Stimulation Interval Research Articles

Kinematic Effects of Combined Subthalamic and Dorsolateral Nigral Deep Brain Stimulation in Parkinson's Disease.

Additional stimulation of the substantia nigra (SNr) has been proposed to target axial symptoms and gait impairment in patients with Parkinson's disease (PD). This study aimed to characterize effects of combined deep brain stimulation (DBS) of the subthalamic nucleus (STN) and SNr on gait performance in PD and to map stimulation sites within the SNr. In a double-blinded crossover design, 10 patients with PD and gait impairment underwent clinical examination and kinematic assessment with STN DBS, combined STN+SNr DBS and OFF DBS 30 minutes after reprogramming. To confirm stimulation within the SNr, electrodes, active contacts, and stimulation volumes were modeled in a common space and overlap with atlases of SNr was computed. Overlap of stimulation volumes with dorsolateral SNr was confirmed for all patients. UPDRS III, scoring of freezing during turning and transitioning, stride length, stride velocity, and range of motion of shank, knee, arm, and trunk as well as peak velocities during turning and transitions and turn duration were improved with STN DBS compared to OFF. On cohort level, no further improvement was observed with combined STN+SNr DBS but additive improvement of spatiotemporal gait parameters was observed in individual subjects. Combined high frequency DBS of the STN and dorsolateral SNr did not consistently result in additional short-term kinematic or clinical benefit compared to STN DBS. Stimulation intervals, frequency, and patient selection for target symptoms as well as target region within the SNr need further refinement in future trials.

Performance Evaluation of AE Sensors Installed Like Hydrophones in Adaptive Monitoring Networks During a Decametre-Scale Hydraulic Stimulation Experiment

AbstractIn the framework of the STIMTEC and STIMTEC-X hydraulic stimulation experiments at the Reiche Zeche mine, Freiberg (Germany), we installed acoustic emission (AE) sensors for the recording of picoseismicity both conventionally using pneumatic coupling and experimentally like a hydrophone, i.e. the sensors were placed in the borehole without a further coupling system or cementing. We investigate performance measures of the hydrophone-like acoustic emission (HAE) sensors such as frequency bandwidth, sensitivity, first motion polarity, coupling and placement quality to assess the sensor’s applicability in adaptive monitoring networks. HAE sensors can be paired with hydraulic equipment, especially with the double packer probe used for stimulation at the decametre scale because the monitored frequency content differs from injection-related noise. This offers a unique opportunity to improve the network geometry and consequently the quality of a seismic catalogue. We analyse the sensor characteristics using active ultrasonic transmission measurements from boreholes with different orientations in the rock volume, noise measurements preceding active centre punch hits in the access galleries and passive recordings of induced acoustic emission events. HAE sensors placed in water-filled boreholes show good sensitivity performance even without optimal coupling to the crystalline rock for recording distances up to 17 m. The HAE sensors record the wavefield adequately for first-arrival identification, polarity picking and amplitude characteristics but are less suitable for detecting S-waves. Due to the borehole geometry HAE sensors record waves with incidence angles from the side, resulting in opposite polarity compared to side-view AE sensors as observed in the field and lab. We discuss the advantages of adaptive monitoring networks with HAE sensors being optimally placed for each stimulation interval configuration anew to improve seismic event detection and quality of event hypocentre locations during hydraulic stimulations. We show that we are able to significantly reduce the azimuthal gap, halve the location uncertainties and improve the network coverage for the purpose of focal mechanism estimations.

Electrical Stimulation of Temporal and Limbic Circuitry Produces Distinct Responses in Human Ventral Temporal Cortex.

The human ventral temporal cortex (VTC) is highly connected to integrate visual perceptual inputs with feedback from cognitive and emotional networks. In this study, we used electrical brain stimulation to understand how different inputs from multiple brain regions drive unique electrophysiological responses in the VTC. We recorded intracranial EEG data in 5 patients (3 female) implanted with intracranial electrodes for epilepsy surgery evaluation. Pairs of electrodes were stimulated with single-pulse electrical stimulation, and corticocortical evoked potential responses were measured at electrodes in the collateral sulcus and lateral occipitotemporal sulcus of the VTC. Using a novel unsupervised machine learning method, we uncovered 2-4 distinct response shapes, termed basis profile curves (BPCs), at each measurement electrode in the 11-500 ms after stimulation interval. Corticocortical evoked potentials of unique shape and high amplitude were elicited following stimulation of several regions and classified into a set of four consensus BPCs across subjects. One of the consensus BPCs was primarily elicited by stimulation of the hippocampus; another by stimulation of the amygdala; a third by stimulation of lateral cortical sites, such as the middle temporal gyrus; and the final one by stimulation of multiple distributed sites. Stimulation also produced sustained high-frequency power decreases and low-frequency power increases that spanned multiple BPC categories. Characterizing distinct shapes in stimulation responses provides a novel description of connectivity to the VTC and reveals significant differences in input from cortical and limbic structures.SIGNIFICANCE STATEMENT Disentangling the numerous input influences on highly connected areas in the brain is a critical step toward understanding how brain networks work together to coordinate human behavior. Single-pulse electrical stimulation is an effective tool to accomplish this goal because the shapes and amplitudes of signals recorded from electrodes are informative of the synaptic physiology of the stimulation-driven inputs. We focused on targets in the ventral temporal cortex, an area strongly implicated in visual object perception. By using a data-driven clustering algorithm, we identified anatomic regions with distinct input connectivity profiles to the ventral temporal cortex. Examining high-frequency power changes revealed possible modulation of excitability at the recording site induced by electrical stimulation of connected regions.

Understanding the impacts of intermittent electro field on the bioelectrochemical aniline degradation system: Performance, microbial community and functional enzyme

On account of the lack of a sustainable electron donor source and the inhibitory effect of aniline on denitrogenation make it tough to achieve simultaneous removal of aniline and nitrogen. Herein, the strategy of adjusting electric field mode was applied to the electro-enhanced sequential batch reactors (E-SBRs: R1 (continuous ON), R2 (2 h-ON/2 h-OFF), R3 (12 h-ON/12 h-OFF), R4 (in the aerobic phase ON), R5 (in the anoxic phase ON)) to treat aniline wastewater. Aniline removal rate reached approximately 99% in the five systems. Decreasing electrical stimulation interval from 12 to 2 h significantly improved the electron utilization efficiency for aniline degradation and nitrogen metabolism. The total nitrogen removal was achieved from 70.31% to 75.63%. Meanwhile, the hydrogenotrophic denitrifiers of Hydrogenophaga, Thauera, and Rhodospirillales, enriched in reactors of minor electrical stimulation interval. Accordingly, the expression of functional enzyme related to electron transport was incremental with the proper electrical stimulation frequency.

Stimulation parameters for motor evoked potentials during intraoperative spinal cord monitoring. A systematic review

ObjectiveThe aim of this systematic review was to find the optimal stimulation parameters for muscle recorded transcranial electrical stimulation motor evoked potential (mTc-MEP) and D-wave monitoring during spinal cord monitoring. MethodsA PRISMA systematic search in Medline and EMBASE and a QUADAS-2 quality evaluation was performed to identify studies that compared stimulation parameters consisting of stimulation location, number of pulses, pulse duration, interstimulus interval, double train (DTS) or recurrent train stimulation (RTS) and intertrain interval (ITI) for performing mTc-MEP and D-wave monitoring. Only studies that used total intravenous anaesthesia (TIVA) were included. ResultsTen studies that compared stimulation parameters for performing mTc-MEP monitoring (stimulation location n = 4, number of pulses n = 2, pulse duration n = 1, interstimulus interval n = 4, DTS n = 1, RTS n = 2, ITI n = 2) were included. No studies compared stimulation parameters (stimulation location and pulse duration) for performing D-wave monitoring. ConclusionsFew studies examined the optimal stimulation parameters for monitoring mTc-MEPs and no studies were included for D-wave monitoring. There is a need for prospective research to investigate the optimal stimulation parameters for mTc-MEP with the use of TIVA and D-wave monitoring. SignificanceFor mTc-MEP monitoring, a table is provided in which the recommended stimulation parameters are stated.

Spatial characteristics of closed-loop TMS-EEG with occipital alpha-phase synchronized

ObjectiveIn a previous study, we designed a closed-loop TMS-EEG system synchronized with occipital alpha-phase, verified its phase prediction accuracy and discussed the reactivity indicators of the closed-loop system. However, the research on connectivity indicators of closed-loop TMS-EEG was remained lacking. In this study, the purpose of our research is to discuss the spatial characteristics of closed-loop TMS-EEG data with occipital alpha-phase synchronization. MethodWe collected 30 healthy college students’ closed-loop TMS-EEG data (15 men and 15 women, age 25.23 ± 2.74 years old) with 3–4 s as the stimulation interval, 100 % of the resting motor threshold (RMT) as the stimulation strength, and the left primary motor cortex (M1) as the target area, and calculated each frequency-band connectivity and brain network difference of these data under different alpha phase conditions (rising edge, falling edge, peak and trough). In addition, we also calculated the spatial complexity characterized by the perturbational complexity index (PCI) of the closed-loop TMS-EEG data. ResultsThe occipital lobe alpha phase EEG had a significant modulation effect on the gamma network, with the connectivity of the many channels under the phase180 condition being stronger than that under the phase 0 condition. Similarly, under the condition of phase 0, the gamma network had the lowest clustering coefficient (F = 7.592, df = 2.079, p = 0.001), the longest shortest path length (F = 7.638, df = 2.163, p = 0.001), and the largest small world attribute (F = 6.195, df = 2.422, p = 0.020), while the results were opposite under the phase180 condition. There were no significant differences in PCI values (F = 2.231, df = 2.538, p = 0.103) among the four phase conditions, but there was a smaller coefficient of intertrial PCI variation when stimulated at the phase90 condition (F = 3.275, df = 2.793, p = 0.029). ConclusionWe have comprehensively discussed the spatial characteristics of closed-loop TMS-EEG with occipital alpha-phase synchronization and hope that our research will be instructive for future work on closed-loop TMS.

Processing of sensory, painful and vestibular stimuli in the thalamus

ObjectivesThe thalamus plays an important role in the mediation and integration of various stimuli (e.g., somatosensory, pain, and vestibular). Whether a stimulus-specific and topographic organization of the thalamic nuclei exists is still unknown. The aim of our study was to define a functional, in vivo map of multimodal sensory processing within the human thalamus.MethodsTwenty healthy individuals (10 women, 21–34 years old) participated. Defined sensory stimuli were applied to both hands (innocuous touch, mechanical pain, and heat pain) and the vestibular organ (galvanic stimulation) during 3 T functional MRI.ResultsBilateral thalamic activations could be detected for touch, mechanical pain, and vestibular stimulation within the left medio-dorsal and right anterior thalamus. Heat pain did not lead to thalamic activation at all. Stimuli applied to the left body side resulted in stronger activation patterns. Comparing an early with a late stimulation interval, the mentioned activation patterns were far more pronounced within the early stimulation interval.ConclusionsThe right anterior and ventral-anterior nucleus and the left medio-dorsal nucleus appear to be important for the processing of multimodal sensory information. In addition, galvanic stimulation is processed more laterally compared to mechanical pain. The observed changes in activity within the thalamic nuclei depending on the stimulation interval suggest that the stimuli are processed in a thalamic network rather than a distinct nucleus. In particular, the vestibular network within the thalamus recruits bilateral nuclei, rendering the thalamus an important integrative structure for vestibular function.

M2 Muscarinic Receptor-Dependent Contractions of Airway Smooth Muscle are Inhibited by Activation of β-Adrenoceptors.

Beta-adrenoceptor (β-AR) agonists inhibit cholinergic contractions of airway smooth muscle (ASM), but the underlying mechanisms are unclear. ASM cells express M3 and M2 muscarinic receptors, but the bronchoconstrictor effects of acetylcholine are believed to result from activation of M3Rs, while the role of the M2Rs is confined to offsetting β-AR-dependent relaxations. However, a profound M2R-mediated hypersensitization of M3R-dependent contractions of ASM was recently reported, indicating an important role for M2Rs in cholinergic contractions of ASM. Here, we investigated if M2R-dependent contractions of murine bronchial rings were inhibited by activation of β-ARs. M2R-dependent contractions were apparent at low frequency (2Hz)electric field stimulation (EFS) and short (10s) stimulus intervals.The β1-AR agonist, denopamine inhibited EFS-evoked contractions of ASM induced by reduction in stimulus interval from 100 to 10 sand was more effective at inhibiting contractions evoked by EFS at 2than 20 Hz.Denopamine also abolished carbachol-evoked contractions that were resistant to the M3R antagonist 4-DAMP, similar to the effects of the M2R antagonists, methoctramine and AFDX-116. The inhibitory effects of denopamine on EFS-evoked contractions of ASM were smaller in preparations taken from M2R -/- mice, compared to wild-type (WT) controls. In contrast, inhibitory effects of the β3-AR agonist, BRL37344, on EFS-evoked contractions of detrusor strips taken from M2R -/- mice were greater than WT controls. These data suggest that M2R-dependent contractions of ASM were inhibited by activation of β1-ARs and that genetic ablation of M2Rs decreased the efficacy of β-AR agonists on cholinergic contractions.

Optimization of Seating Position and Stimulation Pattern in Functional Electrical Stimulation Cycling: Simulation Study.

Two significant challenges facing functional electrical stimulation (FES) cycling are the low power output and early onset of muscle fatigue, mainly due to the non-physiological and superficial recruitment of motor units and weakness of the antagonistic muscles. Thus optimization of the cycling biomechanical properties and stimulation pattern to achieve maximum output power with minimum applied electrical stimulus is of great importance. To find the optimal seating position and stimulation pattern, the previous works either ignored the muscle's force-velocity and force-length properties or employed complicated muscle models which was a massive barrier to clinical experiments. In this work, an easy-to-use and precise muscle model in conjunction with Jacobian-based torque transfer functions were adopted to determine the optimal seating position, trunk angle, crank arm length, and stimulation intervals. Furthermore, the impact of muscle force-velocity factor in finding the optimal seating position and stimulation intervals was investigated. The simulation models showed the trivial effect of the force-velocity factor on the resulting optimal seating position of six healthy simulated subjects. This method can enhance the FES-cycling performance and shorten the time-consuming process of muscle model identification for optimization purposes.

Instant classification for the spatially-coded BCI.

The spatially-coded SSVEP BCI exploits changes in the topography of the steady-state visual evoked response to visual flicker stimulation in the extrafoveal field of view. In contrast to frequency-coded SSVEP BCIs, the operator does not gaze into any flickering lights; therefore, this paradigm can reduce visual fatigue. Other advantages include high classification accuracies and a simplified stimulation setup. Previous studies of the paradigm used stimulation intervals of a fixed duration. For frequency-coded SSVEP BCIs, it has been shown that dynamically adjusting the trial duration can increase the system's information transfer rate (ITR). We therefore investigated whether a similar increase could be achieved for spatially-coded BCIs by applying dynamic stopping methods. To this end we introduced a new stopping criterion which combines the likelihood of the classification result and its stability across larger data windows. Whereas the BCI achieved an average ITR of 28.4±6.4 bits/min with fixed intervals, dynamic intervals increased the performance to 81.1±44.4 bits/min. Users were able to maintain performance up to 60 minutes of continuous operation. We suggest that the dynamic response time might have worked as a kind of temporal feedback which allowed operators to optimize their brain signals and compensate fatigue.

OIDA: An optimal interval detection algorithm for automatized determination of stimulation patterns for FES-Cycling in individuals with SCI

BackgroundFES-Cycling is an exciting recreational activity, which allows certain individuals after spinal cord injury or stroke to exercise their paralyzed muscles. The key for a successful application is to activate the right muscles at the right time.MethodsWhile a stimulation pattern is usually determined empirically, we propose an approach using the torque feedback provided by a commercially available crank power-meter installed on a standard trike modified for FES-Cycling. By analysing the difference between active (with stimulation) and passive (without stimulation) torques along a full pedalling cycle, it is possible to differentiate between contributing and resisting phases for a particular muscle group. In this article we present an algorithm for the detection of optimal stimulation intervals and demonstrate its functionality, bilaterally for the quadriceps and hamstring muscles, in one subject with complete SCI on a home trainer. Stimulation patterns were automatically determined for two sensor input modalities: the crank-angle and a normalized thigh-angle (i.e. cycling phase, measured via inertial measurement units). In contrast to previous studies detecting automatic stimulation intervals on motorised ergo-cycles, our approach does not rely on a constant angular velocity provided by a motor, thus being applicable to the domain of mobile FES-Cycling.ResultsThe algorithm was successfully able to identify stimulation intervals, individually for the subject’s left and right quadriceps and hamstring muscles. Smooth cycling was achieved without further adaptation, for both input signals (i.e. crank-angle and normalized thigh-angle).ConclusionThe automatic determination of stimulation patterns, on basis of the positive net-torque generated during electrical stimulation, can help to reduce the duration of the initial fitting phase and to improve the quality of pedalling during a FES-Cycling session. In contrast to previous works, the presented algorithm does not rely on a constant angular velocity and thus can be effectively implemented into mobile FES-Cycling systems. As each muscle or muscle group is assessed individually, our algorithm can be used to evaluate the efficiency of novel electrode configurations and thus could promote increased performances during FES-Cycling.

Theta‐gamma phase‐amplitude coupling explains the advantage of auditory plus visual gamma entrainment in Alzheimer’s therapy

AbstractBackgroundImpairment of gamma oscillations has been observed in cognitive disorders like Alzheimer’s disease (AD). Gamma entrainment using 40Hz auditory or visual stimulation has been proposed as a potential treatment for AD (Adaikkan et al., Trends in Neuroscience 2020; Sedghizadeh et al. Alzheimer’s and Dementia 2020), while simultaneous use of both modalities has been reported to show superior therapeutic results (Martorell et al., Cell 2019; Suk et al. Alzheimer’s and Dementia 2020). Gamma and theta oscillations are both produced in the hippocampal area and interact with each other. Evidence shows that the interaction between these bands leads to their phase‐amplitude coupling (PAC) in the frontal cortex (Amemiya et al., Cell Reports 2018). The current study assesses the effects of 40Hz auditory and visual stimulation on the theta‐gamma PAC, and suggests that the superior performance of multimodal entrainment can be explained by this marker.Method10 cognitively healthy participants were included in this study. Each participant was seated in a dark and quiet room and underwent three sessions of sensory stimulation (visual, auditory, and simultaneous (multimodal) visual and auditory) in a randomized order. Each session consisted of 60 trials of 5s stimulation and 5s rest. The auditory stimulation consisted of a 40Hz clicking sound modulated with a career frequency of 5kHz. The visual stimulation was generated using white LEDs flickering at 40Hz. EEG data were acquired and the theta‐gamma PAC was calculated using the time‐frequency mean vector length (tf‐MVL) method (Munia et al., Scientific Reports 2019).ResultThe PAC value for theta (4‐8Hz) and gamma oscillations near the stimulation frequency (39‐41Hz) on the Fz channel showed a significant increase during the multimodal stimulation intervals compared to the resting state, whereas the increase was not significant during the single‐modal stimulations compared to rest. The multimodal stimulation also involved more brain areas and resulted in a higher PAC compared to single‐modal stimulation.ConclusionEntraining gamma oscillations using simultaneous auditory and visual stimulation results in markedly superior theta‐gamma PAC compared to entrainment with single modalities. This superiority can explain the advantages reported for multimodal entrainment in AD therapy experiments.

Optogenetic control of cancer cell survival in ChR2‐transfected HeLa cells

Optogenetics is a molecular biological technique involving transfection of cells with photosensitive proteins and the subsequent study of their biological effects. The aim of this study was to evaluate the effect of blue light on the survival of HeLa cells, transfected with channelrhodopsin-2 (ChR2). HeLa wild-type cells were transfected with a plasmid that contained the gene for ChR2. Transfection and channel function were evaluated by real-time polymerase chain reaction (RT-PCR), fluorescence imaging using green fluorescent protein (GFP) and flow cytometry for intracellular calcium changes using a Fura Red probe. We developed a platform for optogenetic stimulation for use within the cell culture incubator. Different stimulation procedures using blue light (467nm) were applied for up to 24h. Cell survival was determined by flow cytometry using propidium iodide and rhodamine probes. Change in cell survival showed a statistically significant (p<0.05) inverse association with the frequency and time of application of the light stimulus. This change seemed to be associated with the ChR2 cis-trans-isomerization cycle. Cell death was associated with high concentrations of calcium in the cytoplasm and stimulation intervals less than the period of isomerization. It is possible to transfect HeLa cells with ChR2 and control their survival under blue light stimulation. We suggest that this practice should be considered in the future development of optogenetic systems in biological or biomedical research.

Anodal tDCS augments and preserves working memory beyond time-on-task deficits

Transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex (DLPFC) has been shown to promote working memory (WM), however, its efficacy against time-on-task-related performance decline and associated cognitive fatigue remains uncertain. This study examined the impact of anodal tDCS of the left DLPFC on performance during a fatiguing visuospatial WM test. We adopted a repeated measures design, where 32 healthy adults (16 female), underwent anodal, control and sham tDCS on separate days. They completed an hour long two-back test, with stimulation intensity, onset, and duration set at 1 mA, at the 20th minute for 10 minutes respectively. Task performance, subjective responses, and heart rate variability (HRV) were captured during the experiment. Anodal tDCS substantially improved WM relative to sham tDCS and control in both sexes. These benefits lasted beyond the stimulation interval, and were unique across performance measures. However, no perceptual changes in subjective effort or fatigue levels were noted between conditions, although participants reported greater discomfort during stimulation. While mood and sleepiness changed with time-on-task, reflecting fatigue, these were largely similar across conditions. HRV increased under anodal tDCS and control, and plateaued under sham tDCS. We found that short duration anodal tDCS at 1 mA was an effective countermeasure to time-on-task deficits during a visuospatial two-back task, with enhancement and preservation of WM capacity. However, these improvements were not available at a perceptual level. Therefore, wider investigations are necessary to determine “how” such solutions will be operationalized in the field, especially within human-centered systems.

O-169 Conventional ovarian stimulation with gonadotropins depletes the developmental proteome of mouse oocytes, reducing their size and compromising their fetal yield

Abstract Study question Does conventional ovarian stimulation with gonadotropins alter the molecular composition, size, and developmental fitness of superovulated mouse oocytes? Summary answer Ovarian stimulation perturbs 31% of developmental proteome vs. 2% of transcriptome, yielding smaller oocytes that form blastocysts with less primitive endoderm and diminished fetal yield. What is known already Prior mouse studies aimed to assess the impact of superovulation on oocyte and embryo quality provided variable results. Aberrations were observed in some studies but not in others, and were associated with a variable time spent in the oviduct until retrieval for in vitro culture. Although the natural ovarian cycle lasts 4 days in mice, the conventional stimulation protocol time spans 2 days. No genome-wide studies have been devoted yet to the global gene expression of superovulated mouse oocytes and derivative embryos, to determine if gene products accumulate to the same extent as in natural cycles. Study design, size, duration Approx. 1100 female mice were injected, half with serial equine and human chorionic gonadotropin, eCG and hCG, to induce superovulation; the other half were injected with saline as control. Both groups were mated to vasectomized or fertile males to obtain, respectively, metaphase II and fertilized oocytes. These were removed from the oviducts, and followed up in vitro to blastocyst, or in vivo to term after surgical transfer to naturally cycling females. Participants/materials, setting, methods B6C3F1 oocytes (n= ∼16000) from superovulation (10 I.U. eCG+hCG) or natural ovulation were measured for diameter, and upon fertilization, they were cultured in KSOM(aa) to collect preimplantation stages for analyses (mass spectrometry; RNA sequencing; immunofluorescence for counting of trophectoderm, epiblast, and primitive endoderm cells). Embryos at the 4-cell stage were transplanted to naturally cycling females (8/female, 45 recipients). Results were compared between natural ovulation and superovulation with 48h (conventional) or 72h interval of eCG-hCG stimulation. Main results and the role of chance Preimplantation embryos of superovulated oocytes were affected in 31% of the proteins (893 / 2855) vs. 2% of the transcripts (482 / 21784), compared to natural counterparts (adj.P&amp;lt;0.05, Wilcoxon test). Gene set enrichment analysis of the perturbed proteome returned the top-terms ‘thin zona pellucida’ (ZP1, ZP2, ZP3) and ‘abnormal inner cell mass apoptosis’ (DAB2, STAT3). Microscope measurements verified a thinner zona pellucida (p = 0.077, Wilcoxon test) along with a smaller diameter (p &amp;lt; 0.0001, Wilcoxon test) of superovulated oocytes, which gave rise to blastocysts deficient in primitive endoderm (p &amp;lt; 0.013, Fisher’s exact test). Since 529 of the 893 differently expressed proteins were depleted, we considered that ovarian stimulation provided insufficient time for protein accumulation. Increasing the eCG-hCG interval from 48 h (conventional) to 72 h restored oocytes’ diameters, and improved their fetal output from 25% to 59%, compared to 54% of natural ovulation (15 embryo transfers per group). Conversely, oocytes lost part of their developmental potential to the micromanipulation-assisted reduction of their volume. This study provides evidence of an additional novel effect of exposure to gonadotropins on mouse oocyte quality, whose mechanism is mediated not by the stimulated genital tract, but by the time-dependent accumulation of proteins in oocytes. Limitations, reasons for caution This is an animal model study based on one mouse strain. Ovarian stimulation protocols differ between mice and humans. There can be yet other, more subtle or long-term differences between superovulated and naturally ovulated oocytes, than those described here. Proteome and transcriptome analysis cover much, but not everything. Wider implications of the findings There is a trade-off between oocyte quantity and quality in mice subjected to superovulation. Cytological and molecular deficits define a ‘small oocyte syndrome’. Problematic is not so much the gonadotropin treatment, rather its timing. An evidence-based protocol for superovulation may be different from that used currently in mice. Trial registration number Not applicable

Brittleness modeling selects optimum stimulation zone in shaly source rocks in the Whangai Formation, New Zealand

Within New Zealand, the East Coast Basin represents the primary shale oil and gas play in which the Whangai Formation is widespread. This formation is oil and gas prone and prevalent throughout a large area of the East Coast Basin and is typically composed of the Upper Calcareous, Porangahau, and Rakauroa Members. The primary goal of this study was to develop an integrated methodology to define the best stimulation intervals in the formation. To do this, we evaluated four different definitions of the brittleness index for the Rakauroa Member, the only member drilled in the three study wells. A Python-based automated process was specifically developed for this purpose and uses four indexes: elastic parameters, internal friction coefficient, mineralogy, and total organic carbon content. Through this process, these four indexes were analytically combined to select intervals with the highest brittleness values and identify the optimum stimulation interval and most desirable perforation intervals in the pay zone. Our results show that the Whangai Formation contains 25% clay (and reaching up to 70% clay content in some intervals) and a maximum organic matter content of 2.54%. The geomechanical model indicates a uniform distribution of high pore pressure across the entire reservoir section. The interval between 1497 and 1750 m in the Opoutama-1 well located in the Coastal block presents high combined brittleness indexes, indicating excellent characteristics from a stimulation standpoint.

Cortical Excitability in Temporal Lobe Epilepsy with Bilateral Tonic-Clonic Seizures.

We investigated motor cortical excitability (CE) in unilateral temporal lobe epilepsy (TLE) and its relationship to bilateral tonic-clonic seizure (BTCS) using paired-pulse transcranial magnetic stimulation (TMS). In this cross-sectional study, we enrolled 46 unilateral TLE patients and 16 age-and sex-matched healthy controls. Resting motor thresholds (RMT); short-interval intracortical inhibition (SICI, GABAA receptor-mediated); facilitation (ICF, glutamatergic-mediated) with interstimulus intervals (ISIs) of 2, 5, 10, and 15 ms; and long-interval intracortical inhibition (LICI, GABAB receptor-mediated) with ISIs of 200-400 ms were measured via paired-pulse TMS. Comparisons were made between controls and patients with TLE, and then among the TLE subgroups (no BTCS, infrequent BTCS and frequent BTCS subgroup). Compared with controls, TLE patients had higher RMT, lower SICI and higher LICI in both hemispheres, and higher ICF in the ipsilateral hemisphere. In patients with frequent BTCS, cortical hyperexcitability in the ipsilateral hemisphere was found in a parameter-dependent manner (SICI decreased at a stimulation interval of 5 ms, and ICF increased at a stimulation interval of 15 ms) compared with patients with infrequent or no BTCS. Our results demonstrate that motor cortical hyper-excitability in the ipsilateral hemisphere underlies the epileptogenic network of patients with active BTCS, which is more extensive than those with infrequent or no BTCS.

Deep Brain Stimulation Impedance Decreases Over Time Even When Stimulation Settings Are Held Constant.

Objectives: To study whether and to what extent the therapeutic impedance and current change under long-term deep brain stimulation (DBS) with constant stimulation settings, which could inform the role of constant current stimulation.Methods: Therapy impedance and current measurements were retrospectively collected from patients with Parkinson’s disease (PD) undergoing DBS of the subthalamic nucleus (STN) or essential tremor (ET) undergoing ventral intermediate nucleus (VIM). Baseline and follow-up measurements were obtained for intervals of at least 6 months without changes in stimulation settings. The single longest interval of constant stimulation for each electrode was included. Temporal trends in impedance and current were analyzed as absolute and relative differences and as the rate of change.Results: Impedance and current data from 79 electrodes (60 in STN, 19 in VIM) in 44 patients (32 with PD, 12 with ET) met inclusion criteria. The duration between baseline and follow-up measurements with constant stimulation settings was 17 months (median, with an interquartile range of 12–26 months) in the mixed group. Therapy impedance decreased by 27 ± 12 Ω/year (mean ± 2 standard errors; p < 0.0001), and therapy current increased at a rate of 0.142 ± 0.063 mA/year (p < 0.0001). Similar results were observed in the STN and VIM subgroups.Conclusions: Impedance decreases gradually over time, even when stimulation settings are kept constant. The rate of decrease is smaller than previously reported, suggesting that changes in stimulation settings contribute to impedance drift. Stimulation-independent impedance drift is gradual but relevant to constant-current programming.

Neuroimaging mechanisms of high-frequency repetitive transcranial magnetic stimulation for treatment of amnestic mild cognitive impairment: a double-blind randomized sham-controlled trial.

Individuals with amnestic mild cognitive impairment (aMCI) have a high risk of developing Alzheimer's disease. Although repetitive transcranial magnetic stimulation (rTMS) is considered a potentially effective treatment for cognitive impairment in patients with aMCI, the neuroimaging mechanisms are poorly understood. Therefore, we performed a double-blind randomized sham-controlled trial in which rTMS was applied to the left dorsolateral prefrontal cortex of aMCI patients recruited from a community near the Third Hospital Affiliated to Sun Yat-sen University, China. Twenty-four patients with aMCI were randomly assigned to receive true rTMS (treatment group, n = 12, 6 men and 6 women; age 65.08 ± 4.89 years) or sham stimulation (sham group, n = 12, 5 men and 7 women; age 64.67 ± 4.77 years). rTMS parameters included a stimulation frequency of 10 Hz, stimulation duration of 2 seconds, stimulation interval of 8 seconds, 20 repetitions at 80% of the motor threshold, and 400 pulses per session. rTMS/sham stimulation was performed five times per week over a period of 4 consecutive weeks. Our results showed that compared with baseline, Montreal Cognitive Assessment scores were significantly increased and the value of the amplitude of low-frequency fluctuation (ALFF) was significantly increased at the end of treatment and 1 month after treatment. Compared with the sham group, the ALFF values in the right inferior frontal gyrus, triangular part of the inferior frontal gyrus, right precuneus, left angular gyrus, and right supramarginal gyrus were significantly increased, and the ALFF values in the right superior frontal gyrus were significantly decreased in the treatment group. These findings suggest that high-frequency rTMS can effectively improve cognitive function in aMCI patients and alter spontaneous brain activity in cognitive-related brain areas. This study was approved by the Ethics Committee of Shenzhen Baoan Hospital of Southern Medical University, China (approval No. BYL20190901) on September 3, 2019, and registered in the Chinese Clinical Trials Registry (registration No. ChiCTR1900028180) on December 14, 2019.

Occipital Nerve Stimulation in Chronic Migraine: The Relationship Between Perceived Sensory Quality, Perceived Sensory Location, and Clinical Efficacy-A Prospective, Observational, Non-Interventional Study.

IntroductionOccipital nerve stimulation (ONS) is used to treat therapy-resistant chronic migraine. Clinical use has resulted in a wide intraindividual and interindividual variation of clinical efficacy. The aim of this study was to analyze a potential relationship between sociodemographic variables, headache parameters, perceived sensory quality, perceived sensory location, as well as clinical efficacy.MethodsThirty-two subjects (21.9% male, mean age 45.77 years) suffering from chronic migraine refractory to other treatment and therefore treated with ONS were included in this study. We used a computer-based imaging method for mapping the ONS-induced perceived sensory location, the perceived spatial sensory field size, as well as the perceived sensory quality in a long-term course over 21 months in weekly time intervals. Additionally, the effect of ONS on the migraine headache was documented weekly by the participants using a verbal rating scale. Over the observation period, a total of 808 individual weekly data sets were recorded and a potential relationship between ONS-induced perceptions and headache parameters could be analyzed.ResultsWe found that 48.9% of stimulation intervals were reported as effective by patients. Women displayed a significantly higher responder rate than men. The reported effectiveness did not differ depending on age, the average number of migraine days per month, the MIDAS score, or the duration of the migraine disorder prior to ONS treatment. Implantation with trial period led to significantly lower responder rates than without the trial period. The most frequently perceived sensory quality of “tingling” was found significantly more frequently in non-responders than in responders. Responders displayed significantly lower pleasantness scores for their reported perceptions than non-responders. Sensations that were spatially perceived above the line connecting the external acoustic meati with the external occipital protuberance (MOP line) led to patients reporting a positive clinical effect significantly more frequently than sensations spatially perceived below the MOP line. Spatially small fields of sensory perception were correlated with a higher responder rate than those covering broader areas.ConclusionsThe ONS-induced sensory location, the size of the spatial sensory field, as well as the sensory quality are significantly correlated with the reported clinical effectiveness. The results suggest that besides surgical technique, the individual and continuous programming of the stimulation parameters is clinically relevant in increasing the therapeutic effectiveness.