatest for the linear model (15.8%) and least for the nonlinear Hill Huxley type model (7.8%). No significant error differences were observed between the trained versus untrained limbs, although model parameter values were significantly altered with training. This study confirmed that nonlinear models most accurately predict both trained and untrained paralyzed muscle force properties. Moreover, the optimized model parameter values were responsive to the relative physiological state of the paralyzed muscle (trained versus untrained). These findings are relevant for the design and control of neuro-prosthetic devices for those with SCI.

Numerical optimization methods for controlled systems with parameters

NASA Astrophysics Data System (ADS)

Tyatyushkin, A. I.

2017-10-01

First- and second-order numerical methods for optimizing controlled dynamical systems with parameters are discussed. In unconstrained-parameter problems, the control parameters are optimized by applying the conjugate gradient method. A more accurate numerical solution in these problems is produced by Newton's method based on a second-order functional increment formula. Next, a general optimal control problem with state constraints and parameters involved on the righthand sides of the controlled system and in the initial conditions is considered. This complicated problem is reduced to a mathematical programming one, followed by the search for optimal parameter values and control functions by applying a multimethod algorithm. The performance of the proposed technique is demonstrated by solving application problems.

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

Estimation of an Optimal Stimulus Amplitude for Using Vestibular Stochastic Stimulation to Improve Balance Function

NASA Technical Reports Server (NTRS)

Goel, R.; Kofman, I.; DeDios, Y. E.; Jeevarajan, J.; Stepanyan, V.; Nair, M.; Congdon, S.; Fregia, M.; Peters, B.; Cohen, H.;

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.

Machining Parameters Optimization using Hybrid Firefly Algorithm and Particle Swarm Optimization

NASA Astrophysics Data System (ADS)

Farahlina Johari, Nur; Zain, Azlan Mohd; Haszlinna Mustaffa, Noorfa; Udin, Amirmudin

2017-09-01

Firefly Algorithm (FA) is a metaheuristic algorithm that is inspired by the flashing behavior of fireflies and the phenomenon of bioluminescent communication and the algorithm is used to optimize the machining parameters (feed rate, depth of cut, and spindle speed) in this research. The algorithm is hybridized with Particle Swarm Optimization (PSO) to discover better solution in exploring the search space. Objective function of previous research is used to optimize the machining parameters in turning operation. The optimal machining cutting parameters estimated by FA that lead to a minimum surface roughness are validated using ANOVA test.

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.

Simultaneous Intrinsic and Extrinsic Parameter Identification of a Hand-Mounted Laser-Vision Sensor

PubMed Central

Lee, Jong Kwang; Kim, Kiho; Lee, Yongseok; Jeong, Taikyeong

2011-01-01

In this paper, we propose a simultaneous intrinsic and extrinsic parameter identification of a hand-mounted laser-vision sensor (HMLVS). A laser-vision sensor (LVS), consisting of a camera and a laser stripe projector, is used as a sensor component of the robotic measurement system, and it measures the range data with respect to the robot base frame using the robot forward kinematics and the optical triangulation principle. For the optimal estimation of the model parameters, we applied two optimization techniques: a nonlinear least square optimizer and a particle swarm optimizer. Best-fit parameters, including both the intrinsic and extrinsic parameters of the HMLVS, are simultaneously obtained based on the least-squares criterion. From the simulation and experimental results, it is shown that the parameter identification problem considered was characterized by a highly multimodal landscape; thus, the global optimization technique such as a particle swarm optimization can be a promising tool to identify the model parameters for a HMLVS, while the nonlinear least square optimizer often failed to find an optimal solution even when the initial candidate solutions were selected close to the true optimum. The proposed optimization method does not require good initial guesses of the system parameters to converge at a very stable solution and it could be applied to a kinematically dissimilar robot system without loss of generality. PMID:22164104

Assessment of Cultivation Factors that Affect Biomass and Geraniol Production in Transgenic Tobacco Cell Suspension Cultures

PubMed Central

Vasilev, Nikolay; Schmitz, Christian; Grömping, Ulrike; Fischer, Rainer; Schillberg, Stefan

2014-01-01

A large-scale statistical experimental design was used to determine essential cultivation parameters that affect biomass accumulation and geraniol production in transgenic tobacco (Nicotiana tabacum cv. Samsun NN) cell suspension cultures. The carbohydrate source played a major role in determining the geraniol yield and factors such as filling volume, inoculum size and light were less important. Sucrose, filling volume and inoculum size had a positive effect on geraniol yield by boosting growth of plant cell cultures whereas illumination of the cultures stimulated the geraniol biosynthesis. We also found that the carbohydrates sucrose and mannitol showed polarizing effects on biomass and geraniol accumulation. Factors such as shaking frequency, the presence of conditioned medium and solubilizers had minor influence on both plant cell growth and geraniol content. When cells were cultivated under the screened conditions for all the investigated factors, the cultures produced ∼5.2 mg/l geraniol after 12 days of cultivation in shaking flasks which is comparable to the yield obtained in microbial expression systems. Our data suggest that industrial experimental designs based on orthogonal arrays are suitable for the selection of initial cultivation parameters prior to the essential medium optimization steps. Such designs are particularly beneficial in the early optimization steps when many factors must be screened, increasing the statistical power of the experiments without increasing the demand on time and resources. PMID:25117009

Assessment of cultivation factors that affect biomass and geraniol production in transgenic tobacco cell suspension cultures.

PubMed

Vasilev, Nikolay; Schmitz, Christian; Grömping, Ulrike; Fischer, Rainer; Schillberg, Stefan

2014-01-01

A large-scale statistical experimental design was used to determine essential cultivation parameters that affect biomass accumulation and geraniol production in transgenic tobacco (Nicotiana tabacum cv. Samsun NN) cell suspension cultures. The carbohydrate source played a major role in determining the geraniol yield and factors such as filling volume, inoculum size and light were less important. Sucrose, filling volume and inoculum size had a positive effect on geraniol yield by boosting growth of plant cell cultures whereas illumination of the cultures stimulated the geraniol biosynthesis. We also found that the carbohydrates sucrose and mannitol showed polarizing effects on biomass and geraniol accumulation. Factors such as shaking frequency, the presence of conditioned medium and solubilizers had minor influence on both plant cell growth and geraniol content. When cells were cultivated under the screened conditions for all the investigated factors, the cultures produced ∼ 5.2 mg/l geraniol after 12 days of cultivation in shaking flasks which is comparable to the yield obtained in microbial expression systems. Our data suggest that industrial experimental designs based on orthogonal arrays are suitable for the selection of initial cultivation parameters prior to the essential medium optimization steps. Such designs are particularly beneficial in the early optimization steps when many factors must be screened, increasing the statistical power of the experiments without increasing the demand on time and resources.

Stimulation of the nervous system for the management of seizures: current and future developments.

PubMed

Murphy, Jerome V; Patil, Arunangelo

2003-01-01

Vagal nerve stimulation (VNS) for the treatment of refractory epilepsy appears to have started from the theory that since VNS can alter the EEG, it may influence epilepsy. It proved effective in several models of epilepsy and was then tried in short-term, open-label and double-blind trials, leading to approval in Canada, Europe and the US. Follow-up observations in these patients demonstrated continued improvement in seizure control for up to 2 years. Close to 50% of treated patients have achieved at least a 50% reduction in seizure frequency. This therapy was also useful as rescue therapy for ongoing seizures in some patients; many patients are more alert. The initial trials were completed in patients >/=12 years of age with refractory partial seizures. Subsequently, similar benefits were shown in patients with tuberous sclerosis complex, Lennox-Gastaut syndrome, hypothalamic hamartomas and primary generalised seizures. Implanting the generator and leads is technically easy, and complications are few. The method of action is largely unknown, although VNS appears to alter metabolic activity in specific brain nuclei. Considering that improvement in mood is frequently found in patients using VNS, it has undergone trials in patients with depression. Other illnesses deserving exploration with this unusual therapy are Alzheimer's disease and autism. Some aspects of VNS have proven disappointing. Although patients have fewer seizures, the number of antiepileptic drugs they take is not significantly reduced. In addition, there is no way to accurately predict the end of life of the generator. Optimal stimulation parameters, if they exist, are unknown. Deep brain stimulation is a new method for controlling medically refractory seizures. It is based on the observation that thalamic stimulation can influence the EEG over a wide area. Several thalamic nuclei have been the object of stimulation in different groups of patients. Intraoperative brain imaging is essential for electrode placement. The procedure is done under local anaesthesia. Experience with this therapy is currently limited, but growing.

The Role of Cervical and Ocular Vestibular Evoked Myogenic Potentials in the Assessment of Patients with Vestibular Schwannomas

PubMed Central

Chiarovano, Elodie; Darlington, Cynthia; Vidal, Pierre-Paul; Lamas, Georges; de Waele, Catherine

2014-01-01

Objectives To investigate the clinical utility of VEMPs in patients suffering from unilateral vestibular schwannoma (VS) and to determine the optimal stimulation parameter (air conducted sound, bone conducted vibration) for evaluating the function of the vestibular nerve. Methods Data were obtained in 63 patients with non-operated VS, and 20 patients operated on VS. Vestibular function was assessed by caloric, cervical and ocular VEMP testing. 37/63 patients with conclusive ACS ocular VEMPs responses were studied separately. Results In the 63 non-operated VS patients, cVEMPs were abnormal in 65.1% of patients in response to AC STB and in 49.2% of patients to AC clicks. In the 37/63 patients with positive responses from the unaffected side, oVEMPs were abnormal in 75.7% of patients with ACS, in 67.6% with AFz and in 56.8% with mastoid BCV stimulation. In 16% of the patients, VEMPs were the only abnormal test (normal caloric and normal hearing). Among the 26 patients who did not show oVEMP responses on either side with ACS, oVEMPs responses could be obtained with AFz (50%) and with mastoid stimulation (89%). Conclusions The VEMP test demonstrated significant clinical value as it yielded the only abnormal test results in some patients suffering from a unilateral vestibular schwannoma. For oVEMPs, we suggest that ACS stimulation should be the initial test. In patients who responded to ACS and who had normal responses, BCV was not required. In patients with abnormal responses on the affected side using ACS, BCV at AFz should be used to confirm abnormal function of the superior vestibular nerve. In patients who exhibited no responses on either side to ACS, BCV was the only approach allowing assessment of the function of the superior vestibular nerve. We favor using AFz stimulation first because it is easier to perform in clinical practice than mastoid stimulation. PMID:25137289

The Importance of the Numerical Resolution of the Laplace Equation in the optimization of a Neuronal Stimulation Technique

NASA Astrophysics Data System (ADS)

Faria, Paula

2010-09-01

For the past few years, the potential of transcranial direct current stimulation (tDCS) for the treatment of several pathologies has been investigated. Knowledge of the current density distribution is an important factor in optimizing such applications of tDCS. For this goal, we used the finite element method to solve the Laplace equation in a spherical head model in order to investigate the three dimensional distribution of the current density and the variation of its intensity with depth using different electrodes montages: the traditional one with two sponge electrodes and new electrode montages: with sponge and EEG electrodes and with EEG electrodes varying the numbers of electrodes. The simulation results confirm the effectiveness of the mixed system which may allow the use of tDCS and EEG recording concomitantly and may help to optimize this neuronal stimulation technique. The numerical results were used in a promising application of tDCS in epilepsy.

Comparing the force ripple during asynchronous and conventional stimulation.

PubMed

Downey, Ryan J; Tate, Mark; Kawai, Hiroyuki; Dixon, Warren E

2014-10-01

Asynchronous stimulation has been shown to reduce fatigue during electrical stimulation; however, it may also exhibit a force ripple. We quantified the ripple during asynchronous and conventional single-channel transcutaneous stimulation across a range of stimulation frequencies. The ripple was measured during 5 asynchronous stimulation protocols, 2 conventional stimulation protocols, and 3 volitional contractions in 12 healthy individuals. Conventional 40 Hz and asynchronous 16 Hz stimulation were found to induce contractions that were as smooth as volitional contractions. Asynchronous 8, 10, and 12 Hz stimulation induced contractions with significant ripple. Lower stimulation frequencies can reduce fatigue; however, they may also lead to increased ripple. Future efforts should study the relationship between force ripple and the smoothness of the evoked movements in addition to the relationship between stimulation frequency and NMES-induced fatigue to elucidate an optimal stimulation frequency for asynchronous stimulation. © 2014 Wiley Periodicals, Inc.

Parameter meta-optimization of metaheuristics of solving specific NP-hard facility location problem

NASA Astrophysics Data System (ADS)

Skakov, E. S.; Malysh, V. N.

2018-03-01

The aim of the work is to create an evolutionary method for optimizing the values of the control parameters of metaheuristics of solving the NP-hard facility location problem. A system analysis of the tuning process of optimization algorithms parameters is carried out. The problem of finding the parameters of a metaheuristic algorithm is formulated as a meta-optimization problem. Evolutionary metaheuristic has been chosen to perform the task of meta-optimization. Thus, the approach proposed in this work can be called “meta-metaheuristic”. Computational experiment proving the effectiveness of the procedure of tuning the control parameters of metaheuristics has been performed.

Electrical stimulation of gut motility guided by an in silico model

NASA Astrophysics Data System (ADS)

Barth, Bradley B.; Henriquez, Craig S.; Grill, Warren M.; Shen, Xiling

2017-12-01

Objective. Neuromodulation of the central and peripheral nervous systems is becoming increasingly important for treating a diverse set of diseases—ranging from Parkinson’s Disease and epilepsy to chronic pain. However, neuromodulation of the gastrointestinal (GI) tract has achieved relatively limited success in treating functional GI disorders, which affect a significant population, because the effects of stimulation on the enteric nervous system (ENS) and gut motility are not well understood. Here we develop an integrated neuromechanical model of the ENS and assess neurostimulation strategies for enhancing gut motility, validated by in vivo experiments. Approach. The computational model included a network of enteric neurons, smooth muscle fibers, and interstitial cells of Cajal, which regulated propulsion of a virtual pellet in a model of gut motility. Main results. Simulated extracellular stimulation of ENS-mediated motility revealed that sinusoidal current at 0.5 Hz was more effective at increasing intrinsic peristalsis and reducing colon transit time than conventional higher frequency rectangular current pulses, as commonly used for neuromodulation therapy. Further analysis of the model revealed that the 0.5 Hz sinusoidal currents were more effective at modulating the pacemaker frequency of interstitial cells of Cajal. To test the predictions of the model, we conducted in vivo electrical stimulation of the distal colon while measuring bead propulsion in awake rats. Experimental results confirmed that 0.5 Hz sinusoidal currents were more effective than higher frequency pulses at enhancing gut motility. Significance. This work demonstrates an in silico GI neuromuscular model to enable GI neuromodulation parameter optimization and suggests that low frequency sinusoidal currents may improve the efficacy of GI pacing.

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.

An interval-possibilistic basic-flexible programming method for air quality management of municipal energy system through introducing electric vehicles.

PubMed

Yu, L; Li, Y P; Huang, G H; Shan, B G

2017-09-01

Contradictions of sustainable transportation development and environmental issues have been aggravated significantly and been one of the major concerns for energy systems planning and management. A heavy emphasis is placed on stimulation of electric vehicles (EVs) to handle these problems associated with various complexities and uncertainties in municipal energy system (MES). In this study, an interval-possibilistic basic-flexible programming (IPBFP) method is proposed for planning MES of Qingdao, where uncertainties expressed as interval-flexible variables and interval-possibilistic parameters can be effectively reflected. Support vector regression (SVR) is used for predicting electricity demand of the city under various scenarios. Solutions of EVs stimulation levels and satisfaction levels in association with flexible constraints and predetermined necessity degrees are analyzed, which can help identify the optimized energy-supply patterns that could plunk for improvement of air quality and hedge against violation of soft constraints. Results disclose that largely developing EVs can help facilitate the city's energy system with an environment-effective way. However, compared to the rapid growth of transportation, the EVs' contribution of improving the city's air quality is limited. It is desired that, to achieve an environmentally sustainable MES, more concerns should be focused on the integration of increasing renewable energy resources, stimulating EVs as well as improving energy transmission, transport and storage. Copyright © 2017 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2015-04-01

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

Multi-objective optimization of combustion, performance and emission parameters in a jatropha biodiesel engine using Non-dominated sorting genetic algorithm-II

NASA Astrophysics Data System (ADS)

Dhingra, Sunil; Bhushan, Gian; Dubey, Kashyap Kumar

2014-03-01

The present work studies and identifies the different variables that affect the output parameters involved in a single cylinder direct injection compression ignition (CI) engine using jatropha biodiesel. Response surface methodology based on Central composite design (CCD) is used to design the experiments. Mathematical models are developed for combustion parameters (Brake specific fuel consumption (BSFC) and peak cylinder pressure (Pmax)), performance parameter brake thermal efficiency (BTE) and emission parameters (CO, NO x , unburnt HC and smoke) using regression techniques. These regression equations are further utilized for simultaneous optimization of combustion (BSFC, Pmax), performance (BTE) and emission (CO, NO x , HC, smoke) parameters. As the objective is to maximize BTE and minimize BSFC, Pmax, CO, NO x , HC, smoke, a multiobjective optimization problem is formulated. Nondominated sorting genetic algorithm-II is used in predicting the Pareto optimal sets of solution. Experiments are performed at suitable optimal solutions for predicting the combustion, performance and emission parameters to check the adequacy of the proposed model. The Pareto optimal sets of solution can be used as guidelines for the end users to select optimal combination of engine output and emission parameters depending upon their own requirements.

Efficient and reliable characterization of the corticospinal system using transcranial magnetic stimulation.

PubMed

Kukke, Sahana N; Paine, Rainer W; Chao, Chi-Chao; de Campos, Ana C; Hallett, Mark

2014-06-01

The purpose of this study is to develop a method to reliably characterize multiple features of the corticospinal system in a more efficient manner than typically done in transcranial magnetic stimulation studies. Forty transcranial magnetic stimulation pulses of varying intensity were given over the first dorsal interosseous motor hot spot in 10 healthy adults. The first dorsal interosseous motor-evoked potential size was recorded during rest and activation to create recruitment curves. The Boltzmann sigmoidal function was fit to the data, and parameters relating to maximal motor-evoked potential size, curve slope, and stimulus intensity leading to half-maximal motor-evoked potential size were computed from the curve fit. Good to excellent test-retest reliability was found for all corticospinal parameters at rest and during activation with 40 transcranial magnetic stimulation pulses. Through the use of curve fitting, important features of the corticospinal system can be determined with fewer stimuli than typically used for the same information. Determining the recruitment curve provides a basis to understand the state of the corticospinal system and select subject-specific parameters for transcranial magnetic stimulation testing quickly and without unnecessary exposure to magnetic stimulation. This method can be useful in individuals who have difficulty in maintaining stillness, including children and patients with motor disorders.

Optimal Designs for the Rasch Model

ERIC Educational Resources Information Center

Grasshoff, Ulrike; Holling, Heinz; Schwabe, Rainer

2012-01-01

In this paper, optimal designs will be derived for estimating the ability parameters of the Rasch model when difficulty parameters are known. It is well established that a design is locally D-optimal if the ability and difficulty coincide. But locally optimal designs require that the ability parameters to be estimated are known. To attenuate this…

Optimization Under Uncertainty for Electronics Cooling Design

NASA Astrophysics Data System (ADS)

Bodla, Karthik K.; Murthy, Jayathi Y.; Garimella, Suresh V.

Optimization under uncertainty is a powerful methodology used in design and optimization to produce robust, reliable designs. Such an optimization methodology, employed when the input quantities of interest are uncertain, produces output uncertainties, helping the designer choose input parameters that would result in satisfactory thermal solutions. Apart from providing basic statistical information such as mean and standard deviation in the output quantities, auxiliary data from an uncertainty based optimization, such as local and global sensitivities, help the designer decide the input parameter(s) to which the output quantity of interest is most sensitive. This helps the design of experiments based on the most sensitive input parameter(s). A further crucial output of such a methodology is the solution to the inverse problem - finding the allowable uncertainty range in the input parameter(s), given an acceptable uncertainty range in the output quantity of interest...

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.

Study on loading path optimization of internal high pressure forming process

NASA Astrophysics Data System (ADS)

Jiang, Shufeng; Zhu, Hengda; Gao, Fusheng

2017-09-01

In the process of internal high pressure forming, there is no formula to describe the process parameters and forming results. The article use numerical simulation to obtain several input parameters and corresponding output result, use the BP neural network to found their mapping relationship, and with weighted summing method make each evaluating parameters to set up a formula which can evaluate quality. Then put the training BP neural network into the particle swarm optimization, and take the evaluating formula of the quality as adapting formula of particle swarm optimization, finally do the optimization and research at the range of each parameters. The results show that the parameters obtained by the BP neural network algorithm and the particle swarm optimization algorithm can meet the practical requirements. The method can solve the optimization of the process parameters in the internal high pressure forming process.

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

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.

DNA methyltransferase mediates dose-dependent stimulation of neural stem cell proliferation by folate.

PubMed

Li, Wen; Yu, Min; Luo, Suhui; Liu, Huan; Gao, Yuxia; Wilson, John X; Huang, Guowei

2013-07-01

The proliferative response of neural stem cells (NSCs) to folate may play a critical role in the development, function and repair of the central nervous system. It is important to determine the dose-dependent effects of folate in NSC cultures that are potential sources of transplantable cells for therapies for neurodegenerative diseases. To determine the optimal concentration and mechanism of action of folate for stimulation of NSC proliferation in vitro, NSCs were exposed to folic acid or 5-methyltetrahydrofolate (5-MTHF) (0-200 μmol/L) for 24, 48 or 72 h. Immunocytochemistry and methyl thiazolyl tetrazolium assay showed that the optimal concentration of folic acid for NSC proliferation was 20-40 μmol/L. Stimulation of NSC proliferation by folic acid was associated with DNA methyltransferase (DNMT) activation and was attenuated by the DNMT inhibitor zebularine, which implies that folate dose-dependently stimulates NSC proliferation through a DNMT-dependent mechanism. Based on these new findings and previously published evidence, we have identified a mechanism by which folate stimulates NSC growth. Copyright © 2013 Elsevier Inc. All rights reserved.

Chaos minimization in DC-DC boost converter using circuit parameter optimization

NASA Astrophysics Data System (ADS)

Sudhakar, N.; Natarajan, Rajasekar; Gourav, Kumar; Padmavathi, P.

2017-11-01

DC-DC converters are prone to several types of nonlinear phenomena including bifurcation, quasi periodicity, intermittency and chaos. These undesirable effects must be controlled for periodic operation of the converter to ensure the stability. In this paper an effective solution to control of chaos in solar fed DC-DC boost converter is proposed. Controlling of chaos is significantly achieved using optimal circuit parameters obtained through Bacterial Foraging Optimization Algorithm. The optimization renders the suitable parameters in minimum computational time. The obtained results are compared with the operation of traditional boost converter. Further the obtained results with BFA optimized parameter ensures the operations of the converter are within the controllable region. To elaborate the study of bifurcation analysis with optimized and unoptimized parameters are also presented.

Optimal Bayesian Adaptive Design for Test-Item Calibration.

PubMed

van der Linden, Wim J; Ren, Hao

2015-06-01

An optimal adaptive design for test-item calibration based on Bayesian optimality criteria is presented. The design adapts the choice of field-test items to the examinees taking an operational adaptive test using both the information in the posterior distributions of their ability parameters and the current posterior distributions of the field-test parameters. Different criteria of optimality based on the two types of posterior distributions are possible. The design can be implemented using an MCMC scheme with alternating stages of sampling from the posterior distributions of the test takers' ability parameters and the parameters of the field-test items while reusing samples from earlier posterior distributions of the other parameters. Results from a simulation study demonstrated the feasibility of the proposed MCMC implementation for operational item calibration. A comparison of performances for different optimality criteria showed faster calibration of substantial numbers of items for the criterion of D-optimality relative to A-optimality, a special case of c-optimality, and random assignment of items to the test takers.

Application of dragonfly algorithm for optimal performance analysis of process parameters in turn-mill operations- A case study

NASA Astrophysics Data System (ADS)

Vikram, K. Arun; Ratnam, Ch; Lakshmi, VVK; Kumar, A. Sunny; Ramakanth, RT

2018-02-01

Meta-heuristic multi-response optimization methods are widely in use to solve multi-objective problems to obtain Pareto optimal solutions during optimization. This work focuses on optimal multi-response evaluation of process parameters in generating responses like surface roughness (Ra), surface hardness (H) and tool vibration displacement amplitude (Vib) while performing operations like tangential and orthogonal turn-mill processes on A-axis Computer Numerical Control vertical milling center. Process parameters like tool speed, feed rate and depth of cut are considered as process parameters machined over brass material under dry condition with high speed steel end milling cutters using Taguchi design of experiments (DOE). Meta-heuristic like Dragonfly algorithm is used to optimize the multi-objectives like ‘Ra’, ‘H’ and ‘Vib’ to identify the optimal multi-response process parameters combination. Later, the results thus obtained from multi-objective dragonfly algorithm (MODA) are compared with another multi-response optimization technique Viz. Grey relational analysis (GRA).

Application of genetic algorithm in modeling on-wafer inductors for up to 110 Ghz

NASA Astrophysics Data System (ADS)

Liu, Nianhong; Fu, Jun; Liu, Hui; Cui, Wenpu; Liu, Zhihong; Liu, Linlin; Zhou, Wei; Wang, Quan; Guo, Ao

2018-05-01

In this work, the genetic algorithm has been introducted into parameter extraction for on-wafer inductors for up to 110 GHz millimeter-wave operations, and nine independent parameters of the equivalent circuit model are optimized together. With the genetic algorithm, the model with the optimized parameters gives a better fitting accuracy than the preliminary parameters without optimization. Especially, the fitting accuracy of the Q value achieves a significant improvement after the optimization.

ConvAn: a convergence analyzing tool for optimization of biochemical networks.

PubMed

Kostromins, Andrejs; Mozga, Ivars; Stalidzans, Egils

2012-01-01

Dynamic models of biochemical networks usually are described as a system of nonlinear differential equations. In case of optimization of models for purpose of parameter estimation or design of new properties mainly numerical methods are used. That causes problems of optimization predictability as most of numerical optimization methods have stochastic properties and the convergence of the objective function to the global optimum is hardly predictable. Determination of suitable optimization method and necessary duration of optimization becomes critical in case of evaluation of high number of combinations of adjustable parameters or in case of large dynamic models. This task is complex due to variety of optimization methods, software tools and nonlinearity features of models in different parameter spaces. A software tool ConvAn is developed to analyze statistical properties of convergence dynamics for optimization runs with particular optimization method, model, software tool, set of optimization method parameters and number of adjustable parameters of the model. The convergence curves can be normalized automatically to enable comparison of different methods and models in the same scale. By the help of the biochemistry adapted graphical user interface of ConvAn it is possible to compare different optimization methods in terms of ability to find the global optima or values close to that as well as the necessary computational time to reach them. It is possible to estimate the optimization performance for different number of adjustable parameters. The functionality of ConvAn enables statistical assessment of necessary optimization time depending on the necessary optimization accuracy. Optimization methods, which are not suitable for a particular optimization task, can be rejected if they have poor repeatability or convergence properties. The software ConvAn is freely available on www.biosystems.lv/convan. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Multi-Response Parameter Interval Sensitivity and Optimization for the Composite Tape Winding Process.

PubMed

Deng, Bo; Shi, Yaoyao; Yu, Tao; Kang, Chao; Zhao, Pan

2018-01-31

The composite tape winding process, which utilizes a tape winding machine and prepreg tapes, provides a promising way to improve the quality of composite products. Nevertheless, the process parameters of composite tape winding have crucial effects on the tensile strength and void content, which are closely related to the performances of the winding products. In this article, two different object values of winding products, including mechanical performance (tensile strength) and a physical property (void content), were respectively calculated. Thereafter, the paper presents an integrated methodology by combining multi-parameter relative sensitivity analysis and single-parameter sensitivity analysis to obtain the optimal intervals of the composite tape winding process. First, the global multi-parameter sensitivity analysis method was applied to investigate the sensitivity of each parameter in the tape winding processing. Then, the local single-parameter sensitivity analysis method was employed to calculate the sensitivity of a single parameter within the corresponding range. Finally, the stability and instability ranges of each parameter were distinguished. Meanwhile, the authors optimized the process parameter ranges and provided comprehensive optimized intervals of the winding parameters. The verification test validated that the optimized intervals of the process parameters were reliable and stable for winding products manufacturing.

Multi-Response Parameter Interval Sensitivity and Optimization for the Composite Tape Winding Process

PubMed Central

Yu, Tao; Kang, Chao; Zhao, Pan

2018-01-01

The composite tape winding process, which utilizes a tape winding machine and prepreg tapes, provides a promising way to improve the quality of composite products. Nevertheless, the process parameters of composite tape winding have crucial effects on the tensile strength and void content, which are closely related to the performances of the winding products. In this article, two different object values of winding products, including mechanical performance (tensile strength) and a physical property (void content), were respectively calculated. Thereafter, the paper presents an integrated methodology by combining multi-parameter relative sensitivity analysis and single-parameter sensitivity analysis to obtain the optimal intervals of the composite tape winding process. First, the global multi-parameter sensitivity analysis method was applied to investigate the sensitivity of each parameter in the tape winding processing. Then, the local single-parameter sensitivity analysis method was employed to calculate the sensitivity of a single parameter within the corresponding range. Finally, the stability and instability ranges of each parameter were distinguished. Meanwhile, the authors optimized the process parameter ranges and provided comprehensive optimized intervals of the winding parameters. The verification test validated that the optimized intervals of the process parameters were reliable and stable for winding products manufacturing. PMID:29385048

Optimization of microphysics in the Unified Model, using the Micro-genetic algorithm.

NASA Astrophysics Data System (ADS)

Jang, J.; Lee, Y.; Lee, H.; Lee, J.; Joo, S.

2016-12-01

This study focuses on parameter optimization of microphysics in the Unified Model (UM) using the Micro-genetic algorithm (Micro-GA). We need the optimization of microphysics in UM. Because, Microphysics in the Numerical Weather Prediction (NWP) model is important to Quantitative Precipitation Forecasting (QPF). The Micro-GA searches for optimal parameters on the basis of fitness function. The five parameters are chosen. The target parameters include x1, x2 related to raindrop size distribution, Cloud-rain correlation coefficient, Surface droplet number and Droplet taper height. The fitness function is based on the skill score that is BIAS and Critical Successive Index (CSI). An interface between UM and Micro-GA is developed and applied to three precipitation cases in Korea. The cases are (ⅰ) heavy rainfall in the Southern area because of typhoon NAKRI, (ⅱ) heavy rainfall in the Youngdong area, and (ⅲ) heavy rainfall in the Seoul metropolitan area. When the optimized result is compared to the control result (using the UM default value, CNTL), the optimized result leads to improvements in precipitation forecast, especially for heavy rainfall of the late forecast time. Also, we analyze the skill score of precipitation forecasts in terms of various thresholds of CNTL, Optimized result, and experiments on each optimized parameter for five parameters. Generally, the improvement is maximized when the five optimized parameters are used simultaneously. Therefore, this study demonstrates the ability to improve Korean precipitation forecasts by optimizing microphysics in UM.

Differential Modulation of Excitatory and Inhibitory Neurons during Periodic Stimulation

PubMed Central

Mahmud, Mufti; Vassanelli, Stefano

2016-01-01

Non-invasive transcranial neuronal stimulation, in addition to deep brain stimulation, is seen as a promising therapeutic and diagnostic approach for an increasing number of neurological diseases such as epilepsy, cluster headaches, depression, specific type of blindness, and other central nervous system disfunctions. Improving its effectiveness and widening its range of use may strongly rely on development of proper stimulation protocols that are tailored to specific brain circuits and that are based on a deep knowledge of different neuron types response to stimulation. To this aim, we have performed a simulation study on the behavior of excitatory and inhibitory neurons subject to sinusoidal stimulation. Due to the intrinsic difference in membrane conductance properties of excitatory and inhibitory neurons, we show that their firing is differentially modulated by the wave parameters. We analyzed the behavior of the two neuronal types for a broad range of stimulus frequency and amplitude and demonstrated that, within a small-world network prototype, parameters tuning allow for a selective enhancement or suppression of the excitation/inhibition ratio. PMID:26941602

[Temporal and spatial heterogeneity analysis of optimal value of sensitive parameters in ecological process model: The BIOME-BGC model as an example.

PubMed

Li, Yi Zhe; Zhang, Ting Long; Liu, Qiu Yu; Li, Ying

2018-01-01

The ecological process models are powerful tools for studying terrestrial ecosystem water and carbon cycle at present. However, there are many parameters for these models, and weather the reasonable values of these parameters were taken, have important impact on the models simulation results. In the past, the sensitivity and the optimization of model parameters were analyzed and discussed in many researches. But the temporal and spatial heterogeneity of the optimal parameters is less concerned. In this paper, the BIOME-BGC model was used as an example. In the evergreen broad-leaved forest, deciduous broad-leaved forest and C3 grassland, the sensitive parameters of the model were selected by constructing the sensitivity judgment index with two experimental sites selected under each vegetation type. The objective function was constructed by using the simulated annealing algorithm combined with the flux data to obtain the monthly optimal values of the sensitive parameters at each site. Then we constructed the temporal heterogeneity judgment index, the spatial heterogeneity judgment index and the temporal and spatial heterogeneity judgment index to quantitatively analyze the temporal and spatial heterogeneity of the optimal values of the model sensitive parameters. The results showed that the sensitivity of BIOME-BGC model parameters was different under different vegetation types, but the selected sensitive parameters were mostly consistent. The optimal values of the sensitive parameters of BIOME-BGC model mostly presented time-space heterogeneity to different degrees which varied with vegetation types. The sensitive parameters related to vegetation physiology and ecology had relatively little temporal and spatial heterogeneity while those related to environment and phenology had generally larger temporal and spatial heterogeneity. In addition, the temporal heterogeneity of the optimal values of the model sensitive parameters showed a significant linear correlation with the spatial heterogeneity under the three vegetation types. According to the temporal and spatial heterogeneity of the optimal values, the parameters of the BIOME-BGC model could be classified in order to adopt different parameter strategies in practical application. The conclusion could help to deeply understand the parameters and the optimal values of the ecological process models, and provide a way or reference for obtaining the reasonable values of parameters in models application.

Hippocampal Closed-Loop Modeling and Implications for Seizure Stimulation Design

PubMed Central

Sandler, Roman A.; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.; Marmarelis, Vasilis Z.

2016-01-01

Objective Traditional hippocampal modeling has focused on the series of feedforward synapses known as the trisynaptic pathway. However, feedback connections from CA1 back to the hippocampus through the Entorhinal Cortex (EC) actually make the hippocampus a closed-loop system. By constructing a functional closed-loop model of the hippocampus, one may learn how both physiological and epileptic oscillations emerge and design efficient neurostimulation patterns to abate such oscillations. Approach Point process input-output models where estimated from recorded rodent hippocampal data to describe the nonlinear dynamical transformation from CA3→CA1, via the Schaffer-Collateral synapse, and CA1→CA3 via the EC. Each Volterra-like subsystem was composed of linear dynamics (Principal Dynamic Modes) followed by static nonlinearities. The two subsystems were then wired together to produce the full closed-loop model of the hippocampus. Main Results Closed-loop connectivity was found to be necessary for the emergence of theta resonances as seen in recorded data, thus validating the model. The model was then used to identify frequency parameters for the design of neurostimulation patterns to abate seizures. Significance DBS is a new and promising therapy for intractable seizures. Currently, there is no efficient way to determine optimal frequency parameters for DBS, or even whether periodic or broadband stimuli are optimal. Data-based computational models have the potential to be used as a testbed for designing optimal DBS patterns for individual patients. However, in order for these models to be successful they must incorporate the complex closed-loop structure of the seizure focus. This study serves as a proof-of-concept of using such models to design efficient personalized DBS patterns for epilepsy. PMID:26355815

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.

Constraining neutron guide optimizations with phase-space considerations

NASA Astrophysics Data System (ADS)

Bertelsen, Mads; Lefmann, Kim

2016-09-01

We introduce a method named the Minimalist Principle that serves to reduce the parameter space for neutron guide optimization when the required beam divergence is limited. The reduced parameter space will restrict the optimization to guides with a minimal neutron intake that are still theoretically able to deliver the maximal possible performance. The geometrical constraints are derived using phase-space propagation from moderator to guide and from guide to sample, while assuming that the optimized guides will achieve perfect transport of the limited neutron intake. Guide systems optimized using these constraints are shown to provide performance close to guides optimized without any constraints, however the divergence received at the sample is limited to the desired interval, even when the neutron transport is not limited by the supermirrors used in the guide. As the constraints strongly limit the parameter space for the optimizer, two control parameters are introduced that can be used to adjust the selected subspace, effectively balancing between maximizing neutron transport and avoiding background from unnecessary neutrons. One parameter is needed to describe the expected focusing abilities of the guide to be optimized, going from perfectly focusing to no correlation between position and velocity. The second parameter controls neutron intake into the guide, so that one can select exactly how aggressively the background should be limited. We show examples of guides optimized using these constraints which demonstrates the higher signal to noise than conventional optimizations. Furthermore the parameter controlling neutron intake is explored which shows that the simulated optimal neutron intake is close to the analytically predicted, when assuming that the guide is dominated by multiple scattering events.

Real-time parameter optimization based on neural network for smart injection molding

NASA Astrophysics Data System (ADS)

Lee, H.; Liau, Y.; Ryu, K.

2018-03-01

The manufacturing industry has been facing several challenges, including sustainability, performance and quality of production. Manufacturers attempt to enhance the competitiveness of companies by implementing CPS (Cyber-Physical Systems) through the convergence of IoT(Internet of Things) and ICT(Information & Communication Technology) in the manufacturing process level. Injection molding process has a short cycle time and high productivity. This features have been making it suitable for mass production. In addition, this process is used to produce precise parts in various industry fields such as automobiles, optics and medical devices. Injection molding process has a mixture of discrete and continuous variables. In order to optimized the quality, variables that is generated in the injection molding process must be considered. Furthermore, Optimal parameter setting is time-consuming work to predict the optimum quality of the product. Since the process parameter cannot be easily corrected during the process execution. In this research, we propose a neural network based real-time process parameter optimization methodology that sets optimal process parameters by using mold data, molding machine data, and response data. This paper is expected to have academic contribution as a novel study of parameter optimization during production compare with pre - production parameter optimization in typical studies.

Optimization of wavelengths sets for multispectral reflectance imaging of rat olfactory bulb activation in vivo

NASA Astrophysics Data System (ADS)

Renaud, Rémi; Bendahmane, Mounir; Chery, Romain; Martin, Claire; Gurden, Hirac; Pain, Frederic

2012-06-01

Wide field multispectral imaging of light backscattered by brain tissues provides maps of hemodynamics changes (total blood volume and oxygenation) following activation. This technique relies on the fit of the reflectance images obtain at two or more wavelengths using a modified Beer-Lambert law1,2. It has been successfully applied to study the activation of several sensory cortices in the anesthetized rodent using visible light1-5. We have carried out recently the first multispectral imaging in the olfactory bulb6 (OB) of anesthetized rats. However, the optimization of wavelengths choice has not been discussed in terms of cross talk and uniqueness of the estimated parameters (blood volume and saturation maps) although this point was shown to be crucial for similar studies in Diffuse Optical Imaging in humans7-10. We have studied theoretically and experimentally the optimal sets of wavelength for multispectral imaging of rodent brain activation in the visible. Sets of optimal wavelengths have been identified and validated in vivo for multispectral imaging of the OB of rats following odor stimulus. We studied the influence of the wavelengths sets on the magnitude and time courses of the oxy- and deoxyhemoglobin concentration variations as well as on the spatial extent of activated brain areas following stimulation. Beyond the estimation of hemodynamic parameters from multispectral reflectance data, we observed repeatedly and for all wavelengths a decrease of light reflectance. For wavelengths longer than 590 nm, these observations differ from those observed in the somatosensory and barrel cortex and question the basis of the reflectance changes during activation in the OB. To solve this issue, Monte Carlo simulations (MCS) have been carried out to assess the relative contribution of absorption, scattering and anisotropy changes to the intrinsic optical imaging signals in somatosensory cortex (SsC) and OB model.

Coherent control of alkali cluster fragmentation dynamics

NASA Astrophysics Data System (ADS)

Lindinger, Albrecht; Lupulescu, Cosmin; Bartelt, Andreas; Vajda, Štefan; Wöste, Ludger

2003-06-01

Metal clusters exhibit extraordinary chemical and catalytic properties, which sensitively depend upon their size. This behavior makes them interesting candidates for the real-time analysis of ultrafast photo-induced processes—ultimately leading to coherent control scenarii. We have performed transient multi-photon ionization experiments on small alkali clusters of different size in order to probe their wave packet dynamics, structural reorientations, charge transfers and dissociative events in different vibrationally excited electronic states including their ground state. The observed processes were highly dependent on the irradiated pulse parameters, like its phase, amplitude and duration; an emphasis to employ a feedback control system for generating the optimum pulse shapes. Their spectral and temporal behavior reflects interesting properties about the investigated system and the irradiated photochemical process. We present first the vibrational dynamics of bound, dissociated, and pre-dissociated electronically excited states of alkali dimers and trimers. The scheme for observing the wave packet dynamics in the electronic ground state using stimulated Raman-pumping is shown. Since the employed pulse parameters significantly influence the efficiency of the irradiated dynamic pathways photo-induced fragmentation experiments on bifurcating reaction channels were carried out. In these experiments different branching ionization and fragmentation pathways of electronically excited Na 2K were investigated. By employing an evolutionary algorithm for optimizing the phase and amplitude of the applied laser field, the yield of the resulting parent or fragment ions could significantly be influenced and interesting features could be concluded from the obtained optimum pulse shapes revealing the characteristic molecular oscillation period. Moreover, the influence on the optimal pulse shape due to fragmentation from larger clusters into NaK is obtained. The substructure of the optimal pulse shape thereby offers new insight into the fragmentation channel during the control process. Characteristic motions of the involved wave packets are proposed, in order to explain the optimized dynamic dissociation pathways.

Effects of Bilateral Repetitive Transcranial Magnetic Stimulation on Post-Stroke Dysphagia.

PubMed

Park, Eunhee; Kim, Min Su; Chang, Won Hyuk; Oh, Su Mi; Kim, Yun Kwan; Lee, Ahee; Kim, Yun-Hee

Optimal protocol of repetitive transcranial magnetic stimulation (rTMS) on post-stroke dysphagia remains uncertain with regard to its clinical efficacy. The aim of the present study is to investigate the effects of high-frequency rTMS at the bilateral motor cortices over the cortical representation of the mylohyoid muscles in the patients with post-stroke dysphagia. This study was a single-blind, randomized controlled study with a blinded observer. Thirty-five stroke patients were randomly divided into three intervention groups: the bilateral stimulation group, the unilateral stimulation group, and the sham stimulation group. For the bilateral stimulation group, 500 pulses of 10 Hz rTMS over the ipsilesional and 500 pulses of 10 Hz rTMS over the contralesional motor cortices over the cortical areas that project to the mylohyoid muscles were administered daily for 2 consecutive weeks. For the unilateral stimulation group, 500 pulses of 10 Hz rTMS over the ipsilesional motor cortex over the cortical representation of the mylohyoid muscle and the same amount of sham rTMS over the contralesional hemisphere were applied. For the sham stimulation group, sham rTMS was applied at the bilateral motor cortices. Clinical swallowing function and videofluoroscopic swallowing studies were assessed before the intervention (T0), immediately after the intervention (T1) and 3 weeks after the intervention (T2) using Clinical Dysphagia Scale (CDS), Dysphagia Outcome and Severity Scale (DOSS), Penetration Aspiration Scale (PAS), and Videofluoroscopic Dysphagia Scale (VDS). There were significant time and intervention interaction effects in the CDS, DOSS, PAS, and VDS scores (p < 0.05). In the direct comparison of the changes in the swallowing parameters among the three groups, the change in CDS scores at T1 and T2 showed a significantly higher improvement in the bilateral simulation group than in two other groups (p < 0.05). There was a significantly larger change in the DOSS, PAS, and VDS scores at T1 in the bilateral stimulation group than in two other groups (p < 0.05). The results of the present study provide substantial evidence that 10 Hz rTMS at the bilateral motor cortices over the cortical areas projecting to the mylohyoid muscles is effective as an additional treatment strategy to traditional dysphagia therapies. Copyright © 2016. Published by Elsevier Inc.

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.

An intracellular analysis of the visual responses of neurones in cat visual cortex.

PubMed Central

Douglas, R J; Martin, K A; Whitteridge, D

1991-01-01

1. Extracellular and intracellular recordings were made from neurones in the visual cortex of the cat in order to compare the subthreshold membrane potentials, reflecting the input to the neurone, with the output from the neurone seen as action potentials. 2. Moving bars and edges, generated under computer control, were used to stimulate the neurones. The membrane potential was digitized and averaged for a number of trials after stripping the action potentials. Comparison of extracellular and intracellular discharge patterns indicated that the intracellular impalement did not alter the neurones' properties. Input resistance of the neurone altered little during stable intracellular recordings (30 min-2 h 50 min). 3. Intracellular recordings showed two distinct patterns of membrane potential changes during optimal visual stimulation. The patterns corresponded closely to the division of S-type (simple) and C-type (complex) receptive fields. Simple cells had a complex pattern of membrane potential fluctuations, involving depolarizations alternating with hyperpolarizations. Complex cells had a simple single sustained plateau of depolarization that was often followed but not preceded by a hyperpolarization. In both simple and complex cells the depolarizations led to action potential discharges. The hyperpolarizations were associated with inhibition of action potential discharge. 4. Stimulating simple cells with non-optimal directions of motion produced little or no hyperpolarization of the membrane in most cases, despite a lack of action potential output. Directional complex cells always produced a single plateau of depolarization leading to action potential discharge in both the optimal and non-optimal directions of motion. The directionality could not be predicted on the basis of the position of the hyperpolarizing inhibitory potentials found in the optimal direction. 5. Stimulation of simple cells with non-optimal orientations occasionally produced slight hyperpolarizations and inhibition of action potential discharge. Complex cells, which had broader orientation tuning than simple cells, could show marked hyperpolarization for non-optimal orientations, but this was not generally the case. 6. The data do not support models of directionality and orientation that rely solely on strong inhibitory mechanisms to produce stimulus selectivity. PMID:1804981

Measurement of Young's modulus in the in vivo human vocal folds.

PubMed

Tran, Q T; Berke, G S; Gerratt, B R; Kreiman, J

1993-08-01

Currently, surgeons have no objective means to evaluate and optimize results of phonosurgery intraoperatively. Instead, they usually judge the vocal folds subjectively by visual inspection or by listening to the voice. This paper describes a new device that measures Young's (elastic) modulus values for the human vocal fold intraoperatively. Physiologically, the modulus of the vocal fold may be important in determining the nature of vocal fold vibration in normal and pathologic states. This study also reports the effect of recurrent laryngeal nerve stimulation on Young's modulus of the human vocal folds, measured by means of transcutaneous nerve stimulation techniques. Young's modulus increased with increases in current stimulation to the recurrent laryngeal nerve. Ultimately, Young's modulus values may assist surgeons in optimizing the results of various phonosurgeries.

Static Magnetic Field Therapy: A Critical Review of Treatment Parameters

PubMed Central

Wahbeh, Helané; Harling, Noelle; Connelly, Erin; Schiffke, Heather C.; Forsten, Cora; Gregory, William L.; Markov, Marko S.; Souder, James J.; Elmer, Patricia; King, Valerie

2009-01-01

Static magnetic field (SMF) therapy, applied via a permanent magnet attached to the skin, is used by people worldwide for self-care. Despite a lack of established SMF dosage and treatment regimens, multiple studies are conducted to evaluate SMF therapy effectiveness. Our objectives in conducting this review are to:(i) summarize SMF research conducted in humans; (ii) critically evaluate reporting quality of SMF dosages and treatment parameters and (iii) propose a set of criteria for reporting SMF treatment parameters in future clinical trials. We searched 27 electronic databases and reference lists. Only English language human studies were included. Excluded were studies of electromagnetic fields, transcranial magnetic stimulation, magnets placed on acupuncture points, animal studies, abstracts, posters and editorials. Data were extracted on clinical indication, study design and 10 essential SMF parameters. Three reviewers assessed quality of reporting and calculated a quality assessment score for each of the 10 treatment parameters. Fifty-six studies were reviewed, 42 conducted in patient populations and 14 in healthy volunteers. The SMF treatment parameters most often and most completely described were site of application, magnet support device and frequency and duration of application. Least often and least completely described were characteristics of the SMF: magnet dimensions, measured field strength and estimated distance of the magnet from the target tissue. Thirty-four (61%) of studies failed to provide enough detail about SMF dosage to permit protocol replication by other investigators. Our findings highlight the need to optimize SMF dosing parameters for individual clinical conditions before proceeding to a full-scale clinical trial. PMID:18955243

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

PubMed

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

2017-07-17

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

Stimulation seeking and hyperactivity in children with ADHD. Attention Deficit Hyperactivity Disorder.

PubMed

Antrop, I; Roeyers, H; Van Oost, P; Buysse, A

2000-02-01

Thirty hyperactive and 30 non-hyperactive children were confronted with a delay, consisting of a waiting situation of 15 minutes, either with or without extra stimulation provided by the presentation of a videotape. The behaviour of the child during the waiting period was videotaped and later coded by two naive observers. In line with theories that emphasise the stimulation-seeking function of hyperactive behaviours, such as the optimal stimulation account and the delay aversion theory, a group by stimulation effect was hypothesised. For two categories of activity this was found, with ADHD children displaying more activity than non-ADHD children in the no-stimulation but not in the stimulation condition. These data provide support for the stimulation-seeking function of certain features of ADHD hyperactivity.

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.

Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms.

PubMed

Sdrulla, Andrei D; Guan, Yun; Raja, Srinivasa N

2018-03-11

Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple randomized controlled studies have demonstrated efficacy for difficult-to-treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non-standard, stimulation waveforms such as high-frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy. © 2018 World Institute of Pain.

Optimization of Gas Metal Arc Welding Process Parameters

NASA Astrophysics Data System (ADS)

Kumar, Amit; Khurana, M. K.; Yadav, Pradeep K.

2016-09-01

This study presents the application of Taguchi method combined with grey relational analysis to optimize the process parameters of gas metal arc welding (GMAW) of AISI 1020 carbon steels for multiple quality characteristics (bead width, bead height, weld penetration and heat affected zone). An orthogonal array of L9 has been implemented to fabrication of joints. The experiments have been conducted according to the combination of voltage (V), current (A) and welding speed (Ws). The results revealed that the welding speed is most significant process parameter. By analyzing the grey relational grades, optimal parameters are obtained and significant factors are known using ANOVA analysis. The welding parameters such as speed, welding current and voltage have been optimized for material AISI 1020 using GMAW process. To fortify the robustness of experimental design, a confirmation test was performed at selected optimal process parameter setting. Observations from this method may be useful for automotive sub-assemblies, shipbuilding and vessel fabricators and operators to obtain optimal welding conditions.

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

PubMed Central

Canbeyli, Resit

2013-01-01

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

Optimizing a Rodent Model of Parkinson's Disease for Exploring the Effects and Mechanisms of Deep Brain Stimulation

PubMed Central

Nowak, Karl; Mix, Eilhard; Gimsa, Jan; Strauss, Ulf; Sriperumbudur, Kiran Kumar; Benecke, Reiner; Gimsa, Ulrike

2011-01-01

Deep brain stimulation (DBS) has become a treatment for a growing number of neurological and psychiatric disorders, especially for therapy-refractory Parkinson's disease (PD). However, not all of the symptoms of PD are sufficiently improved in all patients, and side effects may occur. Further progress depends on a deeper insight into the mechanisms of action of DBS in the context of disturbed brain circuits. For this, optimized animal models have to be developed. We review not only charge transfer mechanisms at the electrode/tissue interface and strategies to increase the stimulation's energy-efficiency but also the electrochemical, electrophysiological, biochemical and functional effects of DBS. We introduce a hemi-Parkinsonian rat model for long-term experiments with chronically instrumented rats carrying a backpack stimulator and implanted platinum/iridium electrodes. This model is suitable for (1) elucidating the electrochemical processes at the electrode/tissue interface, (2) analyzing the molecular, cellular and behavioral stimulation effects, (3) testing new target regions for DBS, (4) screening for potential neuroprotective DBS effects, and (5) improving the efficacy and safety of the method. An outlook is given on further developments of experimental DBS, including the use of transgenic animals and the testing of closed-loop systems for the direct on-demand application of electric stimulation. PMID:21603182

Response characteristics of periodontal mechanoreceptors to mechanical stimulation of canine and incisor teeth in the cat.

PubMed

Tabata, T; Suzuki, T; Watanabe, M

1995-09-01

The alveolar bone that overlies the labial aspect of the root of the right lower canine tooth was pared down until paper thin. Thirty-five periodontal mechanosensitive (PM) units sensitive to stimulation of the canine and incisor and to punctate stimulation through the thinned bone of the periodontal ligament of the canine were recorded from the inferior alveolar nerve rostral to the masseter muscle. The units showed a sustained and directionally selective response to pressure applied to the teeth. The optimal directions of stimulation for each tooth in the receptive field were parallel and oriented linguolabially. When the canine was stimulated mechanically in the optimal stimulus direction, the interspike intervals of the responses were relatively regular in most PM units (91%). The conditioning and test stimuli were applied to the adjacent canine and third incisor. The conditioning stimulus (0.10 N) was given to one of these teeth in the optimal stimulus direction. The test stimulus (0.02 N or 0.05 N) was applied to the adjacent tooth in the opposite direction in order to examine the effect of mechanical spreading of the conditioning stimulus on the adjacent tooth. In most PM units, the spike discharges evoked by the conditioning stimulus given to the incisor were stopped by the test stimulus given to the canine. When the given stimuli were reversed, the firings evoked by the conditioning stimulus were slightly depressed by the test stimulus. After removing the spot-like PM receptor site(s) in the paper-thin area of bone, all units but one did not respond to stimulation. These results provide evidence that neurones with multiple-tooth receptive fields and regular spike-interval responses recorded from the inferior alveolar nerve come from the mechanical spreading effect of the stimulation of one tooth on an adjacent tooth through the trans-septal fibre system and that neurones with irregular-interval responses are due to the ramification of PM fibres peripherally.

Idealized Experiments for Optimizing Model Parameters Using a 4D-Variational Method in an Intermediate Coupled Model of ENSO

NASA Astrophysics Data System (ADS)

Gao, Chuan; Zhang, Rong-Hua; Wu, Xinrong; Sun, Jichang

2018-04-01

Large biases exist in real-time ENSO prediction, which can be attributed to uncertainties in initial conditions and model parameters. Previously, a 4D variational (4D-Var) data assimilation system was developed for an intermediate coupled model (ICM) and used to improve ENSO modeling through optimized initial conditions. In this paper, this system is further applied to optimize model parameters. In the ICM used, one important process for ENSO is related to the anomalous temperature of subsurface water entrained into the mixed layer ( T e), which is empirically and explicitly related to sea level (SL) variation. The strength of the thermocline effect on SST (referred to simply as "the thermocline effect") is represented by an introduced parameter, α Te. A numerical procedure is developed to optimize this model parameter through the 4D-Var assimilation of SST data in a twin experiment context with an idealized setting. Experiments having their initial condition optimized only, and having their initial condition plus this additional model parameter optimized, are compared. It is shown that ENSO evolution can be more effectively recovered by including the additional optimization of this parameter in ENSO modeling. The demonstrated feasibility of optimizing model parameters and initial conditions together through the 4D-Var method provides a modeling platform for ENSO studies. Further applications of the 4D-Var data assimilation system implemented in the ICM are also discussed.

Using a 4D-Variational Method to Optimize Model Parameters in an Intermediate Coupled Model of ENSO

NASA Astrophysics Data System (ADS)

Gao, C.; Zhang, R. H.

2017-12-01

Large biases exist in real-time ENSO prediction, which is attributed to uncertainties in initial conditions and model parameters. Previously, a four dimentional variational (4D-Var) data assimilation system was developed for an intermediate coupled model (ICM) and used to improve ENSO modeling through optimized initial conditions. In this paper, this system is further applied to optimize model parameters. In the ICM used, one important process for ENSO is related to the anomalous temperature of subsurface water entrained into the mixed layer (Te), which is empirically and explicitly related to sea level (SL) variation, written as Te=αTe×FTe (SL). The introduced parameter, αTe, represents the strength of the thermocline effect on sea surface temperature (SST; referred as the thermocline effect). A numerical procedure is developed to optimize this model parameter through the 4D-Var assimilation of SST data in a twin experiment context with an idealized setting. Experiments having initial condition optimized only and having initial condition plus this additional model parameter optimized both are compared. It is shown that ENSO evolution can be more effectively recovered by including the additional optimization of this parameter in ENSO modeling. The demonstrated feasibility of optimizing model parameter and initial condition together through the 4D-Var method provides a modeling platform for ENSO studies. Further applications of the 4D-Var data assimilation system implemented in the ICM are also discussed.

Flight Test Validation of Optimal Input Design and Comparison to Conventional Inputs

NASA Technical Reports Server (NTRS)

Morelli, Eugene A.

1997-01-01

A technique for designing optimal inputs for aerodynamic parameter estimation was flight tested on the F-18 High Angle of Attack Research Vehicle (HARV). Model parameter accuracies calculated from flight test data were compared on an equal basis for optimal input designs and conventional inputs at the same flight condition. In spite of errors in the a priori input design models and distortions of the input form by the feedback control system, the optimal inputs increased estimated parameter accuracies compared to conventional 3-2-1-1 and doublet inputs. In addition, the tests using optimal input designs demonstrated enhanced design flexibility, allowing the optimal input design technique to use a larger input amplitude to achieve further increases in estimated parameter accuracy without departing from the desired flight test condition. This work validated the analysis used to develop the optimal input designs, and demonstrated the feasibility and practical utility of the optimal input design technique.

Integrated controls design optimization

DOEpatents

Lou, Xinsheng; Neuschaefer, Carl H.

2015-09-01

A control system (207) for optimizing a chemical looping process of a power plant includes an optimizer (420), an income algorithm (230) and a cost algorithm (225) and a chemical looping process models. The process models are used to predict the process outputs from process input variables. Some of the process in puts and output variables are related to the income of the plant; and some others are related to the cost of the plant operations. The income algorithm (230) provides an income input to the optimizer (420) based on a plurality of input parameters (215) of the power plant. The cost algorithm (225) provides a cost input to the optimizer (420) based on a plurality of output parameters (220) of the power plant. The optimizer (420) determines an optimized operating parameter solution based on at least one of the income input and the cost input, and supplies the optimized operating parameter solution to the power plant.

Somatic Treatments for Mood Disorders

PubMed Central

Rosa, Moacyr A; Lisanby, Sarah H

2012-01-01

Somatic treatments for mood disorders represent a class of interventions available either as a stand-alone option, or in combination with psychopharmacology and/or psychotherapy. Here, we review the currently available techniques, including those already in clinical use and those still under research. Techniques are grouped into the following categories: (1) seizure therapies, including electroconvulsive therapy and magnetic seizure therapy, (2) noninvasive techniques, including repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and cranial electric stimulation, (3) surgical approaches, including vagus nerve stimulation, epidural electrical stimulation, and deep brain stimulation, and (4) technologies on the horizon. Additionally, we discuss novel approaches to the optimization of each treatment, and new techniques that are under active investigation. PMID:21976043

Pediatric stroke and transcranial direct current stimulation: methods for rational individualized dose optimization

PubMed Central

Gillick, Bernadette T.; Kirton, Adam; Carmel, Jason B.; Minhas, Preet; Bikson, Marom

2014-01-01

Background: Transcranial direct current stimulation (tDCS) has been investigated mainly in adults and doses may not be appropriate in pediatric applications. In perinatal stroke where potential applications are promising, rational adaptation of dosage for children remains under investigation. Objective: Construct child-specific tDCS dosing parameters through case study within a perinatal stroke tDCS safety and feasibility trial. Methods: 10-year-old subject with a diagnosis of presumed perinatal ischemic stroke and hemiparesis was identified. T1 magnetic resonance imaging (MRI) scans used to derive computerized model for current flow and electrode positions. Workflow using modeling results and consideration of dosage in previous clinical trials was incorporated. Prior ad hoc adult montages vs. de novo optimized montages provided distinct risk benefit analysis. Approximating adult dose required consideration of changes in both peak brain current flow and distribution which further tradeoff between maximizing efficacy and adding safety factors. Electrode size, position, current intensity, compliance voltage, and duration were controlled independently in this process. Results: Brain electric fields modeled and compared to values previously predicted models (Datta et al., 2011; Minhas et al., 2012). Approximating conservative brain current flow patterns and intensities used in previous adult trials for comparable indications, the optimal current intensity established was 0.7 mA for 10 min with a tDCS C3/C4 montage. Specifically 0.7 mA produced comparable peak brain current intensity of an average adult receiving 1.0 mA. Electrode size of 5 × 7 cm2 with 1.0 mA and low-voltage tDCS was employed to maximize tolerability. Safety and feasibility confirmed with subject tolerating the session well and no serious adverse events. Conclusion: Rational approaches to dose customization, with steps informed by computational modeling, may improve guidance for pediatric stroke tDCS trials. PMID:25285077

An RCT into the effects of neurofeedback on neurocognitive functioning compared to stimulant medication and physical activity in children with ADHD.

PubMed

Geladé, Katleen; Bink, Marleen; Janssen, Tieme W P; van Mourik, Rosa; Maras, Athanasios; Oosterlaan, Jaap

2017-04-01

Neurofeedback (NFB) is a potential alternative treatment for children with ADHD that aims to optimize brain activity. Whereas most studies into NFB have investigated behavioral effects, less attention has been paid to the effects on neurocognitive functioning. The present randomized controlled trial (RCT) compared neurocognitive effects of NFB to (1) optimally titrated methylphenidate (MPH) and (2) a semi-active control intervention, physical activity (PA), to control for non-specific effects. Using a multicentre three-way parallel group RCT design, children with ADHD, aged 7-13, were randomly allocated to NFB (n = 39), MPH (n = 36) or PA (n = 37) over a period of 10-12 weeks. NFB comprised theta/beta training at CZ. The PA intervention was matched in frequency and duration to NFB. MPH was titrated using a double-blind placebo controlled procedure to determine the optimal dose. Neurocognitive functioning was assessed using parameters derived from the auditory oddball-, stop-signal- and visual spatial working memory task. Data collection took place between September 2010 and March 2014. Intention-to-treat analyses showed improved attention for MPH compared to NFB and PA, as reflected by decreased response speed during the oddball task [η p 2  = 0.21, p < 0.001], as well as improved inhibition, impulsivity and attention, as reflected by faster stop signal reaction times, lower commission and omission error rates during the stop-signal task (range η p 2  = 0.09-0.18, p values <0.008). Working memory improved over time, irrespective of received treatment (η p 2  = 0.17, p < 0.001). Overall, stimulant medication showed superior effects over NFB to improve neurocognitive functioning. Hence, the findings do not support theta/beta training applied as a stand-alone treatment in children with ADHD.

Hybrid computer optimization of systems with random parameters

NASA Technical Reports Server (NTRS)

White, R. C., Jr.

1972-01-01

A hybrid computer Monte Carlo technique for the simulation and optimization of systems with random parameters is presented. The method is applied to the simultaneous optimization of the means and variances of two parameters in the radar-homing missile problem treated by McGhee and Levine.

Optimal configuration of microstructure in ferroelectric materials by stochastic optimization

NASA Astrophysics Data System (ADS)

Jayachandran, K. P.; Guedes, J. M.; Rodrigues, H. C.

2010-07-01

An optimization procedure determining the ideal configuration at the microstructural level of ferroelectric (FE) materials is applied to maximize piezoelectricity. Piezoelectricity in ceramic FEs differs significantly from that of single crystals because of the presence of crystallites (grains) possessing crystallographic axes aligned imperfectly. The piezoelectric properties of a polycrystalline (ceramic) FE is inextricably related to the grain orientation distribution (texture). The set of combination of variables, known as solution space, which dictates the texture of a ceramic is unlimited and hence the choice of the optimal solution which maximizes the piezoelectricity is complicated. Thus, a stochastic global optimization combined with homogenization is employed for the identification of the optimal granular configuration of the FE ceramic microstructure with optimum piezoelectric properties. The macroscopic equilibrium piezoelectric properties of polycrystalline FE is calculated using mathematical homogenization at each iteration step. The configuration of grains characterized by its orientations at each iteration is generated using a randomly selected set of orientation distribution parameters. The optimization procedure applied to the single crystalline phase compares well with the experimental data. Apparent enhancement of piezoelectric coefficient d33 is observed in an optimally oriented BaTiO3 single crystal. Based on the good agreement of results with the published data in single crystals, we proceed to apply the methodology in polycrystals. A configuration of crystallites, simultaneously constraining the orientation distribution of the c-axis (polar axis) while incorporating ab-plane randomness, which would multiply the overall piezoelectricity in ceramic BaTiO3 is also identified. The orientation distribution of the c-axes is found to be a narrow Gaussian distribution centered around 45°. The piezoelectric coefficient in such a ceramic is found to be nearly three times as that of the single crystal. Our optimization model provide designs for materials with enhanced piezoelectric performance, which would stimulate further studies involving materials possessing higher spontaneous polarization.

[Effects of TWP on capacity of muscle contraction].

PubMed

Zhang, Yun; Yu, Jingrui; Lü, Guangneng; Li, Keyong; Xu, Jianguo

2003-04-01

To investigate the direct effects of Tripterygium Wilfordii Polyglycosidium (TWP) on capability of muscle contraction. Using electronic stimulator to stimulate the phrenic nerve of the isolated phrenic nerve diaphragm preparation of 30 rats or directly stimulate the isolated gastrocnemius muscle preparation of 45 toads in vitro, we studied the effects of TWP on capability of muscle intrinsic contraction. TWP in 20 mg/L increased the amplitude of muscle contraction in initial 60 min but did not make further increase of the amplitude of muscle contraction from 60 min to 90 min in the isolated phrenic nerve diaphragm preparation of rat under one-third optimal stimulus. TWP in 40 mg/L and in 60 mg/L did not cause decrease of amplitude of muscle contraction in initial 60 min in isolated phrenic nerve diaphragm preparation of rat under one-third optimal stimulus. TWP in 60 mg/L did not cause decrease of tension of signal-contraction in initial 30 min in isolated gastrocnemius muscle preparation of toad under one-third optimal direct stimulus. Solvent DMSO could obviously reduce the tension of muscle contraction both in isolated phrenic nerve diaphragm preparation of rat and in isolated gastrocnemius muscle preparation of toad under one-third optimal stimulus. TWP can limitedly enhance the capability of muscle contraction; Solvent DMSO can restrain muscle contraction.

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.

Cellular immunocompetence in melanoma: effect of extent of disease and immunotherapy.

PubMed Central

Lui, V. K.; Karpuchas, J.; Dent, P. B.; McCulloch, P. B.; Blajchman, M. A.

1975-01-01

Cell mediated immunocompetence was measured serially in 35 patients with malignant melanoma in order to determine the effect of extent of disease and prognosis as well as the influence of BCG immunotherapy on immune reactivity. Compared with normal adult controls, statistically significant lymphopenia occurred only in patients with widespread disease. Seventeen of 21 patients with negative pre-therapy PPD skin test converted to skin test positivity. PHA blastogenesis was depressed only in patients in the pre-terminal stages of their disease using optimal mitogen concentrations for stimulation. Threshold concentrations of this mitogen more clearly demonstrated a depressed responsiveness which correlated in severity with extent of disease. PPD induced blastogenesis was normal or increased in the majority of patients; however, the degree of stimulation by PPD was less in the BCG induced convertors than in those patients who were skin test positive before BCG treatment. Comparison of the pre- and post BCG assessments reveals no significant differences except in relation to PPD conversion. We conclude that using threshold concentrations of PHA, impaired responses are regularly associated with disease beyond the regional lymph nodes. Routine assessment of lymphocyte function by these parameters did not provide information that was not available from clinical evaluation. PMID:1233077

EEG controlled neuromuscular electrical stimulation of the upper limb for stroke patients

NASA Astrophysics Data System (ADS)

Tan, Hock Guan; Shee, Cheng Yap; Kong, Keng He; Guan, Cuntai; Ang, Wei Tech

2011-03-01

This paper describes the Brain Computer Interface (BCI) system and the experiments to allow post-acute (<3 months) stroke patients to use electroencephalogram (EEG) to trigger neuromuscular electrical stimulation (NMES)-assisted extension of the wrist/fingers, which are essential pre-requisites for useful hand function. EEG was recorded while subjects performed motor imagery of their paretic limb, and then analyzed to determine the optimal frequency range within the mu-rhythm, with the greatest attenuation. Aided by visual feedback, subjects then trained to regulate their mu-rhythm EEG to operate the BCI to trigger NMES of the wrist/finger. 6 post-acute stroke patients successfully completed the training, with 4 able to learn to control and use the BCI to initiate NMES. This result is consistent with the reported BCI literacy rate of healthy subjects. Thereafter, without the loss of generality, the controller of the NMES is developed and is based on a model of the upper limb muscle (biceps/triceps) groups to determine the intensity of NMES required to flex or extend the forearm by a specific angle. The muscle model is based on a phenomenological approach, with parameters that are easily measured and conveniently implemented.

Stress for Success: How to Optimize Your Performance.

ERIC Educational Resources Information Center

Gmelch, Walter H.

1983-01-01

This article explores linkages between stress and effective job performance: while too much stress can lead to burnout, too little stressful stimulation can result in boredom. Generating the proper amount of stress for optimal job performance is discussed. (PP)

3D Biomimetic Magnetic Structures for Static Magnetic Field Stimulation of Osteogenesis.

PubMed

Paun, Irina Alexandra; Popescu, Roxana Cristina; Calin, Bogdan Stefanita; Mustaciosu, Cosmin Catalin; Dinescu, Maria; Luculescu, Catalin Romeo

2018-02-07

We designed, fabricated and optimized 3D biomimetic magnetic structures that stimulate the osteogenesis in static magnetic fields. The structures were fabricated by direct laser writing via two-photon polymerization of IP-L780 photopolymer and were based on ellipsoidal, hexagonal units organized in a multilayered architecture. The magnetic activity of the structures was assured by coating with a thin layer of collagen-chitosan-hydroxyapatite-magnetic nanoparticles composite. In vitro experiments using MG-63 osteoblast-like cells for 3D structures with gradients of pore size helped us to find an optimum pore size between 20-40 µm. Starting from optimized 3D structures, we evaluated both qualitatively and quantitatively the effects of static magnetic fields of up to 250 mT on cell proliferation and differentiation, by ALP (alkaline phosphatase) production, Alizarin Red and osteocalcin secretion measurements. We demonstrated that the synergic effect of 3D structure optimization and static magnetic stimulation enhances the bone regeneration by a factor greater than 2 as compared with the same structure in the absence of a magnetic field.

3D Biomimetic Magnetic Structures for Static Magnetic Field Stimulation of Osteogenesis

PubMed Central

Paun, Irina Alexandra; Popescu, Roxana Cristina; Calin, Bogdan Stefanita; Mustaciosu, Cosmin Catalin; Dinescu, Maria; Luculescu, Catalin Romeo

2018-01-01

We designed, fabricated and optimized 3D biomimetic magnetic structures that stimulate the osteogenesis in static magnetic fields. The structures were fabricated by direct laser writing via two-photon polymerization of IP-L780 photopolymer and were based on ellipsoidal, hexagonal units organized in a multilayered architecture. The magnetic activity of the structures was assured by coating with a thin layer of collagen-chitosan-hydroxyapatite-magnetic nanoparticles composite. In vitro experiments using MG-63 osteoblast-like cells for 3D structures with gradients of pore size helped us to find an optimum pore size between 20–40 µm. Starting from optimized 3D structures, we evaluated both qualitatively and quantitatively the effects of static magnetic fields of up to 250 mT on cell proliferation and differentiation, by ALP (alkaline phosphatase) production, Alizarin Red and osteocalcin secretion measurements. We demonstrated that the synergic effect of 3D structure optimization and static magnetic stimulation enhances the bone regeneration by a factor greater than 2 as compared with the same structure in the absence of a magnetic field. PMID:29414875

Teaching-learning-based Optimization Algorithm for Parameter Identification in the Design of IIR Filters

NASA Astrophysics Data System (ADS)

Singh, R.; Verma, H. K.

2013-12-01

This paper presents a teaching-learning-based optimization (TLBO) algorithm to solve parameter identification problems in the designing of digital infinite impulse response (IIR) filter. TLBO based filter modelling is applied to calculate the parameters of unknown plant in simulations. Unlike other heuristic search algorithms, TLBO algorithm is an algorithm-specific parameter-less algorithm. In this paper big bang-big crunch (BB-BC) optimization and PSO algorithms are also applied to filter design for comparison. Unknown filter parameters are considered as a vector to be optimized by these algorithms. MATLAB programming is used for implementation of proposed algorithms. Experimental results show that the TLBO is more accurate to estimate the filter parameters than the BB-BC optimization algorithm and has faster convergence rate when compared to PSO algorithm. TLBO is used where accuracy is more essential than the convergence speed.

Optimization of a Thermodynamic Model Using a Dakota Toolbox Interface

NASA Astrophysics Data System (ADS)

Cyrus, J.; Jafarov, E. E.; Schaefer, K. M.; Wang, K.; Clow, G. D.; Piper, M.; Overeem, I.

2016-12-01

Scientific modeling of the Earth physical processes is an important driver of modern science. The behavior of these scientific models is governed by a set of input parameters. It is crucial to choose accurate input parameters that will also preserve the corresponding physics being simulated in the model. In order to effectively simulate real world processes the models output data must be close to the observed measurements. To achieve this optimal simulation, input parameters are tuned until we have minimized the objective function, which is the error between the simulation model outputs and the observed measurements. We developed an auxiliary package, which serves as a python interface between the user and DAKOTA. The package makes it easy for the user to conduct parameter space explorations, parameter optimizations, as well as sensitivity analysis while tracking and storing results in a database. The ability to perform these analyses via a Python library also allows the users to combine analysis techniques, for example finding an approximate equilibrium with optimization then immediately explore the space around it. We used the interface to calibrate input parameters for the heat flow model, which is commonly used in permafrost science. We performed optimization on the first three layers of the permafrost model, each with two thermal conductivity coefficients input parameters. Results of parameter space explorations indicate that the objective function not always has a unique minimal value. We found that gradient-based optimization works the best for the objective functions with one minimum. Otherwise, we employ more advanced Dakota methods such as genetic optimization and mesh based convergence in order to find the optimal input parameters. We were able to recover 6 initially unknown thermal conductivity parameters within 2% accuracy of their known values. Our initial tests indicate that the developed interface for the Dakota toolbox could be used to perform analysis and optimization on a `black box' scientific model more efficiently than using just Dakota.

Systematic evaluation of the impact of stimulation intensity on neuroplastic after-effects induced by transcranial direct current stimulation.

PubMed

Jamil, Asif; Batsikadze, Giorgi; Kuo, Hsiao-I; Labruna, Ludovica; Hasan, Alkomiet; Paulus, Walter; Nitsche, Michael A

2017-02-15

Applications of transcranial direct current stimulation to modulate human neuroplasticity have increased in research and clinical settings. However, the need for longer-lasting effects, combined with marked inter-individual variability, necessitates a deeper understanding of the relationship between stimulation parameters and physiological effects. We systematically investigated the full DC intensity range (0.5-2.0 mA) for both anodal and cathodal tDCS in a sham-controlled repeated measures design, monitoring changes in motor-cortical excitability via transcranial magnetic stimulation up to 2 h after stimulation. For both tDCS polarities, the excitability after-effects did not linearly correlate with increasing DC intensity; effects of lower intensities (0.5, 1.0 mA) showed equal, if not greater effects in motor-cortical excitability. Further, while intra-individual responses showed good reliability, inter-individual sensitivity to TMS accounted for a modest percentage of the variance in the early after-effects of 1.0 mA anodal tDCS, which may be of practical relevance for future optimizations. Contemporary non-invasive neuromodulatory techniques, such as transcranial direct current stimulation (tDCS), have shown promising potential in both restituting impairments in cortical physiology in clinical settings, as well as modulating cognitive abilities in the healthy population. However, neuroplastic after-effects of tDCS are highly dependent on stimulation parameters, relatively short lasting, and not expectedly uniform between individuals. The present study systematically investigates the full range of current intensity between 0.5 and 2.0 mA on left primary motor cortex (M1) plasticity, as well as the impact of individual-level covariates on explaining inter-individual variability. Thirty-eight healthy subjects were divided into groups of anodal and cathodal tDCS. Five DC intensities (sham, 0.5, 1.0, 1.5 and 2.0 mA) were investigated in separate sessions. Using transcranial magnetic stimulation (TMS), 25 motor-evoked potentials (MEPs) were recorded before, and 10 time points up to 2 h following 15 min of tDCS. Repeated-measures ANOVAs indicated a main effect of intensity for both anodal and cathodal tDCS. With anodal tDCS, all active intensities resulted in equivalent facilitatory effects relative to sham while for cathodal tDCS, only 1.0 mA resulted in sustained excitability diminution. An additional experiment conducted to assess intra-individual variability revealed generally good reliability of 1.0 mA anodal tDCS (ICC(2,1) = 0.74 over the first 30 min). A post hoc analysis to discern sources of inter-individual variability confirmed a previous finding in which individual TMS SI 1mV (stimulus intensity for 1 mV MEP amplitude) sensitivity correlated negatively with 1.0 mA anodal tDCS effects on excitability. Our study thus provides further insights on the extent of non-linear intensity-dependent neuroplastic after-effects of anodal and cathodal tDCS. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Aggregation Pheromone System: A Real-parameter Optimization Algorithm using Aggregation Pheromones as the Base Metaphor

NASA Astrophysics Data System (ADS)

Tsutsui, Shigeyosi

This paper proposes an aggregation pheromone system (APS) for solving real-parameter optimization problems using the collective behavior of individuals which communicate using aggregation pheromones. APS was tested on several test functions used in evolutionary computation. The results showed APS could solve real-parameter optimization problems fairly well. The sensitivity analysis of control parameters of APS is also studied.

An optimal generic model for multi-parameters and big data optimizing: a laboratory experimental study

NASA Astrophysics Data System (ADS)

Utama, D. N.; Ani, N.; Iqbal, M. M.

2018-03-01

Optimization is a process for finding parameter (parameters) that is (are) able to deliver an optimal value for an objective function. Seeking an optimal generic model for optimizing is a computer science study that has been being practically conducted by numerous researchers. Generic model is a model that can be technically operated to solve any varieties of optimization problem. By using an object-oriented method, the generic model for optimizing was constructed. Moreover, two types of optimization method, simulated-annealing and hill-climbing, were functioned in constructing the model and compared to find the most optimal one then. The result said that both methods gave the same result for a value of objective function and the hill-climbing based model consumed the shortest running time.

Selecting and optimizing eco-physiological parameters of Biome-BGC to reproduce observed woody and leaf biomass growth of Eucommia ulmoides plantation in China using Dakota optimizer

NASA Astrophysics Data System (ADS)

Miyauchi, T.; Machimura, T.

2013-12-01

In the simulation using an ecosystem process model, the adjustment of parameters is indispensable for improving the accuracy of prediction. This procedure, however, requires much time and effort for approaching the simulation results to the measurements on models consisting of various ecosystem processes. In this study, we tried to apply a general purpose optimization tool in the parameter optimization of an ecosystem model, and examined its validity by comparing the simulated and measured biomass growth of a woody plantation. A biometric survey of tree biomass growth was performed in 2009 in an 11-year old Eucommia ulmoides plantation in Henan Province, China. Climate of the site was dry temperate. Leaf, above- and below-ground woody biomass were measured from three cut trees and converted into carbon mass per area by measured carbon contents and stem density. Yearly woody biomass growth of the plantation was calculated according to allometric relationships determined by tree ring analysis of seven cut trees. We used Biome-BGC (Thornton, 2002) to reproduce biomass growth of the plantation. Air temperature and humidity from 1981 to 2010 was used as input climate condition. The plant functional type was deciduous broadleaf, and non-optimizing parameters were left default. 11-year long normal simulations were performed following a spin-up run. In order to select optimizing parameters, we analyzed the sensitivity of leaf, above- and below-ground woody biomass to eco-physiological parameters. Following the selection, optimization of parameters was performed by using the Dakota optimizer. Dakota is an optimizer developed by Sandia National Laboratories for providing a systematic and rapid means to obtain optimal designs using simulation based models. As the object function, we calculated the sum of relative errors between simulated and measured leaf, above- and below-ground woody carbon at each of eleven years. In an alternative run, errors at the last year (at the field survey) were weighted for priority. We compared some gradient-based global optimization methods of Dakota starting with the default parameters of Biome-BGC. In the result of sensitive analysis, carbon allocation parameters between coarse root and leaf, between stem and leaf, and SLA had high contribution on both leaf and woody biomass changes. These parameters were selected to be optimized. The measured leaf, above- and below-ground woody biomass carbon density at the last year were 0.22, 1.81 and 0.86 kgC m-2, respectively, whereas those simulated in the non-optimized control case using all default parameters were 0.12, 2.26 and 0.52 kgC m-2, respectively. After optimizing the parameters, the simulated values were improved to 0.19, 1.81 and 0.86 kgC m-2, respectively. The coliny global optimization method gave the better fitness than efficient global and ncsu direct method. The optimized parameters showed the higher carbon allocation rates to coarse roots and leaves and the lower SLA than the default parameters, which were consistent to the general water physiological response in a dry climate. The simulation using the weighted object function resulted in the closer simulations to the measurements at the last year with the lower fitness during the previous years.

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.

A Fully-Implantable Cochlear Implant SoC with Piezoelectric Middle-Ear Sensor and Arbitrary Waveform Neural Stimulation.

PubMed

Yip, Marcus; Jin, Rui; Nakajima, Hideko Heidi; Stankovic, Konstantina M; Chandrakasan, Anantha P

2015-01-01

A system-on-chip for an invisible, fully-implantable cochlear implant is presented. Implantable acoustic sensing is achieved by interfacing the SoC to a piezoelectric sensor that detects the sound-induced motion of the middle ear. Measurements from human cadaveric ears demonstrate that the sensor can detect sounds between 40 and 90 dB SPL over the speech bandwidth. A highly-reconfigurable digital sound processor enables system power scalability by reconfiguring the number of channels, and provides programmable features to enable a patient-specific fit. A mixed-signal arbitrary waveform neural stimulator enables energy-optimal stimulation pulses to be delivered to the auditory nerve. The energy-optimal waveform is validated with in-vivo measurements from four human subjects which show a 15% to 35% energy saving over the conventional rectangular waveform. Prototyped in a 0.18 μ m high-voltage CMOS technology, the SoC in 8-channel mode consumes 572 μ W of power including stimulation. The SoC integrates implantable acoustic sensing, sound processing, and neural stimulation on one chip to minimize the implant size, and proof-of-concept is demonstrated with measurements from a human cadaver ear.

Method for Household Refrigerators Efficiency Increasing

NASA Astrophysics Data System (ADS)

Lebedev, V. V.; Sumzina, L. V.; Maksimov, A. V.

2017-11-01

The relevance of working processes parameters optimization in air conditioning systems is proved in the work. The research is performed with the use of the simulation modeling method. The parameters optimization criteria are considered, the analysis of target functions is given while the key factors of technical and economic optimization are considered in the article. The search for the optimal solution at multi-purpose optimization of the system is made by finding out the minimum of the dual-target vector created by the Pareto method of linear and weight compromises from target functions of the total capital costs and total operating costs. The tasks are solved in the MathCAD environment. The research results show that the values of technical and economic parameters of air conditioning systems in the areas relating to the optimum solutions’ areas manifest considerable deviations from the minimum values. At the same time, the tendencies for significant growth in deviations take place at removal of technical parameters from the optimal values of both the capital investments and operating costs. The production and operation of conditioners with the parameters which are considerably deviating from the optimal values will lead to the increase of material and power costs. The research allows one to establish the borders of the area of the optimal values for technical and economic parameters at air conditioning systems’ design.

Deep Brain Stimulation to Alleviate Freezing of Gait and Cognitive Dysfunction in Parkinson's Disease: Update on Current Research and Future Perspectives.

PubMed

Huang, Chuyi; Chu, Heling; Zhang, Yan; Wang, Xiaoping

2018-01-01

Freezing of gait (FOG) is a gait disorder featured by recurrent episodes of temporary gait halting and mainly found in advanced Parkinson's disease (PD). FOG has a severe impact on the quality of life of patients with PD. The pathogenesis of FOG is unclear and considered to be related to several brain areas and neural circuits. Its close connection with cognitive disorder has been proposed and some researchers explain the pathogenesis using the cognitive model theory. FOG occurs concurrently with cognitive disorder in some PD patients, who are poorly responsive to medication therapy. Deep brain stimulation (DBS) proves effective for FOG in PD patients. Cognitive impairment plays a role in the formation of FOG. Therefore, if DBS works by improving the cognitive function, both two challenging conditions can be ameliorated by DBS. We reviewed the clinical studies related to DBS for FOG in PD patients over the past decade. In spite of the varying stimulation parameters used in different studies, DBS of either subthalamic nucleus (STN) or pedunculopontine nucleus (PPN) alone or in combination can improve the symptoms of FOG. Moreover, the treatment efficacy can last for 1-2 years and DBS is generally safe. Although few studies have been conducted concerning the use of DBS for cognitive disorder in FOG patients, the existing studies seem to indicate that PPN is a potential therapeutic target to both FOG and cognitive disorder. However, most of the studies have a small sample size and involve sporadic cases, so it remains uncertain which nucleus is the optimal target of stimulation. Prospective clinical trials with a larger sample size are needed to systematically assess the efficacy of DBS for FOG and cognitive disorder.

Dependences of the geometrical parameters of cell community on stimulation voltage and frequency in chick embryonic cardiomyocytes

NASA Astrophysics Data System (ADS)

Fujii, Koki; Nomura, Fumimasa; Kaneko, Tomoyuki

2018-03-01

To investigate the optimal conditions for electrical stimulation, communities of lined-up chick embryonic cardiomyocytes were evaluated in terms of their threshold voltage for pacing (PVMin) and the half-maximum paced frequency (PF50), with a focus on the following factors: (1) the orientation of the major axis of cell communities to the electric field (EF) direction as the external factor; (2) the number of cells in a cell community, the length of the cell community, and the mean length of cells comprising the community as the internal factors. Firstly, PVMin decreased with increasing length of the cell network oriented parallel to the EF. PVMin was approximately 0.041 ± 0.025 V/mm when the community was sufficiently long. On the other hand, PVMin in the orthogonal orientation was constant at 1.7 ± 0.047 V/mm with no dependence on the length of the cell network. Secondly, we found that PF50 increased with increasing length of the cell network or the number of cells in the network; the PF50 values were 2.03 ± 0.05 and 3.39 ± 0.05 Hz when the respective cell network lengths were 100 µm (n = 43) and more than 300 µm (n = 6) and the cells were oriented parallel to the EF. These findings indicate that it is important to suppress ventricular fibrillation with minimal efficient stimulation by considering the EF direction with respect to the orientation of cardiomyocytes. Furthermore, expanded cells showed the loss of ability to respond to stimulation at higher frequencies. Cardiomyocytes combined with seeded fibroblasts as a cell network at a low density are a possible model of a ventricular remodeling heart.

Phase dependent modulation of tremor amplitude in essential tremor through thalamic stimulation

PubMed Central

Cagnan, Hayriye; Brittain, John-Stuart; Little, Simon; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Joint, Carole; Fitzgerald, James; Green, Alexander L.; Aziz, Tipu

2013-01-01

High frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor. The latter could be exploited to improve deep brain stimulation, particularly if tremor suppression could be reinforced by cumulative effects. Accordingly, we stimulated 10 patients with essential tremor and thalamic electrodes, while recording tremor amplitude and phase. Stimulation near the postural tremor frequency entrained tremor. Tremor amplitude was also modulated depending on the phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in one half of the tremor cycle reduced median tremor amplitude by ∼10%, while those in the opposite half of the tremor cycle increased tremor amplitude by a similar amount. At optimal phase alignment tremor suppression reached 27%. Moreover, tremor amplitude showed a non-linear increase in the degree of suppression with successive stimuli; tremor suppression was increased threefold if a stimulus was preceded by four stimuli with a similar phase relationship with respect to the tremor, suggesting cumulative, possibly plastic, effects. The present results pave the way for a stimulation system that tracks tremor phase to control when deep brain stimulation pulses are delivered to treat essential tremor. This would allow treatment effects to be maximized by focussing stimulation on the optimal phase for suppression and by ensuring that this is repeated over many cycles so as to harness cumulative effects. Such a system might potentially achieve tremor control with far less power demand and greater specificity than current high frequency stimulation approaches, and may lower the risk for tolerance and rebound. PMID:24038075

A parameters optimization method for planar joint clearance model and its application for dynamics simulation of reciprocating compressor

NASA Astrophysics Data System (ADS)

Hai-yang, Zhao; Min-qiang, Xu; Jin-dong, Wang; Yong-bo, Li

2015-05-01

In order to improve the accuracy of dynamics response simulation for mechanism with joint clearance, a parameter optimization method for planar joint clearance contact force model was presented in this paper, and the optimized parameters were applied to the dynamics response simulation for mechanism with oversized joint clearance fault. By studying the effect of increased clearance on the parameters of joint clearance contact force model, the relation of model parameters between different clearances was concluded. Then the dynamic equation of a two-stage reciprocating compressor with four joint clearances was developed using Lagrange method, and a multi-body dynamic model built in ADAMS software was used to solve this equation. To obtain a simulated dynamic response much closer to that of experimental tests, the parameters of joint clearance model, instead of using the designed values, were optimized by genetic algorithms approach. Finally, the optimized parameters were applied to simulate the dynamics response of model with oversized joint clearance fault according to the concluded parameter relation. The dynamics response of experimental test verified the effectiveness of this application.

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.

Electrical stimulation of the motor cortex enhances treatment outcome in post-stroke aphasia.

PubMed

Meinzer, Marcus; Darkow, Robert; Lindenberg, Robert; Flöel, Agnes

2016-04-01

Transcranial direct current stimulation has shown promise to improve recovery in patients with post-stroke aphasia, but previous studies have only assessed stimulation effects on impairment parameters, and evidence for long-term maintenance of transcranial direct current stimulation effects from randomized, controlled trials is lacking. Moreover, due to the variability of lesions and functional language network reorganization after stroke, recent studies have used advanced functional imaging or current modelling to determine optimal stimulation sites in individual patients. However, such approaches are expensive, time consuming and may not be feasible outside of specialized research centres, which complicates incorporation of transcranial direct current stimulation in day-to-day clinical practice. Stimulation of an ancillary system that is functionally connected to the residual language network, namely the primary motor system, would be more easily applicable, but effectiveness of such an approach has not been explored systematically. We conducted a randomized, parallel group, sham-controlled, double-blind clinical trial and 26 patients with chronic aphasia received a highly intensive naming therapy over 2 weeks (8 days, 2 × 1.5 h/day). Concurrently, anodal-transcranial direct current stimulation was administered to the left primary motor cortex twice daily at the beginning of each training session. Naming ability for trained items (n = 60 pictures that could not be named during repeated baseline assessments), transfer to untrained items (n = 284 pictures) and generalization to everyday communication were assessed immediately post-intervention and 6 months later. Naming ability for trained items was significantly improved immediately after the end of the intervention in both the anodal (Cohen's d = 3.67) and sham-transcranial direct current stimulation groups (d = 2.10), with a trend for larger gains in the anodal-transcranial direct current stimulation group (d = 0.71). Treatment effects for trained items were significantly better maintained in the anodal-transcranial direct current stimulation group 6 months later (d = 1.19). Transfer to untrained items was significantly larger in the anodal-transcranial direct current stimulation group after the training (d = 1.49) and during the 6 month follow-up assessment (d = 3.12). Transfer effects were only maintained in the anodal-transcranial direct current stimulation group. Functional communication was significantly more improved in the anodal-transcranial direct current stimulation group at both time points compared to patients treated with sham-transcranial direct current stimulation (d = 0.75-0.99). Our results provide the first evidence from a randomized, controlled trial that transcranial direct current stimulation can improve both function and activity-related outcomes in chronic aphasia, with medium to large effect sizes, and that these effects are maintained over extended periods of time. These effects were achieved with an easy-to-implement and thus clinically feasible motor-cortex montage that may represent a promising 'backdoor' approach to improve language recovery after stroke. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Enhancing motor performance improvement by personalizing non-invasive cortical stimulation with concurrent functional near-infrared spectroscopy and multi-modal motor measurements

NASA Astrophysics Data System (ADS)

Khan, Bilal; Hodics, Timea; Hervey, Nathan; Kondraske, George; Stowe, Ann; Alexandrakis, George

2015-03-01

Transcranial direct current stimulation (tDCS) is a non-invasive cortical stimulation technique that can facilitate task specific plasticity that can improve motor performance. Current tDCS interventions uniformly apply a chosen electrode montage to a subject population without personalizing electrode placement for optimal motor gains. We propose a novel perturbation tDCS (ptDCS) paradigm for determining a personalized electrode montage in which tDCS intervention yields maximal motor performance improvements during stimulation. PtDCS was applied to ten healthy adults and five stroke patients with upper hemiparesis as they performed an isometric wrist flexion task with their non-dominant arm. Simultaneous recordings of torque applied to a stationary handle, muscle activity by electromyography (EMG), and cortical activity by functional near-infrared spectroscopy (fNIRS) during ptDCS helped interpret how cortical activity perturbations by any given electrode montage related to changes in muscle activity and task performance quantified by a Reaction Time (RT) X Error product. PtDCS enabled quantifying the effect on task performance of 20 different electrode pair montages placed over the sensorimotor cortex. Interestingly, the electrode montage maximizing performance in all healthy adults did not match any of the ones being explored in current literature as a means of improving the motor performance of stroke patients. Furthermore, the optimal montage was found to be different in each stroke patient and the resulting motor gains were very significant during stimulation. This study supports the notion that task-specific ptDCS optimization can lend itself to personalizing the rehabilitation of patients with brain injury.

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.

Closed-loop neuromodulation of spinal sensorimotor circuits controls refined locomotion after complete spinal cord injury.

PubMed

Wenger, Nikolaus; Moraud, Eduardo Martin; Raspopovic, Stanisa; Bonizzato, Marco; DiGiovanna, Jack; Musienko, Pavel; Morari, Manfred; Micera, Silvestro; Courtine, Grégoire

2014-09-24

Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with spinal cord injury. With common neuromodulation devices, electrical stimulation parameters are tuned manually and remain constant during movement. We developed a mechanistic framework to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats. We first uncovered relationships between neuromodulation parameters and recruitment of distinct sensorimotor circuits, resulting in predictive adjustments of leg kinematics. Second, we established a technological platform with embedded control policies that integrated robust movement feedback and feed-forward control loops in real time. These developments allowed us to conceive a neuroprosthetic system that controlled a broad range of foot trajectories during continuous locomotion in paralyzed rats. Animals with complete spinal cord injury performed more than 1000 successive steps without failure, and were able to climb staircases of various heights and lengths with precision and fluidity. Beyond therapeutic potential, these findings provide a conceptual and technical framework to personalize neuromodulation treatments for other neurological disorders. Copyright © 2014, American Association for the Advancement of Science.

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

Preliminary Evidence of the Effects of High-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) on Swallowing Functions in Post-Stroke Individuals with Chronic Dysphagia

ERIC Educational Resources Information Center

Cheng, Ivy K. Y.; Chan, Karen M. K.; Wong, C. S.; Cheung, Raymond T. F.

2015-01-01

Background: There is growing evidence of potential benefits of repetitive transcranial magnetic stimulation (rTMS) in the rehabilitation of dysphagia. However, the site and frequency of stimulation for optimal effects are not clear. Aims: The aim of this pilot study is to investigate the short-term effects of high-frequency 5 Hz rTMS applied to…

Multihormonal regulation of thyroglobulin production by the OVNIS 6H thyroid cell line.

PubMed

Aouani, A; Hovsépian, S; Fayet, G

1988-02-01

The hormonal regulation of thyroglobulin production has been studied using a clone of the ovine thyroid cell line: OVNIS 6H. 3 among the 6 hormones proposed for serum replacement are required for an optimal thyroglobulin production; insulin, hydrocortisone and thyrotropin. Insulin alone stimulates thyroglobulin production. The presence of insulin is also required to observe hydrocortisone and TSH stimulations. Newborn calf serum inhibits thyroglobulin production. The best conditions for optimal thyroglobulin expression and TSH responsiveness are obtained in serum-free medium supplemented with 5 micrograms/ml insulin, 100 nM hydrocortisone and 1 mU/ml TSH.

Combined genetic algorithm and multiple linear regression (GA-MLR) optimizer: Application to multi-exponential fluorescence decay surface.

PubMed

Fisz, Jacek J

2006-12-07

The optimization approach based on the genetic algorithm (GA) combined with multiple linear regression (MLR) method, is discussed. The GA-MLR optimizer is designed for the nonlinear least-squares problems in which the model functions are linear combinations of nonlinear functions. GA optimizes the nonlinear parameters, and the linear parameters are calculated from MLR. GA-MLR is an intuitive optimization approach and it exploits all advantages of the genetic algorithm technique. This optimization method results from an appropriate combination of two well-known optimization methods. The MLR method is embedded in the GA optimizer and linear and nonlinear model parameters are optimized in parallel. The MLR method is the only one strictly mathematical "tool" involved in GA-MLR. The GA-MLR approach simplifies and accelerates considerably the optimization process because the linear parameters are not the fitted ones. Its properties are exemplified by the analysis of the kinetic biexponential fluorescence decay surface corresponding to a two-excited-state interconversion process. A short discussion of the variable projection (VP) algorithm, designed for the same class of the optimization problems, is presented. VP is a very advanced mathematical formalism that involves the methods of nonlinear functionals, algebra of linear projectors, and the formalism of Fréchet derivatives and pseudo-inverses. Additional explanatory comments are added on the application of recently introduced the GA-NR optimizer to simultaneous recovery of linear and weakly nonlinear parameters occurring in the same optimization problem together with nonlinear parameters. The GA-NR optimizer combines the GA method with the NR method, in which the minimum-value condition for the quadratic approximation to chi(2), obtained from the Taylor series expansion of chi(2), is recovered by means of the Newton-Raphson algorithm. The application of the GA-NR optimizer to model functions which are multi-linear combinations of nonlinear functions, is indicated. The VP algorithm does not distinguish the weakly nonlinear parameters from the nonlinear ones and it does not apply to the model functions which are multi-linear combinations of nonlinear functions.

Realization and optimization of a 1 ns pulsewidth multi-stage 250 kW peak power monolithic Yb doped fiber amplifier at 1064 nm

NASA Astrophysics Data System (ADS)

Morasse, Bertrand; Plourde, Estéban

2017-02-01

We present a simple way to achieve and optimize hundreds of kW peak power pulsed output using a monolithic amplifier chain based on solid core double cladding fiber tightly packaged. A fiber pigtailed current driven diode is used to produce nanosecond pulses at 1064 nm. We present how to optimize the use of Fabry-Perot versus DFB type diode along with the proper wavelength locking using a fiber Bragg grating. The optimization of the two pre-amplifiers with respect to the pump wavelength and Yb inversions is presented. We explain how to manage ASE using core and cladding pumping and by using single pass and double pass amplifier. ASE rejection within the Yb fiber itself and with the use of bandpass filter is discussed. Maximizing the amplifier conversion efficiency with regards to the fiber parameters, glass matrix and signal wavelength is described in details. We present how to achieve high peak power at the power amplifier stage using large core/cladding diameter ratio highly doped Yb fibers pumped at 975 nm. The effect of pump bleaching on the effective Yb fiber length is analyzed carefully. We demonstrate that counter-pumping brings little advantage in very short length amplifier. Dealing with the self-pulsation limit of stimulated Brillouin scattering is presented with the adjustment of the seed pulsewidth and linewidth. Future prospects for doubling the output peak power are discussed.

Comparison of two cannulation methods for assessment of intracavernosal pressure in a rat model

PubMed Central

Luo, Lianmin; Wang, Jiamin; Li, Ermao; Luo, Jintai; Liu, Luhao; Wan, ShawPong

2018-01-01

Intracavernous pressure (ICP) measurement is a well-established technique for assessing the erectile function, which was performed by cannulating either crus or shaft of the penis. However, there are no studies concerning the experimental performance of the two cannulation sites yet. The aim of this study was to compare the measuring outcomes using two different cannulation sites. To validate the capacity of our study, both normal and the castration-induced erectile dysfunction rat models were conducted. Fifty adult male Sprague-Dawley rats were randomized equally into two groups: an intact group and a castration group. Five rats from each group firstly underwent different stimulation parameters to detect the optimal erectile responses. The residual rats in each group were further assigned into two subgroups (n = 10 per subgroup) according to two different cannulation sites (crus or shaft of the corpus cavernosum). The ICP values were compared between groups after different interventions. The optimal parameters for mean maximum ICP were recorded at 2.5V and a frequency of 15 Hz. The rats under the two different cannulation sites tended to show similar ICP values in both the intact and the castration groups. However, the success rate in monitoring ICP was significantly higher in the groups cannulating into the shaft of the penis compared to the crus (100% vs. 70%; P = 0.02). Our data suggested that the method of cannulation into the penile shaft could serve as a better alternative for the ICP measurement in rats. PMID:29486011

[Review on infrared temperature characteristics of acupoints in recent 10 years].

PubMed

Lin, Min; Wei, Haiyan; Zhao, Ling; Zhao, Jizhong; Cheng, Ke; Deng, Haiping; Shen, Xueyong; Zhang, Haimeng

2017-04-12

In the paper, the study was reviewed on the infrared temperature characteristics of acupoints in recent 10 years. CNKI, WANFANG, VIP, SciVerse ScienceDirect and Springer databases were retrieved, with"infrared thermal imaging" and "acupoint" as the key words. The retrieving time was from January 1, 2006 to December 31, 2016. Totally, 468 relevant papers were searched and 169 papers of them were read carefully on acupoint infrared temperature. In terms of physiological condition, pathological condition and the stimulation methods such as acupuncture, moxibustion, tuina , embedding therapy and cupping therapy, the general situation was reviewed on the infrared temperature characteristics of acupoints separately. It was found that the study on infrared temperature characteristics of acupoints in physiological condition was limited and the characteristics discovered were not enough to systematically review the physiological and physical properties of acupoints. The study in terms of the pathological condition objectively reflected the effects and rules of diseases. It was showed in the study of acupoint infrared temperature characteristics after stimulation that the changes of infrared thermal imaging tempe-rature at some specific region induced by different therapies and parameters might be used to deduce the potential mechanism and optimal parameters or schemes of intervention method and contributed to the formation and deve-lopment of quantitative diagnosis and treatment. The authors believe that the study on infrared temperature characteristics of acupoint provides the active significance in the exploration on the physiological and physical characteristics of acupoint, the effects and rules of diseases as well as the quantitative diagnosis and treatment.

Noninvasive brain stimulation by radioelectric asymmetric conveyor in the treatment of agoraphobia: open-label, naturalistic study

PubMed Central

Mannu, Piero; Rinaldi, Salvatore; Fontani, Vania; Castagna, Alessandro; Margotti, Matteo Lotti

2011-01-01

Background Agoraphobia is considered to be the most serious complication of panic disorder. It involves progressive development of debilitating anxiety symptoms related to being in situations where one would be extremely embarrassed and could not be rescued in the case of a panic attack. This study aimed to investigate the efficacy of noninvasive brain stimulation using a radioelectric asymmetric conveyor (REAC) for agoraphobia. Patients and methods Twenty-three patients (3 males and 20 females) suffering from agoraphobia and without a history of panic disorder were evaluated by a psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and the Agoraphobia Scale (AS). The patients were subjected to two 18-session cycles of noninvasive brain stimulation with the REAC, according to an established therapeutic protocol called neuropsycho-physical optimization. Results Analyzing the anxiety and avoidance parameters of the AS after the first and second cycles of REAC treatment revealed variation in levels of response to treatment, including weak (AS item 7), moderate (AS items 10 and 13), and good responses (AS items 1–6, 8, 9, 11, 12, and 14–20). Conclusion These results highlight the potential of the REAC to treat complex clinical situations such as agoraphobia, which is typically resistant to pharmacologic treatments. Furthermore, these data show the advantages of REAC treatment, even compared with modern cognitive behavioral therapy, including a relatively rapid and “stable” clinical response (just over 6 months) and economic cost. PMID:22163156

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.

Comparison of Optimal Design Methods in Inverse Problems

PubMed Central

Banks, H. T.; Holm, Kathleen; Kappel, Franz

2011-01-01

Typical optimal design methods for inverse or parameter estimation problems are designed to choose optimal sampling distributions through minimization of a specific cost function related to the resulting error in parameter estimates. It is hoped that the inverse problem will produce parameter estimates with increased accuracy using data collected according to the optimal sampling distribution. Here we formulate the classical optimal design problem in the context of general optimization problems over distributions of sampling times. We present a new Prohorov metric based theoretical framework that permits one to treat succinctly and rigorously any optimal design criteria based on the Fisher Information Matrix (FIM). A fundamental approximation theory is also included in this framework. A new optimal design, SE-optimal design (standard error optimal design), is then introduced in the context of this framework. We compare this new design criteria with the more traditional D-optimal and E-optimal designs. The optimal sampling distributions from each design are used to compute and compare standard errors; the standard errors for parameters are computed using asymptotic theory or bootstrapping and the optimal mesh. We use three examples to illustrate ideas: the Verhulst-Pearl logistic population model [13], the standard harmonic oscillator model [13] and a popular glucose regulation model [16, 19, 29]. PMID:21857762

Multiresponse Optimization of Process Parameters in Turning of GFRP Using TOPSIS Method

PubMed Central

Parida, Arun Kumar; Routara, Bharat Chandra

2014-01-01

Taguchi's design of experiment is utilized to optimize the process parameters in turning operation with dry environment. Three parameters, cutting speed (v), feed (f), and depth of cut (d), with three different levels are taken for the responses like material removal rate (MRR) and surface roughness (R a). The machining is conducted with Taguchi L9 orthogonal array, and based on the S/N analysis, the optimal process parameters for surface roughness and MRR are calculated separately. Considering the larger-the-better approach, optimal process parameters for material removal rate are cutting speed at level 3, feed at level 2, and depth of cut at level 3, that is, v 3-f 2-d 3. Similarly for surface roughness, considering smaller-the-better approach, the optimal process parameters are cutting speed at level 1, feed at level 1, and depth of cut at level 3, that is, v 1-f 1-d 3. Results of the main effects plot indicate that depth of cut is the most influencing parameter for MRR but cutting speed is the most influencing parameter for surface roughness and feed is found to be the least influencing parameter for both the responses. The confirmation test is conducted for both MRR and surface roughness separately. Finally, an attempt has been made to optimize the multiresponses using technique for order preference by similarity to ideal solution (TOPSIS) with Taguchi approach. PMID:27437503

Improving flood forecasting capability of physically based distributed hydrological model by parameter optimization

NASA Astrophysics Data System (ADS)

Chen, Y.; Li, J.; Xu, H.

2015-10-01

Physically based distributed hydrological models discrete the terrain of the whole catchment into a number of grid cells at fine resolution, and assimilate different terrain data and precipitation to different cells, and are regarded to have the potential to improve the catchment hydrological processes simulation and prediction capability. In the early stage, physically based distributed hydrological models are assumed to derive model parameters from the terrain properties directly, so there is no need to calibrate model parameters, but unfortunately, the uncertanties associated with this model parameter deriving is very high, which impacted their application in flood forecasting, so parameter optimization may also be necessary. There are two main purposes for this study, the first is to propose a parameter optimization method for physically based distributed hydrological models in catchment flood forecasting by using PSO algorithm and to test its competence and to improve its performances, the second is to explore the possibility of improving physically based distributed hydrological models capability in cathcment flood forecasting by parameter optimization. In this paper, based on the scalar concept, a general framework for parameter optimization of the PBDHMs for catchment flood forecasting is first proposed that could be used for all PBDHMs. Then, with Liuxihe model as the study model, which is a physically based distributed hydrological model proposed for catchment flood forecasting, the improverd Particle Swarm Optimization (PSO) algorithm is developed for the parameter optimization of Liuxihe model in catchment flood forecasting, the improvements include to adopt the linear decreasing inertia weight strategy to change the inertia weight, and the arccosine function strategy to adjust the acceleration coefficients. This method has been tested in two catchments in southern China with different sizes, and the results show that the improved PSO algorithm could be used for Liuxihe model parameter optimization effectively, and could improve the model capability largely in catchment flood forecasting, thus proven that parameter optimization is necessary to improve the flood forecasting capability of physically based distributed hydrological model. It also has been found that the appropriate particle number and the maximum evolution number of PSO algorithm used for Liuxihe model catchment flood forcasting is 20 and 30, respectively.

Electrically evoked compound action potentials recorded from the sheep spinal cord.

PubMed

Parker, John L; Karantonis, Dean M; Single, Peter S; Obradovic, Milan; Laird, James; Gorman, Robert B; Ladd, Leigh A; Cousins, Michael J

2013-01-01

The study aims to characterize the electrical response of dorsal column axons to depolarizing stimuli to help understand the mechanisms of spinal cord stimulation (SCS) for the relief of chronic pain. We recorded electrically evoked compound action potentials (ECAPs) during SCS in 10 anesthetized sheep using stimulating and recording electrodes on the same epidural SCS leads. A novel stimulating and recording system allowed artifact contamination of the ECAP to be minimized. The ECAP in the sheep spinal cord demonstrates a triphasic morphology, with P1, N1, and P2 peaks. The amplitude of the ECAP varies along the length of the spinal cord, with minimum amplitudes recorded from electrodes positioned over each intervertebral disc, and maximum amplitudes recorded in the midvertebral positions. This anatomically correlated depression of ECAP also correlates with the areas of the spinal cord with the highest thresholds for stimulation; thus regions of weakest response invariably had least sensitivity to stimulation by as much as a factor of two. The choice of stimulating electrode location can therefore have a profound effect on the power consumption for an implanted stimulator for SCS. There may be optimal positions for stimulation in the sheep, and this observation may translate to humans. Almost no change in conduction velocity (∼100 ms) was observed with increasing currents from threshold to twice threshold, despite increased Aβ fiber recruitment. Amplitude of sheep Aβ fiber potentials during SCS exhibit dependence on electrode location, highlighting potential optimization of Aβ recruitment and power consumption in SCS devices. © 2013 International Neuromodulation Society.

Short and Long Term Effects of Left and Bilateral Repetitive Transcranial Magnetic Stimulation in Schizophrenia Patients with Auditory Verbal Hallucinations: A Randomized Controlled Trial

PubMed Central

Bais, Leonie; Vercammen, Ans; Stewart, Roy; van Es, Frank; Visser, Bert; Aleman, André; Knegtering, Henderikus

2014-01-01

Background Repetitive transcranial magnetic stimulation of the left temporo-parietal junction area has been studied as a treatment option for auditory verbal hallucinations. Although the right temporo-parietal junction area has also shown involvement in the genesis of auditory verbal hallucinations, no studies have used bilateral stimulation. Moreover, little is known about durability effects. We studied the short and long term effects of 1 Hz treatment of the left temporo-parietal junction area in schizophrenia patients with persistent auditory verbal hallucinations, compared to sham stimulation, and added an extra treatment arm of bilateral TPJ area stimulation. Methods In this randomized controlled trial, 51 patients diagnosed with schizophrenia and persistent auditory verbal hallucinations were randomly allocated to treatment of the left or bilateral temporo-parietal junction area or sham treatment. Patients were treated for six days, twice daily for 20 minutes. Short term efficacy was measured with the Positive and Negative Syndrome Scale (PANSS), the Auditory Hallucinations Rating Scale (AHRS), and the Positive and Negative Affect Scale (PANAS). We included follow-up measures with the AHRS and PANAS at four weeks and three months. Results The interaction between time and treatment for Hallucination item P3 of the PANSS showed a trend for significance, caused by a small reduction of scores in the left group. Although self-reported hallucination scores, as measured with the AHRS and PANAS, decreased significantly during the trial period, there were no differences between the three treatment groups. Conclusion We did not find convincing evidence for the efficacy of left-sided rTMS, compared to sham rTMS. Moreover, bilateral rTMS was not superior over left rTMS or sham in improving AVH. Optimizing treatment parameters may result in stronger evidence for the efficacy of rTMS treatment of AVH. Moreover, future research should consider investigating factors predicting individual response. Trial Registration Dutch Trial Register NTR1813 PMID:25329799

Transcranial infrared laser stimulation improves rule-based, but not information-integration, category learning in humans.

PubMed

Blanco, Nathaniel J; Saucedo, Celeste L; Gonzalez-Lima, F

2017-03-01

This is the first randomized, controlled study comparing the cognitive effects of transcranial laser stimulation on category learning tasks. Transcranial infrared laser stimulation is a new non-invasive form of brain stimulation that shows promise for wide-ranging experimental and neuropsychological applications. It involves using infrared laser to enhance cerebral oxygenation and energy metabolism through upregulation of the respiratory enzyme cytochrome oxidase, the primary infrared photon acceptor in cells. Previous research found that transcranial infrared laser stimulation aimed at the prefrontal cortex can improve sustained attention, short-term memory, and executive function. In this study, we directly investigated the influence of transcranial infrared laser stimulation on two neurobiologically dissociable systems of category learning: a prefrontal cortex mediated reflective system that learns categories using explicit rules, and a striatally mediated reflexive learning system that forms gradual stimulus-response associations. Participants (n=118) received either active infrared laser to the lateral prefrontal cortex or sham (placebo) stimulation, and then learned one of two category structures-a rule-based structure optimally learned by the reflective system, or an information-integration structure optimally learned by the reflexive system. We found that prefrontal rule-based learning was substantially improved following transcranial infrared laser stimulation as compared to placebo (treatment X block interaction: F(1, 298)=5.117, p=0.024), while information-integration learning did not show significant group differences (treatment X block interaction: F(1, 288)=1.633, p=0.202). These results highlight the exciting potential of transcranial infrared laser stimulation for cognitive enhancement and provide insight into the neurobiological underpinnings of category learning. Copyright © 2017 Elsevier Inc. All rights reserved.

State estimation bias induced by optimization under uncertainty and error cost asymmetry is likely reflected in perception.

PubMed

Shimansky, Y P

2011-05-01

It is well known from numerous studies that perception can be significantly affected by intended action in many everyday situations, indicating that perception and related decision-making is not a simple, one-way sequence, but a complex iterative cognitive process. However, the underlying functional mechanisms are yet unclear. Based on an optimality approach, a quantitative computational model of one such mechanism has been developed in this study. It is assumed in the model that significant uncertainty about task-related parameters of the environment results in parameter estimation errors and an optimal control system should minimize the cost of such errors in terms of the optimality criterion. It is demonstrated that, if the cost of a parameter estimation error is significantly asymmetrical with respect to error direction, the tendency to minimize error cost creates a systematic deviation of the optimal parameter estimate from its maximum likelihood value. Consequently, optimization of parameter estimate and optimization of control action cannot be performed separately from each other under parameter uncertainty combined with asymmetry of estimation error cost, thus making the certainty equivalence principle non-applicable under those conditions. A hypothesis that not only the action, but also perception itself is biased by the above deviation of parameter estimate is supported by ample experimental evidence. The results provide important insights into the cognitive mechanisms of interaction between sensory perception and planning an action under realistic conditions. Implications for understanding related functional mechanisms of optimal control in the CNS are discussed.

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.

Stimulation sites in the subthalamic nucleus projected onto a mean 3-D atlas of the thalamus and basal ganglia.

PubMed

Sarnthein, Johannes; Péus, Dominik; Baumann-Vogel, Heide; Baumann, Christian R; Sürücü, Oguzkan

2013-09-01

In patients with severe forms of Parkinson's disease (PD), deep brain stimulation (DBS) commonly targets the subthalamic nucleus (STN). Recently, the mean 3-D Morel-Atlas of the basal ganglia and the thalamus was introduced. It combines information contained in histological data from ten post-mortem brains. We were interested whether the Morel-Atlas is applicable for the visualization of stimulation sites. In a consecutive PD patient series, we documented preoperative MRI planning, intraoperative target adjustment based on electrophysiological and neurological testing, and perioperative CT target reconstruction. The localization of the DBS electrodes and the optimal stimulation sites were projected onto the Morel-Atlas. We included 20 patients (median age 62 years). The active contact had mean coordinates Xlat = ±12.1 mm, Yap = -1.8 mm, Zvert = -3.2 mm. There was a significant difference between the initially planned site and the coordinates of the postoperative active contact site (median 2.2 mm). The stimulation site was, on average, more anterior and more dorsal. The electrode contact used for optimal stimulation was found within the STN of the atlas in 38/40 (95 %) of implantations. The cluster of stimulation sites in individual patients-as deduced from preoperative MR, intraoperative electrophysiology and neurological testing-showed a high degree of congruence with the atlas. The mean 3D Morel Atlas is thus a useful tool for postoperative target visualization. This represents the first clinical evaluation of the recently created atlas.

A stochastic optimization model under modeling uncertainty and parameter certainty for groundwater remediation design--part I. Model development.

PubMed

He, L; Huang, G H; Lu, H W

2010-04-15

Solving groundwater remediation optimization problems based on proxy simulators can usually yield optimal solutions differing from the "true" ones of the problem. This study presents a new stochastic optimization model under modeling uncertainty and parameter certainty (SOMUM) and the associated solution method for simultaneously addressing modeling uncertainty associated with simulator residuals and optimizing groundwater remediation processes. This is a new attempt different from the previous modeling efforts. The previous ones focused on addressing uncertainty in physical parameters (i.e. soil porosity) while this one aims to deal with uncertainty in mathematical simulator (arising from model residuals). Compared to the existing modeling approaches (i.e. only parameter uncertainty is considered), the model has the advantages of providing mean-variance analysis for contaminant concentrations, mitigating the effects of modeling uncertainties on optimal remediation strategies, offering confidence level of optimal remediation strategies to system designers, and reducing computational cost in optimization processes. 2009 Elsevier B.V. All rights reserved.

Genetic Algorithm Optimizes Q-LAW Control Parameters

NASA Technical Reports Server (NTRS)

Lee, Seungwon; von Allmen, Paul; Petropoulos, Anastassios; Terrile, Richard

2008-01-01

A document discusses a multi-objective, genetic algorithm designed to optimize Lyapunov feedback control law (Q-law) parameters in order to efficiently find Pareto-optimal solutions for low-thrust trajectories for electronic propulsion systems. These would be propellant-optimal solutions for a given flight time, or flight time optimal solutions for a given propellant requirement. The approximate solutions are used as good initial solutions for high-fidelity optimization tools. When the good initial solutions are used, the high-fidelity optimization tools quickly converge to a locally optimal solution near the initial solution. Q-law control parameters are represented as real-valued genes in the genetic algorithm. The performances of the Q-law control parameters are evaluated in the multi-objective space (flight time vs. propellant mass) and sorted by the non-dominated sorting method that assigns a better fitness value to the solutions that are dominated by a fewer number of other solutions. With the ranking result, the genetic algorithm encourages the solutions with higher fitness values to participate in the reproduction process, improving the solutions in the evolution process. The population of solutions converges to the Pareto front that is permitted within the Q-law control parameter space.

New generation photoelectric converter structure optimization using nano-structured materials

NASA Astrophysics Data System (ADS)

Dronov, A.; Gavrilin, I.; Zheleznyakova, A.

2014-12-01

In present work the influence of anodizing process parameters on PAOT geometric parameters for optimizing and increasing ETA-cell efficiency was studied. During the calculations optimal geometrical parameters were obtained. Parameters such as anodizing current density, electrolyte composition and temperature, as well as the anodic oxidation process time were selected for this investigation. Using the optimized TiO2 photoelectrode layer with 3,6 μm porous layer thickness and pore diameter more than 80 nm the ETA-cell efficiency has been increased by 3 times comparing to not nanostructured TiO2 photoelectrode.

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.

A model for flexi-bar to evaluate intervertebral disc and muscle forces in exercises.

PubMed

Abdollahi, Masoud; Nikkhoo, Mohammad; Ashouri, Sajad; Asghari, Mohsen; Parnianpour, Mohamad; Khalaf, Kinda

2016-10-01

This study developed and validated a lumped parameter model for the FLEXI-BAR, a popular training instrument that provides vibration stimulation. The model which can be used in conjunction with musculoskeletal-modeling software for quantitative biomechanical analyses, consists of 3 rigid segments, 2 torsional springs, and 2 torsional dashpots. Two different sets of experiments were conducted to determine the model's key parameters including the stiffness of the springs and the damping ratio of the dashpots. In the first set of experiments, the free vibration of the FLEXI-BAR with an initial displacement at its end was considered, while in the second set, forced oscillations of the bar were studied. The properties of the mechanical elements in the lumped parameter model were derived utilizing a non-linear optimization algorithm which minimized the difference between the model's prediction and the experimental data. The results showed that the model is valid (8% error) and can be used for simulating exercises with the FLEXI-BAR for excitations in the range of the natural frequency. The model was then validated in combination with AnyBody musculoskeletal modeling software, where various lumbar disc, spinal muscles and hand muscles forces were determined during different FLEXI-BAR exercise simulations. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

A practical model of thin disk regenerative amplifier based on analytical expression of ASE lifetime

NASA Astrophysics Data System (ADS)

Zhou, Huang; Chyla, Michal; Nagisetty, Siva Sankar; Chen, Liyuan; Endo, Akira; Smrz, Martin; Mocek, Tomas

2017-12-01

In this paper, a practical model of a thin disk regenerative amplifier has been developed based on an analytical approach, in which Drew A. Copeland [1] had evaluated the loss rate of the upper state laser level due to ASE and derived the analytical expression of the effective life-time of the upper-state laser level by taking the Lorentzian stimulated emission line-shape and total internal reflection into account. By adopting the analytical expression of effective life-time in the rate equations, we have developed a less numerically intensive model for predicting and analyzing the performance of a thin disk regenerative amplifier. Thanks to the model, optimized combination of various parameters can be obtained to avoid saturation, period-doubling bifurcation or first pulse suppression prior to experiments. The effective life-time due to ASE is also analyzed against various parameters. The simulated results fit well with experimental data. By fitting more experimental results with numerical model, we can improve the parameters of the model, such as reflective factor which is used to determine the weight of boundary reflection within the influence of ASE. This practical model will be used to explore the scaling limits imposed by ASE of the thin disk regenerative amplifier being developed in HiLASE Centre.

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.

Optimization and evaluation of a proportional derivative controller for planar arm movement.

PubMed

Jagodnik, Kathleen M; van den Bogert, Antonie J

2010-04-19

In most clinical applications of functional electrical stimulation (FES), the timing and amplitude of electrical stimuli have been controlled by open-loop pattern generators. The control of upper extremity reaching movements, however, will require feedback control to achieve the required precision. Here we present three controllers using proportional derivative (PD) feedback to stimulate six arm muscles, using two joint angle sensors. Controllers were first optimized and then evaluated on a computational arm model that includes musculoskeletal dynamics. Feedback gains were optimized by minimizing a weighted sum of position errors and muscle forces. Generalizability of the controllers was evaluated by performing movements for which the controller was not optimized, and robustness was tested via model simulations with randomly weakened muscles. Robustness was further evaluated by adding joint friction and doubling the arm mass. After optimization with a properly weighted cost function, all PD controllers performed fast, accurate, and robust reaching movements in simulation. Oscillatory behavior was seen after improper tuning. Performance improved slightly as the complexity of the feedback gain matrix increased. Copyright 2009 Elsevier Ltd. All rights reserved.

Optimization and evaluation of a proportional derivative controller for planar arm movement

PubMed Central

Jagodnik, Kathleen M.; van den Bogert, Antonie J.

2013-01-01

In most clinical applications of functional electrical stimulation (FES), the timing and amplitude of electrical stimuli have been controlled by open-loop pattern generators. The control of upper extremity reaching movements, however, will require feedback control to achieve the required precision. Here we present three controllers using proportional derivative (PD) feedback to stimulate six arm muscles, using two joint angle sensors. Controllers were first optimized and then evaluated on a computational arm model that includes musculoskeletal dynamics. Feedback gains were optimized by minimizing a weighted sum of position errors and muscle forces. Generalizability of the controllers was evaluated by performing movements for which the controller was not optimized, and robustness was tested via model simulations with randomly weakened muscles. Robustness was further evaluated by adding joint friction and doubling the arm mass. After optimization with a properly weighted cost function, all PD controllers performed fast, accurate, and robust reaching movements in simulation. Oscillatory behavior was seen after improper tuning. Performance improved slightly as the complexity of the feedback gain matrix increased. PMID:20097345

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.

JuPOETs: a constrained multiobjective optimization approach to estimate biochemical model ensembles in the Julia programming language.

PubMed

Bassen, David M; Vilkhovoy, Michael; Minot, Mason; Butcher, Jonathan T; Varner, Jeffrey D

2017-01-25

Ensemble modeling is a promising approach for obtaining robust predictions and coarse grained population behavior in deterministic mathematical models. Ensemble approaches address model uncertainty by using parameter or model families instead of single best-fit parameters or fixed model structures. Parameter ensembles can be selected based upon simulation error, along with other criteria such as diversity or steady-state performance. Simulations using parameter ensembles can estimate confidence intervals on model variables, and robustly constrain model predictions, despite having many poorly constrained parameters. In this software note, we present a multiobjective based technique to estimate parameter or models ensembles, the Pareto Optimal Ensemble Technique in the Julia programming language (JuPOETs). JuPOETs integrates simulated annealing with Pareto optimality to estimate ensembles on or near the optimal tradeoff surface between competing training objectives. We demonstrate JuPOETs on a suite of multiobjective problems, including test functions with parameter bounds and system constraints as well as for the identification of a proof-of-concept biochemical model with four conflicting training objectives. JuPOETs identified optimal or near optimal solutions approximately six-fold faster than a corresponding implementation in Octave for the suite of test functions. For the proof-of-concept biochemical model, JuPOETs produced an ensemble of parameters that gave both the mean of the training data for conflicting data sets, while simultaneously estimating parameter sets that performed well on each of the individual objective functions. JuPOETs is a promising approach for the estimation of parameter and model ensembles using multiobjective optimization. JuPOETs can be adapted to solve many problem types, including mixed binary and continuous variable types, bilevel optimization problems and constrained problems without altering the base algorithm. JuPOETs is open source, available under an MIT license, and can be installed using the Julia package manager from the JuPOETs GitHub repository.

Design of transcranial magnetic stimulation coils with optimal trade-off between depth, focality, and energy.

PubMed

Gomez, Luis J; Goetz, Stefan M; Peterchev, Angel V

2018-08-01

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique used for research and clinical applications. Existent TMS coils are limited in their precision of spatial targeting (focality), especially for deeper targets. This paper presents a methodology for designing TMS coils to achieve optimal trade-off between the depth and focality of the induced electric field (E-field), as well as the energy required by the coil. A multi-objective optimization technique is used for computationally designing TMS coils that achieve optimal trade-offs between E-field focality, depth, and energy (fdTMS coils). The fdTMS coil winding(s) maximize focality (minimize the volume of the brain region with E-field above a given threshold) while reaching a target at a specified depth and not exceeding predefined peak E-field strength and required coil energy. Spherical and MRI-derived head models are used to compute the fundamental depth-focality trade-off as well as focality-energy trade-offs for specific target depths. Across stimulation target depths of 1.0-3.4 cm from the brain surface, the suprathreshold volume can be theoretically decreased by 42%-55% compared to existing TMS coil designs. The suprathreshold volume of a figure-8 coil can be decreased by 36%, 44%, or 46%, for matched, doubled, or quadrupled energy. For matched focality and energy, the depth of a figure-8 coil can be increased by 22%. Computational design of TMS coils could enable more selective targeting of the induced E-field. The presented results appear to be the first significant advancement in the depth-focality trade-off of TMS coils since the introduction of the figure-8 coil three decades ago, and likely represent the fundamental physical limit.

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

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 Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy

DTIC Science & Technology

2015-09-01

Award Number: W81XWH-11-1-0384 TITLE: Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells : Implications for...Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells : Implications for Cancer Vaccine Therapy 5b. GRANT NUMBER CA100463 5c...Listeria monocytogenes (Lm) on human dendritic cells (DCs) to optimize Lm-based DC cancer vaccines. The project aims are: 1) Compare the activation and

Optimal Control Method of Robot End Position and Orientation Based on Dynamic Tracking Measurement

NASA Astrophysics Data System (ADS)

Liu, Dalong; Xu, Lijuan

2018-01-01

In order to improve the accuracy of robot pose positioning and control, this paper proposed a dynamic tracking measurement robot pose optimization control method based on the actual measurement of D-H parameters of the robot, the parameters is taken with feedback compensation of the robot, according to the geometrical parameters obtained by robot pose tracking measurement, improved multi sensor information fusion the extended Kalan filter method, with continuous self-optimal regression, using the geometric relationship between joint axes for kinematic parameters in the model, link model parameters obtained can timely feedback to the robot, the implementation of parameter correction and compensation, finally we can get the optimal attitude angle, realize the robot pose optimization control experiments were performed. 6R dynamic tracking control of robot joint robot with independent research and development is taken as experimental subject, the simulation results show that the control method improves robot positioning accuracy, and it has the advantages of versatility, simplicity, ease of operation and so on.

Design of Experiments for the Thermal Characterization of Metallic Foam

NASA Technical Reports Server (NTRS)

Crittenden, Paul E.; Cole, Kevin D.

2003-01-01

Metallic foams are being investigated for possible use in the thermal protection systems of reusable launch vehicles. As a result, the performance of these materials needs to be characterized over a wide range of temperatures and pressures. In this paper a radiation/conduction model is presented for heat transfer in metallic foams. Candidates for the optimal transient experiment to determine the intrinsic properties of the model are found by two methods. First, an optimality criterion is used to find an experiment to find all of the parameters using one heating event. Second, a pair of heating events is used to determine the parameters in which one heating event is optimal for finding the parameters related to conduction, while the other heating event is optimal for finding the parameters associated with radiation. Simulated data containing random noise was analyzed to determine the parameters using both methods. In all cases the parameter estimates could be improved by analyzing a larger data record than suggested by the optimality criterion.

Optimization of seismic isolation systems via harmony search

NASA Astrophysics Data System (ADS)

Melih Nigdeli, Sinan; Bekdaş, Gebrail; Alhan, Cenk

2014-11-01

In this article, the optimization of isolation system parameters via the harmony search (HS) optimization method is proposed for seismically isolated buildings subjected to both near-fault and far-fault earthquakes. To obtain optimum values of isolation system parameters, an optimization program was developed in Matlab/Simulink employing the HS algorithm. The objective was to obtain a set of isolation system parameters within a defined range that minimizes the acceleration response of a seismically isolated structure subjected to various earthquakes without exceeding a peak isolation system displacement limit. Several cases were investigated for different isolation system damping ratios and peak displacement limitations of seismic isolation devices. Time history analyses were repeated for the neighbouring parameters of optimum values and the results proved that the parameters determined via HS were true optima. The performance of the optimum isolation system was tested under a second set of earthquakes that was different from the first set used in the optimization process. The proposed optimization approach is applicable to linear isolation systems. Isolation systems composed of isolation elements that are inherently nonlinear are the subject of a future study. Investigation of the optimum isolation system parameters has been considered in parametric studies. However, obtaining the best performance of a seismic isolation system requires a true optimization by taking the possibility of both near-fault and far-fault earthquakes into account. HS optimization is proposed here as a viable solution to this problem.

Sequential ensemble-based optimal design for parameter estimation: SEQUENTIAL ENSEMBLE-BASED OPTIMAL DESIGN

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

Man, Jun; Zhang, Jiangjiang; Li, Weixuan

2016-10-01

The ensemble Kalman filter (EnKF) has been widely used in parameter estimation for hydrological models. The focus of most previous studies was to develop more efficient analysis (estimation) algorithms. On the other hand, it is intuitively understandable that a well-designed sampling (data-collection) strategy should provide more informative measurements and subsequently improve the parameter estimation. In this work, a Sequential Ensemble-based Optimal Design (SEOD) method, coupled with EnKF, information theory and sequential optimal design, is proposed to improve the performance of parameter estimation. Based on the first-order and second-order statistics, different information metrics including the Shannon entropy difference (SD), degrees ofmore » freedom for signal (DFS) and relative entropy (RE) are used to design the optimal sampling strategy, respectively. The effectiveness of the proposed method is illustrated by synthetic one-dimensional and two-dimensional unsaturated flow case studies. It is shown that the designed sampling strategies can provide more accurate parameter estimation and state prediction compared with conventional sampling strategies. Optimal sampling designs based on various information metrics perform similarly in our cases. The effect of ensemble size on the optimal design is also investigated. Overall, larger ensemble size improves the parameter estimation and convergence of optimal sampling strategy. Although the proposed method is applied to unsaturated flow problems in this study, it can be equally applied in any other hydrological problems.« less

A Short-Term and High-Resolution System Load Forecasting Approach Using Support Vector Regression with Hybrid Parameters Optimization

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

Jiang, Huaiguang

This work proposes an approach for distribution system load forecasting, which aims to provide highly accurate short-term load forecasting with high resolution utilizing a support vector regression (SVR) based forecaster and a two-step hybrid parameters optimization method. Specifically, because the load profiles in distribution systems contain abrupt deviations, a data normalization is designed as the pretreatment for the collected historical load data. Then an SVR model is trained by the load data to forecast the future load. For better performance of SVR, a two-step hybrid optimization algorithm is proposed to determine the best parameters. In the first step of themore » hybrid optimization algorithm, a designed grid traverse algorithm (GTA) is used to narrow the parameters searching area from a global to local space. In the second step, based on the result of the GTA, particle swarm optimization (PSO) is used to determine the best parameters in the local parameter space. After the best parameters are determined, the SVR model is used to forecast the short-term load deviation in the distribution system.« less

Parameter Selection and Performance Comparison of Particle Swarm Optimization in Sensor Networks Localization.

PubMed

Cui, Huanqing; Shu, Minglei; Song, Min; Wang, Yinglong

2017-03-01

Localization is a key technology in wireless sensor networks. Faced with the challenges of the sensors' memory, computational constraints, and limited energy, particle swarm optimization has been widely applied in the localization of wireless sensor networks, demonstrating better performance than other optimization methods. In particle swarm optimization-based localization algorithms, the variants and parameters should be chosen elaborately to achieve the best performance. However, there is a lack of guidance on how to choose these variants and parameters. Further, there is no comprehensive performance comparison among particle swarm optimization algorithms. The main contribution of this paper is three-fold. First, it surveys the popular particle swarm optimization variants and particle swarm optimization-based localization algorithms for wireless sensor networks. Secondly, it presents parameter selection of nine particle swarm optimization variants and six types of swarm topologies by extensive simulations. Thirdly, it comprehensively compares the performance of these algorithms. The results show that the particle swarm optimization with constriction coefficient using ring topology outperforms other variants and swarm topologies, and it performs better than the second-order cone programming algorithm.

Parameter Selection and Performance Comparison of Particle Swarm Optimization in Sensor Networks Localization

PubMed Central

Cui, Huanqing; Shu, Minglei; Song, Min; Wang, Yinglong

2017-01-01

Localization is a key technology in wireless sensor networks. Faced with the challenges of the sensors’ memory, computational constraints, and limited energy, particle swarm optimization has been widely applied in the localization of wireless sensor networks, demonstrating better performance than other optimization methods. In particle swarm optimization-based localization algorithms, the variants and parameters should be chosen elaborately to achieve the best performance. However, there is a lack of guidance on how to choose these variants and parameters. Further, there is no comprehensive performance comparison among particle swarm optimization algorithms. The main contribution of this paper is three-fold. First, it surveys the popular particle swarm optimization variants and particle swarm optimization-based localization algorithms for wireless sensor networks. Secondly, it presents parameter selection of nine particle swarm optimization variants and six types of swarm topologies by extensive simulations. Thirdly, it comprehensively compares the performance of these algorithms. The results show that the particle swarm optimization with constriction coefficient using ring topology outperforms other variants and swarm topologies, and it performs better than the second-order cone programming algorithm. PMID:28257060

Application of the advanced engineering environment for optimization energy consumption in designed vehicles

NASA Astrophysics Data System (ADS)

Monica, Z.; Sękala, A.; Gwiazda, A.; Banaś, W.

2016-08-01

Nowadays a key issue is to reduce the energy consumption of road vehicles. In particular solution one could find different strategies of energy optimization. The most popular but not sophisticated is so called eco-driving. In this strategy emphasized is particular behavior of drivers. In more sophisticated solution behavior of drivers is supported by control system measuring driving parameters and suggesting proper operation of the driver. The other strategy is concerned with application of different engineering solutions that aid optimization the process of energy consumption. Such systems take into consideration different parameters measured in real time and next take proper action according to procedures loaded to the control computer of a vehicle. The third strategy bases on optimization of the designed vehicle taking into account especially main sub-systems of a technical mean. In this approach the optimal level of energy consumption by a vehicle is obtained by synergetic results of individual optimization of particular constructional sub-systems of a vehicle. It is possible to distinguish three main sub-systems: the structural one the drive one and the control one. In the case of the structural sub-system optimization of the energy consumption level is related with the optimization or the weight parameter and optimization the aerodynamic parameter. The result is optimized body of a vehicle. Regarding the drive sub-system the optimization of the energy consumption level is related with the fuel or power consumption using the previously elaborated physical models. Finally the optimization of the control sub-system consists in determining optimal control parameters.

Noninvasive Brain Stimulation in Pediatric Attention-Deficit Hyperactivity Disorder (ADHD): A Review.

PubMed

Rubio, Belen; Boes, Aaron D; Laganiere, Simon; Rotenberg, Alexander; Jeurissen, Danique; Pascual-Leone, Alvaro

2016-05-01

Attention-deficit hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in the pediatric population. The clinical management of ADHD is currently limited by a lack of reliable diagnostic biomarkers and inadequate therapy for a minority of patients who do not respond to standard pharmacotherapy. There is optimism that noninvasive brain stimulation may help to address these limitations. Transcranial magnetic stimulation and transcranial direct current stimulation are 2 methods of noninvasive brain stimulation that modulate cortical excitability and brain network activity. Transcranial magnetic stimulation can be used diagnostically to probe cortical neurophysiology, whereas daily use of repetitive transcranial magnetic stimulation or transcranial direct current stimulation can induce long-lasting and potentially therapeutic changes in targeted networks. In this review, we highlight research showing the potential diagnostic and therapeutic applications of transcranial magnetic stimulation and transcranial direct current stimulation in pediatric ADHD. We also discuss the safety and ethics of using these tools in the pediatric population. © The Author(s) 2015.

Low-dose cone-beam CT via raw counts domain low-signal correction schemes: Performance assessment and task-based parameter optimization (Part II. Task-based parameter optimization).

PubMed

Gomez-Cardona, Daniel; Hayes, John W; Zhang, Ran; Li, Ke; Cruz-Bastida, Juan Pablo; Chen, Guang-Hong

2018-05-01

Different low-signal correction (LSC) methods have been shown to efficiently reduce noise streaks and noise level in CT to provide acceptable images at low-radiation dose levels. These methods usually result in CT images with highly shift-variant and anisotropic spatial resolution and noise, which makes the parameter optimization process highly nontrivial. The purpose of this work was to develop a local task-based parameter optimization framework for LSC methods. Two well-known LSC methods, the adaptive trimmed mean (ATM) filter and the anisotropic diffusion (AD) filter, were used as examples to demonstrate how to use the task-based framework to optimize filter parameter selection. Two parameters, denoted by the set P, for each LSC method were included in the optimization problem. For the ATM filter, these parameters are the low- and high-signal threshold levels p l and p h ; for the AD filter, the parameters are the exponents δ and γ in the brightness gradient function. The detectability index d' under the non-prewhitening (NPW) mathematical observer model was selected as the metric for parameter optimization. The optimization problem was formulated as an unconstrained optimization problem that consisted of maximizing an objective function d'(P), where i and j correspond to the i-th imaging task and j-th spatial location, respectively. Since there is no explicit mathematical function to describe the dependence of d' on the set of parameters P for each LSC method, the optimization problem was solved via an experimentally measured d' map over a densely sampled parameter space. In this work, three high-contrast-high-frequency discrimination imaging tasks were defined to explore the parameter space of each of the LSC methods: a vertical bar pattern (task I), a horizontal bar pattern (task II), and a multidirectional feature (task III). Two spatial locations were considered for the analysis, a posterior region-of-interest (ROI) located within the noise streaks region and an anterior ROI, located further from the noise streaks region. Optimal results derived from the task-based detectability index metric were compared to other operating points in the parameter space with different noise and spatial resolution trade-offs. The optimal operating points determined through the d' metric depended on the interplay between the major spatial frequency components of each imaging task and the highly shift-variant and anisotropic noise and spatial resolution properties associated with each operating point in the LSC parameter space. This interplay influenced imaging performance the most when the major spatial frequency component of a given imaging task coincided with the direction of spatial resolution loss or with the dominant noise spatial frequency component; this was the case of imaging task II. The performance of imaging tasks I and III was influenced by this interplay in a smaller scale than imaging task II, since the major frequency component of task I was perpendicular to imaging task II, and because imaging task III did not have strong directional dependence. For both LSC methods, there was a strong dependence of the overall d' magnitude and shape of the contours on the spatial location within the phantom, particularly for imaging tasks II and III. The d' value obtained at the optimal operating point for each spatial location and imaging task was similar when comparing the LSC methods studied in this work. A local task-based detectability framework to optimize the selection of parameters for LSC methods was developed. The framework takes into account the potential shift-variant and anisotropic spatial resolution and noise properties to maximize the imaging performance of the CT system. Optimal parameters for a given LSC method depend strongly on the spatial location within the image object. © 2018 American Association of Physicists in Medicine.

Recursive Branching Simulated Annealing Algorithm

NASA Technical Reports Server (NTRS)

Bolcar, Matthew; Smith, J. Scott; Aronstein, David

2012-01-01

This innovation is a variation of a simulated-annealing optimization algorithm that uses a recursive-branching structure to parallelize the search of a parameter space for the globally optimal solution to an objective. The algorithm has been demonstrated to be more effective at searching a parameter space than traditional simulated-annealing methods for a particular problem of interest, and it can readily be applied to a wide variety of optimization problems, including those with a parameter space having both discrete-value parameters (combinatorial) and continuous-variable parameters. It can take the place of a conventional simulated- annealing, Monte-Carlo, or random- walk algorithm. In a conventional simulated-annealing (SA) algorithm, a starting configuration is randomly selected within the parameter space. The algorithm randomly selects another configuration from the parameter space and evaluates the objective function for that configuration. If the objective function value is better than the previous value, the new configuration is adopted as the new point of interest in the parameter space. If the objective function value is worse than the previous value, the new configuration may be adopted, with a probability determined by a temperature parameter, used in analogy to annealing in metals. As the optimization continues, the region of the parameter space from which new configurations can be selected shrinks, and in conjunction with lowering the annealing temperature (and thus lowering the probability for adopting configurations in parameter space with worse objective functions), the algorithm can converge on the globally optimal configuration. The Recursive Branching Simulated Annealing (RBSA) algorithm shares some features with the SA algorithm, notably including the basic principles that a starting configuration is randomly selected from within the parameter space, the algorithm tests other configurations with the goal of finding the globally optimal solution, and the region from which new configurations can be selected shrinks as the search continues. The key difference between these algorithms is that in the SA algorithm, a single path, or trajectory, is taken in parameter space, from the starting point to the globally optimal solution, while in the RBSA algorithm, many trajectories are taken; by exploring multiple regions of the parameter space simultaneously, the algorithm has been shown to converge on the globally optimal solution about an order of magnitude faster than when using conventional algorithms. Novel features of the RBSA algorithm include: 1. More efficient searching of the parameter space due to the branching structure, in which multiple random configurations are generated and multiple promising regions of the parameter space are explored; 2. The implementation of a trust region for each parameter in the parameter space, which provides a natural way of enforcing upper- and lower-bound constraints on the parameters; and 3. The optional use of a constrained gradient- search optimization, performed on the continuous variables around each branch s configuration in parameter space to improve search efficiency by allowing for fast fine-tuning of the continuous variables within the trust region at that configuration point.

A survey of techniques for architecting and managing GPU register file

DOE PAGES

Mittal, Sparsh

2016-04-07

To support their massively-multithreaded architecture, GPUs use very large register file (RF) which has a capacity higher than even L1 and L2 caches. In total contrast, traditional CPUs use tiny RF and much larger caches to optimize latency. Due to these differences, along with the crucial impact of RF in determining GPU performance, novel and intelligent techniques are required for managing GPU RF. In this paper, we survey the techniques for designing and managing GPU RF. We discuss techniques related to performance, energy and reliability aspects of RF. To emphasize the similarities and differences between the techniques, we classify themmore » along several parameters. Lastly, the aim of this paper is to synthesize the state-of-art developments in RF management and also stimulate further research in this area.« less

A survey of techniques for architecting and managing GPU register file

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

Mittal, Sparsh

To support their massively-multithreaded architecture, GPUs use very large register file (RF) which has a capacity higher than even L1 and L2 caches. In total contrast, traditional CPUs use tiny RF and much larger caches to optimize latency. Due to these differences, along with the crucial impact of RF in determining GPU performance, novel and intelligent techniques are required for managing GPU RF. In this paper, we survey the techniques for designing and managing GPU RF. We discuss techniques related to performance, energy and reliability aspects of RF. To emphasize the similarities and differences between the techniques, we classify themmore » along several parameters. Lastly, the aim of this paper is to synthesize the state-of-art developments in RF management and also stimulate further research in this area.« less

Optimizing Photosynthetic and Respiratory Parameters Based on the Seasonal Variation Pattern in Regional Net Ecosystem Productivity Obtained from Atmospheric Inversion

NASA Astrophysics Data System (ADS)

Chen, Z.; Chen, J.; Zheng, X.; Jiang, F.; Zhang, S.; Ju, W.; Yuan, W.; Mo, G.

2014-12-01

In this study, we explore the feasibility of optimizing ecosystem photosynthetic and respiratory parameters from the seasonal variation pattern of the net carbon flux. An optimization scheme is proposed to estimate two key parameters (Vcmax and Q10) by exploiting the seasonal variation in the net ecosystem carbon flux retrieved by an atmospheric inversion system. This scheme is implemented to estimate Vcmax and Q10 of the Boreal Ecosystem Productivity Simulator (BEPS) to improve its NEP simulation in the Boreal North America (BNA) region. Simultaneously, in-situ NEE observations at six eddy covariance sites are used to evaluate the NEE simulations. The results show that the performance of the optimized BEPS is superior to that of the BEPS with the default parameter values. These results have the implication on using atmospheric CO2 data for optimizing ecosystem parameters through atmospheric inversion or data assimilation techniques.

Gaussian mass optimization for kernel PCA parameters

NASA Astrophysics Data System (ADS)

Liu, Yong; Wang, Zulin

2011-10-01

This paper proposes a novel kernel parameter optimization method based on Gaussian mass, which aims to overcome the current brute force parameter optimization method in a heuristic way. Generally speaking, the choice of kernel parameter should be tightly related to the target objects while the variance between the samples, the most commonly used kernel parameter, doesn't possess much features of the target, which gives birth to Gaussian mass. Gaussian mass defined in this paper has the property of the invariance of rotation and translation and is capable of depicting the edge, topology and shape information. Simulation results show that Gaussian mass leads a promising heuristic optimization boost up for kernel method. In MNIST handwriting database, the recognition rate improves by 1.6% compared with common kernel method without Gaussian mass optimization. Several promising other directions which Gaussian mass might help are also proposed at the end of the paper.

Activity In Children With ADHD During Waiting Situations In The Classroom: A Pilot Study

ERIC Educational Resources Information Center

Antrop, Inge; Buysse, Ann; Roeyers, Herbert; Van Oost, Paulette

2005-01-01

Background: According to the optimal stimulation theory and the delay aversion hypothesis, children with attention deficit hyperactivity disorder (ADHD) experience difficulties when they are confronted with low levels of stimulation and delay, respectively. Aim: This study investigated the activity level of children with ADHD during waiting…

Effects of Color Stimulation and Information on the Copying Performance of Attention-Problem Adolescents.

ERIC Educational Resources Information Center

Zentall, Sydney S.; And Others

The optimal stimulaton theory (which proposes that hyperactive children are more readily underaroused than nonhyperactive children and should thus derive greater gains from stimulation added to repetitive copying tasks than comparisons) was tested with 16 adolescents, rating high on attention and behavior problems, and 16 controls. Matched pairs…

Improved Microseismicity Detection During Newberry EGS Stimulations

DOE Data Explorer

Templeton, Dennise

2013-10-01

Effective enhanced geothermal systems (EGS) require optimal fracture networks for efficient heat transfer between hot rock and fluid. Microseismic mapping is a key tool used to infer the subsurface fracture geometry. Traditional earthquake detection and location techniques are often employed to identify microearthquakes in geothermal regions. However, most commonly used algorithms may miss events if the seismic signal of an earthquake is small relative to the background noise level or if a microearthquake occurs within the coda of a larger event. Consequently, we have developed a set of algorithms that provide improved microearthquake detection. Our objective is to investigate the microseismicity at the DOE Newberry EGS site to better image the active regions of the underground fracture network during and immediately after the EGS stimulation. Detection of more microearthquakes during EGS stimulations will allow for better seismic delineation of the active regions of the underground fracture system. This improved knowledge of the reservoir network will improve our understanding of subsurface conditions, and allow improvement of the stimulation strategy that will optimize heat extraction and maximize economic return.

Improved Microseismicity Detection During Newberry EGS Stimulations

DOE Data Explorer

Templeton, Dennise

2013-11-01

Effective enhanced geothermal systems (EGS) require optimal fracture networks for efficient heat transfer between hot rock and fluid. Microseismic mapping is a key tool used to infer the subsurface fracture geometry. Traditional earthquake detection and location techniques are often employed to identify microearthquakes in geothermal regions. However, most commonly used algorithms may miss events if the seismic signal of an earthquake is small relative to the background noise level or if a microearthquake occurs within the coda of a larger event. Consequently, we have developed a set of algorithms that provide improved microearthquake detection. Our objective is to investigate the microseismicity at the DOE Newberry EGS site to better image the active regions of the underground fracture network during and immediately after the EGS stimulation. Detection of more microearthquakes during EGS stimulations will allow for better seismic delineation of the active regions of the underground fracture system. This improved knowledge of the reservoir network will improve our understanding of subsurface conditions, and allow improvement of the stimulation strategy that will optimize heat extraction and maximize economic return.

Feasibility of employing model-based optimization of pulse amplitude and electrode distance for effective tumor electropermeabilization.

PubMed

Sel, Davorka; Lebar, Alenka Macek; Miklavcic, Damijan

2007-05-01

In electrochemotherapy (ECT) electropermeabilization, parameters (pulse amplitude, electrode setup) need to be customized in order to expose the whole tumor to electric field intensities above permeabilizing threshold to achieve effective ECT. In this paper, we present a model-based optimization approach toward determination of optimal electropermeabilization parameters for effective ECT. The optimization is carried out by minimizing the difference between the permeabilization threshold and electric field intensities computed by finite element model in selected points of tumor. We examined the feasibility of model-based optimization of electropermeabilization parameters on a model geometry generated from computer tomography images, representing brain tissue with tumor. Continuous parameter subject to optimization was pulse amplitude. The distance between electrode pairs was optimized as a discrete parameter. Optimization also considered the pulse generator constraints on voltage and current. During optimization the two constraints were reached preventing the exposure of the entire volume of the tumor to electric field intensities above permeabilizing threshold. However, despite the fact that with the particular needle array holder and pulse generator the entire volume of the tumor was not permeabilized, the maximal extent of permeabilization for the particular case (electrodes, tissue) was determined with the proposed approach. Model-based optimization approach could also be used for electro-gene transfer, where electric field intensities should be distributed between permeabilizing threshold and irreversible threshold-the latter causing tissue necrosis. This can be obtained by adding constraints on maximum electric field intensity in optimization procedure.

Bayesian Optimization for Neuroimaging Pre-processing in Brain Age Classification and Prediction

PubMed Central

Lancaster, Jenessa; Lorenz, Romy; Leech, Rob; Cole, James H.

2018-01-01

Neuroimaging-based age prediction using machine learning is proposed as a biomarker of brain aging, relating to cognitive performance, health outcomes and progression of neurodegenerative disease. However, even leading age-prediction algorithms contain measurement error, motivating efforts to improve experimental pipelines. T1-weighted MRI is commonly used for age prediction, and the pre-processing of these scans involves normalization to a common template and resampling to a common voxel size, followed by spatial smoothing. Resampling parameters are often selected arbitrarily. Here, we sought to improve brain-age prediction accuracy by optimizing resampling parameters using Bayesian optimization. Using data on N = 2003 healthy individuals (aged 16–90 years) we trained support vector machines to (i) distinguish between young (<22 years) and old (>50 years) brains (classification) and (ii) predict chronological age (regression). We also evaluated generalisability of the age-regression model to an independent dataset (CamCAN, N = 648, aged 18–88 years). Bayesian optimization was used to identify optimal voxel size and smoothing kernel size for each task. This procedure adaptively samples the parameter space to evaluate accuracy across a range of possible parameters, using independent sub-samples to iteratively assess different parameter combinations to arrive at optimal values. When distinguishing between young and old brains a classification accuracy of 88.1% was achieved, (optimal voxel size = 11.5 mm3, smoothing kernel = 2.3 mm). For predicting chronological age, a mean absolute error (MAE) of 5.08 years was achieved, (optimal voxel size = 3.73 mm3, smoothing kernel = 3.68 mm). This was compared to performance using default values of 1.5 mm3 and 4mm respectively, resulting in MAE = 5.48 years, though this 7.3% improvement was not statistically significant. When assessing generalisability, best performance was achieved when applying the entire Bayesian optimization framework to the new dataset, out-performing the parameters optimized for the initial training dataset. Our study outlines the proof-of-principle that neuroimaging models for brain-age prediction can use Bayesian optimization to derive case-specific pre-processing parameters. Our results suggest that different pre-processing parameters are selected when optimization is conducted in specific contexts. This potentially motivates use of optimization techniques at many different points during the experimental process, which may improve statistical sensitivity and reduce opportunities for experimenter-led bias. PMID:29483870

Optimization and Simulation of SLM Process for High Density H13 Tool Steel Parts

NASA Astrophysics Data System (ADS)

Laakso, Petri; Riipinen, Tuomas; Laukkanen, Anssi; Andersson, Tom; Jokinen, Antero; Revuelta, Alejandro; Ruusuvuori, Kimmo

This paper demonstrates the successful printing and optimization of processing parameters of high-strength H13 tool steel by Selective Laser Melting (SLM). D-Optimal Design of Experiments (DOE) approach is used for parameter optimization of laser power, scanning speed and hatch width. With 50 test samples (1×1×1cm) we establish parameter windows for these three parameters in relation to part density. The calculated numerical model is found to be in good agreement with the density data obtained from the samples using image analysis. A thermomechanical finite element simulation model is constructed of the SLM process and validated by comparing the calculated densities retrieved from the model with the experimentally determined densities. With the simulation tool one can explore the effect of different parameters on density before making any printed samples. Establishing a parameter window provides the user with freedom for parameter selection such as choosing parameters that result in fastest print speed.

Probability distribution functions for unit hydrographs with optimization using genetic algorithm

NASA Astrophysics Data System (ADS)

Ghorbani, Mohammad Ali; Singh, Vijay P.; Sivakumar, Bellie; H. Kashani, Mahsa; Atre, Atul Arvind; Asadi, Hakimeh

2017-05-01

A unit hydrograph (UH) of a watershed may be viewed as the unit pulse response function of a linear system. In recent years, the use of probability distribution functions (pdfs) for determining a UH has received much attention. In this study, a nonlinear optimization model is developed to transmute a UH into a pdf. The potential of six popular pdfs, namely two-parameter gamma, two-parameter Gumbel, two-parameter log-normal, two-parameter normal, three-parameter Pearson distribution, and two-parameter Weibull is tested on data from the Lighvan catchment in Iran. The probability distribution parameters are determined using the nonlinear least squares optimization method in two ways: (1) optimization by programming in Mathematica; and (2) optimization by applying genetic algorithm. The results are compared with those obtained by the traditional linear least squares method. The results show comparable capability and performance of two nonlinear methods. The gamma and Pearson distributions are the most successful models in preserving the rising and recession limbs of the unit hydographs. The log-normal distribution has a high ability in predicting both the peak flow and time to peak of the unit hydrograph. The nonlinear optimization method does not outperform the linear least squares method in determining the UH (especially for excess rainfall of one pulse), but is comparable.

Fuzzy logic controller optimization

DOEpatents

Sepe, Jr., Raymond B; Miller, John Michael

2004-03-23

A method is provided for optimizing a rotating induction machine system fuzzy logic controller. The fuzzy logic controller has at least one input and at least one output. Each input accepts a machine system operating parameter. Each output produces at least one machine system control parameter. The fuzzy logic controller generates each output based on at least one input and on fuzzy logic decision parameters. Optimization begins by obtaining a set of data relating each control parameter to at least one operating parameter for each machine operating region. A model is constructed for each machine operating region based on the machine operating region data obtained. The fuzzy logic controller is simulated with at least one created model in a feedback loop from a fuzzy logic output to a fuzzy logic input. Fuzzy logic decision parameters are optimized based on the simulation.

Attitude determination and parameter estimation using vector observations - Theory

NASA Technical Reports Server (NTRS)

Markley, F. Landis

1989-01-01

Procedures for attitude determination based on Wahba's loss function are generalized to include the estimation of parameters other than the attitude, such as sensor biases. Optimization with respect to the attitude is carried out using the q-method, which does not require an a priori estimate of the attitude. Optimization with respect to the other parameters employs an iterative approach, which does require an a priori estimate of these parameters. Conventional state estimation methods require a priori estimates of both the parameters and the attitude, while the algorithm presented in this paper always computes the exact optimal attitude for given values of the parameters. Expressions for the covariance of the attitude and parameter estimates are derived.

A local segmentation parameter optimization approach for mapping heterogeneous urban environments using VHR imagery

NASA Astrophysics Data System (ADS)

Grippa, Tais; Georganos, Stefanos; Lennert, Moritz; Vanhuysse, Sabine; Wolff, Eléonore

2017-10-01

Mapping large heterogeneous urban areas using object-based image analysis (OBIA) remains challenging, especially with respect to the segmentation process. This could be explained both by the complex arrangement of heterogeneous land-cover classes and by the high diversity of urban patterns which can be encountered throughout the scene. In this context, using a single segmentation parameter to obtain satisfying segmentation results for the whole scene can be impossible. Nonetheless, it is possible to subdivide the whole city into smaller local zones, rather homogeneous according to their urban pattern. These zones can then be used to optimize the segmentation parameter locally, instead of using the whole image or a single representative spatial subset. This paper assesses the contribution of a local approach for the optimization of segmentation parameter compared to a global approach. Ouagadougou, located in sub-Saharan Africa, is used as case studies. First, the whole scene is segmented using a single globally optimized segmentation parameter. Second, the city is subdivided into 283 local zones, homogeneous in terms of building size and building density. Each local zone is then segmented using a locally optimized segmentation parameter. Unsupervised segmentation parameter optimization (USPO), relying on an optimization function which tends to maximize both intra-object homogeneity and inter-object heterogeneity, is used to select the segmentation parameter automatically for both approaches. Finally, a land-use/land-cover classification is performed using the Random Forest (RF) classifier. The results reveal that the local approach outperforms the global one, especially by limiting confusions between buildings and their bare-soil neighbors.

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

Optimal Duration for Voice Rest After Vocal Fold Surgery: Randomized Controlled Clinical Study.

PubMed

Kaneko, Mami; Shiromoto, Osamu; Fujiu-Kurachi, Masako; Kishimoto, Yo; Tateya, Ichiro; Hirano, Shigeru

2017-01-01

Voice rest is commonly recommended after phonomicrosurgery to prevent worsening of vocal fold injuries. However, the most effective duration of voice rest is unknown. Recently, early vocal stimulation was recommended as a means to improve wound healing. The purpose of this study is to examine the optimal duration of voice rest after phonomicrosurgery. Randomized controlled clinical study. Patients undergoing phonomicrosurgery for leukoplakia, carcinoma in situ, vocal fold polyp, Reinke's edema, and cyst were chosen. Participants were randomly assigned to voice rest for 3 or 7 postoperative days. Voice therapy was administered to both groups after voice rest. Grade, roughness, breathiness, asthenia, and strain (GRBAS) scale, stroboscopic examination, aerodynamic assessment, acoustic analysis, and Voice Handicap Index-10 (VHI-10) were performed pre- and postoperatively at 1, 3, and 6 months. Stroboscopic examination evaluated normalized mucosal wave amplitude (NMWA). Parameters were compared between both groups. Thirty-one patients were analyzed (3-day group, n = 16; 7-day group, n = 15). Jitter, shimmer, and VHI-10 were significantly better in the 3-day group at 1 month post operation. GRBAS was significantly better in the 3-day group at 1 and 3 months post operation, and NMWA was significantly better in the 3-day group at 1, 3, and 6 months post operation compared to the 7-day group. The data suggest that 3 days of voice rest followed by voice therapy may lead to better wound healing of the vocal fold compared to 7 days of voice rest. Appropriate mechanical stimulation during early stages of vocal fold wound healing may lead to favorable functional recovery. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

The Influence of Maternal and Household Resources, and Parental Psychosocial Child Stimulation on Early Childhood Development: A Cross-Sectional Study of Children 36–59 Months in Honduras

PubMed Central

Urke, Helga Bjørnøy; Contreras, Mariela; Matanda, Dennis Juma

2018-01-01

Optimal early childhood development (ECD) is currently jeopardized for more than 250 million children under five in low- and middle-income countries. The Sustainable Development Goals has called for a renewed emphasis on children’s wellbeing, encompassing a holistic approach that ensures nurturing care to facilitate optimal child development. In vulnerable contexts, the extent of a family’s available resources can influence a child’s potential of reaching its optimal development. Few studies have examined these relationships in low- and middle-income countries using nationally representative samples. The present paper explored the relationships between maternal and paternal psychosocial stimulation of the child as well as maternal and household resources and ECD among 2729 children 36–59 months old in Honduras. Data from the Demographic and Health Surveys conducted in 2011–2012 was used. Adjusted logistic regression analyses showed that maternal psychosocial stimulation was positively and significantly associated with ECD in the full, rural, and lowest wealth quintile samples. These findings underscore the importance of maternal engagement in facilitating ECD but also highlight the role of context when designing tailored interventions to improve ECD. PMID:29735895

A new adaptive light beam focusing principle for scanning light stimulation systems.

PubMed

Bitzer, L A; Meseth, M; Benson, N; Schmechel, R

2013-02-01

In this article a novel principle to achieve optimal focusing conditions or rather the smallest possible beam diameter for scanning light stimulation systems is presented. It is based on the following methodology: First, a reference point on a camera sensor is introduced where optimal focusing conditions are adjusted and the distance between the light focusing optic and the reference point is determined using a laser displacement sensor. In a second step, this displacement sensor is used to map the topography of the sample under investigation. Finally, the actual measurement is conducted, using optimal focusing conditions in each measurement point at the sample surface, that are determined by the height difference between camera sensor and the sample topography. This principle is independent of the measurement values, the optical or electrical properties of the sample, the used light source, or the selected wavelength. Furthermore, the samples can be tilted, rough, bent, or of different surface materials. In the following the principle is implemented using an optical beam induced current system, but basically it can be applied to any other scanning light stimulation system. Measurements to demonstrate its operation are shown, using a polycrystalline silicon solar cell.

Genetic algorithm optimization of transcutaneous energy transmission systems for implantable ventricular assist devices.

PubMed

Byron, Kelly; Bluvshtein, Vlad; Lucke, Lori

2013-01-01

Transcutaneous energy transmission systems (TETS) wirelessly transmit power through the skin. TETS is particularly desirable for ventricular assist devices (VAD), which currently require cables through the skin to power the implanted pump. Optimizing the inductive link of the TET system is a multi-parameter problem. Most current techniques to optimize the design simplify the problem by combining parameters leading to sub-optimal solutions. In this paper we present an optimization method using a genetic algorithm to handle a larger set of parameters, which leads to a more optimal design. Using this approach, we were able to increase efficiency while also reducing power variability in a prototype, compared to a traditional manual design method.

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.

Optimal input shaping for Fisher identifiability of control-oriented lithium-ion battery models

NASA Astrophysics Data System (ADS)

Rothenberger, Michael J.

This dissertation examines the fundamental challenge of optimally shaping input trajectories to maximize parameter identifiability of control-oriented lithium-ion battery models. Identifiability is a property from information theory that determines the solvability of parameter estimation for mathematical models using input-output measurements. This dissertation creates a framework that exploits the Fisher information metric to quantify the level of battery parameter identifiability, optimizes this metric through input shaping, and facilitates faster and more accurate estimation. The popularity of lithium-ion batteries is growing significantly in the energy storage domain, especially for stationary and transportation applications. While these cells have excellent power and energy densities, they are plagued with safety and lifespan concerns. These concerns are often resolved in the industry through conservative current and voltage operating limits, which reduce the overall performance and still lack robustness in detecting catastrophic failure modes. New advances in automotive battery management systems mitigate these challenges through the incorporation of model-based control to increase performance, safety, and lifespan. To achieve these goals, model-based control requires accurate parameterization of the battery model. While many groups in the literature study a variety of methods to perform battery parameter estimation, a fundamental issue of poor parameter identifiability remains apparent for lithium-ion battery models. This fundamental challenge of battery identifiability is studied extensively in the literature, and some groups are even approaching the problem of improving the ability to estimate the model parameters. The first approach is to add additional sensors to the battery to gain more information that is used for estimation. The other main approach is to shape the input trajectories to increase the amount of information that can be gained from input-output measurements, and is the approach used in this dissertation. Research in the literature studies optimal current input shaping for high-order electrochemical battery models and focuses on offline laboratory cycling. While this body of research highlights improvements in identifiability through optimal input shaping, each optimal input is a function of nominal parameters, which creates a tautology. The parameter values must be known a priori to determine the optimal input for maximizing estimation speed and accuracy. The system identification literature presents multiple studies containing methods that avoid the challenges of this tautology, but these methods are absent from the battery parameter estimation domain. The gaps in the above literature are addressed in this dissertation through the following five novel and unique contributions. First, this dissertation optimizes the parameter identifiability of a thermal battery model, which Sergio Mendoza experimentally validates through a close collaboration with this dissertation's author. Second, this dissertation extends input-shaping optimization to a linear and nonlinear equivalent-circuit battery model and illustrates the substantial improvements in Fisher identifiability for a periodic optimal signal when compared against automotive benchmark cycles. Third, this dissertation presents an experimental validation study of the simulation work in the previous contribution. The estimation study shows that the automotive benchmark cycles either converge slower than the optimized cycle, or not at all for certain parameters. Fourth, this dissertation examines how automotive battery packs with additional power electronic components that dynamically route current to individual cells/modules can be used for parameter identifiability optimization. While the user and vehicle supervisory controller dictate the current demand for these packs, the optimized internal allocation of current still improves identifiability. Finally, this dissertation presents a robust Bayesian sequential input shaping optimization study to maximize the conditional Fisher information of the battery model parameters without prior knowledge of the nominal parameter set. This iterative algorithm only requires knowledge of the prior parameter distributions to converge to the optimal input trajectory.

Estimating model parameters for an impact-produced shock-wave simulation: Optimal use of partial data with the extended Kalman filter

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

Kao, Jim; Flicker, Dawn; Ide, Kayo

2006-05-20

This paper builds upon our recent data assimilation work with the extended Kalman filter (EKF) method [J. Kao, D. Flicker, R. Henninger, S. Frey, M. Ghil, K. Ide, Data assimilation with an extended Kalman filter for an impact-produced shock-wave study, J. Comp. Phys. 196 (2004) 705-723.]. The purpose is to test the capability of EKF in optimizing a model's physical parameters. The problem is to simulate the evolution of a shock produced through a high-speed flyer plate. In the earlier work, we have showed that the EKF allows one to estimate the evolving state of the shock wave from amore » single pressure measurement, assuming that all model parameters are known. In the present paper, we show that imperfectly known model parameters can also be estimated accordingly, along with the evolving model state, from the same single measurement. The model parameter optimization using the EKF can be achieved through a simple modification of the original EKF formalism by including the model parameters into an augmented state variable vector. While the regular state variables are governed by both deterministic and stochastic forcing mechanisms, the parameters are only subject to the latter. The optimally estimated model parameters are thus obtained through a unified assimilation operation. We show that improving the accuracy of the model parameters also improves the state estimate. The time variation of the optimized model parameters results from blending the data and the corresponding values generated from the model and lies within a small range, of less than 2%, from the parameter values of the original model. The solution computed with the optimized parameters performs considerably better and has a smaller total variance than its counterpart using the original time-constant parameters. These results indicate that the model parameters play a dominant role in the performance of the shock-wave hydrodynamic code at hand.« less

A kinetic investigation of interacting, stimulated T cells identifies conditions for rapid functional enhancement, minimal phenotype differentiation, and improved adoptive cell transfer tumor eradication.

PubMed

Zhou, Jing; Bethune, Michael T; Malkova, Natalia; Sutherland, Alexander M; Comin-Anduix, Begonya; Su, Yapeng; Baltimore, David; Ribas, Antoni; Heath, James R

2018-01-01

For adoptive cell transfer (ACT) immunotherapy of tumor-reactive T cells, an effective therapeutic outcome depends upon cell dose, cell expansion in vivo through a minimally differentiated phenotype, long term persistence, and strong cytolytic effector function. An incomplete understanding of the biological coupling between T cell expansion, differentiation, and response to stimulation hinders the co-optimization of these factors. We report on a biophysical investigation of how the short-term kinetics of T cell functional activation, through molecular stimulation and cell-cell interactions, competes with phenotype differentiation. T cells receive molecular stimulation for a few minutes to a few hours in bulk culture. Following this priming period, the cells are then analyzed at the transcriptional level, or isolated as single cells, with continuing molecular stimulation, within microchambers for analysis via 11-plex secreted protein assays. We resolve a rapid feedback mechanism, promoted by T cell-T cell contact interactions, which strongly amplifies T cell functional performance while yielding only minimal phenotype differentiation. When tested in mouse models of ACT, optimally primed T cells lead to complete tumor eradication. A similar kinetic process is identified in CD8+ and CD4+ T cells collected from a patient with metastatic melanoma.

A kinetic investigation of interacting, stimulated T cells identifies conditions for rapid functional enhancement, minimal phenotype differentiation, and improved adoptive cell transfer tumor eradication

PubMed Central

Zhou, Jing; Bethune, Michael T.; Malkova, Natalia; Sutherland, Alexander M.; Comin-Anduix, Begonya; Su, Yapeng; Baltimore, David; Ribas, Antoni

2018-01-01

For adoptive cell transfer (ACT) immunotherapy of tumor-reactive T cells, an effective therapeutic outcome depends upon cell dose, cell expansion in vivo through a minimally differentiated phenotype, long term persistence, and strong cytolytic effector function. An incomplete understanding of the biological coupling between T cell expansion, differentiation, and response to stimulation hinders the co-optimization of these factors. We report on a biophysical investigation of how the short-term kinetics of T cell functional activation, through molecular stimulation and cell-cell interactions, competes with phenotype differentiation. T cells receive molecular stimulation for a few minutes to a few hours in bulk culture. Following this priming period, the cells are then analyzed at the transcriptional level, or isolated as single cells, with continuing molecular stimulation, within microchambers for analysis via 11-plex secreted protein assays. We resolve a rapid feedback mechanism, promoted by T cell—T cell contact interactions, which strongly amplifies T cell functional performance while yielding only minimal phenotype differentiation. When tested in mouse models of ACT, optimally primed T cells lead to complete tumor eradication. A similar kinetic process is identified in CD8+ and CD4+ T cells collected from a patient with metastatic melanoma. PMID:29360859

Using non-invasive brain stimulation to augment motor training-induced plasticity

PubMed Central

Bolognini, Nadia; Pascual-Leone, Alvaro; Fregni, Felipe

2009-01-01

Therapies for motor recovery after stroke or traumatic brain injury are still not satisfactory. To date the best approach seems to be the intensive physical therapy. However the results are limited and functional gains are often minimal. The goal of motor training is to minimize functional disability and optimize functional motor recovery. This is thought to be achieved by modulation of plastic changes in the brain. Therefore, adjunct interventions that can augment the response of the motor system to the behavioural training might be useful to enhance the therapy-induced recovery in neurological populations. In this context, noninvasive brain stimulation appears to be an interesting option as an add-on intervention to standard physical therapies. Two non-invasive methods of inducing electrical currents into the brain have proved to be promising for inducing long-lasting plastic changes in motor systems: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). These techniques represent powerful methods for priming cortical excitability for a subsequent motor task, demand, or stimulation. Thus, their mutual use can optimize the plastic changes induced by motor practice, leading to more remarkable and outlasting clinical gains in rehabilitation. In this review we discuss how these techniques can enhance the effects of a behavioural intervention and the clinical evidence to date. PMID:19292910

TH-E-BRF-06: Kinetic Modeling of Tumor Response to Fractionated Radiotherapy

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

Zhong, H; Gordon, J; Chetty, I

2014-06-15

Purpose: Accurate calibration of radiobiological parameters is crucial to predicting radiation treatment response. Modeling differences may have a significant impact on calibrated parameters. In this study, we have integrated two existing models with kinetic differential equations to formulate a new tumor regression model for calibrating radiobiological parameters for individual patients. Methods: A system of differential equations that characterizes the birth-and-death process of tumor cells in radiation treatment was analytically solved. The solution of this system was used to construct an iterative model (Z-model). The model consists of three parameters: tumor doubling time Td, half-life of dying cells Tr and cellmore » survival fraction SFD under dose D. The Jacobian determinant of this model was proposed as a constraint to optimize the three parameters for six head and neck cancer patients. The derived parameters were compared with those generated from the two existing models, Chvetsov model (C-model) and Lim model (L-model). The C-model and L-model were optimized with the parameter Td fixed. Results: With the Jacobian-constrained Z-model, the mean of the optimized cell survival fractions is 0.43±0.08, and the half-life of dying cells averaged over the six patients is 17.5±3.2 days. The parameters Tr and SFD optimized with the Z-model differ by 1.2% and 20.3% from those optimized with the Td-fixed C-model, and by 32.1% and 112.3% from those optimized with the Td-fixed L-model, respectively. Conclusion: The Z-model was analytically constructed from the cellpopulation differential equations to describe changes in the number of different tumor cells during the course of fractionated radiation treatment. The Jacobian constraints were proposed to optimize the three radiobiological parameters. The developed modeling and optimization methods may help develop high-quality treatment regimens for individual patients.« less

Advanced titration to treat a floppy epiglottis in selective upper airway stimulation.

PubMed

Heiser, Clemens

2016-09-01

The following report presents a case of a patient with high residual apnea-hypopnea index at 6 months following implantation of an upper airway stimulation device who improved significantly after advanced titration via drug-induced sedated endoscopy by changing the electrode configuration for stimulation from bipolar to monopolar. This case demonstrates the utility of postsurgical advanced titration to optimize programming settings for improved clinical outcomes. Laryngoscope, 126:S22-S24, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

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

Optimization of GATE and PHITS Monte Carlo code parameters for uniform scanning proton beam based on simulation with FLUKA general-purpose code

NASA Astrophysics Data System (ADS)

Kurosu, Keita; Takashina, Masaaki; Koizumi, Masahiko; Das, Indra J.; Moskvin, Vadim P.

2014-10-01

Although three general-purpose Monte Carlo (MC) simulation tools: Geant4, FLUKA and PHITS have been used extensively, differences in calculation results have been reported. The major causes are the implementation of the physical model, preset value of the ionization potential or definition of the maximum step size. In order to achieve artifact free MC simulation, an optimized parameters list for each simulation system is required. Several authors have already proposed the optimized lists, but those studies were performed with a simple system such as only a water phantom. Since particle beams have a transport, interaction and electromagnetic processes during beam delivery, establishment of an optimized parameters-list for whole beam delivery system is therefore of major importance. The purpose of this study was to determine the optimized parameters list for GATE and PHITS using proton treatment nozzle computational model. The simulation was performed with the broad scanning proton beam. The influences of the customizing parameters on the percentage depth dose (PDD) profile and the proton range were investigated by comparison with the result of FLUKA, and then the optimal parameters were determined. The PDD profile and the proton range obtained from our optimized parameters list showed different characteristics from the results obtained with simple system. This led to the conclusion that the physical model, particle transport mechanics and different geometry-based descriptions need accurate customization in planning computational experiments for artifact-free MC simulation.

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.

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.

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.

Non-adaptive and adaptive hybrid approaches for enhancing water quality management

NASA Astrophysics Data System (ADS)

Kalwij, Ineke M.; Peralta, Richard C.

2008-09-01

SummaryUsing optimization to help solve groundwater management problems cost-effectively is becoming increasingly important. Hybrid optimization approaches, that combine two or more optimization algorithms, will become valuable and common tools for addressing complex nonlinear hydrologic problems. Hybrid heuristic optimizers have capabilities far beyond those of a simple genetic algorithm (SGA), and are continuously improving. SGAs having only parent selection, crossover, and mutation are inefficient and rarely used for optimizing contaminant transport management. Even an advanced genetic algorithm (AGA) that includes elitism (to emphasize using the best strategies as parents) and healing (to help assure optimal strategy feasibility) is undesirably inefficient. Much more efficient than an AGA is the presented hybrid (AGCT), which adds comprehensive tabu search (TS) features to an AGA. TS mechanisms (TS probability, tabu list size, search coarseness and solution space size, and a TS threshold value) force the optimizer to search portions of the solution space that yield superior pumping strategies, and to avoid reproducing similar or inferior strategies. An AGCT characteristic is that TS control parameters are unchanging during optimization. However, TS parameter values that are ideal for optimization commencement can be undesirable when nearing assumed global optimality. The second presented hybrid, termed global converger (GC), is significantly better than the AGCT. GC includes AGCT plus feedback-driven auto-adaptive control that dynamically changes TS parameters during run-time. Before comparing AGCT and GC, we empirically derived scaled dimensionless TS control parameter guidelines by evaluating 50 sets of parameter values for a hypothetical optimization problem. For the hypothetical area, AGCT optimized both well locations and pumping rates. The parameters are useful starting values because using trial-and-error to identify an ideal combination of control parameter values for a new optimization problem can be time consuming. For comparison, AGA, AGCT, and GC are applied to optimize pumping rates for assumed well locations of a complex large-scale contaminant transport and remediation optimization problem at Blaine Naval Ammunition Depot (NAD). Both hybrid approaches converged more closely to the optimal solution than the non-hybrid AGA. GC averaged 18.79% better convergence than AGCT, and 31.9% than AGA, within the same computation time (12.5 days). AGCT averaged 13.1% better convergence than AGA. The GC can significantly reduce the burden of employing computationally intensive hydrologic simulation models within a limited time period and for real-world optimization problems. Although demonstrated for a groundwater quality problem, it is also applicable to other arenas, such as managing salt water intrusion and surface water contaminant loading.

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.

Application of Layered Perforation Profile Control Technique to Low Permeable Reservoir

NASA Astrophysics Data System (ADS)

Wei, Sun

2018-01-01

it is difficult to satisfy the demand of profile control of complex well section and multi-layer reservoir by adopting the conventional profile control technology, therefore, a research is conducted on adjusting the injection production profile with layered perforating parameters optimization. i.e. in the case of coproduction for multi-layer, water absorption of each layer is adjusted by adjusting the perforating parameters, thus to balance the injection production profile of the whole well section, and ultimately enhance the oil displacement efficiency of water flooding. By applying the relationship between oil-water phase percolation theory/perforating damage and capacity, a mathematic model of adjusting the injection production profile with layered perforating parameters optimization, besides, perforating parameters optimization software is programmed. Different types of optimization design work are carried out according to different geological conditions and construction purposes by using the perforating optimization design software; furthermore, an application test is done for low permeable reservoir, and the water injection profile tends to be balanced significantly after perforation with optimized parameters, thereby getting a good application effect on site.

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

Optimization of return electrodes in neurostimulating arrays

NASA Astrophysics Data System (ADS)

Flores, Thomas; Goetz, Georges; Lei, Xin; Palanker, Daniel

2016-06-01

Objective. High resolution visual prostheses require dense stimulating arrays with localized inputs of individual electrodes. We study the electric field produced by multielectrode arrays in electrolyte to determine an optimal configuration of return electrodes and activation sequence. Approach. To determine the boundary conditions for computation of the electric field in electrolyte, we assessed current dynamics using an equivalent circuit of a multielectrode array with interleaved return electrodes. The electric field modeled with two different boundary conditions derived from the equivalent circuit was then compared to measurements of electric potential in electrolyte. To assess the effect of return electrode configuration on retinal stimulation, we transformed the computed electric fields into retinal response using a model of neural network-mediated stimulation. Main results. Electric currents at the capacitive electrode-electrolyte interface redistribute over time, so that boundary conditions transition from equipotential surfaces at the beginning of the pulse to uniform current density in steady state. Experimental measurements confirmed that, in steady state, the boundary condition corresponds to a uniform current density on electrode surfaces. Arrays with local return electrodes exhibit improved field confinement and can elicit stronger network-mediated retinal response compared to those with a common remote return. Connecting local return electrodes enhances the field penetration depth and allows reducing the return electrode area. Sequential activation of the pixels in large monopolar arrays reduces electrical cross-talk and improves the contrast in pattern stimulation. Significance. Accurate modeling of multielectrode arrays helps optimize the electrode configuration to maximize the spatial resolution, contrast and dynamic range of retinal prostheses.

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.

Regenerative Medicine and Restoration of Joint Function

DTIC Science & Technology

2012-10-01

identify the parameters that generate anatomically shaped bone substitutes of optimal composition and structure with an articulating profile. 2) to develop...strengths. An in vivo study in rabbits to evaluate these materials are ongoing. Task 2. Optimization of SFF Rolling Compaction Parameters : The work is...ongoing related to optimizing SFF rolling compaction parameters to control the density of green samples. We have used CPP powders for these studies

Search Parameter Optimization for Discrete, Bayesian, and Continuous Search Algorithms

DTIC Science & Technology

2017-09-01

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS SEARCH PARAMETER OPTIMIZATION FOR DISCRETE , BAYESIAN, AND CONTINUOUS SEARCH ALGORITHMS by...to 09-22-2017 4. TITLE AND SUBTITLE SEARCH PARAMETER OPTIMIZATION FOR DISCRETE , BAYESIAN, AND CON- TINUOUS SEARCH ALGORITHMS 5. FUNDING NUMBERS 6...simple search and rescue acts to prosecuting aerial/surface/submersible targets on mission. This research looks at varying the known discrete and

An optimized proportional-derivative controller for the human upper extremity with gravity.

PubMed

Jagodnik, Kathleen M; Blana, Dimitra; van den Bogert, Antonie J; Kirsch, Robert F

2015-10-15

When Functional Electrical Stimulation (FES) is used to restore movement in subjects with spinal cord injury (SCI), muscle stimulation patterns should be selected to generate accurate and efficient movements. Ideally, the controller for such a neuroprosthesis will have the simplest architecture possible, to facilitate translation into a clinical setting. In this study, we used the simulated annealing algorithm to optimize two proportional-derivative (PD) feedback controller gain sets for a 3-dimensional arm model that includes musculoskeletal dynamics and has 5 degrees of freedom and 22 muscles, performing goal-oriented reaching movements. Controller gains were optimized by minimizing a weighted sum of position errors, orientation errors, and muscle activations. After optimization, gain performance was evaluated on the basis of accuracy and efficiency of reaching movements, along with three other benchmark gain sets not optimized for our system, on a large set of dynamic reaching movements for which the controllers had not been optimized, to test ability to generalize. Robustness in the presence of weakened muscles was also tested. The two optimized gain sets were found to have very similar performance to each other on all metrics, and to exhibit significantly better accuracy, compared with the three standard gain sets. All gain sets investigated used physiologically acceptable amounts of muscular activation. It was concluded that optimization can yield significant improvements in controller performance while still maintaining muscular efficiency, and that optimization should be considered as a strategy for future neuroprosthesis controller design. Published by Elsevier Ltd.

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.

Utility of coupling nonlinear optimization methods with numerical modeling software

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

Murphy, M.J.

1996-08-05

Results of using GLO (Global Local Optimizer), a general purpose nonlinear optimization software package for investigating multi-parameter problems in science and engineering is discussed. The package consists of the modular optimization control system (GLO), a graphical user interface (GLO-GUI), a pre-processor (GLO-PUT), a post-processor (GLO-GET), and nonlinear optimization software modules, GLOBAL & LOCAL. GLO is designed for controlling and easy coupling to any scientific software application. GLO runs the optimization module and scientific software application in an iterative loop. At each iteration, the optimization module defines new values for the set of parameters being optimized. GLO-PUT inserts the new parametermore » values into the input file of the scientific application. GLO runs the application with the new parameter values. GLO-GET determines the value of the objective function by extracting the results of the analysis and comparing to the desired result. GLO continues to run the scientific application over and over until it finds the ``best`` set of parameters by minimizing (or maximizing) the objective function. An example problem showing the optimization of material model is presented (Taylor cylinder impact test).« less

Estimating cellular parameters through optimization procedures: elementary principles and applications.

PubMed

Kimura, Akatsuki; Celani, Antonio; Nagao, Hiromichi; Stasevich, Timothy; Nakamura, Kazuyuki

2015-01-01

Construction of quantitative models is a primary goal of quantitative biology, which aims to understand cellular and organismal phenomena in a quantitative manner. In this article, we introduce optimization procedures to search for parameters in a quantitative model that can reproduce experimental data. The aim of optimization is to minimize the sum of squared errors (SSE) in a prediction or to maximize likelihood. A (local) maximum of likelihood or (local) minimum of the SSE can efficiently be identified using gradient approaches. Addition of a stochastic process enables us to identify the global maximum/minimum without becoming trapped in local maxima/minima. Sampling approaches take advantage of increasing computational power to test numerous sets of parameters in order to determine the optimum set. By combining Bayesian inference with gradient or sampling approaches, we can estimate both the optimum parameters and the form of the likelihood function related to the parameters. Finally, we introduce four examples of research that utilize parameter optimization to obtain biological insights from quantified data: transcriptional regulation, bacterial chemotaxis, morphogenesis, and cell cycle regulation. With practical knowledge of parameter optimization, cell and developmental biologists can develop realistic models that reproduce their observations and thus, obtain mechanistic insights into phenomena of interest.

Control Parameters Optimization Based on Co-Simulation of a Mechatronic System for an UA-Based Two-Axis Inertially Stabilized Platform.

PubMed

Zhou, Xiangyang; Zhao, Beilei; Gong, Guohao

2015-08-14

This paper presents a method based on co-simulation of a mechatronic system to optimize the control parameters of a two-axis inertially stabilized platform system (ISP) applied in an unmanned airship (UA), by which high control performance and reliability of the ISP system are achieved. First, a three-dimensional structural model of the ISP is built by using the three-dimensional parametric CAD software SOLIDWORKS(®); then, to analyze the system's kinematic and dynamic characteristics under operating conditions, dynamics modeling is conducted by using the multi-body dynamics software ADAMS™, thus the main dynamic parameters such as displacement, velocity, acceleration and reaction curve are obtained, respectively, through simulation analysis. Then, those dynamic parameters were input into the established MATLAB(®) SIMULINK(®) controller to simulate and test the performance of the control system. By these means, the ISP control parameters are optimized. To verify the methods, experiments were carried out by applying the optimized parameters to the control system of a two-axis ISP. The results show that the co-simulation by using virtual prototyping (VP) is effective to obtain optimized ISP control parameters, eventually leading to high ISP control performance.

Control Parameters Optimization Based on Co-Simulation of a Mechatronic System for an UA-Based Two-Axis Inertially Stabilized Platform

PubMed Central

Zhou, Xiangyang; Zhao, Beilei; Gong, Guohao

2015-01-01

This paper presents a method based on co-simulation of a mechatronic system to optimize the control parameters of a two-axis inertially stabilized platform system (ISP) applied in an unmanned airship (UA), by which high control performance and reliability of the ISP system are achieved. First, a three-dimensional structural model of the ISP is built by using the three-dimensional parametric CAD software SOLIDWORKS®; then, to analyze the system’s kinematic and dynamic characteristics under operating conditions, dynamics modeling is conducted by using the multi-body dynamics software ADAMS™, thus the main dynamic parameters such as displacement, velocity, acceleration and reaction curve are obtained, respectively, through simulation analysis. Then, those dynamic parameters were input into the established MATLAB® SIMULINK® controller to simulate and test the performance of the control system. By these means, the ISP control parameters are optimized. To verify the methods, experiments were carried out by applying the optimized parameters to the control system of a two-axis ISP. The results show that the co-simulation by using virtual prototyping (VP) is effective to obtain optimized ISP control parameters, eventually leading to high ISP control performance. PMID:26287210

Finding optimal vaccination strategies under parameter uncertainty using stochastic programming.

PubMed

Tanner, Matthew W; Sattenspiel, Lisa; Ntaimo, Lewis

2008-10-01

We present a stochastic programming framework for finding the optimal vaccination policy for controlling infectious disease epidemics under parameter uncertainty. Stochastic programming is a popular framework for including the effects of parameter uncertainty in a mathematical optimization model. The problem is initially formulated to find the minimum cost vaccination policy under a chance-constraint. The chance-constraint requires that the probability that R(*)

Picosecond laser ablation of polyamide electrospun nanofibers

NASA Astrophysics Data System (ADS)

Götze, Marco; Krimig, Olaf; Kürbitz, Tobias; Henning, Sven; Heilmann, Andreas; Hillrichs, Georg

2017-02-01

Electrospun nanofibers mats have a great potential in tissue engineering and regenerative medicine. Their high porosity and enormous volume to surface ratio stimulate the growth and adhesion of mammalian cells and serve as a stable support structure. These suitable properties can be further optimized by structuring of the nanofibers. Ultrashort pulsed lasers can be used for modifying of the electrospun nanofibers without significant heat exposure. It seems also possible to generate very fine cuts from the fiber mats. In this study, polyamide electrospun nanofibers samples were processed with picosecond UV-laser irradiation (λ = 355 nm, τ = 15 ps). The samples were processed in dry, wet and immersed condition. To optimize cutting and structuring of nanofiber tissue flakes, the influence of different laser parameters on line widths, edge quality, heat-affected zone (HAZ) and the contamination of the fibers by ablated particles (debris) were examined. One additional aim was the minimization of the flake size. It was possible to generate nanofiber flakes in the sub-millimeter range. The quality of the nanofiber flakes could be improved by ablation near the ablation threshold of the material. For cutting under wet conditions shrinking of the flakes has to be taken into account.

SU-D-12A-06: A Comprehensive Parameter Analysis for Low Dose Cone-Beam CT Reconstruction

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

Lu, W; Southern Medical University, Guangzhou; Yan, H

Purpose: There is always a parameter in compressive sensing based iterative reconstruction (IR) methods low dose cone-beam CT (CBCT), which controls the weight of regularization relative to data fidelity. A clear understanding of the relationship between image quality and parameter values is important. The purpose of this study is to investigate this subject based on experimental data and a representative advanced IR algorithm using Tight-frame (TF) regularization. Methods: Three data sets of a Catphan phantom acquired at low, regular and high dose levels are used. For each tests, 90 projections covering a 200-degree scan range are used for reconstruction. Threemore » different regions-of-interest (ROIs) of different contrasts are used to calculate contrast-to-noise ratios (CNR) for contrast evaluation. A single point structure is used to measure modulation transfer function (MTF) for spatial-resolution evaluation. Finally, we analyze CNRs and MTFs to study the relationship between image quality and parameter selections. Results: It was found that: 1) there is no universal optimal parameter. The optimal parameter value depends on specific task and dose level. 2) There is a clear trade-off between CNR and resolution. The parameter for the best CNR is always smaller than that for the best resolution. 3) Optimal parameters are also dose-specific. Data acquired under a high dose protocol require less regularization, yielding smaller optimal parameter values. 4) Comparing with conventional FDK images, TF-based CBCT images are better under a certain optimally selected parameters. The advantages are more obvious for low dose data. Conclusion: We have investigated the relationship between image quality and parameter values in the TF-based IR algorithm. Preliminary results indicate optimal parameters are specific to both the task types and dose levels, providing guidance for selecting parameters in advanced IR algorithms. This work is supported in part by NIH (1R01CA154747-01)« less

Robust design optimization using the price of robustness, robust least squares and regularization methods

NASA Astrophysics Data System (ADS)

Bukhari, Hassan J.

2017-12-01

In this paper a framework for robust optimization of mechanical design problems and process systems that have parametric uncertainty is presented using three different approaches. Robust optimization problems are formulated so that the optimal solution is robust which means it is minimally sensitive to any perturbations in parameters. The first method uses the price of robustness approach which assumes the uncertain parameters to be symmetric and bounded. The robustness for the design can be controlled by limiting the parameters that can perturb.The second method uses the robust least squares method to determine the optimal parameters when data itself is subjected to perturbations instead of the parameters. The last method manages uncertainty by restricting the perturbation on parameters to improve sensitivity similar to Tikhonov regularization. The methods are implemented on two sets of problems; one linear and the other non-linear. This methodology will be compared with a prior method using multiple Monte Carlo simulation runs which shows that the approach being presented in this paper results in better performance.

Experimental design approach to the process parameter optimization for laser welding of martensitic stainless steels in a constrained overlap configuration

NASA Astrophysics Data System (ADS)

Khan, M. M. A.; Romoli, L.; Fiaschi, M.; Dini, G.; Sarri, F.

2011-02-01

This paper presents an experimental design approach to process parameter optimization for the laser welding of martensitic AISI 416 and AISI 440FSe stainless steels in a constrained overlap configuration in which outer shell was 0.55 mm thick. To determine the optimal laser-welding parameters, a set of mathematical models were developed relating welding parameters to each of the weld characteristics. These were validated both statistically and experimentally. The quality criteria set for the weld to determine optimal parameters were the minimization of weld width and the maximization of weld penetration depth, resistance length and shearing force. Laser power and welding speed in the range 855-930 W and 4.50-4.65 m/min, respectively, with a fiber diameter of 300 μm were identified as the optimal set of process parameters. However, the laser power and welding speed can be reduced to 800-840 W and increased to 4.75-5.37 m/min, respectively, to obtain stronger and better welds.

Optimization of process parameters in drilling of fibre hybrid composite using Taguchi and grey relational analysis

NASA Astrophysics Data System (ADS)

Vijaya Ramnath, B.; Sharavanan, S.; Jeykrishnan, J.

2017-03-01

Nowadays quality plays a vital role in all the products. Hence, the development in manufacturing process focuses on the fabrication of composite with high dimensional accuracy and also incurring low manufacturing cost. In this work, an investigation on machining parameters has been performed on jute-flax hybrid composite. Here, the two important responses characteristics like surface roughness and material removal rate are optimized by employing 3 machining input parameters. The input variables considered are drill bit diameter, spindle speed and feed rate. Machining is done on CNC vertical drilling machine at different levels of drilling parameters. Taguchi’s L16 orthogonal array is used for optimizing individual tool parameters. Analysis Of Variance is used to find the significance of individual parameters. The simultaneous optimization of the process parameters is done by grey relational analysis. The results of this investigation shows that, spindle speed and drill bit diameter have most effect on material removal rate and surface roughness followed by feed rate.