Evidence of a Goal-Directed Process in Human Pavlovian-Instrumental Transfer

© 2017 APA, all rights reserved). Cues that signal rewards can motivate reward-seeking behaviors, even for outcomes that are not currently desired. Three experiments examined this phenomenon, using an outcome-selective Pavlovian-instrumental transfer (PIT) design and an outcome devaluation procedure. In Experiment 1, participants learned to perform one response to earn crisps points and another response to earn popcorn points. One outcome was then devalued by adulterating it to make it taste unpleasant. On test, overall response choice was biased toward the outcome that had not been devalued, indicating goal-directed control. Stimuli that signaled crisps and popcorn also biased instrumental response choice toward their respective outcomes (a PIT effect). Most importantly, the strength of this bias was not influenced by the devaluation manipulation. In contrast, Experiment 2 demonstrated that when stimuli signaled equal probability of the two outcomes, cue-elicited response choice was sensitive to the devaluation manipulation. Experiment 3 confirmed this conclusion by demonstrating a selective avoidance of the cued, devalued outcome. Together, these data support a goal-directed model of PIT in which expected outcome probability and value make independent contributions to response choice. (PsycINFO Database Recor

Attention and associative learning in humans: An integrative review

This article presents a comprehensive survey of research concerning interactions between associative learning and attention in humans. Four main findings are described. First, attention is biased toward stimuli that predict their consequences reliably (learned predictiveness). This finding is consistent with the approach taken by Mackintosh (1975) in his attentional model of associative learning in nonhuman animals. Second, the strength of this attentional bias is modulated by the value of the outcome (learned value). That is, predictors of high-value outcomes receive especially high levels of attention. Third, the related but opposing idea that uncertainty may result in increased attention to stimuli (Pearce & Hall, 1980), receives less support. This suggests that hybrid models of associative learning, incorporating the mechanisms of both the Mackintosh and Pearce-Hall theories, may not be required to explain data from human participants. Rather, a simpler model, in which attention to stimuli is determined by how strongly they are associated with significant outcomes, goes a long way to account for the data on human attentional learning. The last main finding, and an exciting area for future research and theorizing, is that learned predictiveness and learned value modulate both deliberate attentional focus, and more automatic attentional capture. The automatic influence of learning on attention does not appear to fit the traditional view of attention as being either goal-directed or stimulus-driven. Rather, it suggests a new kind of “derived” attention

Dissociable learning processes, associative theory, and testimonial reviews: A comment on Smith and Church (2018

Smith and Church (Psychonomic Bulletin & Review, 25, 1565–1584 2018) present a “testimonial” review of dissociable learning processes in comparative and cognitive psychology, by which we mean they include only the portion of the available evidence that is consistent with their conclusions. For example, they conclude that learning the information-integration category-learning task with immediate feedback is implicit, but do not consider the evidence that people readily report explicit strategies in this task, nor that this task can be accommodated by accounts that make no distinction between implicit and explicit processes. They also consider some of the neuroscience relating to information-integration category learning, but do not report those aspects that are more consistent with an explicit than an implicit account. They further conclude that delay conditioning in humans is implicit, but do not report evidence that delay conditioning requires awareness; nor do they present the evidence that conditioned taste aversion, which should be explicit under their account, can be implicit. We agree with Smith and Church that it is helpful to have a clear definition of associative theory, but suggest that their definition may be unnecessarily restrictive. We propose an alternative definition of associative theory and briefly describe an experimental procedure that we think may better distinguish between associative and non-associative processes

Mechanism of trifluorothymidine potentiation of oxaliplatin-induced cytotoxicity to colorectal cancer cells

Oxaliplatin (OHP) is an anticancer agent that acts by formation of Platinum-DNA (Pt-DNA) adducts resulting in DNA-strand breaks and is used for the treatment of colorectal cancer. The pyrimidine analog trifluorothymidine (TFT) forms together with a thymidine phosphorylase inhibitor (TPI) the anticancer drug formulation TAS-102, in which TPI enhances the bioavailability of TFT in vivo. In this in vitro study the combined cytotoxic effects of OHP with TFT were investigated in human colorectal cancer cells as a model for TAS-102 combinations. In a panel of five colon cancer cell lines (WiDr, H630, Colo320, SNU-C4 and SW1116) we evaluated the OHP-TFT drug combinations using the multiple drug–effect analysis with CalcuSyn software, in which the combination index (CI) indicates synergism (CI<0.9), additivity (CI=0.9–1.1) or antagonism (CI>1.1). Drug target analysis was used for WiDr, H630 and SW1116 to investigate whether there was an increase in Pt-DNA adduct formation, DNA damage induction, cell cycle delay and apoptosis. Trifluorothymidine combined with OHP resulted in synergism for all cell lines (all CI<0.9). This was irrespective of schedule in which either one of the drugs was kept at a constant concentration (using variable drug ratio) or when the two drugs were added in a 1 : 1 IC50-based molar ratio. Synergism could be increased for WiDr using sequential drug treatment schedules. Trifluorothymidine increased Pt-DNA adduct formation significantly in H630 and SW1116 (14.4 and 99.1%, respectively; P<0.05). Platinum-DNA adducts were retained best in SW1116 in the presence of TFT. More DNA-strand breaks were induced in SW1116 and the combination increased DNA damage induction (>20%) compared with OHP alone. Exposure to the drugs induced a clear cell-cycle S-phase arrest, but was dose schedule and cell line dependent. Trifluorothymidine (TFT) and OHP both induced apoptosis, which increased significantly for WiDr and SW1116 after TFT–OHP exposure (18.8 and 20.6% respectively; P<0.05). The basal protein levels of ERCC1 DNA repair enzyme were not related to the DNA damage that was induced in the cell lines. In conclusion, the combination of TFT with the DNA synthesis inhibitor OHP induces synergism in colorectal cancer cells, but is dependent on the dose and treatment schedule used