Search

In recent times, photobiomodulation has been shown to be beneficial in animal models of Parkinson’s disease, improving locomotive behavior and being neuroprotective. Early observations in people with Parkinson’s disease have been positive also, with improvements in the non-motor symptoms of the disease being evident most consistently. Although the precise mechanisms behind these improvements are not clear, two have been proposed: direct stimulation, where light reaches and acts directly on the distressed neurons, and remote stimulation, where light influences cells and/or molecules that provide systemic protection, thereby acting indirectly on distressed neurons. In relation to Parkinson’s disease, given that the major zone of pathology lies deep in the brain and that light from an extracranial or external photobiomodulation device would not reach these vulnerable regions, stimulating the distressed neurons directly would require intracranial delivery of light using a device implanted close to the vulnerable regions. For indirect systemic stimulation, photobiomodulation could be applied to either the head and scalp, using a transcranial helmet, or to a more remote body part (e.g., abdomen, leg). In this review, we discuss the evidence for both the direct and indirect neuroprotective effects of photobiomodulation in Parkinson’s disease and propose that both types of treatment modality, when working together using both intracranial and extracranial devices, provide the best therapeutic option.

Purpose of the study. In order to create the basis for prospective wound coatings the wound healing effect of xerogel based on neutral hydrosol of titanium dioxide was studied. Materials and methods. After modeling the Wistar outbred runoff in 40 male rats, the wound defect on the skin of the intertropatular region was closed with a bandage. The animals were divided into four groups: Four groups: a control group, (10 rats) in which no drugs were applied to the burn surface; 2 – the group of the comparison preparation, 10 males to whom after the modeling of the burn on the wound surface was applied daily the preparation of comparison argosulfan 3 – experimental group № 1, included 10 males to whom after the modeling of the burn on the wound surface was applied daily the xerogel, in a dose of 0.1 ml/100 g of animal body weight, 4 – experimental group № 2, included 10 males, who after modeling the pathology were daily copied on the wound surface, in a dose of 0.2 ml/100 g of animal body weight. Results. The complex of morphofunctional changes in experimental groups included changes in the epidermis – restoration of a more complete epidermal layer with skin appendages. Probably, it is provided not only by direct stimulation of cell proliferation of basal and studded layers, but also by other mechanisms, as indicated by the nuclear cytoplasmic ratio. In the connective tissue base of the wound effect of experimental groups it was noted the formation of a more extensive network of blood vessels of the hemomicrocirculatory channel and a decrease in the signs of venous hyperemia. Conclusions. Thus, the effective dose of xerogel is 2 ml/kg. The revealed complex of local morphofunctional rearrangements allows the xerogel to be used in diseases and conditions characterized by the disturbance of the skin integrity, including a burn lesion.

The study of brain connectomics has led to a rapid evolution in the understanding of human brain function. Traditional localizationist theories are being replaced by more accurate network, or hodologic, approaches that model brain function as widespread processes dependent on cortical and subcortical structures, as well as the white matter tracts (WMTs) that link these areas. Recent surgical literature suggests that WMTs may be more critical to preserve than cortical structures because of the comparably lower capacity of recovery of the former when damaged. Given the relevance of eloquent WMTs to neurologic function and thus quality of life, neurosurgical interventions must be tailored to maximize their preservation. Direct electric stimulation remains a vital tool for identification and avoidance of these critical tracts. Neurosurgeons therefore require proper understanding of the anatomy and function of WMTs, as well as the reported contemporary tasks used during intraoperative stimulation. We review the relevant tracts involved in language, visuospatial, and motor networks and the updated direct electric stimulation-based mapping tasks that aid in their preservation. The dominant-hemisphere language WMTs have been mapped using picture naming, semantic association, word repetition, reading, and writing tasks. For monitoring of vision and spatial functions, the modified picture naming and line bisection tasks, as well as the recording of visual evoked potentials, have been used. Repetitive movements and monitoring of motor evoked potentials and involuntary movements have been applied for preservation of the motor networks.

A very high percentage of the world population doesn’t exercise enough and, as a consequence, is at high risk of developing serious health conditions. Physical inactivity paired with a poor diet is the second cause of death in high income countries. In this paper, I suggest that transcranial direct stimulation (tDCS) holds promise for “couch potatoes” because it could be used to make them more active, without causing any major side-effect. I also argue that other, less safe, tools could be used to achieve the goal of decreasing physical inactivity, insofar as they have overall fewer side-effects than physical inactivity.

Highlights • The functional characterization of callosal connections is informed by anatomical data. • Callosal connections play a conditional driving role depending on the brain state and behavioral demands. • Callosal connections play a modulatory function, in addition to a driving role. • The corpus callosum participates in learning and interhemispheric transfer of sensorimotor habits. • The corpus callosum contributes to language processing and cognitive functions., The brain operates through the synaptic interaction of distant neurons within flexible, often heterogeneous, distributed systems. Histological studies have detailed the connections between distant neurons, but their functional characterization deserves further exploration. Studies performed on the corpus callosum in animals and humans are unique in that they capitalize on results obtained from several neuroscience disciplines. Such data inspire a new interpretation of the function of callosal connections and delineate a novel road map, thus paving the way toward a general theory of cortico-cortical connectivity. Here we suggest that callosal axons can drive their post-synaptic targets preferentially when coupled to other inputs endowing the cortical network with a high degree of conditionality. This might depend on several factors, such as their pattern of convergence-divergence, the excitatory and inhibitory operation mode, the range of conduction velocities, the variety of homotopic and heterotopic projections and, finally, the state-dependency of their firing. We propose that, in addition to direct stimulation of post-synaptic targets, callosal axons often play a conditional driving or modulatory role, which depends on task contingencies, as documented by several recent studies.

SUMMARYTastes are typically thought to evoke innate appetitive or aversive behaviours, prompting food acceptance or rejection. However, research in Drosophila melanogaster indicates that taste responses can be modified through experience-dependent changes in mushroom body circuits. In this study, we develop a novel taste learning paradigm using closed-loop optogenetics. We find that appetitive and aversive taste memories can be formed by pairing gustatory stimuli with optogenetic activation of sensory or dopaminergic neurons associated with reward or punishment. As with olfactory memories, distinct dopaminergic subpopulations drive the parallel formation of short- and long-term appetitive memories. Long-term memories are protein synthesis-dependent and have energetic requirements that are satisfied by a variety of caloric food sources or by direct stimulation of MB-MP1 dopaminergic neurons. Our paradigm affords new opportunities to probe plasticity mechanisms within the taste system and understand the extent to which taste responses depend on experience.

Phosphatidic acid (PA) is a lipid mediator proposed to increase muscle protein synthesis via direct stimulation of the mammalian target of rapamycin (mTOR) and may act as an anabolic supplemental aid. Evidence on the effectiveness of PA as an anabolic supplement is equivocal. We aimed to systematically assess the effect of PA on performance and body composition. Due to the small number of studies, this is a scoping review. A comprehensive search was performed in Pubmed, SPORTDiscus and Web of Science, from the 1 January 2010 to the 31 August 2020. Our search retrieved 2009 articles, which when filtered, resulted in six studies, published between 2012 and 2019, which were analysed further. Five studies were performed in adult male populations and one in an elderly male population. From these, three studies suggested no effect of PA on lean body mass , while the remaining showed a possible positive effect (body composition and performance improvements). In one of these, the supplement included other potentially anabolic substances, precluding an isolated effect of PA. After a thorough analysis of the studies included, the evidence does not support the supplementation with PA to increase performance or improve body composition in young or elderly men.

The maintenance of intestinal homeostasis is necessary for a good quality of life, and strengthening of the intestinal barrier function is thus an important issue. Therefore, we focused on soybean resistant protein (SRP) derived from kori-tofu (freeze-dried tofu), which is a traditional Japanese food, as a functional food component. In this study, to investigate the effect of SRP on the intestinal barrier function and intestinal microbiota, we conducted an SRP free intake experiment in mice. Results showed that ingestion of SRP decreased the serum level of lipopolysaccharide-binding protein and induced the expression of Reg3γ, thereby improving the intestinal barrier function. In addition, SRP intake induced changes in the cecal microbiota, as observed by changes in β-diversity. In particular, in the microbiota, the up-regulation of functional gene pathways related to the bacterial invasion of epithelial cells (ko05100) was observed, suggesting that Reg3γ expression was induced by the direct stimulation of epithelial cells. The results of this study suggest that SRP is a functional food component that may contribute to the maintenance of intestinal homeostasis.

Objectives The primary goal of the study was to investigate electrical cortical auditory evoked potentials (eCAEPs) at maximum comfortable level (MCL) and 50% MCL on three cochlear implant (CI) electrodes and compare them with the acoustic CAEP (aCAEPs), in terms of the amplitude and latency of the P1-N1-P2 complex. This was achieved by comparing the eCAEP obtained with the method described and stimulating single electrodes, via the fitting software spanning the cochlear array and the aCAEP obtained using the HEARLab system at four speech tokens. Design Twenty MED-EL (MED-EL Medical Electronics, Innsbruck, Austria) CI adult users were tested. CAEP recording with HEARLab System was performed with speech tokens /m/, /g/, /t/, and /s/ in free field, presented at 55 dB SPL. eCAEPs were recorded with an Evoked Potential device triggered from the MAX Programming Interface (MED-EL Medical Devices) with 70 msec electrical burst at 0.9 Hz at the apical (1), middle (6), and basal (10 or 11) CI electrode at their MCL and 50% MCL. Results CAEP responses were recorded in 100% of the test subjects for the speech token /t/, 95% for the speech tokens /g/ and /s/, and 90% for the speech token /m/. For eCAEP recordings, in all subjects, it was possible to identify N1 and P2 peaks when stimulating the apical and middle electrodes. This incidence of detection decreased to an 85% chance of stimulation at 50% MCL on the same electrodes. A P1 peak was less evident for all electrodes. There was an overall increase in latency for stimulation at 50% MCL compared with MCL. There was a significant difference in the amplitude of adjacent peaks (P1-N1 and N1-P2) for 50% MCL compared with MCL. The mean of the maximum cross-correlation values were in the range of 0.63 to 0.68 for the four speech tokens. The distribution of the calculated time shift, where the maximum of the cross-correlation was found, was distributed between the speech tokens. The speech token /g/ had the highest number of valid cross-correlations, while the speech token /s/ had the lowest number. Conclusions This study successfully compared aCAEP and eCAEP in CI users. Both acoustic and electrical P1-N1-P2 recordings obtained were clear and reliable, with good correlation. Latency increased with decreasing stimulation level, while amplitude decreased. eCAEP is potentially a better option to verify speech detection at the cortical level because it (1) uses direct stimulation and therefore creates less interference and delay of the sound processor and (2) creates more flexibility with the recording setup and stimulation setting. As such, eCAEP is an alternative method for CI optimization.

Aim The present study aimed to investigate the effects of tDCS on pain score in women with Chronic Pelvic Pain (CPP). Materials & methods A total of 16 women with CPP participated in the present double-blind sham-controlled cross-over study. Each participant received a 20-min 0.3 MA of trans Cranial Direct Stimulation (tDCS) with a current density of 0.1 mA/cm2. In addition to the pain intensity, the Quality of Life (QOL), disability, and depression statuses were assessed prior to and one week after the treatment. Shapiro-Wilks goodness-of-fit test for normality, dependent t-Test, and Wilcoxon Signed- Rank Test were used for data analysis. Values of p Findings Active tDCS treatment was effective in the reduction of pain (p = .0001), improving QOL (208.938 > 193.313, P = .025), and the disability (22.375 Conclusion The positive effects of active tDCS on CPP suggest the need to study the effect of this method on other types of chronic pain.

A series of experiments investigated potential changes in temporal processing during the months following activation of a cochlear implant (CI) and as a function of stimulus level. Experiment 1 tested patients on the day of implant activation and two and six months later. All stimuli were presented using direct stimulation of a single apical electrode. The dependent variables were rate discrimination ratios (RDRs) for pulse trains with rates centred on 120 pulses per second (pps), obtained using an adaptive procedure, and a measure of the upper limit of temporal pitch, obtained using a pitch-ranking procedure.All stimuli were presented at their most comfortable level (MCL). RDRs decreased from 1.23 to 1.16 and the upper limit increased from 357 to 485 pps from 0 to 2 months post-activation, with no overall change from 2 to 6 months. Because MCLs and hence the testing level increased across sessions, two further experiments investigated whether the performance changes observed across sessions could be due to level differences. Experiment 2 re-tested a subset of subjects at 9 months post-activation, using current levels similar to those used at 0 months. Although the stimuli sounded softer, some subjects showed lower RDRs and/or higher upper limits at this re-test. Experiment 3 measured RDRs and the upper limit for a separate group of subjects at levels equal to 60%, 80%, and 100% of the dynamic range. RDRs decreased with increasing level. The upper limit increased with increasing level for most subjects, with two notable exceptions. Implications of the results for temporal plasticity are discussed, along with possible influences of the effects of level and of across-session learning.

Purpose of Review Purpose of the present review is to illustrate the current state of the art concerning continuous intraoperative recurrent laryngeal nerve monitoring (cIONM) for thyroid surgery. Recent Findings cIONM potentially leads to an improved postoperative vocal cord palsy rate, compared to the intermittent technique. There are currently two main approaches for cIONM: either conventional cIONM based on vagal nerve stimulation or experimental methods, which do not require the positioning of a vagal nerve electrode. One of these methods is the recently described technique “LAR-cIONM,” which utilizes the laryngeal adductor reflex. Summary cIONM represents an advancement of intermittent nerve monitoring, which allows for an immediate reaction to signal changes. Threshold values and guidelines to prevent recurrent laryngeal nerve palsy were validated for the direct stimulation of the vagal nerve and require verification for alterative cIONM methods, including LAR-cIONM.

Two new friedelane triterpenoids, 20,20-dimethyl-3,27-dioxo-(D:A)-friedo-olean-27,22α-lactone (20,20-dimethylglaucalactone) (1) and 3α-ethanoyloxy-30-nor-(D:A)- friedo-olean-20(29)-en-27,22α-lactone (3-acetoxyglaucalactone) (2) and four known compounds (3–6) were isolated from the methanolic extract of the roots of Caloncoba glauca (P. Beauv.) Gild (Flacourtiaceae). Their structures were determined by comprehensive spectroscopic analyses (1D and 2D NMR in addition to HRESI-MS). The relative configuration of the 22-oxymethine was determined from the NOESY spectrum. The cardiotonic effects of the crude extract and isolated compounds were tested. The results suggest that the crude extract and 3-acetoxyglaucalactone (2) induced an interesting cardiotonic activity by exerting positive inotropic and chronotropic effects, which might be derived from the direct stimulation of the β-adrenergic pathway through β1-adrenergic receptors or opening of the calcium channel.

In this manuscript, we consider the problem of relating functional connectivity measurements viewed as statistical distributions to outcomes. We demonstrate the utility of using the distribution of connectivity on a study of resting-state functional magnetic resonance imaging association with an intervention. The method uses the estimated density of connectivity between nodes of interest as a functional covariate. Moreover, we demonstrate the utility of the procedure in an instance where connectivity is naturally considered an outcome by reversing the predictor/response relationship using case/control methodology. The method utilizes the density quantile, the density evaluated at empirical quantiles, instead of the empirical density directly. This improved the performance of the method by highlighting tail behavior, though we emphasize that by being flexible and non-parametric, the technique can detect effects related to the central portion of the density. To demonstrate the method in an application, we consider 47 primary progressive aphasia patients with various levels of language abilities. These patients were randomly assigned to two treatment arms, transcranial direct-current stimulation and language therapy versus sham (language therapy only), in a clinical trial. We use the method to analyze the effect of direct stimulation on functional connectivity. As such, we estimate the density of correlations among the regions of interest and study the difference in the density post-intervention between treatment arms. We discover that it is the tail of the density, rather than the mean or lower order moments of the distribution, that demonstrates a significant impact in the classification. The new approach has several benefits. Among them, it drastically reduces the number of multiple comparisons compared with edge-wise analysis. In addition, it allows for the investigation of the impact of functional connectivity on the outcomes where the connectivity is not geometrically localized.

Although the association between cholecystitis and acute coronary syndrome-like symptoms, including chest pain with electrocardiogram (ECG) changes, has been reported previously, it is unclear whether these symptoms can be provoked by direct stimulation to the gallbladder. We present the case of a 44-year-old man who developed coronary artery spasm (CAS) with ST-segment-elevation followed by nonsustained polymorphic ventricular tachycardia during laparoscopic cholecystectomy. The change in ECG occurred only when the gallbladder was manipulated, suggesting that direct stimulation to the gallbladder can cause CAS. Clinicians should be aware that careful ECG monitoring is necessary, especially while the gallbladder is manipulated.

In this review, we summarize the evidence against direct stimulation of insulin-like growth factor 1 receptors (IGF1Rs) by autoantibodies in Graves’ orbitopathy (GO) pathogenesis. We describe a model of thyroid-stimulating hormone (TSH) receptor (TSHR)/IGF1R crosstalk and present evidence that observations indicating IGF1R’s role in GO could be explained by this mechanism. We evaluate the evidence for and against IGF1R as a direct target of stimulating IGF1R antibodies (IGF1RAbs) and conclude that GO pathogenesis does not involve directly stimulating IGF1RAbs. We further conclude that the preponderance of evidence supports TSHR as the direct and only target of stimulating autoantibodies in GO and maintain that the TSHR should remain a major target for further development of a medical therapy for GO in concert with drugs that target TSHR/IGF1R crosstalk.

OBJECTIVESurgery for tumors around the jugular foramen has significant risks of dysphagia and vocal cord palsy due to possible damage to the lower cranial nerve functions. For its treatment, long-term tumor control by maximum resection while avoiding permanent neurological damage is required. To accomplish this challenging goal, the authors developed an intraoperative continuous vagus nerve monitoring system and herein report their experience with this novel neuromonitoring method.METHODSFifty consecutive patients with tumors around the jugular foramen (34 jugular foramen schwannomas, 11 meningiomas, 3 hypoglossal schwannomas, and 2 others) who underwent microsurgical resection under continuous vagus nerve monitoring within an 11-year period were retrospectively investigated. Evoked vagus nerve electromyograms were continuously monitored by direct 1-Hz stimulation to the nerve throughout the microsurgical procedure.RESULTSThe average resection rate was 96.2%, and no additional surgery was required in any of the patients during the follow-up period (average 65.0 months). Extubation immediately after surgery and oral feeding within 10 days postoperatively were each achieved in 49 patients (98.0%). In 7 patients (14.0%), dysphagia and/or hoarseness were mildly worsened postoperatively at the latest follow-up, but tracheostomy or gastrostomy was not required in any of them. Amplitude preservation ratios on intraoperative vagus nerve electromyograms were significantly smaller in patients with postoperative worsening of dysphagia and/or hoarseness (cutoff value 63%, sensitivity 86%, specificity 79%).CONCLUSIONSIntraoperative continuous vagus nerve monitoring enables real-time and quantitative assessment of vagus nerve function and is important for avoiding permanent vagus nerve palsy, while helping to achieve sufficient resection of tumors around the jugular foramen.

Introduction: Intraoperative electrophysiological studies are increasingly used in spinal surgery. However, its use in myelomeningocele (MMC) surgery is still not widespread. The aim of this study was to present our experience in neural placode (NP) and nerve root stimulations in newborns with open MMC. Methods: Eight newborns underwent surgical treatment for thoracolumbar and lumbosacral MMCs. Intraoperative neuromonitoring including free-running electromyography and stimulation of NP, nerve roots, and spinal cord were performed in all cases. Stimulation sites and intensities and distal response’s amplitudes and latencies were recorded. Results: Five patients had thoracolumbar and 3 patients had lumbosacral MMC. Two patients had no movements at the lower extremities while the other had some movements. No response on the lower extremities was obtained in only 1 patient. Responses from the nerve root stimulations were more robust and significant than the placode stimulations. Conclusions: It is clear that the NP and nerve roots originating from the placode are mostly functional and should be preserved during the surgery. Intraoperative neuromonitoring and direct stimulation should be performed during the MMC repair in order to obtain a better neurological outcome.

The brain’s response to sensory input is modulated by prediction. For example, sounds that are produced by one’s own actions, or those that are strongly predicted by environmental cues, are perceived as less salient and elicit an attenuated N1 component in the auditory evoked potential. Here we examined whether the neural response to direct stimulation of the brain is attenuated by prediction in a similar manner. Transcranial magnetic stimulation (TMS) applied over primary motor cortex can be used to gauge the excitability of the motor system. Motor-evoked potentials (MEPs), elicited by TMS and measured in peripheral muscles, are larger when actions are being prepared and smaller when actions are voluntarily suppressed. We tested whether the amplitude of MEPs was attenuated under circumstances where the TMS pulse can be reliably predicted, even though control of the relevant motor effector was never required. Self-initiation of the TMS pulse and reliable cuing of the TMS pulse both attenuated MEP amplitudes, compared to MEPs generated programmatically in an unpredictable manner. These results suggest that predictive coding may be governed by domain-general mechanisms responsible for all forms predictive learning.

Closed-loop Neuroscience is based on the experimental approach where the ongoing brain activity is recorded, processed, and passed back to the brain as sensory feedback or direct stimulation of neural circuits. The artificial closed loops constructed with this approach expand the traditional stimulus-response experimentation. As such, closed-loop Neuroscience provides insights on the function of loops existing in the brain and the ways the flow of neural information could be modified to treat neurological conditions.Neural oscillations, or brain rhythms, are a class of neural activities that have been extensively studied and also utilized in brain rhythm-contingent (BRC) paradigms that incorporate closed loops. In these implementations, instantaneous power and phase of neural oscillations form the signal that is fed back to the brain.Here we addressed the problem of feedback delay in BRC paradigms. In many BRC systems, it is critical to keep the delay short. Long delays could render the intended modification of neural activity impossible because the stimulus is delivered after the targeted neural pattern has already completed. Yet, the processing time needed to extract oscillatory components from the broad-band neural signals can significantly exceed the period of oscillations, which puts a demand for algorithms that could minimize the delay.We used EEG data collected in human subjects to systematically investigate the performance of a range of signal processing methods in the context of minimizing delay in BRC systems. We proposed a family of techniques based on the least-squares filter design – a transparent and simple approach, as it required a single parameter to adjust the accuracy versus latency trade-off. Our algorithm performed on par or better than the state-of the art techniques currently used for the estimation of rhythm envelope and phase in closed-loop EEG paradigms.

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been demonstrated to modulate the motor performance of both healthy individuals and patients with neuromuscular disorders. However, the effect of tDCS on motor control of multiple muscles, which is a prerequisite to change in motor performance, is currently unknown. Using dimensionality reduction analysis, we investigated whether bilateral tDCS over M1 modulates the coordinated activity of 12 muscles. Fifteen healthy men participated in this randomized, double-blind crossover study. Each participant received a 20-min sham and 2-mA stimulation bilaterally over M1 (anode on the right M1 and cathode on the left M1), with a minimum washout period of 4 days. Muscle activation and end-point kinematics were evaluated during a task where participants reached out to a marked target with non-dominant hand as fast as possible, before and immediately after tDCS application. We found decreased similarity in motor modularity and significant changes in muscle activation in a specific motor module, particularly when reaching out to a target placed within arm's length and improved smoothness index of movement only following 2-mA stimulation. These findings indicate that clinicians and researchers need to consider the simultaneous effect of bilateral tDCS over M1 on multiple muscles when they establish tDCS protocol to change in motor performance of patients with neuromuscular deficits.

Bilateral cochlear implants (BICIs) provide improved sound localization and speech understanding in noise compared to unilateral CIs. However, normal-hearing (NH) listeners demonstrate superior binaural processing abilities compared to BICI listeners. This investigation sought to understand differences between NH and BICI listeners' processing of interaural time differences (ITDs) and interaural level differences (ILDs) as a function of fine-structure and envelope rate using an intracranial lateralization task. The NH listeners were presented band-limited acoustical pulse trains and sinusoidally amplitude-modulated tones using headphones, and the BICI listeners were presented single-electrode electrical pulse trains using direct stimulation. Lateralization range increased as fine-structure rate increased for ILDs in BICI listeners. Lateralization range decreased for rates above 100 Hz for fine-structure ITDs, but decreased for rates lower or higher than 100 Hz for envelope ITDs in both groups. Lateralization ranges for ITDs were smaller for BICI listeners on average. After controlling for age, older listeners showed smaller lateralization ranges and BICI listeners had a more rapid decline for ITD sensitivity at 300 pulses per second. This work suggests that age confounds comparisons between NH and BICI listeners in temporal processing tasks and that some NH-BICI binaural processing differences persist even when age differences are adequately addressed.

Modulation of peripheral nerves is an emerging field for neuroprosthesis and bioelectronic medicine. With developing neural interfacing technology (NIT) that directly communicates with peripheral nerves, several powering schemes have been investigated for long-term use of implantable devices such as wireless and conversion of human body energy. Recently, a variety of promising energy harvesters have been demonstrated as alternatives to solve the power supply issue. Triboelectric nanogenerators (TENGs) show promising performance as a power source of a neuro-stimulator since the output of TENGs provides direction stimulation of a nerve. However, there is a lack of research on TENGs for peripheral nerve stimulation. This work introduces a novel water/air-hybrid triboelectric nanogenerator (WATENG) to overcome current drawbacks of liquid based TENGs as well as to achieve efficient nerve stimulation. Furthermore, this study involves comparative demonstration of the efficiency of nerve stimulation induced by exponential and square pulsed waveforms, to verify that TENGs can effectively stimulate nerves and are good candidates for neurostimulators. By combining this device with neural interfaces, selective and force-controlled modulation of leg muscles in rats can be achieved.

The paper describes a classifi system of mechanisms ensuring the promotion of innovative economic development that has three hierarchical levels. The upper level consists of legal, financial and social mechanisms.The legal mechanism means a legislative defi of the rights and obligations of the parties to an innovation process. The fi mechanism includes potential ways to accelerate the innovative development of the economy through direct or indirect investment of monetary assets into the creation and introduction of innovations. The social mechanism is understood as stimulation of the innovative process of economic development in the form of various types of moral encouragement.According to the proposed classification system, a comparative analysis of existing incentive mechanisms in the leading national economies and the Russian Federation is made.Based on the results of the analysis, proposals are made to increase the effectiveness of mechanisms encouraging the innovative activities in Russia.

The ability of the taste system to identify a tastant (what it tastes like) enables animals to recognize and discriminate between the different basic taste qualities1,2. The valence of a tastant (whether it is appetitive or aversive) specifies its hedonic value and elicits the execution of selective behaviours. Here we examine how sweet and bitter are afforded valence versus identity in mice. We show that neurons in the sweet-responsive and bitter-responsive cortex project to topographically distinct areas of the amygdala, with strong segregation of neural projections conveying appetitive versus aversive taste signals. By manipulating selective taste inputs to the amygdala, we show that it is possible to impose positive or negative valence on a neutral water stimulus, and even to reverse the hedonic value of a sweet or bitter tastant. Remarkably, mice with silenced neurons in the amygdala no longer exhibit behaviour that reflects the valence associated with direct stimulation of the taste cortex, or with delivery of sweet and bitter chemicals. Nonetheless, these mice can still identify and discriminate between tastants, just as wild-type controls do. These results help to explain how the taste system generates stereotypic and predetermined attractive and aversive taste behaviours, and support the existence of distinct neural substrates for the discrimination of taste identity and the assignment of valence.

Objective Create a software tool to facilitate tractography-based deep brain stimulation (DBS) electrode targeting within the patient-specific stereotactic coordinate system used in the operating room. Approach: StimVision was developed with Visualization Toolkit libraries and integrates four major components: 1) medical image visualization, 2) tractography visualization, 3) DBS electrode positioning, and 4) DBS activation volume calculation with tractography intersection. Results Initial applications of StimVision are focused on the study of subcallosal cingulate (SCC) DBS for the treatment of depression. Retrospective modeling results on SCC DBS have suggested that direct stimulation of a specific collection of tractographic pathways are necessary for therapeutic benefit; thereby creating a tractography-based DBS surgical targeting hypotheses. StimVision is the tool we created to facilitate prospective clinical evaluation of that hypothesis. Significance Retrospective tractography-based analyses are common in DBS research; however, intraoperative software tools for interactive selection of a tractography-based DBS target are not readily available. StimVision provides an academic research tool to assist clinical implementation of new DBS targeting strategies and postoperative evaluation of targeting outcome.

Background Direct brain stimulation via electrodes implanted for intracranial electroencephalography (iEEG) permits the modulation of endogenous electrical signals with significantly greater spatial and temporal specificity than non-invasive approaches. It also allows for the stimulation of deep brain structures important to memory, such as the hippocampus, that are difficult, if not impossible, to target non-invasively. Direct stimulation studies of these deep memory structures, though, have produced mixed results, with some reporting improvement, some impairment, and others, no consistent changes. Objective/hypothesis We hypothesize that to modulate cognitive function using brain stimulation, it is essential to modulate connected nodes comprising a network, rather than just alter local activity. Methods iEEG data collected while patients performed a spatiotemporal memory retrieval task were used to map frequency-specific, coherent oscillatory activity between different brain regions associated with successful memory retrieval. We used these to identify two target nodes that exhibited selectively stronger coupling for spatial vs. temporal retrieval. In a subsequent session, electrical stimulation - theta-bursts with a fixed phase-lag (0° or 180°) – was applied to the two target regions while patients performed spatiotemporal retrieval. Results Stimulation selectively impaired spatial retrieval while not affecting temporal retrieval, and this selective impairment was associated with theta decoupling of the spatial retrieval network. Conclusion These findings suggest that stimulating tightly connected nodes in a functional network at the appropriate phase-lag may effectively modulate the network function, and while in this case it impaired memory processes, it sets a foundation for further network-based perturbation studies.

Background/purpose: The hypotension in patients during non-surgical root canal treatment (NSRCT) has not yet investigated. This study aimed to assess the mean systolic blood pressure (MSBP), mean diastolic blood pressure (MDBP), and mean arterial blood pressure (MABP) reduction percentages in patients with irreversible pulpitis teeth treated by NSRCT. Materials and methods: We prospectively recruited 111 patients with a total of 138 irreversible pulpitis teeth. All patients underwent two NSRCT sessions. The first NSRCT session involved mainly the removal of vital pulp tissue with the direct stimulation of the dental branches of the trigeminal nerve, and the second NSRCT session included the root canal debridement and enlargement with minimal disturbance to the dental nerves. The blood pressure of each patient was recorded before and during both NSRCT sessions. Results: There were significantly higher reduction percentages of MSBP, MDBP, and MABP in the first NSRCT session than in the second NSRCT session for all treated patients (all the P-values

Summary Objectives Pedicle screw testing is a widely used technique in the field of neuromonitoring for spinal surgery. It was designed by Calancie et al. (1992) in order to detect pedicle breach, one of the major complications of pedicle screw fixation, which can lead to neurological impairment. However, numerous false negative and equivocal results led to its clinical relevance being questioned. We aimed to clarify these discrepancies and characterize electrical parameters underlying this technique. Methods In this setting, our study is divided into two parts: (1) a clinical part assessing the difference between direct pedicle hole via the pedicle perforator stimulation and indirect stimulation via the implanted screw; (2) an in vitro study testing the electrical properties (resistivity and conductivity) on a sample of different commonly used pedicle screws. Results We showed that there were discrepancies between direct perforator stimulation and pedicle screws, especially at high threshold values. These might be attributed to electrical contact discontinuity. In vitro testing revealed that the previously described resistivity variability and the instability of measures are due to the result of slight changes of position of the recording contacts. Conclusion Electrical continuity is crucial in the pedicle screw test technique. This parameter cannot actually be fully ensured and can lead to discrepancies and potentially false negative results. Therefore, we recommend the use of both direct stimulation of the pedicle hole and control testing of the screw. Further studies and improvement of the technique are required to ensure its reliability.

ERBB2 is a ligand-less tyrosine kinase receptor expressed at very low levels in normal tissues; when overexpressed, it is involved in malignant transformation and tumorigenesis in several carcinomas. In cancer cells, ERBB2 represents the preferred partner of other members of the ERBB receptor family, leading to stronger oncogenic signals, by promoting both ERK and AKT activation. The identification of the specific signaling downstream of ERBB2 has been impaired by the lack of a ligand and of an efficient way to selectively activate the receptor. In this paper, we found that antibodies (Abs) targeting different epitopes on the ERBB2 extracellular domain foster the activation of ERBB2 homodimers, and surprisingly induce a unique cytostatic signaling cascade promoting an ERK-dependent ERBB2 Thr

Introduction. Hypoglossal nerve deficit is a possible complication caused by carotid endarterectomy (CEA). The accidental injury of the hypoglossal nerve during surgery is one of the major reasons for permanent hypoglossal nerve palsy. In this study, we investigated the usefulness of intraoperative mapping of the hypoglossal nerve to identify this nerve during CEA. Methods. A total of consecutive patients who underwent CEA for the treatment of symptomatic or asymptomatic carotid artery stenosis were studied. A hand-held probe was used to detect the hypoglossal nerve in the operative field, and the tongue motor evoked potentials (MEPs) were recorded. Results. The tongue MEPs were obtained in all the patients. The invisible hypoglossal nerve was successfully identified without any difficulty when the internal carotid artery was exposed. Intraoperative mapping was particularly useful for identifying the hypoglossal nerve when the hypoglossal nerve passed beneath the posterior belly of the digastric muscle. MEPs were also elicited when the ansa cervicalis was stimulated, although the resulting amplitudes were much smaller than those obtained by direct stimulation of the hypoglossal nerve. Postoperatively, none of the patients presented with permanent hypoglossal nerve palsy, although one patient exhibited transient minor hypoglossal nerve paresis. Conclusion. Intraoperative hypoglossal nerve mapping enabled us to locate the invisible hypoglossal nerve during the exposure of the internal carotid artery accurately without retracting the posterior belly of the digastric muscle and other tissues in the vicinity of the internal carotid artery.

Intraoperative neurophysiology monitoring (NIOM) is based on neurophysiological examinations that are usually carried out in daily clinical practice. However, there are fundamental differences in NIOM than in clinics due to the environment and the need for accuracy and speed of interpretation. The operating room is a hostile place for neurophysiology recording such us EEG, EMG, and evoked potentials because of there are many sources of electricity that can cause interference and artefacts during recording and will ultimately reduce the accuracy and speed of interpretation of NIOM. Technical error can be happening during NIOM and often cannot be corrected because of aseptic and antiseptics practices has been performed in the field of surgery, therefore one should have troubleshooting strategy and preparation in NIOM to overcome this problem. The knowledge of the recognition of artefacts and trouble-shooting during NIOM becomes very important to maintain patient safety during surgery. More than half of the work on NIOM is to overcome NIOM's artefacts and trouble-shooting to get accurate recording results. This topic will discuss practical ways to deal with artefacts and troubleshooting that are often found in NIOM based on experience and the basics of electricity, including how to reduces signal noise, get better recording results and strategy to get reliable and accurate interpretation of NIOM and overcome technical error. This topic will also discuss the safety of NIOM to prevent iatrogenic injury such us tongue laceration in the use of Trans-cranial MEP, induction of seizure in cortical stimulation and prevent neural tissue injury due to direct stimulation. Keywords: Neurophysiology Intra Operative Monitoring (NIOM), artefacts, troubleshooting.

Decline in hematopoietic stem cell (HSC) function with age underlies limited health span of our blood and immune systems. In order to preserve health into older age, it is necessary to understand the nature and timing of initiating events that cause HSC aging. By performing a cross-sectional study in mice, we discover that hallmarks of aging in HSCs and hematopoiesis begin to accumulate by middle age and that the bone marrow (BM) microenvironment at middle age induces and is indispensable for hematopoietic aging. Using unbiased approaches, we find that decreased levels of the longevity-associated molecule IGF1 in the local middle-aged BM microenvironment are a factor causing HSC aging. Direct stimulation of middle-aged HSCs with IGF1 rescues molecular and functional hallmarks of aging, including restored mitochondrial activity. Thus, although decline in IGF1 supports longevity, our work indicates that this also compromises HSC function and limits hematopoietic health span.

Many debilitating neuropsychiatric and neurodegenerative disorders are characterized by dopamine neurotransmitter dysregulation. Monitoring subsecond dopamine release accurately and for extended, clinically relevant timescales is a critical unmet need. Especially valuable has been the development of electrochemical fast-scan cyclic voltammetry implementing microsized carbon fiber probe implants to record fast millisecond changes in dopamine concentrations. Nevertheless, these well-established methods have only been applied in primates with acutely (few hours) implanted sensors. Neurochemical monitoring for long timescales is necessary to improve diagnostic and therapeutic procedures for a wide range of neurological disorders. Strategies for the chronic use of such sensors have recently been established successfully in rodents, but new infrastructures are needed to enable these strategies in primates. Here we report an integrated neurochemical recording platform for monitoring dopamine release from sensors chronically implanted in deep brain structures of nonhuman primates for over 100 days, together with results for behavior-related and stimulation-induced dopamine release. From these chronically implanted probes, we measured dopamine release from multiple sites in the striatum as induced by behavioral performance and reward-related stimuli, by direct stimulation, and by drug administration. We further developed algorithms to automate detection of dopamine. These algorithms could be used to track the effects of drugs on endogenous dopamine neurotransmission, as well as to evaluate the long-term performance of the chronically implanted sensors. Our chronic measurements demonstrate the feasibility of measuring subsecond dopamine release from deep brain circuits of awake, behaving primates in a longitudinally reproducible manner.

Grooming is a common animal behavior that aids in ectoparasite defense. Ectoparasites can stimulate grooming, and natural selection can also favor endogenous mechanisms that evoke periodic bouts of “programmed” grooming to dislodge or kill ectoparasites before they bite or feed. Moreover, grooming can function as a displacement or communication behavior. We compared the grooming behaviors of adult female black-tailed prairie dogs (Cynomys ludovicianus) on colonies with or without flea control via pulicide dust. Roughly 91% of the prairie dogs sampled on the non-dusted colony carried at least one flea, whereas we did not find fleas on two dusted colonies. During focal observations, prairie dogs on the non-dusted colony groomed at higher frequencies and for longer durations than prairie dogs on the dusted colonies, lending support to the hypothesis that fleas stimulated grooming. However, the reduced amount of time spent grooming on the dusted colonies suggested that approximately 25% of grooming might be attributed to factors other than direct stimulation from ectoparasites. Non-dusted colony prairie dogs rarely autogroomed when near each other. Dusted colony prairie dogs autogroomed for shorter durations when far from a burrow opening (refuge), suggesting a trade-off between self-grooming and antipredator defense. Allogrooming was detected only on the non-dusted colony and was limited to adult females grooming young pups. Grooming appears to serve an antiparasitic function in C. ludovicianus. Antiparasitic grooming might aid in defense against fleas that transmit the plague bacterium Yersinia pestis. Plague was introduced to North America ca. 1900 and now has a strong influence on most prairie dog populations, suggesting a magnified effect of grooming on prairie dog fitness.

The spatial auditory change complex (ACC) is a cortical response elicited by a change in place of stimulation. There is growing evidence that it provides a useful objective measure of electrode discrimination in cochlear implant (CI) users. To date, the spatial ACC has only been measured in relatively experienced CI users with one type of device. Early assessment of electrode discrimination could allow auditory stimulation to be optimized during a potentially sensitive period of auditory rehabilitation. In this study we used a direct stimulation paradigm to measure the spatial ACC in both pre- and post-lingually deafened adults. We show that it is feasible to measure the spatial ACC in different CI devices and as early as 1 week after CI switch-on. The spatial ACC has a strong relationship with performance on a behavioural discrimination task and in some cases provides information over and above behavioural testing. We suggest that it may be useful to measure the spatial ACC to guide auditory rehabilitation and improve hearing performance in CI users.

Perceiving the sensory consequences of one's own actions is essential to successfully interact with the environment. Previous studies compared self- (active) and externally generated (passive) movements to investigate the processing of voluntary action-outcomes. Increased temporal binding (intentional binding) as well as increased detection of delays between action and outcome have been observed for active compared to passive movements. Using transcranial direct stimulation (tDCS) it has been shown that left hemispheric anodal stimulation decreased the intentional binding effect. However, whether the left hemisphere contributes to delay detection performance between action and outcome is unknown. We investigated polarization-dependent effects of left and right frontoparietal tDCS on detecting temporal action-outcome discrepancies. We applied anodal and cathodal stimulation to frontal (F3/F4), parietal (CP3/CP4) and frontoparietal (F3/CP4) areas. After stimulation, participants were presented with visual feedback with various delays after a key press. They had to report whether they detected a delay between the key press and the feedback. In half of the trials the key press was self-initiated, in the other half it was externally generated. A main effect of electrode location indicated highest detection performance after frontal stimulation. Furthermore, we found that the advantage for active versus passive conditions was larger for left hemispheric anodal stimulation as compared to cathodal stimulation. Whereas the frontal cortex is related to delay detection performance in general, hemispheric differences seem to support the differentiation of self-initiated versus externally generated movement consequences.

Key points Cerebellar nuclei (CN) neurons can be classified into four groups according to their action potential (AP) waveform, corresponding to four types of neurons previously characterized. Half of the APs are generated by excitatory events, suggesting that excitatory inputs play a key role in generating CN outputs. Analysis of post-synaptic potentials reveals that the probability of excitatory inputs generating an AP is 0.1. The input from climbing fibre collaterals is characterized by a pair of synaptic potentials with a distinct interpair interval of 4.5 ms. The probability of climbing fibre collaterals initiating an AP in CN neurons is 0.15. Abstract It is commonly agreed that the main function of the cerebellar system is to provide well-timed signals used for the execution of motor commands or prediction of sensory inputs. This function is manifested as a temporal sequence of spiking that should be expressed in the cerebellar nuclei (CN) projection neurons. Whether spiking activity is generated by excitation or release from inhibition is still a hotly debated issue. In an attempt to resolve this debate, we recorded intracellularly from CN neurons in anaesthetized mice and performed an analysis of synaptic activity that yielded a number of important observations. First, we demonstrate that CN neurons can be classified into four groups. Second, shape-index plots of the excitatory events suggest that they are distributed over the entire dendritic tree. Third, the rise time of excitatory events is linearly related to amplitude, suggesting that all excitatory events contribute equally to the generation of action potentials (APs). Fourth, we identified a temporal pattern of spontaneous excitatory events that represent climbing fibre inputs and confirm the results by direct stimulation and analysis on harmaline-evoked activity. Finally, we demonstrate that the probability of excitatory inputs generating an AP is 0.1 yet half of the APs are generated by excitatory events. Moreover, the probability of a presumably spontaneous climbing fibre input generating an AP is higher, reaching a mean population value of 0.15. In view of these results, the mode of synaptic integration at the level of the CN should be re-considered.

International audience; Intraoperative direct stimulation during surgery while awake is considered to be the gold standard for identifying eloquent cortical sites. Only a few studies have referenced the psychologic impact of this event in the pediatric population.OBJECTIVE:The aim of this clinical study is to present the psychologic aspects of surgery while awake in children. We question the psychiatric contraindications and age limits, as well as the impact on children, with particular attention to the psychologic conditioning and experience of these patients.METHODS:Seven patients aged 8-16 years old with brain lesions were operated on while awake between 2008 and 2015. Data collected included perception and memories of surgery and diagnosis and also their real-life experience after surgery. Symptoms of posttraumatic stress disorder or acute stress were investigated.RESULTS:None of the children had initial psychiatric problems. No psychiatric diagnosis was made before surgery. The child psychiatrist did not contraindicate any child for this procedure. Patients experienced little anticipatory anxiety. No child presented symptoms of posttraumatic stress disorder or acute stress.CONCLUSIONS:The results are encouraging, allowing us to contemplate using brain surgery while awake for children without particular worries about the psychologic aspect.Copyright © 2017 Elsevier Inc. All rights reserved.

Sequential stream segregation by normal hearing (NH) and cochlear implant (CI) listeners was investigated using an irregular rhythm detection (IRD) task. Pure tones and narrowband noises of different bandwidths were presented monaurally to older and younger NH listeners via headphones. For CI users, stimuli were delivered as pure tones via soundfield and via direct electrical stimulation. Results confirmed that tonal pitch is not essential for stream segregation by NH listeners and that aging does not reduce NH listeners' stream segregation. CI listeners' stream segregation was significantly poorer than NH listeners' with pure tone stimuli. With direct stimulation, however, CI listeners showed significantly stronger stream segregation, with a mean normalized pattern similar to NH listeners, implying that the CI speech processors possibly degraded acoustic cues. CI listeners' performance on an electrode discrimination task indicated that cues that are salient enough to make two electrodes highly discriminable may not be sufficiently salient for stream segregation, and that gap detection/discrimination, which must depend on perceptual electrode differences, did not play a role in the IRD task. Although the IRD task does not encompass all aspects of full stream segregation, these results suggest that some CI listeners may demonstrate aspects of stream segregation.

Direct stimulation of peripheral nerves can successfully provide sensory feedback to amputees while using hand prostheses. Recent clinical studies have addressed this important limitation of current prostheses solutions using different implantable electrode concepts. Longevity of the electrodes is key to success. We have improved the long-term stability of the polyimide-based transverse intrafascicular multichannel electrode (TIME) that showed promising performance in clinical trials by integration of silicon carbide adhesion layers. The TIMEs were implanted in the median and ulnar nerves of three trans-radial amputees for up to six months. Here, we present the characterization of the electrical properties of the thin-film metallization as well as material status post explantationem for the first time. The TIMEs showed reliable performance in terms of eliciting sensation and stayed within the electrochemical safe limits maintaining a good working range with respect to amplitude modulation. After termination of the trials and explantation of the probes, no signs of corrosion or morphological change to the thin-film metallization was observed by means of electrochemical and optical analysis. Damage to the metallization was assigned exclusively to mechanical impacts during explantation and handling. The results indicate that thin-film metallization on polymer substrates is applicable in permanent implant system.

A major function of the hippocampus is to link discontiguous events in memory. This process can be studied in animals using Pavlovian trace conditioning, a procedure where the conditional stimulus (CS) and unconditional stimulus (US) are separated in time. While the majority of studies have found that trace conditioning requires the dorsal segment of the hippocampus, others have not. This variability could be due to the use of lesion and pharmacological techniques, which lack cell specificity and temporal precision. More recent studies using optogenetic tools find that trace fear acquisition is disrupted by decreases in dorsal CA1 (dCA1) activity while increases lead to learning enhancements. However, comparing these results is difficult given that some studies manipulated the activity of CA1 pyramidal neurons directly and others did so indirectly (e.g., via stimulation of entorhinal cortex inputs). The goal of the current experiments, therefore, was to compare the effects of direct CA1 excitation and inhibition on the encoding and expression of trace fear memories. Our data indicates that stimulation of ArchT in dCA1 pyramidal neurons reduces activity and impairs both the acquisition and retrieval of trace fear. Unlike previous work, direct stimulation of CA1 with ChR2 increases activity and produces deficits in trace fear learning and expression. We hypothesize that this is due to the artificial nature of optogenetic stimulation, which could disrupt processing throughout the hippocampus and in downstream structures.