Differential impacts of healthy cognitive aging on directed and random exploration.

Deciding whether to explore unknown opportunities or exploit well-known options is a ubiquitous part of our everyday lives. Extensive work in college students suggests that young people make explore-exploit decisions using a mixture of information seeking and random behavioral variability. Whether, and to what extent, older adults use the same strategies is unknown. To address this question, 51 older adults (ages 65-74) and 32 younger adults (ages 18-25) completed the Horizon Task, a gambling task that quantifies information seeking and behavioral variability as well as how these strategies are controlled for the purposes of exploration. Qualitatively, we found that older adults performed similar to younger adults on this task, increasing both their information seeking and behavioral variability when it was adaptive to explore. Quantitively, however, there were substantial differences between the age groups, with older adults showing less information seeking overall and less reliance on variability as a means to explore. In addition, we found a subset of approximately 26% of older adults whose information seeking was close to zero, avoiding informative options even when they were clearly the better choice. Unsurprisingly, these "information avoiders" performed worse on the task. In contrast, task performance in the remaining "information seeking" older adults was comparable to that of younger adults suggesting that age-related differences in explore-exploit decision making may be adaptive except when they are taken to extremes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Epigenetic-related transcriptional reprogramming elucidated by identification and validation of a novel reference gene combination for RT-qPCR studies in porcine oocytes of contrasting quality.

BACKGROUND: Reliable RT-qPCR results are dependent on appropriate normalisation. Oocyte maturation studies can be challenging in this respect, as the stage of development can distinctively affect reference gene transcript abundance. The aim of this study was to validate the use of reference genes in oocyte in vitro maturation RT-qPCR studies, and thereafter, examine the abundance of transcripts supporting histone modification during oocyte and early embryo development in oocytes of contrasting quality. METHODS AND RESULTS: Total RNA from oocytes from prepubertal gilts and sows was extracted either directly succeeding follicle aspiration or after 44 h in vitro maturation, followed by RT-qPCR. The stability of YWHAG, HPRT1, ACTB, GAPDH, HMBS and PFKP, was analysed by NormFinder and further cross-validated by assessing results generated following application of different combinations of potential reference genes for normalisation of the RT-qPCR data. Combining ACTB and PFKP generated high stability according to NormFinder and concordant results. Applying this normalisation, gilt derived oocytes displayed significantly higher abundance than oocytes from sows of almost all the epigenetic-related transcripts studied (HDAC2, SIRT1, SALL4, KDM1A, KDM1B, KDM5A), both before and after maturation. CONCLUSIONS: This study identified the combined use of ACTB and PFKP as the optimal normalisation for porcine oocyte RT-qPCR data. In oocytes collected from prepubertal gilts, transcription did not appear to be silenced at the time of aspiration, and accumulation of transcripts supporting histone modification facilitating proper fertilization and further embryo development seemed delayed. The results imply the epigenetic-related transcripts may have potential as markers of oocyte quality.

Age-group differences in trust-related decision-making and learning.

Facial impressions contribute to evaluations of trustworthiness. Older adults are especially vulnerable to trust violations, incurring risks for deception and exploitation. Using the newly developed social Iowa Gambling Task (S-IGT), we examined age-group differences in the impact of facial trustworthiness on decision-making and learning. In the congruent condition (CS-IGT), advantageous decks were paired with trustworthy faces and disadvantageous decks with untrustworthy faces. In the incongruent condition (IS-IGT), this pairing was reversed. Younger (n = 143) and older (n = 129) participants completed either the standard Iowa Gambling Task (IGT), CS-IGT, or IS-IGT. Both age groups preferred trustworthy faces in their initial choices. Older adults performed worse than younger adults across all tasks over time. Further, compared to younger adults, older adults performed worse on the IS-IGT, suggesting that incongruent facial cues interfered with older adults' performance, which aligns with reduced sensitivity to negative social reputations in aging. Multilevel modeling also indicated that age-group differences were most pronounced across all tasks in the last 40 trials. Together these findings suggest that differences between younger and older adults in experience-dependent decision-making are magnified in social contexts that involve a "wolf in sheep's clothing," which may reflect age-related difficulties in integrating incongruent information.

The psychophysiology of Mastermind: Characterizing response times and blinking in a high-stakes television game show.

Television game shows have proven to be a valuable resource for studying human behavior under conditions of high stress and high stakes. However, previous work has focused mostly on choices-ignoring much of the rich visual information that is available on screen. Here, we take a first step to extracting more of this information by investigating the response times and blinking of contestants in the BBC show Mastermind. In Mastermind, contestants answer rapid-fire quiz questions while a camera slowly zooms in on their faces. By labeling contestants' behavior and blinks from 25 episodes, we asked how accuracy, response times, and blinking varied over the course of the game. For accuracy and response times, we tested whether contestants responded more accurately and more slowly after an error-exhibiting the "post-error increase in accuracy" and "post-error slowing" which has been repeatedly observed in the lab. For blinking, we tested whether blink rates varied according to the cognitive demands of the game-decreasing during periods of cognitive load, such as when pondering a response, and increasing at event boundaries in the task, such as the start of a question. In contrast to the lab, evidence for post-error changes in accuracy and response time was weak, with only marginal effects observed. In line with the lab, blinking varied over the course of the game much as we predicted. Overall, our findings demonstrate the potential of extracting dynamic signals from game shows to study the psychophysiology of behavior in the real world.

Cumulus Cell and Oocyte Gene Expression in Prepubertal Gilts and Sows Identifies Cumulus Cells as a Prime Informative Parameter of Oocyte Quality.

Cumulus cells (CCs) are pivotal during oocyte development. This study aimed to identify novel marker genes for porcine oocyte quality by examining the expression of selected genes in CCs and oocytes, employing the model of oocytes from prepubertal animals being of reduced quality compared to those from adult animals. Total RNA was extracted either directly after follicle aspiration or after in vitro maturation, followed by RT-qPCR. Immature gilt CCs accumulated BBOX1 transcripts, involved in L-carnitine biosynthesis, to a 14.8-fold higher level (p < 0.05) relative to sows, while for CPT2, participating in fatty acid oxidation, the level was 0.48 (p < 0.05). While showing no differences between gilt and sow CCs after maturation, CPT2 and BBOX1 levels in oocytes were higher in gilts at both time points. The apparent delayed lipid metabolism and reduced accumulation of ALDOA and G6PD transcripts in gilt CCs after maturation, implying downregulation of glycolysis and the pentose phosphate pathway, suggest gilt cumulus-oocyte complexes have inadequate ATP stores and oxidative stress balance compared to sows at the end of maturation. Reduced expression of BBOX1 and higher expression of CPT2 in CCs before maturation and higher expression of G6PD and ALDOA after maturation are new potential markers of oocyte quality.

Childhood unpredictability and the development of exploration.

Early in development, the process of exploration helps children gather new information that fosters learning about the world. Yet, it is unclear how childhood experiences may influence the way humans approach new learning. What influences decisions to exploit known, familiar options versus trying a novel alternative? We found that childhood unpredictability, characterized by unpredictable caregiving and unstable living environments, was associated with reduced exploratory behavior. This effect holds while controlling for individual differences, including anxiety and stress. Individuals who perceived their childhoods as unpredictable explored less and were instead more likely to repeat previous choices (habitual responding). They were also more sensitive to uncertainty than to potential rewards, even when the familiar options yielded lower rewards. We examined these effects across multiple task contexts and via both in-person (N = 78) and online replication (N = 84) studies among 10- to 13-y-olds. Results are discussed in terms of the potential cascading effects of unpredictable environments on the development of decision-making and the effects of early experience on subsequent learning.

Frontal-midline theta and posterior alpha oscillations index early processing of spatial representations during active navigation.

Previous research has demonstrated that humans combine multiple sources of spatial information such as self-motion and landmark cues while navigating through an environment. However, it is unclear whether this involves comparing multiple representations obtained from different sources during navigation (parallel hypothesis) or building a representation first based on self-motion cues and then combining with landmarks later (serial hypothesis). We tested these two hypotheses (parallel vs serial) in an active navigation task using wireless mobile scalp EEG recordings. Participants walked through an immersive virtual hallway with or without conflicts between self-motion and landmarks (i.e., intersections) and pointed toward the starting position of the hallway. We employed the oscillatory signals recorded during mobile wireless scalp EEG as a means of identifying when participant representations based on self-motion versus landmark cues might have first emerged. We found that path segments, including intersections present early during navigation, were more strongly associated with later pointing error, regardless of when they appeared during encoding. We also found that there was sufficient information contained within the frontal-midline theta and posterior alpha oscillatory signals in the earliest segments of navigation involving intersections to decode condition (i.e., conflicting vs not conflicting). Together, these findings suggest that intersections play a pivotal role in the early development of spatial representations, suggesting that memory representations for the geometry of walked paths likely develop early during navigation, in support of the parallel hypothesis.

Sperm quality parameters, fertilizing potential, metabolites, and DNA methylation in cold-stored and cryopreserved milt from Atlantic salmon (Salmo salar L.).

Cold storage and freezing/thawing of milt may affect sperm functionality and the subsequent fertilization ability of milt. This study aimed to investigate sperm quality parameters and fertilization potential of Atlantic salmon milt, stored cold and subsequently cryopreserved, using different storage conditions. The objective was also to assess if analysis of milt metabolites and sperm DNA methylation signatures could be applicable to further elucidate sperm quality and fertilization following preservation. Milt samples were collected from eight mature Atlantic salmon males and stored for 4 days at 2°C and 8°C. Samples were taken on day one of storage at 2°C and on day four of storage at 2°C and 8°C. Storage for 4 days at 8°C is expected to be detrimental to sperm quality, and was included to create contrasts. Correspondingly, aliquots of cold-stored milt were prepared for cryopreservation, resulting in a total of six experimental conditions. Samples from all six experimental conditions were used in fertilization trials and analyzed for sperm viability, motility, ATP content, DNA fragmentation index, and High DNA stainability. In addition, milt samples from four of the males were analyzed for targeted metabolites and DNA methylation signatures by reduced representation bisulfite sequencing. The fertilization trials were performed using sperm:egg ratios of 75 × 103 and 500 × 103, respectively. Storage duration, temperature, and cryopreservation of cold-stored milt influenced several sperm quality parameters, metabolites, and DNA methylation signatures. The total motility, progressive motility, ATP, and velocity parameters were the sperm parameters with the strongest correlation to fertilization rates (p < 0.01). Several metabolites were correlated with fertility rates in both cold-stored and cryopreserved samples (p < 0.05). The fertilizing capacity of cold-stored milt was significantly reduced after 4 days of storage at 8°C, while corresponding cryopreserved milt showed reduced fertilization at both storage temperatures (2°C and 8°C) (p < 0.05). The results indicate that cryopreservation of milt stored for 1 day does not compromise either fertilization ability or DNA methylation signatures.

Frontal-midline theta and posterior alpha oscillations index early processing of spatial representations during active navigation.

Previous research has demonstrated that humans combine multiple sources of spatial information such as self-motion and landmark cues, while navigating through an environment. However, it is unclear whether this involves comparing multiple representations obtained from different sources during navigation (parallel hypothesis) or building a representation first based on self-motion cues and then combining with landmarks later (serial hypothesis). We tested these two hypotheses (parallel vs. serial) in an active navigation task using wireless mobile scalp EEG recordings. Participants walked through an immersive virtual hallway with or without conflicts between self-motion and landmarks (i.e., intersections) and pointed toward the starting position of the hallway. We employed the oscillatory signals recorded during mobile wireless scalp EEG as means of identifying when participant representations based on self-motion vs. landmark cues might have first emerged. We found that path segments, including intersections present early during navigation, were more strongly associated with later pointing error, regardless of when they appeared during encoding. We also found that there was sufficient information contained within the frontal-midline theta and posterior alpha oscillatory signals in the earliest segments of navigation involving intersections to decode condition (i.e., conflicting vs. not conflicting). Together, these findings suggest that intersections play a pivotal role in the early development of spatial representations, suggesting that memory representations for the geometry of walked paths likely develop early during navigation, in support of the parallel hypothesis.

Distinct genome-wide DNA methylation and gene expression signatures in classical monocytes from African American patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a multisystem autoimmune disorder that has an unclear etiology and disproportionately affects women and African Americans. Despite this, African Americans are dramatically underrepresented in SSc research. Additionally, monocytes show heightened activation in SSc and in African Americans relative to European Americans. In this study, we sought to investigate DNA methylation and gene expression patterns in classical monocytes in a health disparity population. METHODS: Classical monocytes (CD14+ + CD16-) were FACS-isolated from 34 self-reported African American women. Samples from 12 SSc patients and 12 healthy controls were hybridized on MethylationEPIC BeadChip array, while RNA-seq was performed on 16 SSc patients and 18 healthy controls. Analyses were computed to identify differentially methylated CpGs (DMCs), differentially expressed genes (DEGs), and CpGs associated with changes in gene expression (eQTM analysis). RESULTS: We observed modest DNA methylation and gene expression differences between cases and controls. The genes harboring the top DMCs, the top DEGs, as well as the top eQTM loci were enriched for metabolic processes. Genes involved in immune processes and pathways showed a weak upregulation in the transcriptomic analysis. While many genes were newly identified, several other have been previously reported as differentially methylated or expressed in different blood cells from patients with SSc, supporting for their potential dysregulation in SSc. CONCLUSIONS: While contrasting with results found in other blood cell types in largely European-descent groups, the results of this study support that variation in DNA methylation and gene expression exists among different cell types and individuals of different genetic, clinical, social, and environmental backgrounds. This finding supports the importance of including diverse, well-characterized patients to understand the different roles of DNA methylation and gene expression variability in the dysregulation of classical monocytes in diverse populations, which might help explaining the health disparities.

The effects of time horizon and guided choices on explore-exploit decisions in rodents.

Humans and animals have to balance the need for exploring new options with exploiting known options that yield good outcomes. This tradeoff is known as the explore-exploit dilemma. To better understand the neural mechanisms underlying how humans and animals address the explore-exploit dilemma, a good animal behavioral model is critical. Most previous rodents explore-exploit studies used ethologically unrealistic operant boxes and reversal learning paradigms in which the decision to abandon a bad option is confounded by the need for exploring a novel option for information collection, making it difficult to separate different drives and heuristics for exploration. In this study, we investigated how rodents make explore-exploit decisions using a spatial navigation horizon task (Wilson et al., 2014) adapted to rats to address the above limitations. We compared the rats' performance to that of humans using identical measures. We showed that rats use prior information to effectively guide exploration. In addition, rats use information-driven directed exploration like humans, but the extent to which they explore has the opposite dependance on time horizon than humans. Moreover, we found that free choices and guided choices have different influences on exploration in rodents, a finding that has not yet been tested in humans. This study reveals that the explore-exploit spatial behavior of rats is more complex than previously thought. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Prediction of high fecal propionate-to-butyrate ratios using 16S rRNA-based detection of bacterial groups with liquid array diagnostics.

Butyrate and propionate represent two of three main short-chain fatty acids produced by the intestinal microbiota. In healthy populations, their levels are reportedly equimolar, whereas a deviation in their ratio has been observed in various diseased cohorts. Monitoring such a ratio represents a valuable metric; however, it remains a challenge to adopt short-chain fatty acid detection techniques in clinical settings because of the volatile nature of these acids. Here we aimed to estimate short-chain fatty acid information indirectly through a novel, simple quantitative PCR-compatible assay (liquid array diagnostics) targeting a limited number of microbiome 16S markers. Utilizing 15 liquid array diagnostics probes to target microbiome markers selected by a model that combines partial least squares and linear discriminant analysis, the classes (normal vs high propionate-to-butyrate ratio) separated at a threshold of 2.6 with a prediction accuracy of 96%.

Facial Trustworthiness Perception Across the Adult Life Span.

OBJECTIVES: Trust is crucial for successful social interaction across the life span. Perceiver age, facial age, and facial emotion have been shown to influence trustworthiness perception, but the complex interplay between these perceiver and facial characteristics has not been examined. METHOD: Adopting an adult life-span developmental approach, 199 adults (aged 22-78 years) rated the trustworthiness of faces that systematically varied in age (young, middle-aged, and older) and emotion (neutral, happy, sad, fearful, angry, and disgusted) from the FACES Lifespan Database. RESULTS: The study yielded three key results. First, on an aggregated level, facial trustworthiness perception did not differ by perceiver age. Second, all perceivers rated young faces as the most trustworthy, and middle-aged and older (but not young) perceivers rated older faces as least trustworthy. Third, facial emotions signaling threat (fear, anger, and disgust) relative to neutral, happy, and sad expressions moderated age effects on facial trustworthiness perception. DISCUSSION: Findings from this study highlight the impact of perceiver and facial characteristics on facial trustworthiness perception in adulthood and aging and have potential to inform first impression formation, with effects on trait attributions and behavior. This publication also provides normative data on perceived facial trustworthiness for the FACES Lifespan Database.

Postmortem Diagnosis of the Proteus Syndrome by Next Generation Sequencing of Affected Brain Tissue.

We report a case of a somatic overgrowth syndrome diagnosed at forensic autopsy with the aid of next generation sequencing as Proteus syndrome. Somatic overgrowth syndromes result from spontaneous somatic mutations that arise early in development and display a mosaic pattern of expression in patient tissues. Due to the temporal and anatomic heterogeneity of these syndromes, phenotypes vary widely, resulting in clinical overlap. Furthermore, the variable ratio of mutated to nonmutated cells in patient tissue can result in low-level mutations that could be missed using Sanger sequencing. Due to these factors, recent literature points to next generation sequencing (NGS) as an adjunct to diagnosis of these rare entities. A male in his fourth decade of life presented to our forensic autopsy service with physical features suggestive of a somatic overgrowth syndrome. Due to the paucity of clinical information accompanying the individual, a definitive diagnosis based on physical characteristics, alone, was not possible. Next generation sequencing of affected formalin-fixed and paraffin-embedded brain tissue confirmed the presence of the variant in AKT1 (c.49G>A, p.Glu17Lys, in 14.13% of reads) found in Proteus syndrome. To our knowledge, this is the first report of the mosaic variant of AKT1 detected in brain tissue and the first reported case of a postmortem diagnosis of Proteus syndrome with the aid of NGS. We conclude that NGS can be used as an adjunctive method to support a specific diagnosis among the somatic overgrowth syndromes postmortem in the absence of sufficient clinical history.

Combination and competition between path integration and landmark navigation in the estimation of heading direction.

Successful navigation requires the ability to compute one's location and heading from incoming multisensory information. Previous work has shown that this multisensory input comes in two forms: body-based idiothetic cues, from one's own rotations and translations, and visual allothetic cues, from the environment (usually visual landmarks). However, exactly how these two streams of information are integrated is unclear, with some models suggesting the body-based idiothetic and visual allothetic cues are combined, while others suggest they compete. In this paper we investigated the integration of body-based idiothetic and visual allothetic cues in the computation of heading using virtual reality. In our experiment, participants performed a series of body turns of up to 360 degrees in the dark with only a brief flash (300ms) of visual feedback en route. Because the environment was virtual, we had full control over the visual feedback and were able to vary the offset between this feedback and the true heading angle. By measuring the effect of the feedback offset on the angle participants turned, we were able to determine the extent to which they incorporated visual feedback as a function of the offset error. By further modeling this behavior we were able to quantify the computations people used. While there were considerable individual differences in performance on our task, with some participants mostly ignoring the visual feedback and others relying on it almost entirely, our modeling results suggest that almost all participants used the same strategy in which idiothetic and allothetic cues are combined when the mismatch between them is small, but compete when the mismatch is large. These findings suggest that participants update their estimate of heading using a hybrid strategy that mixes the combination and competition of cues.

A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer.

An emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses; however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq). Transcriptomic analyses uncovered impacted biological pathways including PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction pathway, and ECM-receptor interaction. Additionally, 187 genes mapping to the Gene Ontology (GO) terms RNA binding, structural constituent of ribosome, SRP-dependent co-translational protein targeting to membrane and the biological pathways, translation, L13a-mediated translational silencing of Ceruloplasmin expression were differentially expressed (DE) between EA and AA. This signature allowed separation of AA and EA patients, and AA patients with the most severe clinical characteristics. AA patients with elevated expression levels of this genomic signature presented with higher Gleason scores, a greater number of positive core biopsies, elevated dehydroepiandrosterone sulfate levels and serum vitamin D deficiency. Protein-protein interaction (PPI) network analysis revealed a high degree of connectivity between these 187 proteins.

Human inference in changing environments with temporal structure.

To make informed decisions in natural environments that change over time, humans must update their beliefs as new observations are gathered. Studies exploring human inference as a dynamical process that unfolds in time have focused on situations in which the statistics of observations are history-independent. Yet, temporal structure is everywhere in nature and yields history-dependent observations. Do humans modify their inference processes depending on the latent temporal statistics of their observations? We investigate this question experimentally and theoretically using a change-point inference task. We show that humans adapt their inference process to fine aspects of the temporal structure in the statistics of stimuli. As such, humans behave qualitatively in a Bayesian fashion but, quantitatively, deviate away from optimality. Perhaps more importantly, humans behave suboptimally in that their responses are not deterministic, but variable. We show that this variability itself is modulated by the temporal statistics of stimuli. To elucidate the cognitive algorithm that yields this behavior, we investigate a broad array of existing and new models that characterize different sources of suboptimal deviations away from Bayesian inference. While models with "output noise" that corrupts the response-selection process are natural candidates, human behavior is best described by sampling-based inference models, in which the main ingredient is a compressed approximation of the posterior, represented through a modest set of random samples and updated over time. This result comes to complement a growing literature on sample-based representation and learning in humans. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

HumGut: a comprehensive human gut prokaryotic genomes collection filtered by metagenome data.

BACKGROUND: A major bottleneck in the use of metagenome sequencing for human gut microbiome studies has been the lack of a comprehensive genome collection to be used as a reference database. Several recent efforts have been made to re-construct genomes from human gut metagenome data, resulting in a huge increase in the number of relevant genomes. In this work, we aimed to create a collection of the most prevalent healthy human gut prokaryotic genomes, to be used as a reference database, including both MAGs from the human gut and ordinary RefSeq genomes. RESULTS: We screened > 5,700 healthy human gut metagenomes for the containment of > 490,000 publicly available prokaryotic genomes sourced from RefSeq and the recently announced UHGG collection. This resulted in a pool of > 381,000 genomes that were subsequently scored and ranked based on their prevalence in the healthy human metagenomes. The genomes were then clustered at a 97.5% sequence identity resolution, and cluster representatives (30,691 in total) were retained to comprise the HumGut collection. Using the Kraken2 software for classification, we find superior performance in the assignment of metagenomic reads, classifying on average 94.5% of the reads in a metagenome, as opposed to 86% with UHGG and 44% when using standard Kraken2 database. A coarser HumGut collection, consisting of genomes dereplicated at 95% sequence identity-similar to UHGG, classified 88.25% of the reads. HumGut, half the size of standard Kraken2 database and directly comparable to the UHGG size, outperforms them both. CONCLUSIONS: The HumGut collection contains > 30,000 genomes clustered at a 97.5% sequence identity resolution and ranked by human gut prevalence. We demonstrate how metagenomes from IBD-patients map equally well to this collection, indicating this reference is relevant also for studies well outside the metagenome reference set used to obtain HumGut. All data and metadata, as well as helpful code, are available at http://arken.nmbu.no/~larssn/humgut/ . Video Abstract.