Proximity to rewards modulates parameters of effortful control exertion.

The now-classic goal-gradient hypothesis posits that organisms increase effort expenditure as a function of their proximity to a goal. Despite nearly a century having passed since its original formulation, goal-gradient-like behavior in human cognitive performance remains poorly understood: Are we more willing to engage in costly cognitive processing when we are near, versus far, from a goal state? Moreover, the computational mechanisms underpinning these potential goal-gradient effects-for example, whether goal proximity affects fidelity of stimulus encoding, response caution, or other identifiable mechanisms governing speed and accuracy-are unclear. Here, in two experiments, we examine the effect of goal proximity, operationalized as progress toward the completion of a rewarded task block, upon task performance in an attentionally demanding oddball task. Supporting the goal-gradient hypothesis, we found that participants responded more quickly, but not less accurately, when rewards were proximal than when they were distal. Critically, this effect was only observed when participants were given information about goal proximity. Using hierarchical drift diffusion modeling, we found that these apparent goal-gradient performance effects were best explained by a collapsing bound model, in which proximity to a goal reduced response caution and increased information processing. Taken together, these results suggest that goal gradients could help explain the oft-observed fluctuations in engagement of cognitively effortful processing, extending the scope of the goal-gradient hypothesis to the domain of cognitive tasks. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Distinguishing between intrinsic and instrumental sources of the value of choice.

Considerable evidence suggests that people value the freedom to choose. However, it is unclear whether this preference for choice stems purely from choice's intrinsic value, or whether people prefer to choose because it tends to provide instrumental information about desirable outcomes. To address this question, participants completed a novel choice task in which they could freely choose to exert choice or not, manipulating the level of instrumental contingency between participants' choices and eventual outcomes, which we operationalized using the information-theoretic concept of mutual information. Across two experiments (N = 100 each), we demonstrate a marked preference for choice, but importantly found that participants' preference for free choice is weakened when actions are decoupled from outcomes. Taken together, our results demonstrate that a significant factor in people's preference for choice is an assumption about the instrumental value of choice, suggesting against a purely intrinsic value of choice.

Greater reliance on model-free learning in adolescent anorexia nervosa: An examination of dual-system reinforcement learning.

Alterations in learning and decision-making systems are thought to contribute to core features of anorexia nervosa (AN), a psychiatric disorder characterized by persistent dietary restriction and weight loss. Instrumental learning theory identifies a dual-system of habit and goal-directed decision-making, linked to model-free and model-based reinforcement learning algorithms. Difficulty arbitrating between these systems, resulting in an over-reliance on one strategy over the other, has been implicated in compulsivity and extreme goal pursuit, both of which are observed in AN. Characterizing alterations in model-free and model-based systems, and their neural correlates, in AN may clarify mechanisms contributing to symptom heterogeneity (e.g., binge/purge symptoms). This study tested whether adolescents with restricting AN (AN-R; n = 36) and binge/purge AN (AN-BP; n = 20) differentially utilized model-based and model-free learning systems compared to a healthy control group (HC; n = 28) during a Markov two-step decision-making task under conditions of reward and punishment. Associations between model-free and model-based learning and resting-state functional connectivity between neural regions of interest, including orbitofrontal cortex (OFC), nucleus accumbens (NAcc), putamen, and sensory motor cortex (SMC) were examined. AN-R showed higher utilization of model-free learning compared to HC for reward, but attenuated model-free and model-based learning for punishment. In AN-R only, higher model-based learning was associated with stronger OFC-to-left NAcc functional connectivity, regions linked to goal-directed behavior. Greater utilization of model-free learning for reward in AN-R may differentiate this group, particularly during adolescence, and facilitate dietary restriction by prioritizing habitual control in rewarding contexts.

More than a feeling: physiological measures of affect index the integration of effort costs and rewards during anticipatory effort evaluation.

The notion that humans avoid effortful action is one of the oldest and most persistent in psychology. Influential theories of effort propose that effort valuations are made according to a cost-benefit trade-off: we tend to invest mental effort only when the benefits outweigh the costs. While these models provide a useful conceptual framework, the affective components of effort valuation remain poorly understood. Here, we examined whether primitive components of affective response-positive and negative valence, captured via facial electromyography (fEMG)-can be used to better understand valuations of cognitive effort. Using an effortful arithmetic task, we find that fEMG activity in the corrugator supercilii-thought to index negative valence-1) tracks the anticipation and exertion of cognitive effort and 2) is attenuated in the presence of high rewards. Together, these results suggest that activity in the corrugator reflects the integration of effort costs and rewards during effortful decision-making.

Human ageing is associated with more rigid concept spaces.

Prevalence-induced concept change describes a cognitive mechanism by which someone's definition of a concept shifts as the prevalence of instances of that concept changes. While this phenomenon has been established in young adults, it is unclear how it affects older adults. In this study, we explore how prevalence-induced concept change affects older adults' lower-level, perceptual, and higher-order, ethical judgements. We find that older adults are less sensitive to prevalence-induced concept change than younger adults across both domains. Using computational modeling, we demonstrate that these age-related changes in judgements reflect more cautious and deliberate responding in older adults. Based on these findings, we argue that while overly cautious responding by older adults may be maladaptive in some cognitive domains, in the case of prevalence-induced concept change, it might be protective against biased judgements.

Context-dependent choice and evaluation in real-world consumer behavior.

A body of work spanning neuroscience, economics, and psychology indicates that decision-making is context-dependent, which means that the value of an option depends not only on the option in question, but also on the other options in the choice set-or the 'context'. While context effects have been observed primarily in small-scale laboratory studies with tightly constrained, artificially constructed choice sets, it remains to be determined whether these context effects take hold in real-world choice problems, where choice sets are large and decisions driven by rich histories of direct experience. Here, we investigate whether valuations are context-dependent in real-world choice by analyzing a massive restaurant rating dataset as well as two independent replication datasets which provide complementary operationalizations of restaurant choice. We find that users make fewer ratings-maximizing choices in choice sets with higher-rated options-a hallmark of context-dependent choice-and that post-choice restaurant ratings also varied systematically with the ratings of unchosen restaurants. Furthermore, in a follow-up laboratory experiment using hypothetical choice sets matched to the real-world data, we find further support for the idea that subjective valuations of restaurants are scaled in accordance with the choice context, providing corroborating evidence for a general mechanistic-level account of these effects. Taken together, our results provide a potent demonstration of context-dependent choice in real-world choice settings, manifesting both in decisions and subjective valuation of options.

Large-Scale Production of Wholly Cellular Bioinks via the Optimization of Human Induced Pluripotent Stem Cell Aggregate Culture in Automated Bioreactors.

Combining the sustainable culture of billions of human cells and the bioprinting of wholly cellular bioinks offers a pathway toward organ-scale tissue engineering. Traditional 2D culture methods are not inherently scalable due to cost, space, and handling constraints. Here, the suspension culture of human induced pluripotent stem cell-derived aggregates (hAs) is optimized using an automated 250 mL stirred tank bioreactor system. Cell yield, aggregate morphology, and pluripotency marker expression are maintained over three serial passages in two distinct cell lines. Furthermore, it is demonstrated that the same optimized parameters can be scaled to an automated 1 L stirred tank bioreactor system. This 4-day culture results in a 16.6- to 20.4-fold expansion of cells, generating approximately 4 billion cells per vessel, while maintaining >94% expression of pluripotency markers. The pluripotent aggregates can be subsequently differentiated into derivatives of the three germ layers, including cardiac aggregates, and vascular, cortical and intestinal organoids. Finally, the aggregates are compacted into a wholly cellular bioink for rheological characterization and 3D bioprinting. The printed hAs are subsequently differentiated into neuronal and vascular tissue. This work demonstrates an optimized suspension culture-to-3D bioprinting pipeline that enables a sustainable approach to billion cell-scale organ engineering.

Changes in the Prevalence of Thin Bodies Bias Young Women's Judgments About Body Size.

Body dissatisfaction is pervasive among young women in Western countries. Among the many forces that contribute to body dissatisfaction, the overrepresentation of thin bodies in visual media has received notable attention. In this study, we proposed that prevalence-induced concept change may be one of the cognitive mechanisms that explain how beauty standards shift. We conducted a preregistered online experiment with young women (N = 419) and found that when the prevalence of thin bodies in the environment increased, the concept of being overweight expanded to include bodies that would otherwise be judged as "normal." Exploratory analyses revealed significant individual differences in sensitivity to this effect, in terms of women's judgments about other bodies as well as their own. These results suggest that women's judgments about other women's bodies are biased by an overrepresentation of thinness and lend initial support to policies designed to increase size-inclusive representation in the media.

Information about task progress modulates cognitive demand avoidance.

People tend to avoid engaging in cognitively demanding tasks unless it is 'worth our while'-that is, if the benefits outweigh the costs of effortful action. Yet, we seemingly partake in a variety of effortful mental activities (e.g. playing chess, completing Sudoku puzzles) because they impart a sense of progress. Here, we examine the possibility that information about progress-specifically, the number of trials completed of a demanding cognitive control task, relative to the total number of trials to be completed-reduces individuals' aversion to cognitively effort activity, across four experiments. In Experiment 1, we provide an initial demonstration that presenting progress information reduces individuals' avoidance of cognitively demanding activity avoidance using a variant of the well-characterized Demand Selection Task (DST). The subsequent experiments buttress this finding using a more sophisticated within-subjects versions of the DST, independently manipulating progress information and demand level to further demonstrate that, 1) people prefer receiving information about temporal progress in a task, and 2) all else being equal, individuals will choose to engage in tasks that require greater levels of cognitive effort when the more demanding option confers information about their progress in a task. Together, these results suggest that progress information can motivate cognitive effort expenditure and, in some cases, override individuals' default bias towards demand avoidance.

Landauer's Principle a Consequence of Bit Flows, Given Stirling's Approximation.

According to Landauer's principle, at least kBln2T Joules are needed to erase a bit that stores information in a thermodynamic system at temperature T. However, the arguments for the principle rely on a regime where the equipartition principle holds. This paper, by exploring a simple model of a thermodynamic system using algorithmic information theory, shows the energy cost of transferring a bit, or restoring the original state, is kBln2T Joules for a reversible system. The principle is a direct consequence of the statistics required to allocate energy between stored energy states and thermal states, and applies outside the validity of the equipartition principle. As the thermodynamic entropy of a system coincides with the algorithmic entropy of a typical state specifying the momentum degrees of freedom, it can quantify the thermodynamic requirements in terms of bit flows to maintain a system distant from the equilibrium set of states. The approach offers a simple conceptual understanding of entropy, while avoiding problems with the statistical mechanic's approach to the second law of thermodynamics. Furthermore, the classical articulation of the principle can be used to derive the low temperature heat capacities, and is consistent with the quantum version of the principle.

Seizing the opportunity: Lifespan differences in the effects of the opportunity cost of time on cognitive control.

Previous work suggests that lifespan developmental differences in cognitive control reflect maturational and aging-related changes in prefrontal cortex functioning. However, complementary explanations exist: It could be that children and older adults differ from younger adults in how they balance the effort of engaging in control against its potential benefits. Here we test whether the degree of cognitive effort expenditure depends on the opportunity cost of time (average reward rate per unit time): if the average reward rate is high, participants should withhold cognitive effort whereas if it is low, they should invest more. In Experiment 1, we examine this hypothesis in children, adolescents, younger, and older adults, by applying a reward rate manipulation in two cognitive control tasks: a modified Erikson Flanker and a task-switching paradigm. We found that young adults and adolescents reflexively withheld effort when the opportunity cost of time was high, whereas older adults and, to a lesser degree children, invested more resources to accumulate reward as quickly as possible. We tentatively interpret these results in terms of age- and task-specific differences in the processing of the opportunity cost of time. We qualify our findings in a second experiment in younger adults in which we address an alternative explanation of our results and show that the observed age differences in effort expenditure may not result from differences in task difficulty. To conclude, we think that our results present an interesting first step at relating opportunity costs to motivational processes across the lifespan. We frame the implications of further work in this area within a recent developmental model of resource-rationality, which points to developmental sweet spots in cognitive control.

Resource-rational approach to meta-control problems across the lifespan.

Over the last decade, research on cognitive control and decision-making has revealed that individuals weigh the costs and benefits of engaging in or refraining from control and that whether and how they engage in these cost-benefit analyses may change across development and during healthy aging. In the present article, we examine how lifespan age differences in cognitive abilities affect the meta-control of behavioral strategies across the lifespan and how motivation affects these trade-offs. Based on accumulated evidence, we highlight two hypotheses that may explain the existing results better than current models. In contrast to previous theoretical accounts, we assume that age differences in the engagement in cost-benefit trade-offs reflect a resource-rational adaptation to internal and external constraints that arise across the lifespan. This article is categorized under: Psychology > Development and Aging Psychology > Reasoning and Decision Making.

An Economy Viewed as a Far-from-Equilibrium System from the Perspective of Algorithmic Information Theory.

This paper, using Algorithmic Information Theory (AIT), argues that once energy resources are considered, an economy, like an ecology, requires continuous energy to be sustained in a homeostatic state away from the decayed state of its (local) thermodynamic equilibrium. AIT identifies how economic actions and natural laws create an ordered economy through what is seen as computations on a real world Universal Turing Machine (UTM) that can be simulated to within a constant on a laboratory UTM. The shortest, appropriately coded, programme to do this defines the system's information or algorithmic entropy. The computational behaviour of many generations of primitive economic agents can create a more ordered and advanced economy, able to be specified by a relatively short algorithm. The approach allows information flows to be tracked in real-world computational processes where instructions carried in stored energy create order while ejecting disorder. Selection processes implement the Maximum Power Principle while the economy trends towards Maximum Entropy Production, as tools amplify human labour and interconnections create energy efficiency. The approach provides insights into how an advanced economy is a more ordered economy, and tools to investigate the concerns of the Bioeconomists over long term economic survival.

Algorithmic Entropy and Landauer's Principle Link Microscopic System Behaviour to the Thermodynamic Entropy.

Algorithmic information theory in conjunction with Landauer's principle can quantify the cost of maintaining a reversible real-world computational system distant from equilibrium. As computational bits are conserved in an isolated reversible system, bit flows can be used to track the way a highly improbable configuration trends toward a highly probable equilibrium configuration. In an isolated reversible system, all microstates within a thermodynamic macrostate have the same algorithmic entropy. However, from a thermodynamic perspective, when these bits primarily specify stored energy states, corresponding to a fluctuation from the most probable set of states, they represent "potential entropy". However, these bits become "realised entropy" when, under the second law of thermodynamics, they become bits specifying the momentum degrees of freedom. The distance of a fluctuation from equilibrium is identified as the number of computational bits that move from stored energy states to momentum states to define a highly probable or typical equilibrium state. When reversibility applies, from Landauer's principle, it costs k B l n 2 T Joules to move a bit within the system from stored energy states to the momentum states.

Understanding how replication processes can maintain systems away from equilibrium using Algorithmic Information Theory.

Replication can be envisaged as a computational process that is able to generate and maintain order far-from-equilibrium. Replication processes, can self-regulate, as the drive to replicate can counter degradation processes that impact on a system. The capability of replicated structures to access high quality energy and eject disorder allows Landauer's principle, in conjunction with Algorithmic Information Theory, to quantify the entropy requirements to maintain a system far-from-equilibrium. Using Landauer's principle, where destabilising processes, operating under the second law of thermodynamics, change the information content or the algorithmic entropy of a system by ΔH bits, replication processes can access order, eject disorder, and counter the change without outside interventions. Both diversity in replicated structures, and the coupling of different replicated systems, increase the ability of the system (or systems) to self-regulate in a changing environment as adaptation processes select those structures that use resources more efficiently. At the level of the structure, as selection processes minimise the information loss, the irreversibility is minimised. While each structure that emerges can be said to be more entropically efficient, as such replicating structures proliferate, the dissipation of the system as a whole is higher than would be the case for inert or simpler structures. While a detailed application to most real systems would be difficult, the approach may well be useful in understanding incremental changes to real systems and provide broad descriptions of system behaviour.

Demonstrating the stability of albinterferon alfa-2b in the presence of silicone oil.

Silicone oil is often used to decrease glide forces in prefilled syringes and cartridges, common primary container closures for biopharmaceutical products. Silicone oil has been linked to inducing protein aggregation (Diabet Med 1989;6:278; Diabet Care 1987;10:786-790), leading to patient safety and immunogenicity concerns. Because of the silicone oil application process (Biotech Adv 2007;25:318-324), silicone oil levels tend to vary between individual container closures. Various silicone oil levels were applied to a container closure prior to filling and lyophilization of an albumin and interferon alfa-2b fusion protein (albinterferon alfa-2b). Data demonstrated that high silicone oil levels in combination with intended and stress storage conditions had no impact on protein purity, higher order structure, stability trajectory, or biological activity. Subvisible particulate analysis (1-10 µm range) from active and placebo samples from siliconized glass barrels showed similar particle counts. Increases in solution turbidity readings for both active and placebo samples correlated well with increases in silicone oil levels, suggesting that the particles in solution are related to the presence of silicone oil and not large protein aggregates. Results from this study demonstrate that silicone oil is not always detrimental to proteins; nevertheless, assessing the impact of silicone oil on a product case-by-case basis is still recommended.

Identification of novel mutations in the α-galactosidase A gene in patients with Fabry disease: pitfalls of mutation analyses in patients with low α-galactosidase A activity.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the α-galactosidase A (GLA) gene, and the disease is a relatively prevalent cause of left ventricular hypertrophy followed by conduction abnormalities and arrhythmias. Mutation analysis of the GLA gene is a valuable tool for accurate diagnosis of affected families. In this study, we carried out molecular studies of 10 unrelated families diagnosed with Fabry disease. MATERIALS AND METHODS: Genetic analysis of the GLA gene using conventional genomic sequencing was performed in 9 hemizygous males and 6 heterozygous females. In patients with no mutations in coding DNA sequence, multiplex ligation-dependent probe amplification (MLPA) and/or cDNA sequencing were performed. RESULTS: We identified a novel exon 2 deletion (IVS1_IVS2) in a heterozygous female by MLPA, which was undetectable by conventional sequencing methods. In addition, the g.9331G>A mutation that has previously been found only in patients with cardiac Fabry disease was found in 3 unrelated, newly-diagnosed, cardiac Fabry patients by sequencing GLA genomic DNA and cDNA. Two other novel mutations, g.8319A>G and 832delA were also found in addition to 4 previously reported mutations (R112C, C142Y, M296I, and G373D) in 6 other families. CONCLUSIONS: We could identify GLA gene mutations in all hemizygotes and heterozygotes from 10 families with Fabry disease. Mutations in 4 out of 10 families could not be identified by classical genomic analysis, which focuses on exons and the flanking region. Instead, these data suggest that MLPA analysis and cDNA sequence should be considered in genetic testing surveys of patients with Fabry disease.

Palladium-catalyzed insertion of alpha-diazoesters into vinyl halides to generate alpha,beta-unsaturated gamma-amino esters.

As easy as 1, 2, 3: A palladium-catalyzed three-component coupling generates alpha,beta-unsaturated gamma-amino acids in a single step (see scheme). The reaction is believed to involve migration of a vinyl substituent to a highly electrophilic palladium carbene. Unlike previous synthetic approaches, this synthesis provides access to gamma-amino acids with non-natural side chains.

Direct injection of kit ligand-2 lentivirus improves cardiac repair and rescues mice post-myocardial infarction.

Myocardial infarction (MI) and subsequent adverse remodeling cause heart failure. Previously we demonstrated a role for Kit ligand (KL) in improving cardiac function post-MI. KL has two major isoforms; KL-1 is secreted whereas KL-2 is predominantly membrane bound. We demonstrate here first that KL-2-deficient mice have worse survival and an increased heart/bodyweight ratio post-MI compared to mice with reduced c-Kit receptor expression. Next we synthesized recombinant lentiviral vectors (LVs) that engineered functional expression of murine KL-1 and KL-2. For in vivo analyses, we directly injected these LVs into the left ventricle of membrane-bound KL-deficient Sl/Sl(d) or wild-type (WT) mice undergoing MI. Control LV/enGFP injection led to measurable reporter gene expression in hearts. Injection of LV/KL-2 attenuated adverse left ventricular remodeling and dramatically improved survival post-MI in both Sl/Sl(d) and WT mice (from 12 to 71% and 35 to 73%, respectively, versus controls). With regard toward beginning to understand the possible salutary mechanisms involved in this effect, differential staining patterns of Sca-1 and Ly49 on peripheral blood (PB) cells from therapeutically treated animals was found. Our data show that LV/KL-2 gene therapy is a promising treatment for MI.

Palladium-catalyzed carbene insertion and trapping with carbon nucleophiles.

Palladium catalysts are shown to catalyze the three-component coupling of vinyl halides, trimethylsilyldiazomethane, and stabilized carbon nucleophiles. The reaction is believed to proceed through a palladium-carbene intermediate LX(R)PdCHSiMe 3 that undergoes migration of the vinyl substituent to the electrophilic carbene center to generate an eta 3-allylpalladium intermediate. The allylpalladium intermediate is attacked by the carbon nucleophile to generate a vinylsilane product.