Author Correction: EEG Decoding Reveals the Strength and Temporal Dynamics of Goal-Relevant Representations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

EEG Decoding Reveals the Strength and Temporal Dynamics of Goal-Relevant Representations.

Models of action control assume that attentional control settings regulate the processing of lower-level stimulus/response representations. Yet, little is known about how exactly control and sensory/response representations relate to each other to produce goal-directed behavior. Addressing this question requires time-resolved information about the strength of the different, potentially overlapping representations, on a trial-by-trial basis. Using a cued task-switching paradigm, we show that information about relevant representations can be extracted through decoding analyses from the scalp electrophysiological signal (EEG) with high temporal resolution. Peaks in representational strength-indexed through decoding accuracy-proceeded from superficial task cues, to stimulus locations, to features/responses. In addition, attentional-set representations were prominent throughout almost the entire processing cascade. Trial-by-trial analyses provided detailed information about when and to what degree different representations predict performance, with attentional settings emerging as a strong and consistent predictor of within-individual and across-individual variability in performance. Also, the strength of attentional sets was related to target representations early in the post-stimulus period and to feature/response representations at a later period, suggesting control of successive, lower-level representations in a concurrent manner. These results demonstrate a powerful approach towards uncovering different stages of information processing and their relative importance for performance.

Establishing and characterizing patient-derived xenografts using pre-chemotherapy percutaneous biopsy and post-chemotherapy surgical samples from a prospective neoadjuvant breast cancer study.

BACKGROUND: Patient-derived xenografts (PDXs) are increasingly used in cancer research as a tool to inform cancer biology and drug response. Most available breast cancer PDXs have been generated in the metastatic setting. However, in the setting of operable breast cancer, PDX models both sensitive and resistant to chemotherapy are needed for drug development and prospective data are lacking regarding the clinical and molecular characteristics associated with PDX take rate in this setting. METHODS: The Breast Cancer Genome Guided Therapy Study (BEAUTY) is a prospective neoadjuvant chemotherapy (NAC) trial of stage I-III breast cancer patients treated with neoadjuvant weekly taxane+/-trastuzumab followed by anthracycline-based chemotherapy. Using percutaneous tumor biopsies (PTB), we established and characterized PDXs from both primary (untreated) and residual (treated) tumors. Tumor take rate was defined as percent of patients with the development of at least one stably transplantable (passed at least for four generations) xenograft that was pathologically confirmed as breast cancer. RESULTS: Baseline PTB samples from 113 women were implanted with an overall take rate of 27.4% (31/113). By clinical subtype, the take rate was 51.3% (20/39) in triple negative (TN) breast cancer, 26.5% (9/34) in HER2+, 5.0% (2/40) in luminal B and 0% (0/3) in luminal A. The take rate for those with pCR did not differ from those with residual disease in TN (p = 0.999) and HER2+ (p = 0.2401) tumors. The xenografts from 28 of these 31 patients were such that at least one of the xenografts generated had the same molecular subtype as the patient. Among the 35 patients with residual tumor after NAC adequate for implantation, the take rate was 17.1%. PDX response to paclitaxel mirrored the patients' clinical response in all eight PDX tested. CONCLUSIONS: The generation of PDX models both sensitive and resistant to standard NAC is feasible and these models exhibit similar biological and drug response characteristics as the patients' primary tumors. Taken together, these models may be useful for biomarker discovery and future drug development.

Is conflict adaptation due to active regulation or passive carry-over? Evidence from eye movements.

Conflict-adaptation effects (i.e., reduced response-time costs on high-conflict trials following high-conflict trials) supposedly represent our cognitive system's ability to regulate itself according to current processing demands. However, currently it is not clear whether these effects reflect conflict-triggered, active regulation, or passive carry-over of previous-trial control settings. We used eye movements to examine whether the degree of experienced conflict modulates conflict-adaptation effects, as the conflict-triggered regulation view predicts. Across 2 experiments in which participants had to identify a target stimulus based on an endogenous cue while-on conflict trials-having to resist a sudden-onset distractor, we found a clear indication of conflict adaptation. This adaptation effect disappeared however, when participants inadvertently fixated the sudden-onset distractor on the previous trial-that is, when they experienced a high degree of conflict. This pattern of results suggests that conflict adaptation can be explained parsimoniously in terms of a broader memory process that retains recently adopted control settings across trials. (PsycINFO Database Record

A general benevolence dimension that links neural, psychological, economic, and life-span data on altruistic tendencies.

[Correction Notice: An Erratum for this article was reported in Vol 145(10) of Journal of Experimental Psychology: General (see record 2016-46925-004). In the article, there was an error in the Task, Stimuli, and Procedures section. In the 1st sentence in the 6th paragraph, "Following the scanning phase, participants completed self-report questionnaires meant to reflected the Prosocial Disposition construct: the agreeableness scale from the Big F, which includes empathic concern and perspective-taking, and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010)." should have read: "Following the scanning phase, participants completed self-report questionnaires that contained scales to reflect the Prosocial Disposition construct: the Big Five Inventory (BFI; John et al., 1991), from which we used the agreeableness scale to measure prosocial disposition; the Interpersonal Reactivity Index (IRI; Davis, 1980), from which we used the empathic concern and perspective-taking scales; and a scale of personality descriptive adjectives related to altruistic behavior (Wood, Nye, & Saucier, 2010)."] Individual and life span differences in charitable giving are an important economic force, yet the underlying motives are not well understood. In an adult, life span sample, we assessed manifestations of prosocial tendencies across 3 different measurement domains: (a) psychological self-report measures, (b) actual giving choices, and (c) fMRI-derived, neural indicators of "pure altruism." The latter expressed individuals' activity in neural valuation areas when charities received money compared to when oneself received money and thus reflected an altruistic concern for others. Results based both on structural equation modeling and unit-weighted aggregate scores revealed a strong higher-order General Benevolence dimension that accounted for variability across all measurement domains. The fact that the neural measures likely reflect pure altruistic tendencies indicates that General Benevolence is based on a genuine concern for others. Furthermore, General Benevolence exhibited a robust increase across the adult life span, potentially providing an explanation for why older adults typically contribute more to the public good than young adults.

Dynamics of task-set carry-over: evidence from eye-movement analyses.

Trial-to-trial carry-over of task sets (i.e., task-set inertia) is often considered as a primary reason for task-switch costs. Yet, we know little about the dynamics of such carry-over effects, in particular how much they are driven by the most recent trial rather than characterized by a more continuous memory gradient. Using eye-tracking, we examined in a 3-task, switching paradigm whether there is a greater probability of non-target fixations to stimuli associated with the previously relevant attentional set than to those associated with the less-recent set. Indeed, we found strong evidence for more interference (expressed in terms of non-target fixations) from recent than from less-recent tasks and that in particular the interference from pre-switch trials contributed substantially to the overall pattern of response-time switch costs. Moreover, task-set carry-over was dominated by the most-recent trial when subjects could expect task repetitions (with a 33 % switch rate). In comparison, when tasks were selected randomly (with a 66 % switch rate), interference from the most recent trial decreased, whereas interference from less-recent trials increased. In sum, carry-over interference dynamics were characterized both by a gradual recency gradient and expectations about task-transition probabilities. Beyond that, there was little evidence for a unique role of the most-recent trial.

Long-term memory and the control of attentional control.

Task-switch costs and in particular the switch-cost asymmetry (i.e., the larger costs of switching to a dominant than a non-dominant task) are usually explained in terms of trial-to-trial carry-over of task-specific control settings. Here we argue that task switches are just one example of situations that trigger a transition from working-memory maintenance to updating, thereby opening working memory to interference from long-term memory. We used a new paradigm that requires selecting a spatial location either on the basis of a central cue (i.e., endogenous control of attention) or a peripheral, sudden onset (i.e., exogenous control of attention). We found a strong cost asymmetry that occurred even after short interruptions of otherwise single-task blocks (Exp. 1-3), but that was much stronger when participants had experienced the competing task under conditions of conflict (Exp. 1-2). Experiment 3 showed that the asymmetric costs were due to interruptions per se, rather than to associative interference tied to specific interruption activities. Experiment 4 generalized the basic pattern across interruptions varying in length or control demands and Experiment 5 across primary tasks with response-selection conflict rather than attentional conflict. Combined, the results support a model in which costs of selecting control settings arise when (a) potentially interfering memory traces have been encoded in long-term memory and (b) working-memory is forced from a maintenance mode into an updating mode (e.g., through task interruptions), thereby allowing unwanted retrieval of the encoded memory traces.

Representations in working memory yield interference effects found with externally-triggered representations.

An act as simple as flicking a switch involves various stages of processing. Each stage is susceptible to interference from competing representations/processes. Interference at different stages of processing (e.g., perceptual stages versus response selection stages) leads to distinct behavioral, neural, and subjective effects. In the flanker task, for instance, one responds to a visual target and disregards flanking 'distractors.' Theoretically-predicted interference (increased response times, error rates, and subjective 'urges to err') is stronger when distractors and targets are associated with different actions (response interference) than when they look different but are associated with the same action (perceptual interference). Extant versions of the task tax working memory (WM) minimally, but many everyday actions (e.g., searching for keys or holding one's breath) require more WM-based control. To illuminate this uncharted area, we examined the nature of interference in delayed action tasks, which rely on WM. We found that systematic interference arises even when action-related representations are, not triggered solely by external stimuli, but actively held in WM. We discuss these findings with increased emphasis on the under-explored subjective effects of different kinds of interference. The implications of these findings for the study of action production, WM, and conscious processing are entertained.

Traditional response interference effects from anticipated action outcomes: a response-effect compatibility paradigm.

An act as simple as pressing a button involves various stages of processing. Each stage of action production is susceptible to interference from competing representations/processes. For example, in the Simon Effect, interference arises from an incongruence between incidental spatial information and the spatial properties of intended action; in the flanker task, interference arises when visual targets and distracters are associated with different responses (response interference [RI]). Less interference arises in the flanker task when targets and distracters are different in appearance but associated with the same response (perceptual interference [PI]). Interference also stems from the automatic activation of representations associated with the anticipated effects of an action, response-effect (R-E) compatibility (e.g., the presence of a left-pointing arrow after one presses a button on the right will increase interference in future trials). This has been explained by ideomotor theory-that the mental representation of anticipated action-effects are activated automatically by voluntary action and that such representations can cause facilitation or interference by automatically priming their associated action plans. To illuminate the nature of action production and provide additional support for ideomotor theory, we examined for the first time the effects of PI and RI in a new R-E compatibility paradigm.

CYP4F2 genetic variant alters required warfarin dose.

Warfarin is an effective, commonly prescribed anticoagulant used to treat and prevent thrombotic events. Because of historically high rates of drug-associated adverse events, warfarin remains underprescribed. Further, interindividual variability in therapeutic dose mandates frequent monitoring until target anticoagulation is achieved. Genetic polymorphisms involved in warfarin metabolism and sensitivity have been implicated in variability of dose. Here, we describe a novel variant that influences warfarin requirements. To identify additional genetic variants that contribute to warfarin requirements, screening of DNA variants in additional genes that code for drug-metabolizing enzymes and drug transport proteins was undertaken using the Affymetrix drug-metabolizing enzymes and transporters panel. A DNA variant (rs2108622; V433M) in cytochrome P450 4F2 (CYP4F2) was associated with warfarin dose in 3 independent white cohorts of patients stabilized on warfarin representing diverse geographic regions in the United States and accounted for a difference in warfarin dose of approximately 1 mg/day between CC and TT subjects. Genetic variation of CYP4F2 was associated with a clinically relevant effect on warfarin requirement.