Stimulation Strategies Research Articles

Patient-specific functional electrical stimulation strategy based on muscle synergy and walking posture analysis for gait rehabilitation of stroke patients.

ObjectiveTo evaluate a novel multi-channel functional electrical stimulation (FES) rehabilitation method based on the evaluation of patient-specific walking dysfunction.MethodsThis study investigated a novel multi-channel FES-based rehabilitation method that analysed the patient’s muscle synergy and walking posture. A patient-specific FES profile was produced in the pre-evaluation stage by comparing the muscle synergy and walking posture of the patient with those of healthy control subjects. During the rehabilitation phase, this profile was used to determine an appropriate FES pulse width and amplitude for stimulating the patient’s muscles as they walked across a flat surface.ResultsTwo stroke patients with hemiplegic symptoms participated in a clinical evaluation of the proposed method involving a 4-week course of rehabilitation. An evaluation of the rehabilitation results based on a comparison of the pre- and post-rehabilitation muscle synergy and walking posture revealed that the rehabilitation enhanced the muscle synergy similarity between the patients and healthy control subjects and their quantitative walking performance, as measured by a 10-m walk test and walking speed, by up to 23.38% and 30.00%, respectively.ConclusionThese results indicated that the proposed rehabilitation method improved walking ability by improving muscle coordination and adequately supporting weakened muscles in stroke patients.

The stimulation of sense of community on the early childhood’ online learning

The change of conventional learning into online learning process due to COVID-19 pandemic had brought a significant change towards sense of community stimulation. Direct learning activities are needed considering that the early childhood education progress emphasize sense experiences in which a direct interaction between teachers and students. A dynamic interaction could improve roles as a part of society (sense of community). It was designed in the form of descriptive quantitative to find out a clear picture about the sense of community stimulation conducted by the teachers of The Early Childhood Education Program in North Denpasar, Bali. Proportional random sampling was used to choose the participants. Questionnaire was the instruments used in this study in which it was spread by using Google Form. The data were analysed quantitatively by using statistical descriptive in the percentage form. The findings showed that sense of community stimulation done by the early childhood teachers was positive in the percentage of 85,94 %. The other results were viewed from four indicators such as; teachers’ knowledge categorized as positive (79,59%), the sense of community stimulation strategy in the positive category categorized in strongly positive (86,52%), the sense of community stimulation’s planning, strategy categorized into strongly positive, and the collaboration and enrichment were strongly positive (92,16%).

Natural Killer Cells: The Linchpin for Successful Cancer Immunotherapy.

Cancer immunotherapy is a highly successful and rapidly evolving treatment modality that works by augmenting the body’s own immune system. While various immune stimulation strategies such as PD-1/PD-L1 or CTLA-4 checkpoint blockade result in robust responses, even in patients with advanced cancers, the overall response rate is low. While immune checkpoint inhibitors are known to enhance cytotoxic T cells’ antitumor response, current evidence suggests that immune responses independent of cytotoxic T cells, such as Natural Killer (NK) cells, play crucial role in the efficacy of immunotherapeutic interventions. NK cells hold a distinct role in potentiating the innate immune response and activating the adaptive immune system. This review highlights the importance of the early actions of the NK cell response and the pivotal role NK cells hold in priming the immune system and setting the stage for successful response to cancer immunotherapy. Yet, in many patients the NK cell compartment is compromised thus lowering the chances of successful outcomes of many immunotherapies. An overview of mechanisms that can drive NK cell dysfunction and hinder immunotherapy success is provided. Rather than relying on the likely dysfunctional endogenous NK cells to work with immunotherapies, adoptive allogeneic NK cell therapies provide a viable solution to increase response to immunotherapies. This review highlights the advances made in development of NK cell therapeutics for clinical application with evidence supporting their combinatorial application with other immune-oncology approaches to improve outcomes of immunotherapies.

Strategies to Refine Gastric Stimulation and Pacing Protocols: Experimental and Modeling Approaches.

Gastric pacing and stimulation strategies were first proposed in the 1960s to treat motility disorders. However, there has been relatively limited clinical translation of these techniques. Experimental investigations have been critical in advancing our understanding of the control mechanisms that innervate gut function. In this review, we will discuss the use of pacing to modulate the rhythmic slow wave conduction patterns generated by interstitial cells of Cajal in the gastric musculature. In addition, the use of gastric high-frequency stimulation methods that target nerves in the stomach to either inhibit or enhance stomach function will be discussed. Pacing and stimulation protocols to modulate gastric activity, effective parameters and limitations in the existing studies are summarized. Mathematical models are useful to understand complex and dynamic systems. A review of existing mathematical models and techniques that aim to help refine pacing and stimulation protocols are provided. Finally, some future directions and challenges that should be investigated are discussed.

Optimizing deep brain stimulation based on isostable amplitude in essential tremor patient models

Objective. Deep brain stimulation is a treatment for medically refractory essential tremor. To improve the therapy, closed-loop approaches are designed to deliver stimulation according to the system’s state, which is constantly monitored by recording a pathological signal associated with symptoms (e.g. brain signal or limb tremor). Since the space of possible closed-loop stimulation strategies is vast and cannot be fully explored experimentally, how to stimulate according to the state should be informed by modeling. A typical modeling goal is to design a stimulation strategy that aims to maximally reduce the Hilbert amplitude of the pathological signal in order to minimize symptoms. Isostables provide a notion of amplitude related to convergence time to the attractor, which can be beneficial in model-based control problems. However, how isostable and Hilbert amplitudes compare when optimizing the amplitude response to stimulation in models constrained by data is unknown. Approach. We formulate a simple closed-loop stimulation strategy based on models previously fitted to phase-locked deep brain stimulation data from essential tremor patients. We compare the performance of this strategy in suppressing oscillatory power when based on Hilbert amplitude and when based on isostable amplitude. We also compare performance to phase-locked stimulation and open-loop high-frequency stimulation. Main results. For our closed-loop phase space stimulation strategy, stimulation based on isostable amplitude is significantly more effective than stimulation based on Hilbert amplitude when amplitude field computation time is limited to minutes. Performance is similar when there are no constraints, however constraints on computation time are expected in clinical applications. Even when computation time is limited to minutes, closed-loop phase space stimulation based on isostable amplitude is advantageous compared to phase-locked stimulation, and is more efficient than high-frequency stimulation. Significance. Our results suggest a potential benefit to using isostable amplitude more broadly for model-based optimization of stimulation in neurological disorders.

Perturbations both trigger and delay seizures due to generic properties of slow-fast relaxation oscillators.

The mechanisms underlying the emergence of seizures are one of the most important unresolved issues in epilepsy research. In this paper, we study how perturbations, exogenous or endogenous, may promote or delay seizure emergence. To this aim, due to the increasingly adopted view of epileptic dynamics in terms of slow-fast systems, we perform a theoretical analysis of the phase response of a generic relaxation oscillator. As relaxation oscillators are effectively bistable systems at the fast time scale, it is intuitive that perturbations of the non-seizing state with a suitable direction and amplitude may cause an immediate transition to seizure. By contrast, and perhaps less intuitively, smaller amplitude perturbations have been found to delay the spontaneous seizure initiation. By studying the isochrons of relaxation oscillators, we show that this is a generic phenomenon, with the size of such delay depending on the slow flow component. Therefore, depending on perturbation amplitudes, frequency and timing, a train of perturbations causes an occurrence increase, decrease or complete suppression of seizures. This dependence lends itself to analysis and mechanistic understanding through methods outlined in this paper. We illustrate this methodology by computing the isochrons, phase response curves and the response to perturbations in several epileptic models possessing different slow vector fields. While our theoretical results are applicable to any planar relaxation oscillator, in the motivating context of epilepsy they elucidate mechanisms of triggering and abating seizures, thus suggesting stimulation strategies with effects ranging from mere delaying to full suppression of seizures.

Methods for Lowering the Power Consumption of OS-Based Adaptive Deep Brain Stimulation Controllers.

The identification of a new generation of adaptive strategies for deep brain stimulation (DBS) will require the development of mixed hardware–software systems for testing and implementing such controllers clinically. Towards this aim, introducing an operating system (OS) that provides high-level features (multitasking, hardware abstraction, and dynamic operation) as the core element of adaptive deep brain stimulation (aDBS) controllers could expand the capabilities and development speed of new control strategies. However, such software frameworks also introduce substantial power consumption overhead that could render this solution unfeasible for implantable devices. To address this, in this work four techniques to reduce this overhead are proposed and evaluated: a tick-less idle operation mode, reduced and dynamic sampling, buffered read mode, and duty cycling. A dual threshold adaptive deep brain stimulation algorithm for suppressing pathological oscillatory neural activity was implemented along with the proposed energy saving techniques on an energy-efficient OS, YetiOS, running on a STM32L476RE microcontroller. The system was then tested using an emulation environment coupled to a mean field model of the parkinsonian basal ganglia to simulate local field potential (LFPs) which acted as a biomarker for the controller. The OS-based controller alone introduced a power consumption overhead of 10.03 mW for a sampling rate of 1 kHz. This was reduced to 12 μW by applying the proposed tick-less idle mode, dynamic sampling, buffered read and duty cycling techniques. The OS-based controller using the proposed methods can facilitate rapid and flexible testing and implementation of new control methods. Furthermore, the approach has the potential to become a central element in future implantable devices to enable energy-efficient implementation of a wide range of control algorithms across different neurological conditions and hardware platforms.

Phase-Dependent Deep Brain Stimulation: A Review.

Neural oscillations are repetitive patterns of neural activity in the central nervous systems. Oscillations of the neurons in different frequency bands are evident in electroencephalograms and local field potential measurements. These oscillations are understood to be one of the key mechanisms for carrying out normal functioning of the brain. Abnormality in any of these frequency bands of oscillations can lead to impairments in different cognitive and memory functions leading to different pathological conditions of the nervous system. However, the exact role of these neural oscillations in establishing various brain functions is still under investigation. Closed loop deep brain stimulation paradigms with neural oscillations as biomarkers could be used as a mechanism to understand the function of these oscillations. For making use of the neural oscillations as biomarkers to manipulate the frequency band of the oscillation, phase of the oscillation, and stimulation signal are of importance. This paper reviews recent trends in deep brain stimulation systems and their non-invasive counterparts, in the use of phase specific stimulation to manipulate individual neural oscillations. In particular, the paper reviews the methods adopted in different brain stimulation systems and devices for stimulating at a definite phase to further optimize closed loop brain stimulation strategies.

The effect of input noises on the activity of auditory neurons using GLM-based metrics * *Part of this work has been presented at the Int. Conf. of the IEEE Engineering in Medicine and Biology Society (EMBC), Berlin, Germany, 2019. The results and analysis have been substantially expanded.

Objective. The auditory system is extremely efficient in extracting auditory information in the presence of background noise. However, people with auditory implants have a hard time understanding speech in noisy conditions. The neural mechanisms related to the processing of background noise, especially in the inferior colliculus (IC) where the auditory midbrain implant is located, are still not well understood. Understanding the mechanisms of perception in noise could lead to better stimulation or preprocessing strategies for such implants. We thus wish to investigate if there is a difference in the activity of neurons in the IC when presenting noisy vocalizations with different types of noise (stationary vs. non-stationary), input signal-to-noise ratios (SNR) and signal levels. Approach. We developed novel metrics based on a generalized linear model (GLM) to investigate the effect of a given input noise on neural activity. We used these metrics to analyze neural data recorded from the IC in ketamine-anesthetized female Hartley guinea pigs while presenting noisy vocalizations. Main results. We found that non-stationary noise clearly contributes to the multi-unit neural activity in the IC by causing excitation, regardless of the SNR, input level or vocalization type. However, when presenting white or natural stationary noises, a great diversity of responses was observed for the different conditions, where the multi-unit activity of some sites was affected by the presence of noise and the activity of others was not. Significance. The GLM-based metrics allowed the identification of a clear distinction between the effect of white or natural stationary noises and that of non-stationary noise on the multi-unit activity in the IC. This had not been observed before and indicates that the so-called noise invariance in the IC is dependent on the input noisy conditions. This could suggest different preprocessing or stimulation approaches for auditory midbrain implants depending on the noisy conditions.

Mathematical Modeling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation.

New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts (“waves”) of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modeling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test ovarian stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle.

A facile and comprehensive algorithm for electrical response identification in mouse retinal ganglion cells.

Retinal prostheses can restore the basic visual function of patients with retinal degeneration, which relies on effective electrical stimulation to evoke the physiological activities of retinal ganglion cells (RGCs). Current electrical stimulation strategies have defects such as unstable effects and insufficient stimulation positions, therefore, it is crucial to determine the optimal pulse parameters for precise and safe electrical stimulation. Biphasic voltages (cathode-first) with a pulse width of 25 ms and different amplitudes were used to ex vivo stimulate RGCs of three wild-type (WT) mice using a commercial microelectrode array (MEA) recording system. An algorithm is developed to automatically realize both spike-sorting and electrical response identification for the spike signals recorded. Measured from three WT mouse retinas, the total numbers of RGC units and responsive RGC units were 1193 and 151, respectively. In addition, the optimal pulse amplitude range for electrical stimulation was determined to be 0.43 V-1.3 V. The processing results of the automatic algorithm we proposed shows high consistency with those using traditional manual processing. We anticipate the new algorithm can not only speed up the elaborate electrophysiological data processing, but also optimize pulse parameters for the electrical stimulation strategy of neural prostheses.

Brain fMRI during orientation selective epidural spinal cord stimulation

Epidural spinal cord stimulation (ESCS) is widely used for chronic pain treatment, and is also a promising tool for restoring motor function after spinal cord injury. Despite significant positive impact of ESCS, currently available protocols provide limited specificity and efficiency partially due to the limited number of contacts of the leads and to the limited flexibility to vary the spatial distribution of the stimulation field in respect to the spinal cord. Recently, we introduced Orientation Selective (OS) stimulation strategies for deep brain stimulation, and demonstrated their selectivity in rats using functional MRI (fMRI). The method achieves orientation selectivity by controlling the main direction of the electric field gradients using individually driven channels. Here, we introduced a similar OS approach for ESCS, and demonstrated orientation dependent brain activations as detected by brain fMRI. The fMRI activation patterns during spinal cord stimulation demonstrated the complexity of brain networks stimulated by OS-ESCS paradigms, involving brain areas responsible for the transmission of the motor and sensory information. The OS approach may allow targeting ESCS to spinal fibers of different orientations, ultimately making stimulation less dependent on the precision of the electrode implantation.

Color and cellular selectivity of retinal ganglion cell subtypes through frequency modulation of electrical stimulation

Epiretinal prostheses aim at electrically stimulating the inner most surviving retinal cells—retinal ganglion cells (RGCs)—to restore partial sight to the blind. Recent tests in patients with epiretinal implants have revealed that electrical stimulation of the retina results in the percept of color of the elicited phosphenes, which depends on the frequency of stimulation. This paper presents computational results that are predictive of this finding and further support our understanding of the mechanisms of color encoding in electrical stimulation of retina, which could prove pivotal for the design of advanced retinal prosthetics that elicit both percept and color. This provides, for the first time, a directly applicable “amplitude-frequency” stimulation strategy to “encode color” in future retinal prosthetics through a predictive computational tool to selectively target small bistratified cells, which have been shown to contribute to “blue-yellow” color opponency in the retinal circuitry. The presented results are validated with experimental data reported in the literature and correlated with findings in blind patients with a retinal prosthetic implant collected by our group.

Adult mouse dorsal root ganglia neurons form aberrant glutamatergic connections in dissociated cultures.

Cultured sensory neurons can exhibit complex activity patterns following stimulation in terms of increased excitability and interconnected responses of multiple neurons. Although these complex activity patterns suggest a network-like configuration, research so far had little interest in synaptic network formation ability of the sensory neurons. To identify interaction profiles of Dorsal Root Ganglia (DRG) neurons and explore their putative connectivity, we developed an in vitro experimental approach. A double transgenic mouse model, expressing genetically encoded calcium indicator (GECI) in their glutamatergic neurons, was produced. Dissociated DRG cultures from adult mice were prepared with a serum-free protocol and no additional growth factors or cytokines were utilized for neuronal sensitization. DRG neurons were grown on microelectrode arrays (MEA) to induce stimulus-evoked activity with a modality-free stimulation strategy. With an almost single-cell level electrical stimulation, spontaneous and evoked activity of GCaMP6s expressing neurons were detected under confocal microscope. Typical responses were analyzed, and correlated calcium events were detected across individual DRG neurons. Next, correlated responses were successfully blocked by glutamatergic receptor antagonists, which indicated functional synaptic coupling. Immunostaining confirmed the presence of synapses mainly in the axonal terminals, axon-soma junctions and axon-axon intersection sites. Concisely, the results presented here illustrate a new type of neuron-to-neuron interaction in cultured DRG neurons conducted through synapses. The developed assay can be a valuable tool to analyze individual and collective responses of the cultured sensory neurons.

Leave the past behind: women’s reproductive history shows no association with blastocysts’ euploidy and limited association with live birth rates after euploid embryo transfers

Is there an association between patients' reproductive history and the mean euploidy rates per biopsied blastocysts (m-ER) or the live birth rates (LBRs) per first single vitrified-warmed euploid blastocyst transfers? Patients' reproductive history (as annotated during counselling) showed no association with the m-ER, but a lower LBR was reported after euploid blastocyst transfer in women with a history of repeated implantation failure (RIF). Several studies have investigated the association between the m-ER and (i) patients' basal characteristics, (ii) ovarian stimulation strategy and dosage, (iii) culture media and conditions, and (iv) embryo morphology and day of full blastocyst development. Conversely, the expected m-ER due to women's reproductive history (previous live births (LBs), miscarriages, failed IVF cycles and transfers, and lack of euploid blastocysts among prior cohorts of biopsied embryos) still needs investigations. Yet, this information is critical to counsel new patients about a first cycle with preimplantation genetic testing for aneuploidy (PGT-A), but even more so after former adverse outcomes to prevent treatment drop-out. This observational study included all patients undergoing a comprehensive chromosome testing (CCT)-based PGT-A cycle with at least one biopsied blastocyst in the period April 2013-December 2019 at a private IVF clinic (n = 2676 patients undergoing 2676 treatments and producing and 8151 blastocysts). m-ER were investigated according to women's reproductive history of LBs: no/≥1, miscarriages: no/1/>1; failed IVF cycles: no/1/2/>2, and implantation failures after previous transfers: no/1/2/>2. Among the 2676 patients included in this study, 440 (16%) had already undergone PGT-A before the study period; the data from these patients were further clustered according to the presence or absence of euploid embryo(s) in their previous cohort of biopsied blastocysts. The clinical outcomes per first single vitrified-warmed euploid blastocyst transfers (n =1580) were investigated according to the number of patients' previous miscarriages and implantation failures. The procedures involved in this study included ICSI, blastocyst culture, trophectoderm biopsy without hatching in Day 3, CCT-based PGT-A without reporting segmental and/or putative mitotic (or mosaic) aneuploidies and single vitrified-warmed euploid blastocyst transfer. For statistical analysis, Mann-Whitney U or Kruskal-Wallis tests, as well as linear regressions and generalised linear models among ranges of maternal age at oocyte retrieval were performed to identify significant differences for continuous variables. Fisher's exact tests and multivariate logistic regression analyses were instead used for categorical variables. Maternal age at oocyte retrieval was the only variable significantly associated with the m-ER. We defined five clusters (<35 years: 66 ± 31%; 35-37 years: 58 ± 33%; 38-40 years: 43 ± 35%; 40-42 years: 28 ± 34%; and >42 years: 17 ± 31%) and all analyses were conducted among them. The m-ER did not show any association with the number of previous LBs, miscarriages, failed IVF cycles or implantation failures. Among patients who had already undergone PGT-A before the study period, the m-ER did not associate with the absence (or presence) of euploid blastocysts in their former cohort of biopsied embryos. Regarding clinical outcomes of the first single vitrified-warmed euploid blastocyst transfer, the implantation rate was 51%, the miscarriage rate was 14% and the LBR was 44%. This LBR was independent of the number of previous miscarriages, but showed a decreasing trend depending on the number of previous implantation failures, reaching statistical significance when comparing patients with >2 failures and patients with no prior failure (36% versus 47%, P < 0.01; multivariate-OR adjusted for embryo quality and day of full blastocyst development: 0.64, 95% CI 0.48-0.86, P < 0.01). No such differences were shown for previous miscarriage rates. The sample size for treatments following a former completed PGT-A cycle should be larger in future studies. The data should be confirmed from a multicentre perspective. The analysis should be performed also in non-PGT cycles and/or including patients who did not produce blastocysts, in order to investigate a putative association between women's reproductive history with outcomes other than euploidy and LBRs. These data are critical to counsel infertile couples before, during and after a PGT-A cycle, especially to prevent treatment discontinuation due to previous adverse reproductive events. Beyond the 'maternal age effect', the causes of idiopathic recurrent pregnancy loss (RPL) and RIF are likely to be endometrial receptivity and selectivity issues; transferring euploid blastocysts might reduce the risk of a further miscarriage, but more information beyond euploidy are required to improve the prognosis in case of RIF. No funding was received and there are no competing interests. N/A.

Thalamic Local Field Potentials Are Related to Long-Term DBS Effects in Tourette Syndrome.

Background: Local field potential (LFP) recordings helped to clarify the pathophysiology of Tourette syndrome (TS) and to define new strategies for deep brain stimulation (DBS) treatment for refractory TS, based on the delivery of stimulation in accordance with changes in the electrical activity of the DBS target area. However, there is little evidence on the relationship between LFP pattern and DBS outcomes in TS.Objective: To investigate the relationship between LFP oscillations and DBS effects on tics and on obsessive compulsive behavior (OCB) comorbidities.Methods: We retrospectively analyzed clinical data and LFP recordings from 17 patients treated with DBS of the centromedian-parafascicular/ventralis oralis (CM-Pf/VO) complex, and followed for more several years after DBS in the treating center. In these patients, LFPs were recorded either in the acute setting (3–5 days after DBS electrode implant) or in the chronic setting (during impulse generator replacement surgery). LFP oscillations were correlated with the Yale Global Tic Severity Scale (YGTSS) and the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) collected at baseline (before DBS surgery), 1 year after DBS, and at the last follow-up available.Results: We found that, at baseline, in the acute setting, the power of the oscillations included in the 5–15-Hz band, previously identified as TS biomarker, is correlated with the pathophysiology of tics, being significantly correlated with total YGTSS before DBS (Spearman's ρ = 0.701, p = 0.011). The power in the 5–15-Hz band was also correlated with the improvement in Y-BOCS after 1 year of DBS (Spearman's ρ = −0.587, p = 0.045), thus suggesting a relationship with the DBS effects on OCB comorbidities.Conclusions: Our observations confirm that the low-frequency (5–15-Hz) band is a significant biomarker of TS, being related to the severity of tics and, also to the long-term response on OCBs. This represents a step toward both the understanding of the mechanisms underlying DBS effects in TS and the development of adaptive DBS strategies.

Autonomic reactivity to emotion: A marker of sub‐clinical anxiety and depression symptoms?

Anxiety and depression are both characterized by dysregulated autonomic reactivity to emotion. However, most experiments until now have focused on autonomic reactivity to stimuli presented in central vision (CV) even if affective saliency is also observed in peripheral vision (PV). We compared autonomic reactivity to CV and PV emotional stimulation in 58 participants with high anxious (HA) or low anxious (LA) and high depressive (HD) or low depressive (LD) symptomatology, based on STAI-B and BDI scores, respectively. Unpleasant (U), pleasant (P), and neutral (N) pictures from IAPS were presented at three eccentricities (0°: CV; -12 and 12°: PV). Skin conductance (SC), skin temperature, pupillary diameter, and heart rate (HR) were recorded. First, HA participants showed greater pupil dilation to emotional than to neutral stimuli in PV than in CV. Second, in contrast to HD, the valence effect indexed by SC and emotional arousal effect indexed by skin temperature were observed in LD. Third, both anxiety and depression lead to a valence effect indexed by pupillary light reflex and heart rate. These results suggest a hyperreactivity to emotion and hypervigilance to PV in anxiety. Depression is associated with an attenuation of positive effect and a global blunted autonomic reactivity to emotion. Moreover, anxiety mostly modulates the early processes of autonomic reactivity whereas depression mainly affects the later processes. The differential impact of emotional information over the visual field suggests the use of new stimulation strategies in order to attenuate anxious and depressive symptoms.

Naturalistic spatiotemporal modulation of epiretinal stimulation increases the response persistence of retinal ganglion cell

Objective. Retinal stimulation in blind patients evokes the sensation of discrete points of light called phosphenes, which allows them to perform visually guided tasks, such as orientation, navigation, object recognition, object manipulation and reading. However, the clinical benefit of artificial vision in profoundly blind patients is still tenuous, as several engineering and biophysical obstacles keep it far away from natural perception. The relative preservation of the inner retinal neurons in hereditary degenerative retinal diseases, such as retinitis pigmentosa, supports artificial vision through the network-mediated stimulation of retinal ganglion cells (RGCs). However, the response of RGCs to repeated electrical stimulation rapidly declines, primarily because of the intrinsic desensitisation of their excitatory network. In patients, upon repetitive stimulation, phosphenes fade out in less than half of a second, which drastically limits the understanding of the percept. Approach. A more naturalistic stimulation strategy, based on spatiotemporal modulation of electric pulses, could overcome the desensitisation of RGCs. To investigate this hypothesis, we performed network-mediated epiretinal stimulations paired to electrophysiological recordings in retinas explanted from both male and female retinal degeneration 10 mice. Main results. The results showed that the spatial and temporal modulation of the network-mediated epiretinal stimulation prolonged the persistence of the RGC’s response from 400 ms up to 4.2 s. Significance. A time-varied, non-stationary and interrupted stimulation of the retinal network, mimicking involuntary microsaccades, might reduce the fading of the visual percept and improve the clinical efficacy of retinal implants.

Methanogenic crude oil degradation induced by an exogenous microbial community and nutrient injections

Microbial potential of crude oil degradation coupled to methane production has attracted much attention as a basis for microbial enhanced energy recovery (MEER) technology. Here we performed laboratory incubation experiments mimicking in situ temperature and pressure conditions of subsurface oil reservoirs to evaluate the effectiveness of biological augmentation and stimulation for MEER. Using our high temperature and pressure incubation system, we successfully obtained a microbial community capable of methanogenic crude oil degradation from the Yamagata oil reservoir in Japan. To evaluate the potential of biological augmentation, we inoculated the microbial culture from Yamagata into production water from the Akita oil reservoir in which the indigenous microbial community cannot degrade crude oil. We observed methane production associated with toluene degradation, indicating that biological augmentation could be successful. We also evaluated the potential of biological stimulation, i.e. the effects of supplementing with different nutrients on crude oil degradation using the Yamagata oil reservoir sample. Intriguingly, addition of specific yeast extracts (YEs) resulted in notably enhanced methane production associated with the degradation of longer-chain n-alkanes as well as toluene. We further assessed the effectiveness of combining the biological augmentation and stimulation by inoculating the microbial culture from Yamagata together with the effective YE into the Akita production water, and found a large amount of methane production coupled to toluene and n-alkane degradation during the incubation. Taken together, our results suggest that the bio-augmentation and stimulation strategies demonstrated here could be a powerful tool for energy recovery from petroleum reservoirs both with and without innate crude oil degradation.

Effectiveness and Acceptability of Noninvasive Brain and Nerve Stimulation Techniques for Migraine Prophylaxis: A Network Meta-Analysis of Randomized Controlled Trials

Background: Current pharmacologic prophylactic strategies for migraine have exhibited limited efficacy, with response rates as low as 40%–50%. In addition to the limited efficacy, the acceptability of those pharmacologic prophylactic strategies were unacceptable. Although noninvasive brain/nerve stimulation strategies may be effective, the evidence has been inconsistent. The aim of this network meta-analysis (NMA) was to compare strategies of noninvasive brain/nerve stimulation for migraine prophylaxis with respect to their effectiveness and acceptability. Methods: The PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov databases were searched for randomized controlled trials (RCTs). Patients with diagnosis of migraine, either episodic migraine or chronic migraine, were included. The primary outcome was the changes in monthly migraine days and response rate, and the acceptability was defined as the drop-out rate. All NMA procedures were conducted under the frequentist model. Findings: Nineteen randomized controlled trials were included (N=1493; mean age=38.2 years; 82.0% women). We determined that the high frequency repetitive transcranial magnetic stimulation (rTMS) over C3 yielded the most decreased monthly migraine days among all the interventions [mean difference=-8.70 days, 95% confidence intervals (95%CIs): -14.45 to -2.95 compared to sham/control groups]. In addition, high-frequency (100 Hz) transcutaneous occipital nerve stimulation (tONS) over the Oz provided the highest response rate in migraine prophylaxis [rate ratio (RR)=9.00, 95%CIs: 1.24 to 65.16 compared to sham/control groups]. Only alternative frequency (2/100 Hz) tONS over the Oz (RR=0.36, 95%CIs: 0.16 to 0.82) yielded a significantly lower drop-out rate than the sham/control groups did. Interpretation: The current study provided a new direction for the design of more methodologically robust and larger RCTs based on the findings of the potentially beneficial effect on migraine prophylaxis in participants with migraine by different noninvasive brain/nerve stimulation, especially the application of rTMS and tONS. Funding Information: None. Declaration of Interests: The authors report no financial interests or potential conflicts of interest.