scholarly journals Noradrenergic arousal after encoding reverses the course of systems consolidation in humans

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Valentina Krenz ◽  
Tobias Sommer ◽  
Arjen Alink ◽  
Benno Roozendaal ◽  
Lars Schwabe
Keyword(s):  
Time Dependent ◽  
Consolidation Process ◽  
Memory Decline ◽  
Adrenoceptor Antagonist ◽  
Systems Consolidation ◽  
Hippocampal Activity ◽  
Pattern Similarity ◽  
Recognition Testing ◽  
Episodic Memories ◽  
Over Time

AbstractIt is commonly assumed that episodic memories undergo a time-dependent systems consolidation process, during which hippocampus-dependent memories eventually become reliant on neocortical areas. Here we show that systems consolidation dynamics can be experimentally manipulated and even reversed. We combined a single pharmacological elevation of post-encoding noradrenergic activity through the α2-adrenoceptor antagonist yohimbine with fMRI scanning both during encoding and recognition testing either 1 or 28 days later. We show that yohimbine administration, in contrast to placebo, leads to a time-dependent increase in hippocampal activity and multivariate encoding-retrieval pattern similarity, an indicator of episodic reinstatement, between 1 and 28 days. This is accompanied by a time-dependent decrease in neocortical activity. Behaviorally, these neural changes are linked to a reduced memory decline over time after yohimbine intake. These findings indicate that noradrenergic activity shortly after encoding may alter and even reverse systems consolidation in humans, thus maintaining vividness of memories over time.

scholarly journals Changes in patterns of neural activity underlie a time-dependent transformation of memory in rats and humans

2018 ◽  
Author(s):  
Melanie J. Sekeres ◽  
Gordon Winocur ◽  
Morris Moscovitch ◽  
John A.E. Anderson ◽  
Sara Pishdadian ◽  
...  
Keyword(s):  
Memory Trace ◽  
Brain Regions ◽  
Time Dependent ◽  
Memory Representation ◽  
Systems Consolidation ◽  
Different Types ◽  
Episodic Memories ◽  
Context Specific ◽  
Perceptual Detail ◽  
Over Time

AbstractThe dynamic process of memory consolidation involves a reorganization of brain regions that support a memory trace over time, but exactly how the network reorganizes as the memory changes remains unclear. We present novel converging evidence from studies of animals (rats) and humans for the time-dependent reorganization and transformation of different types of memory as measured both by behavior and brain activation. We find that context-specific memories in rats, and naturalistic episodic memories in humans, lose precision over time and activity in the hippocampus decreases. If, however, the retrieved memories retain contextual or perceptual detail, the hippocampus is engaged similarly at recent and remote timepoints. As the interval between the timepoint increases, the medial prefrontal cortex is engaged increasingly during memory retrieval, regardless of the context or the amount of retrieved detail. Moreover, these hippocampal-frontal shifts are accompanied by corresponding changes in a network of cortical structures mediating perceptually-detailed as well as less precise, schematic memories. These findings provide cross-species evidence for the crucial interplay between hippocampus and neocortex that reflects changes in memory representation over time and underlies systems consolidation.

scholarly journals Schemas provide a scaffold for neocortical integration at the cost of memory specificity over time

2020 ◽  
Author(s):  
Sam Audrain ◽  
Mary Pat McAndrews
Keyword(s):  
Neural Representation ◽  
General Context ◽  
Time Pattern ◽  
Memory Specificity ◽  
Systems Consolidation ◽  
Fmri Study ◽  
Pattern Similarity ◽  
The Cost ◽  
Study Participants ◽  
Over Time

SUMMARYMemory transformation is increasingly acknowledged in theoretical accounts of systems consolidation, yet how memory quality and neural representation change over time and how schemas influence this process remains unclear. In this fMRI study, participants encoded and retrieved schema-congruent and incongruent object-scene pairs using a paradigm that probed coarse and detailed memories over 10-minutes and 72-hours. When a congruent schema was available, details were lost over time as representations were integrated in the medial prefrontal cortex (mPFC), and enhanced post-encoding coupling between the anterior hippocampus and mPFC was associated with coarser memories. Over time, pattern similarity in the hippocampus changed such that the posterior hippocampus represented specific details and the anterior hippocampus represented the general context of specific memories, irrespective of congruency. Our findings suggest schemas are used as a scaffold for accelerated consolidation of congruent information, and illustrate change in hippocampal organization of detailed contextual memory over time.

scholarly journals Detection of Acetaminophen and Its Glucuronide in Fingerprint by SALDI Mass Spectrometry Using Zeolite and Study of Time-Dependent Changes in Detected Ion Amount

Analytica ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 66-75
Author(s):  
Toshiki Horikoshi ◽  
Chihiro Kitaoka ◽  
Yosuke Fujii ◽  
Takashi Asano ◽  
Jiawei Xu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Glucuronic Acid ◽  
Laser Desorption ◽  
The Body ◽  
Time Dependent ◽  
Laser Desorption Ionization ◽  
Fingerprint Analysis ◽  
Desorption Ionization ◽  
Acid Conjugate ◽  
Over Time

The ingredients of an antipyretic (acetaminophen, AAP) and their metabolites excreted into fingerprint were detected by surface-assisted laser desorption ionization (SALDI) mass spectrometry using zeolite. In the fingerprint taken 4 h after AAP ingestion, not only AAP but also the glucuronic acid conjugate of AAP (GAAP), caffeine (Caf), ethenzamide (Eth), salicylamide (Sala; a metabolite of Eth), and urea were detected. Fingerprints were collected over time to determine how the amounts of AAP and its metabolite changed with time, and the time dependence of the peak intensities of protonated AAP and GAAP was measured. It was found that the increase of [GAAP+H]+ peak started later than that of [AAP+H]+ peak, reflecting the metabolism of AAP. Both AAP and GAAP reached maximum concentrations approximately 3 h after ingestion, and were excreted from the body with a half-life of approximately 3.3 h. In addition, fingerprint preservation was confirmed by optical microscopy, and fingerprint shape was retained even after laser irradiation of the fingerprint. Our method may be used in fingerprint analysis.

scholarly journals Risk Factors for Prostate Cancer Detection After a Negative Biopsy: A Novel Multivariable Longitudinal Approach

2010 ◽  
Vol 28 (10) ◽  
pp. 1714-1720 ◽  
Author(s):  
Peter H. Gann ◽  
Angela Fought ◽  
Ryan Deaton ◽  
William J. Catalona ◽  
Edward Vonesh
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Specific Antigen ◽  
Time Dependent ◽  
Negative Biopsy ◽  
Gland Volume ◽  
Piecewise Exponential ◽  
Over Time ◽  
Negative Biopsies

Purpose To introduce a novel approach for the time-dependent quantification of risk factors for prostate cancer (PCa) detection after an initial negative biopsy. Patients and Methods Data for 1,871 men with initial negative biopsies and at least one follow-up biopsy were available. Piecewise exponential regression models were developed to quantify hazard ratios (HRs) and define cumulative incidence curves for PCa detection for subgroups with specific patterns of risk factors over time. Factors evaluated included age, race, serum prostate-specific antigen (PSA) concentration, PSA slope, digital rectal examination, dysplastic glands or prostatitis on biopsy, ultrasound gland volume, urinary symptoms, and number of negative biopsies. Results Four hundred sixty-five men had PCa detected, after a mean follow-up time of 2.8 years. All of the factors were independent predictors of PCa detection except for PSA slope, as a result of its correlation with time-dependent PSA level, and race. PSA (HR = 3.90 for > 10 v 2.5 to 3.9 ng/mL), high-grade prostatic intraepithelial neoplasia/atypical glands (HR = 2.97), gland volume (HR = 0.39 for > 50 v < 25 mL), and number of repeat biopsies (HR = 0.36 for two v zero repeat biopsies) were the strongest predictors. Men with high-risk versus low-risk event histories had a 20-fold difference in PCa detection over 5 years. Conclusion Piecewise exponential models provide an approach to longitudinal analysis of PCa risk that allows clinicians to see the interplay of risk factors as they unfold over time for individual patients. With these models, it is possible to identify distinct subpopulations with dramatically different needs for monitoring and repeat biopsy.

QUASI-LINEAR VISCOELASTIC MODELLING OF UNCURED PREPREGS UNDER COMPACTION

2021 ◽  
Author(s):  
SIDDHESH S. KULKARNI ◽  
KAMRAN A. KHAN ◽  
REHAN UMER
Keyword(s):  
Stress Relaxation ◽  
Relaxation Function ◽  
Soft Tissues ◽  
Volume Fraction ◽  
Time Dependent ◽  
Strain History ◽  
Manufacturing Processes ◽  
Fiber Volume ◽  
Consolidation Process ◽  
Thermoset Resin

Reinforcement compaction sometimes referred as consolidation process and is one of the key steps in various composite manufacturing processes such as autoclave and out-of-autoclave processing. The prepregs consist of semi-cured thermoset resin system impregnating the fibers. hence, the prepreg shows strong viscoelastic compaction response, which strongly depends on compaction speed and stress relaxation. modeling of time-dependent response is of utmost importance to understand the behavior of prepregs during different stages of composites manufacturing processes. The quasilinear viscoelastic (QLV) theory has been extensively used for the modeling of viscoelastic response of soft tissues in biomedical applications. In QLV approach, the stress relaxation can be expressed in terms of the nonlinear elastic function and the reduced relaxation function. The constitutive equation can be represented by a convolution integral of the nonlinear strain history, and reduced relaxation function. This study adopted a quasilinear viscoelastic modeling approach to describe the time dependent behavior of uncured-prepregs under compression. The model was modified to account for the compaction behavior of the prepreg under a compressive load. The deformation behavior of the prepreg is usually characterized by the fiber volume fraction, V . In this study, the material used was a 2/2 Twill weave glass prepreg (M26T) supplied by Hexcel® Industries USA. We performed a compaction experiment of the uncured prepreg at room temperature at different displacement rate and subsequent relaxation to describe the viscoelastic behavior of the prepreg. The model parameter calibration was performed using the trust-region-reflective algorithm in matlab to a selected number of test data. The calibrated model was then used to predict the rate dependent compaction and relaxation response of prepregs for different fiber volume fractions and strain rates.

scholarly journals A Tutorial on Evaluating the Time-Varying Discrimination Accuracy of Survival Models Used in Dynamic Decision Making

2018 ◽  
Vol 38 (8) ◽  
pp. 904-916 ◽  
Author(s):  
Aasthaa Bansal ◽  
Patrick J. Heagerty
Keyword(s):  
Decision Making ◽  
Statistical Methods ◽  
Sensitivity And Specificity ◽  
Prognostic Model ◽  
Dynamic Decision Making ◽  
Time Dependent ◽  
Survival Models ◽  
Biliary Cirrhosis ◽  
Time Varying ◽  
Over Time

Many medical decisions involve the use of dynamic information collected on individual patients toward predicting likely transitions in their future health status. If accurate predictions are developed, then a prognostic model can identify patients at greatest risk for future adverse events and may be used clinically to define populations appropriate for targeted intervention. In practice, a prognostic model is often used to guide decisions at multiple time points over the course of disease, and classification performance (i.e., sensitivity and specificity) for distinguishing high-risk v. low-risk individuals may vary over time as an individual’s disease status and prognostic information change. In this tutorial, we detail contemporary statistical methods that can characterize the time-varying accuracy of prognostic survival models when used for dynamic decision making. Although statistical methods for evaluating prognostic models with simple binary outcomes are well established, methods appropriate for survival outcomes are less well known and require time-dependent extensions of sensitivity and specificity to fully characterize longitudinal biomarkers or models. The methods we review are particularly important in that they allow for appropriate handling of censored outcomes commonly encountered with event time data. We highlight the importance of determining whether clinical interest is in predicting cumulative (or prevalent) cases over a fixed future time interval v. predicting incident cases over a range of follow-up times and whether patient information is static or updated over time. We discuss implementation of time-dependent receiver operating characteristic approaches using relevant R statistical software packages. The statistical summaries are illustrated using a liver prognostic model to guide transplantation in primary biliary cirrhosis.

scholarly journals A joint modeling approach for longitudinal microbiome data improves ability to detect microbiome associations with disease

2020 ◽  
Vol 16 (12) ◽  
pp. e1008473
Author(s):  
Pamela N. Luna ◽  
Jonathan M. Mansbach ◽  
Chad A. Shaw
Keyword(s):  
Joint Modeling ◽  
Mixed Effects ◽  
Mixed Effects Model ◽  
Time Dependent ◽  
Time To Event ◽  
Modeling Framework ◽  
Microbial Composition ◽  
Disease Outcomes ◽  
Microbiome Data ◽  
Over Time

Changes in the composition of the microbiome over time are associated with myriad human illnesses. Unfortunately, the lack of analytic techniques has hindered researchers’ ability to quantify the association between longitudinal microbial composition and time-to-event outcomes. Prior methodological work developed the joint model for longitudinal and time-to-event data to incorporate time-dependent biomarker covariates into the hazard regression approach to disease outcomes. The original implementation of this joint modeling approach employed a linear mixed effects model to represent the time-dependent covariates. However, when the distribution of the time-dependent covariate is non-Gaussian, as is the case with microbial abundances, researchers require different statistical methodology. We present a joint modeling framework that uses a negative binomial mixed effects model to determine longitudinal taxon abundances. We incorporate these modeled microbial abundances into a hazard function with a parameterization that not only accounts for the proportional nature of microbiome data, but also generates biologically interpretable results. Herein we demonstrate the performance improvements of our approach over existing alternatives via simulation as well as a previously published longitudinal dataset studying the microbiome during pregnancy. The results demonstrate that our joint modeling framework for longitudinal microbiome count data provides a powerful methodology to uncover associations between changes in microbial abundances over time and the onset of disease. This method offers the potential to equip researchers with a deeper understanding of the associations between longitudinal microbial composition changes and disease outcomes. This new approach could potentially lead to new diagnostic biomarkers or inform clinical interventions to help prevent or treat disease.

scholarly journals Musical instrument engagement across the life course and episodic memory in late life: An analysis of 60 years of longitudinal data from the Wisconsin Longitudinal Study

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253053
Author(s):  
Jamie L. Romeiser ◽  
Dylan M. Smith ◽  
Sean A. P. Clouston
Keyword(s):  
High School ◽  
Episodic Memory ◽  
Cognitive Reserve ◽  
High School Graduates ◽  
Musical Instrument ◽  
Delayed Recall ◽  
Memory Decline ◽  
Musical Engagement ◽  
Rate Of Decline ◽  
Over Time

Background As the global burden of dementia increases, the absence of treatment underscores the need for identification of factors that may improve cognitive reserve–the ability to stave off cognitive decline in old age. The beneficial association between musical instrument engagement and episodic memory has been identified in children, young adults, and older adults. Yet, previous studies in musical instrument engagement have rarely examined the potential for adolescence and adulthood exposures to independently improve cognition, nor have they been linked with the rate of memory decline over time in older adults. We investigated whether adolescent musical instrument engagement and continued musical instrument engagement over the adult life course were separately associated with higher episodic memory, as well as rate of decline in a large longitudinal cohort. Methods Data were from a prospective cohort of high school graduates from 1957. High school music engagement (HSME) was ascertained through graduate yearbooks and assessed as membership in musical performance groups. A questionnaire was used to assess musical engagement through adulthood (MEA) at ages 35, 55, and 65. The episodic memory score was composed of immediate and delayed recall task scores, and was assessed when participants were aged approximately 65 and 72 years old among 5,718 individuals. Linear mixed models were used to assess the association between music, and memory performance and decline over time. Results Of high school graduates who participated in the study, 38.1% played music in high school, and 21.1% played music in adulthood. While musical engagement was more common in those who played in childhood, 40% of those who played continuously as an adult did not play in high school. High HSME (B = 0.348, p = 0.049) and continuous MEA (B = 0.424, p = 0.012) were associated with higher memory scores at age 65 after covariate adjustment. When examining memory decline, the benefits of high HSME decreased over time (B = -0.435, p = 0.048), while the rate of decline did not differ between MEA groups. Exploratory models revealed differential benefits for HSME and immediate recall, and MEA and delayed recall. Conclusion This study provides further evidence that musical engagement in childhood or adulthood is associated with non-musical cognitive reserve. These two exposures may act differentially in different domains of episodic memory. Further work is needed to determine the relationship between musicianship and the rate of cognitive decline.

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