Loudness summation using focused and unfocused electrical stimulation.
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ABSTRACT:
SUBMITTER: Padilla M
PROVIDER: S-EPMC4042455 | biostudies-other | 2014 Feb
REPOSITORIES: biostudies-other
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Project description:Current standards for safe delivery of electrical stimulation to the central nervous system are based on foundational studies which examined post-mortem tissue for histological signs of damage. This set of observations and the subsequently proposed limits to safe stimulation, termed the “Shannon limits,” allow for a simple calculation (using charge per phase and charge density) to determine the intensity of electrical stimulation that can be delivered safely to brain tissue. In the three decades since the Shannon limits were reported, advances in molecular biology have allowed for more nuanced and detailed approaches to be used to expand current understanding of the physiological effects of stimulation. Here, we investigated spatial transcriptomics as a new approach to assess the safety and efficacy of electrical stimulation in the brain. Electrical stimulation was delivered to the rat visual cortex with either acute or chronic electrode implantation procedures (acute: tissue collection 3 hours post-stimulation on the day of surgery; chronic: stimulation delivered 1-month post-implantation, and tissue collection 24 hours later). To explore the influence of device type and stimulation parameters, we used carbon fiber ultramicroelectrode arrays (7 µm diameter) and microwire electrode arrays (50 µm diameter) delivering charge and charge density levels selected above and below reported tissue damage thresholds (range: 2-20 nC, 0.1-1 mC/cm2). Spatial transcriptomics was performed using Visium Spatial Gene Expression Slides (10x Genomics), which enabled simultaneous immunohistochemistry and spatial transcriptomics to directly compare traditional histological metrics to transcriptional profiles within each tissue sample. Our data revealed unique spatial patterns of differentially expressed genes that are related to cellular processes including inflammation, cell cycle progression, and plasticity. Effects were dependent on stimulation parameters and were localized to both traditional and ultra-small device locations. The abundance of data gathered using this approach allows for sophisticated analysis that can be used to generate new hypotheses while also revealing novel potential biomarkers of neurostimulation.
2022-07-01 | GSE202425 | GEO
Project description:Redefining electrical stimulation safety using spatial transcriptomics
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Project description:Research associates processes of fear conditioning and extinction with treatment of anxiety and stress-related disorders. Manipulation of these processes may therefore be beneficial for such treatment. The current study examines the effects of electrical brain stimulation on fear extinction processes in healthy humans in order to assess its potential relevance for treatment enhancement. Forty-five participants underwent a 3-day fear conditioning and extinction paradigm. Electrical stimulation targeting the medial prefrontal cortex was applied during the extinction-learning phase (Day 2). Participants were randomly assigned to three stimulation conditions: direct-current (DC) stimulation, aimed at enhancing extinction-learning; low-frequency alternating-current (AC) stimulation, aimed at interfering with reconsolidation of the activated fear memory; and sham stimulation. The effect of stimulation on these processes was assessed in the subsequent extinction recall phase (Day 3), using skin conductance response and self-reports. Results indicate that AC stimulation potentiated the expression of fear response, whereas DC stimulation led to overgeneralization of fear response to non-reinforced stimuli. The current study demonstrates the capability of electrical stimulation targeting the medial prefrontal cortex to modulate fear extinction processes. However, the stimulation parameters tested here yielded effects opposite to those anticipated and could be clinically detrimental. These results highlight the potential capacity of stimulation to manipulate processes relevant for treatment of anxiety and stress-related disorders, but also emphasize the need for additional research to identify delivery parameters to enable its translation into clinical practice. Clinical trial identifiers: Modulation of Fear Extinction Processes Using Transcranial Electrical Stimulation; https://clinicaltrials.gov/show/NCT02723188; NCT02723188 NCT02723188.
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Project description:Preliminary data [M. Epstein and M. Florentine, Ear. Hear. 30, 234-237 (2009)] obtained using speech stimuli from a visually present talker heard via loudspeakers in a sound-attenuating chamber indicate little difference in loudness when listening with one or two ears (i.e., significantly reduced binaural loudness summation, BLS), which is known as "binaural loudness constancy." These data challenge current understanding drawn from laboratory measurements that indicate a tone presented binaurally is louder than the same tone presented monaurally. Twelve normal listeners were presented recorded spondees, monaurally and binaurally across a wide range of levels via earphones and a loudspeaker with and without visual cues. Statistical analyses of binaural-to-monaural ratios of magnitude estimates indicate that the amount of BLS is significantly less for speech presented via a loudspeaker with visual cues than for stimuli with any other combination of test parameters (i.e., speech presented via earphones or a loudspeaker without visual cues, and speech presented via earphones with visual cues). These results indicate that the loudness of a visually present talker in daily environments is little affected by switching between binaural and monaural listening. This supports the phenomenon of binaural loudness constancy and underscores the importance of ecological validity in loudness research.
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Project description:BackgroundMethods for the electrical inhibition of cardiac excitation have long been sought to control excitability and conduction, but to date remain largely impractical. High-amplitude alternating current (AC) stimulation has been known to extend cardiac action potentials (APs), and has been recently exploited to terminate reentrant arrhythmias by producing reversible conduction blocks. Yet, low-amplitude currents at similar frequencies have been shown to entrain cardiac tissues by generation of repetitive APs, leading in some cases to ventricular fibrillation and hemodynamic collapse in vivo. Therefore, an inhibition method that does not lead to entrainment - irrespective of the stimulation amplitude (bound to fluctuate in an in vivo setting) - is highly desirable.Methodology/principal findingsWe investigated the effects of broader amplitude and frequency ranges on the inhibitory effects of extracellular AC stimulation on HL-1 cardiomyocytes cultured on microelectrode arrays, using both sinusoidal and square waveforms. Our results indicate that, at sufficiently high frequencies, cardiac tissue exhibits a binary response to stimulus amplitude with either prolonged APs or no effect, thereby effectively avoiding the risks of entrainment by repetitive firing observed at lower frequencies. We further demonstrate the ability to precisely define reversible local conduction blocks in beating cultures without influencing the propagation activity in non-blocked areas. The conduction blocks were spatiotemporally controlled by electrode geometry and stimuli duration, respectively, and sustainable for long durations (300 s).Conclusion/significanceInhibition of cardiac excitation induced by high-frequency AC stimulation exhibits a binary response to amplitude above a threshold frequency, enabling the generation of reversible conduction blocks without the risks of entrainment. This inhibition method could yield novel approaches for arrhythmia modeling in vitro, as well as safer and more efficacious tools for in vivo cardiac mapping and radio-frequency ablation guidance applications.
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Project description:Human myogenic progenitor cells (MPCs) were isolated from the gracilis of two patients (1 female and 1 male) undergoing anterior cruciate ligament reconstruction (age 30-34 years) using a human anti-CD56 (1:20, Cat# 355503, Biolegend) antibody for FACS. Cells were passaged 2-3 times in growth media consisting of Ham’s F-10 (Thermofisher), 20% fetal bovine serum (FBS, Atlanta Biological, Minneapolis, MN, USA), 1% penicillin/streptomycin and 10ng/ml basic fibroblast growth-factor (bFGF, Peprotech, Rocky Hill, NJ, USA). Cells were differentiated into myotubes for 5 days using MyoCult differentiation media (Stemcell Technologies, Vancouver, Canada). On the fifth day, fresh media was added just prior to electrical pulse stimulation (E). Cells were then either stimulated at 12 V, 1 Hz, 2 ms for 24 hr (IonOptix C‐Pace EP, Westwood, MA, USA) or had electrodes placed in wells with no stimulation (E(+) or E(-)), followed by immediate RNA extraction using Qiazol (Qiagen, Hilden, Germany).
2021-08-20 | E-MTAB-10833 | biostudies-arrayexpress
Project description:Electrical stimulation for application in tissue engineering and regenerative medicine has received increasing attention in recent years. A variety of stimulation methods, waveforms and amplitudes have been studied. However, a clear choice of optimal stimulation parameters is still not available and is complicated by ambiguous reporting standards. In order to understand underlying cellular mechanisms affected by the electrical stimulation, the knowledge of the actual prevailing field strength or current density is required. Here, we present a comprehensive digital representation, a digital twin, of a basic electrical stimulation device for the electrical stimulation of cells in vitro. The effect of electrochemical processes at the electrode surface was experimentally characterised and integrated into a numerical model of the electrical stimulation. Uncertainty quantification techniques were used to identify the influence of model uncertainties on relevant observables. Different stimulation protocols were compared and it was assessed if the information contained in the monitored stimulation pulses could be related to the stimulation model. We found that our approach permits to model and simulate the recorded rectangular waveforms such that local electric field strengths become accessible. Moreover, we could predict stimulation voltages and currents reliably. This enabled us to define a controlled stimulation setting and to identify significant temperature changes of the cell culture in the monitored voltage data. Eventually, we give an outlook on how the presented methods can be applied in more complex situations such as the stimulation of hydrogels or tissue in vivo.
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