Executive Functions and the Interaction Between Category Learning Systems

Research on the cognitive processes underlying category learning provides evidence for two separate learning systems. A verbal system learns rule-defined (RD) categories and a nonverbal system learns non-rule-defined (NRD) categories. The objective of my dissertation is to explore the interaction between these systems. The verbal system is dominant in that adults tend to use it during initial learning but may switch to the nonverbal system when the verbal system is unsuccessful. The nonverbal system has traditionally been thought to operate independently of executive functions, but recent studies suggest that executive functions may be used to facilitate the transition away from the verbal system. Study 1 investigated whether executive functions play similar roles across systems and which, if any, components of executive functions are most important for the verbal and nonverbal systems. The components of executive functions were associated with both types of category learning but played different roles within each system. Study 2 compared the effects of a temporary and continuous executive function disruption for each system. When executive functions were continuously unavailable, the transition to the nonverbal system was hindered, providing evidence that executive functions are needed to transition between systems. For the verbal system, temporary and continuous interference had similar effects, illustrating that any executive function disruption is detrimental to the verbal system. Studies 3 and 4 experimentally manipulated the interaction between systems. Manipulating the order in which categories were learned affected the initial strengths of the systems. Strengthening the verbal system reduced optimal strategy use on subsequent nonverbal categorization, but the opposite was not true. Increasing stimulus knowledge facilitated rule searching and increased optimal strategy use on nonverbal categorization but not on verbal categorization. Conclusions. The current studies illustrate that the transition between systems is disrupted when executive functions are never fully available and when the verbal system is strengthened, but is facilitated when hypothesis testing is expedited. This research provides insight into the interaction between category learning systems and illustrates that the interaction is mediated by executive functions. Furthermore, executive functions play an important but different role in each system

Perceptual fluency can be used as a cue for categorization decisions.

Learning in the prototype distortion task is thought to involve perceptual learning in which category members experience an enhanced visual response (Ashby & Maddox. Annual Review of Psychology, 56, 149-178, 2005). This response likely leads to more-efficient processing, which in turn may result in a feeling of perceptual fluency for category members. We examined the perceptual-fluency hypothesis by manipulating fluency independently from category membership. We predicted that when perceptual fluency was induced using subliminal priming, this fluency would be misattributed to category membership and would affect categorization decisions. In a prototype distortion task, the participants were more likely to judge stimuli that were not members of the category as category members when the nonmembers were made perceptually fluent with a matching subliminal prime. This result suggests that perceptual fluency can be used as a cue during some categorization decisions. In addition, the results provided converging evidence that some types of categorization are based on perceptual learning

Continuous executive function disruption interferes with application of an information integration categorization strategy.

Category learning is often characterized as being supported by two separate learning systems. A verbal system learns rule-defined (RD) categories that can be described using a verbal rule and relies on executive functions (EFs) to learn via hypothesis testing. A nonverbal system learns non-rule-defined (NRD) categories that cannot be described by a verbal rule and uses automatic, procedural learning. The verbal system is dominant in that adults tend to use it during initial learning but may switch to the nonverbal system when the verbal system is unsuccessful. The nonverbal system has traditionally been thought to operate independently of EFs, but recent studies suggest that EFs may play a role in the nonverbal system-specifically, to facilitate the transition away from the verbal system. Accordingly, continuously interfering with EFs during the categorization process, so that EFs are never fully available to facilitate the transition, may be more detrimental to the nonverbal system than is temporary EF interference. Participants learned an NRD or an RD category while EFs were untaxed, taxed temporarily, or taxed continuously. When EFs were continuously taxed during NRD categorization, participants were less likely to use a nonverbal categorization strategy than when EFs were temporarily taxed, suggesting that when EFs were unavailable, the transition to the nonverbal system was hindered. For the verbal system, temporary and continuous interference had similar effects on categorization performance and on strategy use, illustrating that EFs play an important but different role in each of the category-learning systems

Ascorbic acid and ascorbate-2-phosphate decrease HIF activity and malignant properties of human melanoma cells

Background: Hypoxia inducible factor-1 alpha (HIF-1α) is thought to play a role in melanoma carcinogenesis. Posttranslational regulation of HIF-1α is dependent on Prolyl hydroxylase (PHD 1–3) and Factor Inhibiting HIF (FIH) hydroxylase enzymes, which require ascorbic acid as a co-factor for optimal function. Depleted intra-tumoral ascorbic acid may thus play a role in the loss of HIF-1α regulation in melanoma. These studies assess the ability of ascorbic acid to reduce HIF-1α protein and transcriptional activity in metastatic melanoma and reduce its invasive potential. Methods: HIF-1α protein was evaluated by western blot, while transcriptional activity was measured by HIF-1 HRE-luciferase reporter gene activity. Melanoma cells were treated with ascorbic acid (AA) and ascorbate 2-phosphate (A2P) to assess their ability to reduce HIF-1α accumulation and activity. siRNA was used to deplete cellular PHD2 in order to evaluate this effect on AA’s ability to lower HIF-1α levels. A2P’s effect on invasive activity was measured by the Matrigel invasion assay. Data was analyzed by One-way ANOVA with Tukey’s multiple comparisons test, or Student-T test as appropriate, with p\u3c.05 considered significant. Results: Supplementation with both AA and A2P antagonized normoxic as well as cobalt chloride- and PHD inhibitor ethyl 3, 4-dihydroxybenzoate induced HIF-1α protein stabilization and transcriptional activity. Knockdown of the PHD2 isoform with siRNA did not impede the ability of AA to reduce normoxic HIF-1α protein. Additionally, reducing HIF-1α levels with A2P resulted in a significant reduction in the ability of the melanoma cells to invade through Matrigel. Conclusion: These studies suggest a positive role for AA in regulating HIF-1α in melanoma by demonstrating that supplementation with either AA, or its oxidation-resistant analog A2P, effectively reduces HIF-1α protein and transcriptional activity in metastatic melanoma cells. Our data, while supporting the function of AA as a necessary cofactor for PHD and likely FIH activity, also suggests a potential non-PHD/FIH role for AA in HIF-1α regulation by its continued ability to reduce HIF-1α in the presence of PHD inhibition. The use of the oxidation-resistant AA analog, A2P, to reduce the ability of HIF-1α to promote malignant progression in melanoma cells and enhance their response to therapy warrants further investigation

Parental Buffering in the Context of Poverty: Positive Parenting Behaviors Differentiate Young Children\u27s Stress Reactivity Profiles

Experiencing poverty increases vulnerability for dysregulated hypothalamic–pituitary–adrenal (HPA) axis functioning and compromises long-term health. Positive parenting buffers children from HPA axis reactivity, yet this has primarily been documented among families not experiencing poverty. We tested the theorized power of positive parenting in 124 parent–child dyads recruited from Early Head Start (Mage = 25.21 months) by examining child cortisol trajectories using five samples collected across a standardized stress paradigm. Piecewise latent growth models revealed that positive parenting buffered children\u27s stress responses when controlling for time of day, last stress task completed, and demographics. Positive parenting also interacted with income such that positive parenting was especially protective for cortisol reactivity in families experiencing greater poverty. Findings suggest that positive parenting behaviors are important for protecting children in families experiencing low income from heightened or prolonged physiologic stress reactivity to an acute stressor

The Effect of Self-Focused Attention and Mood on Appearance Dissatisfaction after Mirror-Gazing: An Experimental Study

Background and objectives: Self-focused attention is hypothesized to be a maintenance factor in body dysmorphic disorder (BDD). The aim of this study was to use an experimental paradigm to test this hypothesis by studying the effect of self-focused attention during mirror-gazing on appearance dissatisfaction. Methods: An experimental group design was used, in which 173 women were randomly allocated to one of three conditions before mirror-gazing for 2 min: (a) external focus of attention, (b) self-focus of attention, and (c) self-focus of attention with a negative mood induction. Results: After mirror-gazing, participants across all groups rated themselves as being more dissatisfied with their appearance. In both the self-focus conditions, there was an increase in sadness from pre to post mirror gazing, and there was a significant difference in focus of attention for participants in the self-focused, mood-induced group from pre to post manipulation, suggesting mood induction had more of an effect than focus of attention. Limitations: (1) there was no condition involving an external focus with a negative mood induction, and (2) due to the level of information provided to patients on the nature of the task, we cannot rule out demand characteristics as an influencing factor on our results. Conclusions: Self-focused attention during mirror-gazing may act indirectly to increase appearance dissatisfaction via the effect of negative mood. Further studies are required to establish the relative contribution of self-focused attention and negative mood to increases in appearance dissatisfaction as a function of mirror-gazing

Sleep deprivation causes memory deficits by negatively impacting neuronal connectivity in hippocampal area CA1

Brief periods of sleep loss have long-lasting consequences such as impaired memory consolidation. Structural changes in synaptic connectivity have been proposed as a substrate of memory storage. Here, we examine the impact of brief periods of sleep deprivation on dendritic structure. In mice, we find that five hours of sleep deprivation decreases dendritic spine numbers selectively in hippocampal area CA1 and increased activity of the filamentous actin severing protein cofilin. Recovery sleep normalizes these structural alterations. Suppression of cofilin function prevents spine loss, deficits in hippocampal synaptic plasticity, and impairments in long-term memory caused by sleep deprivation. The elevated cofilin activity is caused by cAMP-degrading phosphodiesterase-4A5 (PDE4A5), which hampers cAMP-PKA-LIMK signaling. Attenuating PDE4A5 function prevents changes in cAMP-PKA-LIMK-cofilin signaling and cognitive deficits associated with sleep deprivation. Our work demonstrates the necessity of an intact cAMP-PDE4-PKA-LIMK-cofilin activation-signaling pathway for sleep deprivation-induced memory disruption and reduction in hippocampal spine density

TCR deep sequencing of transgenic RAG-1-deficient mice reveals endogenous TCR recombination: a cause for caution

The utility of T‐cell receptor (TCR) transgenic mice in medical research has been considerable, with applications ranging from basic biology all the way to translational and clinical investigations. Crossing of TCR transgenic mice with either recombination‐activating gene (RAG)‐1 or RAG‐2 knockouts is frequently used to generate mice with a monoclonal T‐cell repertoire. However, low level productive TCR rearrangement has been reported in RAG‐deficient mice expressing transgenic TCRs. Using deep sequencing, we set out to directly examine and quantify the presence of these endogenous TCRs. Our demonstration that functional nontransgenic TCRs are present in nonmanipulated mice has wide reaching ramifications worthy of critical consideration