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Estimating the rate constant from biosensor data via an adaptive variational Bayesian approach

Ye Zhang, Zhigang Yao, Patrik Forssén, Torgny Fornstedt.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2011--2042.

Abstract:
The means to obtain the rate constants of a chemical reaction is a fundamental open problem in both science and the industry. Traditional techniques for finding rate constants require either chemical modifications of the reactants or indirect measurements. The rate constant map method is a modern technique to study binding equilibrium and kinetics in chemical reactions. Finding a rate constant map from biosensor data is an ill-posed inverse problem that is usually solved by regularization. In this work, rather than finding a deterministic regularized rate constant map that does not provide uncertainty quantification of the solution, we develop an adaptive variational Bayesian approach to estimate the distribution of the rate constant map, from which some intrinsic properties of a chemical reaction can be explored, including information about rate constants. Our new approach is more realistic than the existing approaches used for biosensors and allows us to estimate the dynamics of the interactions, which are usually hidden in a deterministic approximate solution. We verify the performance of the new proposed method by numerical simulations, and compare it with the Markov chain Monte Carlo algorithm. The results illustrate that the variational method can reliably capture the posterior distribution in a computationally efficient way. Finally, the developed method is also tested on the real biosensor data (parathyroid hormone), where we provide two novel analysis tools—the thresholding contour map and the high order moment map—to estimate the number of interactions as well as their rate constants.




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Approximate inference for constructing astronomical catalogs from images

Jeffrey Regier, Andrew C. Miller, David Schlegel, Ryan P. Adams, Jon D. McAuliffe, Prabhat.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1884--1926.

Abstract:
We present a new, fully generative model for constructing astronomical catalogs from optical telescope image sets. Each pixel intensity is treated as a random variable with parameters that depend on the latent properties of stars and galaxies. These latent properties are themselves modeled as random. We compare two procedures for posterior inference. One procedure is based on Markov chain Monte Carlo (MCMC) while the other is based on variational inference (VI). The MCMC procedure excels at quantifying uncertainty, while the VI procedure is 1000 times faster. On a supercomputer, the VI procedure efficiently uses 665,000 CPU cores to construct an astronomical catalog from 50 terabytes of images in 14.6 minutes, demonstrating the scaling characteristics necessary to construct catalogs for upcoming astronomical surveys.




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Sequential decision model for inference and prediction on nonuniform hypergraphs with application to knot matching from computational forestry

Seong-Hwan Jun, Samuel W. K. Wong, James V. Zidek, Alexandre Bouchard-Côté.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1678--1707.

Abstract:
In this paper, we consider the knot-matching problem arising in computational forestry. The knot-matching problem is an important problem that needs to be solved to advance the state of the art in automatic strength prediction of lumber. We show that this problem can be formulated as a quadripartite matching problem and develop a sequential decision model that admits efficient parameter estimation along with a sequential Monte Carlo sampler on graph matching that can be utilized for rapid sampling of graph matching. We demonstrate the effectiveness of our methods on 30 manually annotated boards and present findings from various simulation studies to provide further evidence supporting the efficacy of our methods.




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On sampling from a log-concave density using kinetic Langevin diffusions

Arnak S. Dalalyan, Lionel Riou-Durand.

Source: Bernoulli, Volume 26, Number 3, 1956--1988.

Abstract:
Langevin diffusion processes and their discretizations are often used for sampling from a target density. The most convenient framework for assessing the quality of such a sampling scheme corresponds to smooth and strongly log-concave densities defined on $mathbb{R}^{p}$. The present work focuses on this framework and studies the behavior of the Monte Carlo algorithm based on discretizations of the kinetic Langevin diffusion. We first prove the geometric mixing property of the kinetic Langevin diffusion with a mixing rate that is optimal in terms of its dependence on the condition number. We then use this result for obtaining improved guarantees of sampling using the kinetic Langevin Monte Carlo method, when the quality of sampling is measured by the Wasserstein distance. We also consider the situation where the Hessian of the log-density of the target distribution is Lipschitz-continuous. In this case, we introduce a new discretization of the kinetic Langevin diffusion and prove that this leads to a substantial improvement of the upper bound on the sampling error measured in Wasserstein distance.




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Stable processes conditioned to hit an interval continuously from the outside

Leif Döring, Philip Weissmann.

Source: Bernoulli, Volume 26, Number 2, 980--1015.

Abstract:
Conditioning stable Lévy processes on zero probability events recently became a tractable subject since several explicit formulas emerged from a deep analysis using the Lamperti transformations for self-similar Markov processes. In this article, we derive new harmonic functions and use them to explain how to condition stable processes to hit continuously a compact interval from the outside.




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From Westphalia to South Australia : the story of Franz Heinrich Ernst Siekmann / by Peter Brinkworth.

Siekmann, Francis Heinrich Ernst, 1830-1917.




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From the coalfields of Somerset to the Adelaide Hills and beyond : the story of the Hewish Family : three centuries of one family's journey through time / Maureen Brown.

Hewish Henry -- Family.




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The Yangya Hicks : tales from the Hicks family of Yangya near Gladstone, South Australia, written from the 12th of May 1998 / by Joyce Coralie Hale (nee Hicks) (28.12.1923-17.12.2003).

Hicks (Family)




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A family history Siglin to Siegele 1530 to 2019 : from Ditzingen, Germany over land and sea / Ian G. Siegele.

Germans -- South Australia.




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From Wends we came : the story of Johann and Maria Huppatz & their descendants / compiled by Frank Huppatz and Rone McDonnell.

Huppatz (Family).




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From alms house to first nation : a story of my ancestors in South Australia : a Sherwell family story / by Pamela Coad (nee Sherwell).

Sherwell (Family)




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What Districts Want From Assessments, as They Grapple With the Coronavirus

EdWeek Market Brief asked district officials in a nationwide survey about their most urgent assessment needs, as they cope with COVID-19 and tentatively plan for reopening schools.

The post What Districts Want From Assessments, as They Grapple With the Coronavirus appeared first on Market Brief.




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Letter from J. H Bannatyne to Other Windsor Berry Esq. relating to the Myall Creek Massacre, 17 December 1838




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Item 08: A Logg [Log] Book of the proceedings on Board His Majesty's Ship Swallow, Captain Philip Carteret Commander Commencing from the 20th August 1766 and Ending [21st May 1768]




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Item 10: Log book of the Swallow from 22 August 1767 to 4 June 1768 / by Philip Carteret




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Item 01: Notebooks (2) containing hand written copies of 123 letters from Major William Alan Audsley to his parents, ca. 1916-ca. 1919, transcribed by his father. Also includes original letters (2) written by Major Audsley.




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Item 01: Autograph letter signed, from Hume, Appin, to William E. Riley, concerning an account for money owed by Riley, 4 September 1834




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Sydney in 1848 : illustrated by copper-plate engravings of its principal streets, public buildings, churches, chapels, etc. / from drawings by Joseph Fowles.




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3 NY children die from syndrome possibly linked to COVID-19

Three children have now died in New York state from a possible complication from the coronavirus involving swollen blood vessels and heart problems, Gov. Andrew Cuomo said Saturday. At least 73 children in New York have been diagnosed with symptoms similar to Kawasaki disease — a rare inflammatory condition in children — and toxic shock syndrome.





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Function-Specific Mixing Times and Concentration Away from Equilibrium

Maxim Rabinovich, Aaditya Ramdas, Michael I. Jordan, Martin J. Wainwright.

Source: Bayesian Analysis, Volume 15, Number 2, 505--532.

Abstract:
Slow mixing is the central hurdle is applications of Markov chains, especially those used for Monte Carlo approximations (MCMC). In the setting of Bayesian inference, it is often only of interest to estimate the stationary expectations of a small set of functions, and so the usual definition of mixing based on total variation convergence may be too conservative. Accordingly, we introduce function-specific analogs of mixing times and spectral gaps, and use them to prove Hoeffding-like function-specific concentration inequalities. These results show that it is possible for empirical expectations of functions to concentrate long before the underlying chain has mixed in the classical sense, and we show that the concentration rates we achieve are optimal up to constants. We use our techniques to derive confidence intervals that are sharper than those implied by both classical Markov-chain Hoeffding bounds and Berry-Esseen-corrected central limit theorem (CLT) bounds. For applications that require testing, rather than point estimation, we show similar improvements over recent sequential testing results for MCMC. We conclude by applying our framework to real-data examples of MCMC, providing evidence that our theory is both accurate and relevant to practice.




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Implicit Copulas from Bayesian Regularized Regression Smoothers

Nadja Klein, Michael Stanley Smith.

Source: Bayesian Analysis, Volume 14, Number 4, 1143--1171.

Abstract:
We show how to extract the implicit copula of a response vector from a Bayesian regularized regression smoother with Gaussian disturbances. The copula can be used to compare smoothers that employ different shrinkage priors and function bases. We illustrate with three popular choices of shrinkage priors—a pairwise prior, the horseshoe prior and a g prior augmented with a point mass as employed for Bayesian variable selection—and both univariate and multivariate function bases. The implicit copulas are high-dimensional, have flexible dependence structures that are far from that of a Gaussian copula, and are unavailable in closed form. However, we show how they can be evaluated by first constructing a Gaussian copula conditional on the regularization parameters, and then integrating over these. Combined with non-parametric margins the regularized smoothers can be used to model the distribution of non-Gaussian univariate responses conditional on the covariates. Efficient Markov chain Monte Carlo schemes for evaluating the copula are given for this case. Using both simulated and real data, we show how such copula smoothing models can improve the quality of resulting function estimates and predictive distributions.




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Comment: Statistical Inference from a Predictive Perspective

Alessandro Rinaldo, Ryan J. Tibshirani, Larry Wasserman.

Source: Statistical Science, Volume 34, Number 4, 599--603.

Abstract:
What is the meaning of a regression parameter? Why is this the de facto standard object of interest for statistical inference? These are delicate issues, especially when the model is misspecified. We argue that focusing on predictive quantities may be a desirable alternative.




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Assessing the Causal Effect of Binary Interventions from Observational Panel Data with Few Treated Units

Pantelis Samartsidis, Shaun R. Seaman, Anne M. Presanis, Matthew Hickman, Daniela De Angelis.

Source: Statistical Science, Volume 34, Number 3, 486--503.

Abstract:
Researchers are often challenged with assessing the impact of an intervention on an outcome of interest in situations where the intervention is nonrandomised, the intervention is only applied to one or few units, the intervention is binary, and outcome measurements are available at multiple time points. In this paper, we review existing methods for causal inference in these situations. We detail the assumptions underlying each method, emphasize connections between the different approaches and provide guidelines regarding their practical implementation. Several open problems are identified thus highlighting the need for future research.




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The Importance of Being Clustered: Uncluttering the Trends of Statistics from 1970 to 2015

Laura Anderlucci, Angela Montanari, Cinzia Viroli.

Source: Statistical Science, Volume 34, Number 2, 280--300.

Abstract:
In this paper, we retrace the recent history of statistics by analyzing all the papers published in five prestigious statistical journals since 1970, namely: The Annals of Statistics , Biometrika , Journal of the American Statistical Association , Journal of the Royal Statistical Society, Series B and Statistical Science . The aim is to construct a kind of “taxonomy” of the statistical papers by organizing and clustering them in main themes. In this sense being identified in a cluster means being important enough to be uncluttered in the vast and interconnected world of the statistical research. Since the main statistical research topics naturally born, evolve or die during time, we will also develop a dynamic clustering strategy, where a group in a time period is allowed to migrate or to merge into different groups in the following one. Results show that statistics is a very dynamic and evolving science, stimulated by the rise of new research questions and types of data.




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Comment on “Automated Versus Do-It-Yourself Methods for Causal Inference: Lessons Learned from a Data Analysis Competition”

Susan Gruber, Mark J. van der Laan.

Source: Statistical Science, Volume 34, Number 1, 82--85.

Abstract:
Dorie and co-authors (DHSSC) are to be congratulated for initiating the ACIC Data Challenge. Their project engaged the community and accelerated research by providing a level playing field for comparing the performance of a priori specified algorithms. DHSSC identified themes concerning characteristics of the DGP, properties of the estimators, and inference. We discuss these themes in the context of targeted learning.




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Danny Smith from No Human Being Is Illegal (in all our glory). Collaged photograph by Deborah Kelly and collaborators, 2014-2018.

[London], 2019.




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Sweatsuits Should Be Your Cozy Day Uniform—and These Are Our Favorites From Amazon

This retro style is making a comeback for a reason.




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Brain-Derived Neurotrophic Factor Protection of Cortical Neurons from Serum Withdrawal-Induced Apoptosis Is Inhibited by cAMP

Steven Poser
Jun 1, 2003; 23:4420-4427
Cellular




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Increased Neural Activity in Mesostriatal Regions after Prefrontal Transcranial Direct Current Stimulation and L-DOPA Administration

Benjamin Meyer
Jul 3, 2019; 39:5326-5335
Systems/Circuits




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Head-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysis

JS Taube
Feb 1, 1990; 10:420-435
Articles




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Neural Mechanisms of Visual Working Memory in Prefrontal Cortex of the Macaque

Earl K. Miller
Aug 15, 1996; 16:5154-5167
Articles




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A fronte della diffusione delle criptovalute, le autorità devono essere pronte ad agire - Agustín Carstens

Italian translation of Press Release about BIS General Manager Agustín Carstens giving a speech on "Money in the digital age: what role for central banks?" (6 February 2018)




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2008-04-21: Cartoon Dispatches from Central Asia




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2008-05-15: Cartoon Dispatches from Central Asia




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a frog saying "get out" - :frogon:




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Wintrust Financial Corporation Reports Record Full-Year 2019 Net Income of $355.7 million and Fourth Quarter 2019 Net Income of $86.0 million, up 8% from the Fourth Quarter 2018

To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452.




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Academy maps out engineering challenges for recovery from COVID-19




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A 6-Point Plan to Leapfrog to CX Leadership

Customer experience as a boardroom topic is more relevant than ever. Enterprises are investing significant digital transformation budgets and commissioning large projects to elevate CX. Yet more than 70 percent of digital transformation projects fail to move the needle at scale. One topic that has a substantial impact on CX is the transformation of customer service operations using digital tools.




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Ten MORE egregious lies from 2010 campaign ads




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Live From Lincoln Center




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Central bank innovation - from Switzerland to the world

Speech by Mr Agustín Carstens, General Manager of the BIS, at the Founding Ceremony, Swiss Centre BIS Innovation Hub, Zurich, 8 October 2019.




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Lessons from 25 years of the Bank of Mexico's independence

Speech by Dr Agustín Carstens at the celebration of 25 years of Bank of Mexico independence, Mexico City, 22 November 2019.




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Neural Correlates of Strategy Switching in the Macaque Orbital Prefrontal Cortex

We can adapt flexibly to environment changes and search for the most appropriate rule to a context. The orbital prefrontal cortex (PFo) has been associated with decision making, rule generation and maintenance, and more generally has been considered important for behavioral flexibility. To better understand the neural mechanisms underlying the flexible behavior, we studied the ability to generate a switching signal in monkey PFo when a strategy is changed. In the strategy task, we used a visual cue to instruct two male rhesus monkeys either to repeat their most recent choice (i.e., stay strategy) or to change it (i.e., shift strategy). To identify the strategy switching-related signal, we compared nonswitch and switch trials, which cued the same or a different strategy from the previous trial, respectively. We found that the switching-related signal emerged during the cue presentation and it was combined with the strategy signal in a subpopulation of cells. Moreover, the error analysis showed that the activity of the switch-related cells reflected whether the monkeys erroneously switched or not the strategy, rather than what was required for that trial. The function of the switching signal could be to prompt the use of different strategies when older strategies are no longer appropriate, conferring the ability to adapt flexibly to environmental changes. In our task, the switching signal might contribute to the implementation of the strategy cued, overcoming potential interference effects from the strategy previously cued. Our results support the idea that ascribes to PFo an important role for behavioral flexibility.

SIGNIFICANCE STATEMENT We can flexibly adapt our behavior to a changing environment. One of the prefrontal areas traditionally associated with the ability to adapt to new contingencies is the orbital prefrontal cortex (PFo). We analyzed the switching related activity using a strategy task in which two rhesus monkeys were instructed by a visual cue either to repeat or change their most recent choice, respectively using a stay or a shift strategy. We found that PFo neurons were modulated by the strategy switching signal, pointing to the importance of PFo in behavioral flexibility by generating control over the switching of strategies.




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Interneuron NMDA Receptor Ablation Induces Hippocampus-Prefrontal Cortex Functional Hypoconnectivity after Adolescence in a Mouse Model of Schizophrenia

Although the etiology of schizophrenia is still unknown, it is accepted to be a neurodevelopmental disorder that results from the interaction of genetic vulnerabilities and environmental insults. Although schizophrenia's pathophysiology is still unclear, postmortem studies point toward a dysfunction of cortical interneurons as a central element. It has been suggested that alterations in parvalbumin-positive interneurons in schizophrenia are the consequence of a deficient signaling through NMDARs. Animal studies demonstrated that early postnatal ablation of the NMDAR in corticolimbic interneurons induces neurobiochemical, physiological, behavioral, and epidemiological phenotypes related to schizophrenia. Notably, the behavioral abnormalities emerge only after animals complete their maturation during adolescence and are absent if the NMDAR is deleted during adulthood. This suggests that interneuron dysfunction must interact with development to impact on behavior. Here, we assess in vivo how an early NMDAR ablation in corticolimbic interneurons impacts on mPFC and ventral hippocampus functional connectivity before and after adolescence. In juvenile male mice, NMDAR ablation results in several pathophysiological traits, including increased cortical activity and decreased entrainment to local gamma and distal hippocampal theta rhythms. In addition, adult male KO mice showed reduced ventral hippocampus-mPFC-evoked potentials and an augmented low-frequency stimulation LTD of the pathway, suggesting that there is a functional disconnection between both structures in adult KO mice. Our results demonstrate that early genetic abnormalities in interneurons can interact with postnatal development during adolescence, triggering pathophysiological mechanisms related to schizophrenia that exceed those caused by NMDAR interneuron hypofunction alone.

SIGNIFICANCE STATEMENT NMDAR hypofunction in cortical interneurons has been linked to schizophrenia pathophysiology. How a dysfunction of GABAergic cortical interneurons interacts with maturation during adolescence has not been clarified yet. Here, we demonstrate in vivo that early postnatal ablation of the NMDAR in corticolimbic interneurons results in an overactive but desynchronized PFC before adolescence. Final postnatal maturation during this stage outspreads the impact of the genetic manipulation toward a functional disconnection of the ventral hippocampal-prefrontal pathway, probably as a consequence of an exacerbated propensity toward hippocampal-evoked depotentiation plasticity. Our results demonstrate a complex interaction between genetic and developmental factors affecting cortical interneurons and PFC function.




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Neural Evidence for the Prediction of Animacy Features during Language Comprehension: Evidence from MEG and EEG Representational Similarity Analysis

It has been proposed that people can generate probabilistic predictions at multiple levels of representation during language comprehension. We used magnetoencephalography (MEG) and electroencephalography (EEG), in combination with representational similarity analysis, to seek neural evidence for the prediction of animacy features. In two studies, MEG and EEG activity was measured as human participants (both sexes) read three-sentence scenarios. Verbs in the final sentences constrained for either animate or inanimate semantic features of upcoming nouns, and the broader discourse context constrained for either a specific noun or for multiple nouns belonging to the same animacy category. We quantified the similarity between spatial patterns of brain activity following the verbs until just before the presentation of the nouns. The MEG and EEG datasets revealed converging evidence that the similarity between spatial patterns of neural activity following animate-constraining verbs was greater than following inanimate-constraining verbs. This effect could not be explained by lexical-semantic processing of the verbs themselves. We therefore suggest that it reflected the inherent difference in the semantic similarity structure of the predicted animate and inanimate nouns. Moreover, the effect was present regardless of whether a specific word could be predicted, providing strong evidence for the prediction of coarse-grained semantic features that goes beyond the prediction of individual words.

SIGNIFICANCE STATEMENT Language inputs unfold very quickly during real-time communication. By predicting ahead, we can give our brains a "head start," so that language comprehension is faster and more efficient. Although most contexts do not constrain strongly for a specific word, they do allow us to predict some upcoming information. For example, following the context of "they cautioned the...," we can predict that the next word will be animate rather than inanimate (we can caution a person, but not an object). Here, we used EEG and MEG techniques to show that the brain is able to use these contextual constraints to predict the animacy of upcoming words during sentence comprehension, and that these predictions are associated with specific spatial patterns of neural activity.




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The Effect of Counterfactual Information on Outcome Value Coding in Medial Prefrontal and Cingulate Cortex: From an Absolute to a Relative Neural Code

Adaptive coding of stimuli is well documented in perception, where it supports efficient encoding over a broad range of possible percepts. Recently, a similar neural mechanism has been reported also in value-based decision, where it allows optimal encoding of vast ranges of values in PFC: neuronal response to value depends on the choice context (relative coding), rather than being invariant across contexts (absolute coding). Additionally, value learning is sensitive to the amount of feedback information: providing complete feedback (both obtained and forgone outcomes) instead of partial feedback (only obtained outcome) improves learning. However, it is unclear whether relative coding occurs in all PFC regions and how it is affected by feedback information. We systematically investigated univariate and multivariate feedback encoding in various mPFC regions and compared three modes of neural coding: absolute, partially-adaptive and fully-adaptive.

Twenty-eight human participants (both sexes) performed a learning task while undergoing fMRI scanning. On each trial, they chose between two symbols associated with a certain outcome. Then, the decision outcome was revealed. Notably, in one-half of the trials participants received partial feedback, whereas in the other half they got complete feedback. We used univariate and multivariate analysis to explore value encoding in different feedback conditions.

We found that both obtained and forgone outcomes were encoded in mPFC, but with opposite sign in its ventral and dorsal subdivisions. Moreover, we showed that increasing feedback information induced a switch from absolute to relative coding. Our results suggest that complete feedback information enhances context-dependent outcome encoding.

SIGNIFICANCE STATEMENT This study offers a systematic investigation of the effect of the amount of feedback information (partial vs complete) on univariate and multivariate outcome value encoding, within multiple regions in mPFC and cingulate cortex that are critical for value-based decisions and behavioral adaptation. Moreover, we provide the first comparison of three possible models of neural coding (i.e., absolute, partially-adaptive, and fully-adaptive coding) of value signal in these regions, by using commensurable measures of prediction accuracy. Taken together, our results help build a more comprehensive picture of how the human brain encodes and processes outcome value. In particular, our results suggest that simultaneous presentation of obtained and foregone outcomes promotes relative value representation.




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Ventral Hippocampal Input to the Prelimbic Cortex Dissociates the Context from the Cue Association in Trace Fear Memory

The PFC, through its high degree of interconnectivity with cortical and subcortical brain areas, mediates cognitive and emotional processes in support of adaptive behaviors. This includes the formation of fear memories when the anticipation of threat demands learning about temporal or contextual cues, as in trace fear conditioning. In this variant of fear learning, the association of a cue and shock across an empty trace interval of several seconds requires sustained cue-elicited firing in the prelimbic cortex (PL). However, it is unknown how and when distinct PL afferents contribute to different associative components of memory. Among the prominent inputs to PL, the hippocampus shares with PL a role in both working memory and contextual processing. Here we tested the necessity of direct hippocampal input to the PL for the acquisition of trace-cued fear memory and the simultaneously acquired contextual fear association. Optogenetic silencing of ventral hippocampal (VH) terminals in the PL of adult male Long-Evans rats selectively during paired trials revealed that direct communication between the VH and PL during training is necessary for contextual fear memory, but not for trace-cued fear acquisition. The pattern of the contextual memory deficit and the disruption of local PL firing during optogenetic silencing of VH-PL suggest that the VH continuously updates the PL with the current contextual state of the animal, which, when disrupted during memory acquisition, is detrimental to the subsequent rapid retrieval of aversive contextual associations.

SIGNIFICANCE STATEMENT Learning to anticipate threat from available contextual and discrete cues is crucial for survival. The prelimbic cortex is required for forming fear memories when temporal or contextual complexity is involved, as in trace fear conditioning. However, the respective contribution of distinct prelimbic afferents to the temporal and contextual components of memory is not known. We report that direct input from the ventral hippocampus enables the formation of the contextual, but not trace-cued, fear memory necessary for the subsequent rapid expression of a fear response. This finding dissociates the contextual and working-memory contributions of prelimbic cortex to the formation of a fear memory and demonstrates the crucial role for hippocampal input in contextual fear learning.




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Rapid Release of Ca2+ from Endoplasmic Reticulum Mediated by Na+/Ca2+ Exchange

Phototransduction in Drosophila is mediated by phospholipase C (PLC) and Ca2+-permeable TRP channels, but the function of endoplasmic reticulum (ER) Ca2+ stores in this important model for Ca2+ signaling remains obscure. We therefore expressed a low affinity Ca2+ indicator (ER-GCaMP6-150) in the ER, and measured its fluorescence both in dissociated ommatidia and in vivo from intact flies of both sexes. Blue excitation light induced a rapid (tau ~0.8 s), PLC-dependent decrease in fluorescence, representing depletion of ER Ca2+ stores, followed by a slower decay, typically reaching ~50% of initial dark-adapted levels, with significant depletion occurring under natural levels of illumination. The ER stores refilled in the dark within 100–200 s. Both rapid and slow store depletion were largely unaffected in InsP3 receptor mutants, but were much reduced in trp mutants. Strikingly, rapid (but not slow) depletion of ER stores was blocked by removing external Na+ and in mutants of the Na+/Ca2+ exchanger, CalX, which we immuno-localized to ER membranes in addition to its established localization in the plasma membrane. Conversely, overexpression of calx greatly enhanced rapid depletion. These results indicate that rapid store depletion is mediated by Na+/Ca2+ exchange across the ER membrane induced by Na+ influx via the light-sensitive channels. Although too slow to be involved in channel activation, this Na+/Ca2+ exchange-dependent release explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors exposed to Ca2+-free solutions.

SIGNIFICANCE STATEMENT Phototransduction in Drosophila is mediated by phospholipase C, which activates TRP cation channels by an unknown mechanism. Despite much speculation, it is unknown whether endoplasmic reticulum (ER) Ca2+ stores play any role. We therefore engineered flies expressing a genetically encoded Ca2+ indicator in the photoreceptor ER. Although NCX Na+/Ca2+ exchangers are classically believed to operate only at the plasma membrane, we demonstrate a rapid light-induced depletion of ER Ca2+ stores mediated by Na+/Ca2+ exchange across the ER membrane. This NCX-dependent release was too slow to be involved in channel activation, but explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors bathed in Ca2+-free solutions.




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Sustained Visual Priming Effects Can Emerge from Attentional Oscillation and Temporal Expectation

Priming refers to the influence that a previously encountered object exerts on future responses to similar objects. For many years, visual priming has been known as a facilitation and sometimes an inhibition effect that lasts for an extended period of time. It contrasts with the recent finding of an oscillated priming effect where facilitation and inhibition alternate over time periodically. Here we developed a computational model of visual priming that combines rhythmic sampling of the environment (attentional oscillation) with active preparation for future events (temporal expectation). Counterintuitively, it shows that both the sustained and oscillated priming effects can emerge from an interaction between attentional oscillation and temporal expectation. The interaction also leads to novel predictions, such as the change of visual priming effects with temporal expectation and attentional oscillation. Reanalysis of two published datasets and the results of two new experiments of visual priming tasks with male and female human participants provide support for the model's relevance to human behavior. More generally, our model offers a new perspective that may unify the increasing findings of behavioral and neural oscillations with the classic findings in visual perception and attention.

SIGNIFICANCE STATEMENT There is increasing behavioral and neural evidence that visual attention is a periodic process that sequentially samples different alternatives in the theta frequency range. It contrasts with the classic findings of sustained facilitatory or inhibitory attention effects. How can an oscillatory perceptual process give rise to sustained attention effects? Here we make this connection by proposing a computational model for a "fruit fly" visual priming task and showing both the sustained and oscillated priming effects can have the same origin: an interaction between rhythmic sampling of the environment and active preparation for future events. One unique contribution of our model is to predict how temporal contexts affects priming. It also opens up the possibility of reinterpreting other attention-related classic phenomena.




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The Neural Mechanism of the Social Framing Effect: Evidence from fMRI and tDCS Studies

As an important cognitive bias, the framing effect shows that our decision preferences are sensitive to the verbal description (i.e., frame) of options. This study focuses on the neural underpinnings of the social framing effect, which is based on decision-making regarding other people. A novel paradigm was used in which participants made a trade-off between economic benefits and the feelings of others. This decision was described as either a "harm" to, or "not helping," other persons in two conditions (Harm frame vs Help frame). Both human males and females were recruited. Participants behaved more prosocially for Harm frame compared with Help frame, resulting in a significant social framing effect. Using functional magnetic resonance imaging, Experiment 1 showed that the social framing effect was associated with stronger activation in the temporoparietal junction (TPJ), especially its right part. The functional connectivity between the right TPJ (rTPJ) and medial prefrontal cortex predicted the social framing effect on the group level. In Experiment 2, we used transcranial direct current stimulation to modulate the activity of the rTPJ and found that the social framing effect became more prominent under anodal (excitatory) stimulation, while the nonsocial framing effect elicited by the economic gain/loss gambling frame remained unaffected. The rTPJ results might be associated with moral conflicts modulated by the social consequences of an action or different levels of mentalizing with others under different frame conditions, but alternative interpretations are also worth noting. These findings could help elucidate the psychological mechanisms of the social framing effect.

SIGNIFICANCE STATEMENT Previous studies have suggested that the framing effect is generated from an interaction between the amygdala and anterior cingulate cortex. This opinion, however, is based on findings from nonsocial framing tasks. Recent research has highlighted the importance of distinguishing between the social and nonsocial framing effects. The current study focuses on the social framing effect and finds out that the temporoparietal junction and its functional connectivity with the medial prefrontal cortex play a significant role. Additionally, modulating the activity of this region leads to changes in social (but not nonsocial) framing effect. Broadly speaking, these findings help understand the difference in neural mechanisms between social and nonsocial decision-making. Meanwhile, they might be illuminating to promote helping behavior in society.