Effect of Static and Dynamic Heat Pain Stimulus Profiles on the Temporal Dynamics and Interdependence of Pain Qualities, Intensity, and Affect

2008 ◽  
Vol 100 (4) ◽  
pp. 1706-1715 ◽  
Author(s):  
Javeria A. Hashmi ◽  
Karen D. Davis
Keyword(s):  
Time Course ◽  
Temporal Dynamics ◽  
Constant Intensity ◽  
Dynamic Stimuli ◽  
Temporal Properties ◽  
Dynamic Stimulus ◽  
On Line ◽  
Underlying Mechanisms ◽  
S Peak ◽  
Time To Onset

Acute and chronic pains are characterized by a particular constellation of pain qualities, such as burning, aching, stinging, or sharp feelings. However, the temporal pattern of specific pain qualities and their relationship with pain and affect is not well understood. In addition, little is known about how the temperature time course of the stimulus impacts the temporal dynamics of pain qualities and the relationship between pain qualities. Therefore we applied two types of stimuli to the feet of 16 healthy subjects, each calibrated to evoke a similar pain magnitude (50/100): static stimulus held at constant intensity and dynamic stimulus increased in intensity in small steps. Stimulus runs consisted of three 30-s stimuli (either static or dynamic) with an interstimulus interval of 60 s. Continuous on-line ratings of pain, burning, sharp, stinging, cutting, and annoyance were obtained in separate runs, and the evoked responses were characterized by within-stimulus adaptation (early: 0- to 15-s peak vs. late: 25- to 40-s peak) and by their temporal properties (time to onset, peak, and end). The temporal profile of the burning sensation was similar to the pain and annoyance evoked by the static and dynamic stimuli. However, the sharp, stinging and cutting sensations attenuated in response to the static stimuli ( P < 0.01) but intensified along with pain and affect in response to the dynamic stimuli ( P < 0.05), whereas there was no attenuation in the evoked profiles of pain ( P = 0.61), annoyance ( P = 0.27), or burning quality ( P = 0.27). These data demonstrate that specific pain qualities with known differences in underlying mechanisms have distinct temporal dynamics that depend on the stimulus intensity dynamics.

scholarly journals Strong inhibitory signaling underlies stable temporal dynamics and working memory in spiking neural networks

2020 ◽  
Author(s):  
Robert Kim ◽  
Terrence J. Sejnowski
Keyword(s):  
Working Memory ◽  
Task Performance ◽  
Cortical Neurons ◽  
Temporal Dynamics ◽  
Single Neurons ◽  
Multiple Timescales ◽  
Neural Data ◽  
Temporal Properties ◽  
Underlying Mechanisms ◽  
Inhibitory Signaling

AbstractCortical neurons process information on multiple timescales, and areas important for working memory (WM) contain neurons capable of integrating information over a long timescale. However, the underlying mechanisms for the emergence of neuronal timescales stable enough to support WM are unclear. By analyzing a spiking recurrent neural network (RNN) model trained on a WM task and activity of single neurons in the primate prefrontal cortex, we show that the temporal properties of our model and the neural data are remarkably similar. Dissecting our RNN model revealed strong inhibitory-to-inhibitory connections underlying a disinhibitory microcircuit as a critical component for long neuronal timescales and WM maintenance. We also found that enhancing inhibitory-to-inhibitory connections led to more stable temporal dynamics and improved task performance. Finally, we show that a network with such microcircuitry can perform other tasks without disrupting its pre-existing timescale architecture, suggesting that strong inhibitory signaling underlies a flexible WM network.

Studies on the mechanism of acute inhibition of thyroglobulin hydrolysis by iodine

1985 ◽  
Vol 108 (4) ◽  
pp. 511-517 ◽  
Author(s):  
Nandalal Bagchi ◽  
Birdie Shivers ◽  
Thomas R. Brown
Keyword(s):  
Time Course ◽  
Period 2 ◽  
Iodotyrosine Deiodinase ◽  
Rate Of Hydrolysis ◽  
Underlying Mechanisms ◽  
Excess Iodide ◽  
Sites Of Action ◽  
Hydrolysis Of

Abstract. Iodine in excess is known to acutely inhibit thyroidal secretion. In the present study we have characterized the time course of the iodine effect in vitro and investigated the underlying mechanisms. Labelled thyroid glands were cultured in vitro in medium containing mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the proportion of labelled iodotyrosines and iodothyronines recovered at the end of culture and was used as an index of thyroidal secretion. Thyrotrophin (TSH) administered in vivo acutely stimulated the rate of thyroglobulin hydrolysis. Addition of Nal to the culture medium acutely inhibited both basal and TSH-stimulated thyroglobulin hydrolysis. The effect of iodide was demonstrable after 2 h, maximal after 6 h and was not reversible upon removal of iodide. Iodide abolished the dibutyryl cAMP induced stimulation of thyroglobulin hydrolysis. Iodide required organic binding of iodine for its effect but new protein or RNA synthesis was not necessary. The inhibitory effects of iodide and lysosomotrophic agents such as NH4C1 and chloroquin on thyroglobulin hydrolysis were additive suggesting different sites of action. Iodide added in vitro altered the distribution of label in prelabelled thyroglobulin in a way that suggested increased coupling in the thyroglobulin molecule. These data indicate that 1) the iodide effect occurs progressively over a 6 h period, 2) continued presence of iodide is not necessary once the inhibition is established, 3) iodide exerts its action primarily at a post cAMP, prelysosomal site and 4) the effect requires organic binding of iodine, but not new RNA or protein synthesis. Our data are consistent with the hypothesis that excess iodide acutely inhibits thyroglobulin hydrolysis by increasing the resistance of thyroglobulin to proteolytic degradation through increased iodination and coupling.

scholarly journals Applications of Supercritical Anti-Solvent Process in Preparation of Solid Multicomponent Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 475
Author(s):  
Guijin Liu ◽  
Junjian Li ◽  
Shiming Deng
Keyword(s):  
Solid State ◽  
Solid Dispersions ◽  
Crystal Form ◽  
Great Promise ◽  
Computational Techniques ◽  
Large Contribution ◽  
Continuous Manufacturing ◽  
Multicomponent Systems ◽  
On Line ◽  
Underlying Mechanisms

Solid multicomponent systems (SMS) are gaining an increasingly important role in the pharmaceutical industry, to improve the physicochemical properties of active pharmaceutical ingredients (APIs). In recent years, various processes have been employed for SMS manufacturing. Control of the particle solid-state properties, such as size, morphology, and crystal form is required to optimize the SMS formulation. By utilizing the unique and tunable properties of supercritical fluids, supercritical anti-solvent (SAS) process holds great promise for the manipulation of the solid-state properties of APIs. The SAS techniques have been developed from batch to continuous mode. Their applications in SMS preparation are summarized in this review. Many pharmaceutical co-crystals and solid dispersions have been successfully produced via the SAS process, where the solid-state properties of APIs can be well designed by controlling the operating parameters. The underlying mechanisms on the manipulation of solid-state properties are discussed, with the help of on-line monitoring and computational techniques. With continuous researching, SAS process will give a large contribution to the scalable and continuous manufacturing of desired SMS in the near future.

scholarly journals Combining Mechanistic Modeling and Raman Spectroscopy for Monitoring Antibody Chromatographic Purification

Processes ◽  
2019 ◽  
Vol 7 (10) ◽  
pp. 683 ◽  
Author(s):  
Feidl ◽  
Garbellini ◽  
Luna ◽  
Vogg ◽  
Souquet ◽  
...  
Keyword(s):  
Experimental Data ◽  
Raman Spectroscopy ◽  
Estimation Procedure ◽  
Mechanistic Modeling ◽  
Spectroscopic Techniques ◽  
Chromatographic Purification ◽  
On Line ◽  
Filter Approach ◽  
Underlying Mechanisms ◽  
Combining Information

Chromatography is widely used in biotherapeutics manufacturing, and the corresponding underlying mechanisms are well understood. To enable process control and automation, spectroscopic techniques are very convenient as on-line sensors, but their application is often limited by their sensitivity. In this work, we investigate the implementation of Raman spectroscopy to monitor monoclonal antibody (mAb) breakthrough (BT) curves in chromatographic operations with a low titer harvest. A state estimation procedure is developed by combining information coming from a lumped kinetic model (LKM) and a Raman analyzer in the frame of an extended Kalman filter approach (EKF). A comparison with suitable experimental data shows that this approach allows for the obtainment of reliable estimates of antibody concentrations with reduced noise and increased robustness.

Temporal Dynamics of Shape Analysis in Macaque Visual Area V2

2004 ◽  
Vol 92 (5) ◽  
pp. 3030-3042 ◽  
Author(s):  
Jay Hegdé ◽  
David C. Van Essen
Keyword(s):  
Cortical Neurons ◽  
Time Course ◽  
Temporal Dynamics ◽  
Visual Stimulation ◽  
Signal To Noise Ratio ◽  
Stimulus Onset ◽  
Visual Area ◽  
Response Modulation ◽  
Population Response ◽  
Area V2

The firing rate of visual cortical neurons typically changes substantially during a sustained visual stimulus. To assess whether, and to what extent, the information about shape conveyed by neurons in visual area V2 changes over the course of the response, we recorded the responses of V2 neurons in awake, fixating monkeys while presenting a diverse set of static shape stimuli within the classical receptive field. We analyzed the time course of various measures of responsiveness and stimulus-related response modulation at the level of individual cells and of the population. For a majority of V2 cells, the response modulation was maximal during the initial transient response (40–80 ms after stimulus onset). During the same period, the population response was relatively correlated, in that V2 cells tended to respond similarly to specific subsets of stimuli. Over the ensuing 80–100 ms, the signal-to-noise ratio of individual cells generally declined, but to a lesser degree than the evoked-response rate during the corresponding time bins, and the response profiles became decorrelated for many individual cells. Concomitantly, the population response became substantially decorrelated. Our results indicate that the information about stimulus shape evolves dynamically and relatively rapidly in V2 during static visual stimulation in ways that may contribute to form discrimination.

The time-course of morphosyntactic and semantic priming in late bilinguals: A study of German adjectives

2016 ◽  
Vol 20 (3) ◽  
pp. 435-456 ◽  
Author(s):  
SINA BOSCH ◽  
HELENA KRAUSE ◽  
ALINA LEMINEN
Keyword(s):  
Semantic Processing ◽  
Time Course ◽  
Semantic Information ◽  
Temporal Dynamics ◽  
Native Speaker ◽  
Behavioral Experiment ◽  
Lexical Semantic ◽  
Brain Responses ◽  
L2 Learners ◽  
Spatially Extended

How do late proficient bilinguals process morphosyntactic and lexical-semantic information in their non-native language (L2)? How is this information represented in the L2 mental lexicon? And what are the neural signatures of L2 morphosyntactic and lexical-semantic processing? We addressed these questions in one behavioral and two ERP priming experiments on inflected German adjectives testing a group of advanced late Russian learners of German in comparison to native speaker (L1) controls. While in the behavioral experiment, the L2 learners performed native-like, the ERP data revealed clear L1/L2 differences with respect to the temporal dynamics of grammatical processing. Specifically, our results show that L2 morphosyntactic processing yielded temporally and spatially extended brain responses relative to L1 processing, indicating that grammatical processing of inflected words in an L2 is more demanding and less automatic than in the L1. However, this group of advanced L2 learners showed native-like lexical-semantic processing.

scholarly journals Emergence of neuronal diversity during vertebrate brain development

2019 ◽  
Author(s):  
Bushra Raj ◽  
Jeffrey A. Farrell ◽  
Aaron McKenna ◽  
Jessica L. Leslie ◽  
Alexander F. Schier
Keyword(s):  
Brain Development ◽  
Single Cell ◽  
Time Course ◽  
Temporal Dynamics ◽  
Cell Types ◽  
Developmental Time ◽  
Neural Progenitors ◽  
Neuronal Diversity ◽  
Gene Markers ◽  
Vertebrate Brain

ABSTRACTNeurogenesis in the vertebrate brain comprises many steps ranging from the proliferation of progenitors to the differentiation and maturation of neurons. Although these processes are highly regulated, the landscape of transcriptional changes and progenitor identities underlying brain development are poorly characterized. Here, we describe the first developmental single-cell RNA-seq catalog of more than 200,000 zebrafish brain cells encompassing 12 stages from 12 hours post-fertilization to 15 days post-fertilization. We characterize known and novel gene markers for more than 800 clusters across these timepoints. Our results capture the temporal dynamics of multiple neurogenic waves from embryo to larva that expand neuronal diversity from ∼20 cell types at 12 hpf to ∼100 cell types at 15 dpf. We find that most embryonic neural progenitor states are transient and transcriptionally distinct from long-lasting neural progenitors of post-embryonic stages. Furthermore, we reconstruct cell specification trajectories for the retina and hypothalamus, and identify gene expression cascades and novel markers. Our analysis reveal that late-stage retinal neural progenitors transcriptionally overlap cell states observed in the embryo, while hypothalamic neural progenitors become progressively distinct with developmental time. These data provide the first comprehensive single-cell transcriptomic time course for vertebrate brain development and suggest distinct neurogenic regulatory paradigms between different stages and tissues.

scholarly journals A Three-Pool Model Dissecting Readily Releasable Pool Replenishment at the Calyx of Held

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jun Guo ◽  
Jian-long Ge ◽  
Mei Hao ◽  
Zhi-cheng Sun ◽  
Xin-sheng Wu ◽  
...  
Keyword(s):  
Time Course ◽  
Current View ◽  
Vesicle Recycling ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Central Synapse ◽  
Pool Model ◽  
Underlying Mechanisms ◽  
First Time ◽  
Intense Stimulation

Abstract Although vesicle replenishment is critical in maintaining exo-endocytosis recycling, the underlying mechanisms are not well understood. Previous studies have shown that both rapid and slow endocytosis recycle into a very large recycling pool instead of within the readily releasable pool (RRP) and the time course of RRP replenishment is slowed down by more intense stimulation. This finding contradicts the calcium/calmodulin-dependence of RRP replenishment. Here we address this issue and report a three-pool model for RRP replenishment at a central synapse. Both rapid and slow endocytosis provide vesicles to a large reserve pool (RP) ~42.3 times the RRP size. When moving from the RP to the RRP, vesicles entered an intermediate pool (IP) ~2.7 times the RRP size with slow RP-IP kinetics and fast IP-RRP kinetics, which was responsible for the well-established slow and rapid components of RRP replenishment. Depletion of the IP caused the slower RRP replenishment observed after intense stimulation. These results establish, for the first time, a realistic cycling model with all parameters measured, revealing the contribution of each cycling step in synaptic transmission. The results call for modification of the current view of the vesicle recycling steps and their roles.

scholarly journals An Inactivation Switch Enables Rhythms in a Neurospora Clock Model

2019 ◽  
Vol 20 (12) ◽  
pp. 2985 ◽  
Author(s):  
Abhishek Upadhyay ◽  
Michael Brunner ◽  
Hanspeter Herzel
Keyword(s):  
Feedback Loop ◽  
Design Principle ◽  
Temporal Dynamics ◽  
Model Organism ◽  
Transcription Activator ◽  
White Collar Complex ◽  
Living Organisms ◽  
Underlying Mechanisms ◽  
Molecular Components ◽  
Novel Model

Autonomous endogenous time-keeping is ubiquitous across many living organisms, known as the circadian clock when it has a period of about 24 h. Interestingly, the fundamental design principle with a network of interconnected negative and positive feedback loops is conserved through evolution, although the molecular components differ. Filamentous fungus Neurospora crassa is a well-established chrono-genetics model organism to investigate the underlying mechanisms. The core negative feedback loop of the clock of Neurospora is composed of the transcription activator White Collar Complex (WCC) (heterodimer of WC1 and WC2) and the inhibitory element called FFC complex, which is made of FRQ (Frequency protein), FRH (Frequency interacting RNA Helicase) and CK1a (Casein kinase 1a). While exploring their temporal dynamics, we investigate how limit cycle oscillations arise and how molecular switches support self-sustained rhythms. We develop a mathematical model of 10 variables with 26 parameters to understand the interactions and feedback among WC1 and FFC elements in nuclear and cytoplasmic compartments. We performed control and bifurcation analysis to show that our novel model produces robust oscillations with a wild-type period of 22.5 h. Our model reveals a switch between WC1-induced transcription and FFC-assisted inactivation of WC1. Using the new model, we also study the possible mechanisms of glucose compensation. A fairly simple model with just three nonlinearities helps to elucidate clock dynamics, revealing a mechanism of rhythms’ production. The model can further be utilized to study entrainment and temperature compensation.

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