Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent

Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1

Context specificity of post-error and post-conflict cognitive control adjustments

There has been accumulating evidence that cognitive control can be adaptively regulated by monitoring for processing conflict as an index of online control demands. However, it is not yet known whether top-down control mechanisms respond to processing conflict in a manner specific to the operative task context or confer a more generalized benefit. While previous studies have examined the taskset-specificity of conflict adaptation effects, yielding inconsistent results, controlrelated performance adjustments following errors have been largely overlooked. This gap in the literature underscores recent debate as to whether post-error performance represents a strategic, control-mediated mechanism or a nonstrategic consequence of attentional orienting. In the present study, evidence of generalized control following both high conflict correct trials and errors was explored in a task-switching paradigm. Conflict adaptation effects were not found to generalize across tasksets, despite a shared response set. In contrast, post-error slowing effects were found to extend to the inactive taskset and were predictive of enhanced post-error accuracy. In addition, post-error performance adjustments were found to persist for several trials and across multiple task switches, a finding inconsistent with attentional orienting accounts of post-error slowing. These findings indicate that error-related control adjustments confer a generalized performance benefit and suggest dissociable mechanisms of post-conflict and post-error control. © 2014 Forster, Cho

The role of the striatum in effort-based decision-making in the absence of reward

Decision-making involves weighing costs against benefits, for instance, in terms of the effort it takes to obtain a reward of a given magnitude. This evaluation process has been linked to the dorsal anterior cingulate cortex (dACC) and the striatum, with activation in these brain structures reflecting the discounting effect of effort on reward. Here, we investigate how cognitive effort influences neural choice processes in the absence of an extrinsic reward. Using functional magnetic resonance imaging in humans, we used an effort-based decision-making task in which participants were required to choose between two options for a subsequent flanker task that differed in the amount of cognitive effort. Cognitive effort was manipulated by varying the proportion of incongruent trials associated with each choice option. Choice-locked activation in the striatum was higher when participants chose voluntarily for the more effortful alternative but displayed the opposite trend on forced-choice trials. The dACC revealed a similar, yet only trend-level significant, activation pattern. Our results imply that activation levels in the striatum reflect a cost-benefit analysis, in which a balance is made between effort discounting and the intrinsic motivation to choose a cognitively challenging task. Moreover, our findings indicate that it matters whether this challenge is voluntarily chosen or externally imposed. As such, the present findings contrast with classical findings on effort discounting that found reductions in striatum activation for higher effort by finding enhancements of the same neural circuits when a cognitively challenging task is voluntarily selected and does not entail the danger of losing reward

Detecting and correcting partial errors: Evidence for efficient control without conscious access

Appropriate reactions to erroneous actions are essential to keeping behavior adaptive. Erring, however, is not an all-or-none process: electromyographic (EMG) recordings of the responding muscles have revealed that covert incorrect response activations (termed "partial errors") occur on a proportion of overtly correct trials. The occurrence of such "partial errors" shows that incorrect response activations could be corrected online, before turning into overt errors. In the present study, we showed that, unlike overt errors, such "partial errors" are poorly consciously detected by participants, who could report only one third of their partial errors. Two parameters of the partial errors were found to predict detection: the surface of the incorrect EMG burst (larger for detected) and the correction time (between the incorrect and correct EMG onsets; longer for detected). These two parameters provided independent information. The correct(ive) responses associated with detected partial errors were larger than the "pure-correct" ones, and this increase was likely a consequence, rather than a cause, of the detection. The respective impacts of the two parameters predicting detection (incorrect surface and correction time), along with the underlying physiological processes subtending partial-error detection, are discussed

Performance breakdown effects dissociate from error detection effects in typing

Mistakes in skilled performance are often observed to be slower than correct actions. This error slowing has been associated with cognitive control processes involved in performance monitoring and error detection. A limited literature on skilled actions, however, suggests that preerror actions may also be slower than accurate actions. This contrasts with findings from unskilled, discrete trial tasks, where preerror performance is usually faster than accurate performance. We tested 3 predictions about error-related behavioural changes in continuous typing performance. We asked participants to type 100 sentences without visual feedback. We found that (a) performance before errors was no different in speed than that before correct key-presses, (b) error and posterror key-presses were slower than matched correct key-presses, and (c) errors were preceded by greater variability in speed than were matched correct key-presses. Our results suggest that errors are preceded by a behavioural signature, which may indicate breakdown of fluid cognition, and that the effects of error detection on performance (error and posterror slowing) can be dissociated from breakdown effects (preerror increase in variability). © 2013 © 2013 The Experimental Psychology Society

The effects of attentional bias modification on emotion regulation

BACKGROUND AND OBJECTIVES: In two experiments, we investigated the effects of Attentional Bias Modification (ABM) on emotion regulation, i.e. the manner in which people influence emotional experiences. We hypothesized that decreases in attentional bias to threat would impair upregulation and improve downregulation of negative emotions, while increases in attentional bias to threat would improve upregulation and impair downregulation of negative emotions. METHODS: Using the emotion-in-motion paradigm (Experiment 1, N = 60) and the visual search task (Experiment 2, N = 58), we trained participants to attend to either threatening or positive stimuli and we assessed emotion intensity while observing, upregulating, and downregulating emotions in response to grids of mixed emotional pictures. RESULTS: In Experiment 1, the attend positive group reported more positive emotions while merely watching grids of training pictures and the attend threat group showed impaired upregulation of negative affect. In Experiment 2, the attend threat group reported intensified negative emotions for all three instructions, while the attend positive group remained largely stable over time. LIMITATIONS: We cannot unequivocally attribute these changes in emotion regulation to changes in attentional bias, as neither of the experiments yielded significant changes in attentional bias to threat. CONCLUSIONS: By showing that attentional bias modification procedures affect the manner in which people deal with emotions, we add empirical weight to the conceptual overlap between attentional bias modification and emotion regulation

Reward and Efficacy Modulate the Rate of Anticipatory Pupil Dilation

Pupil size is a well-established marker of cognitive effort, with greater efforts leading to larger pupils. This is particularly true for pupil size during task performance, whereas findings on anticipatory effort triggered by a cue stimulus are less consistent. For example, a recent report by Frömer et al. found that in a cued-Stroop task, behavioral performance and electrophysiological markers of preparatory effort allocation were modulated by cued reward and ‘efficacy’ (the degree to which rewards depended on good performance), but pupil size did not show a comparable pattern. Here, we conceptually replicated this study, employing an alternative approach to the pupillometry analyses. In line with previous findings, we found no modulation of absolute pupil size in the cue-to-target interval. Instead, we observed a significant difference in the rate of pupil dilation in anticipation of the target: pupils dilated more rapidly for high-reward trials in which rewards depended on good performance. This was followed by a significant difference in absolute pupil size within the first hundreds of milliseconds following Stroop stimulus onset, likely reflecting a lagging effect of anticipatory effort allocation. Finally, the slope of pupil dilation was significantly correlated with behavioral response times, and this association was strongest for the high-reward, high-efficacy trials, further supporting that the rate of anticipatory pupil dilation reflects anticipatory effort. We conclude that pupil size is modulated by anticipatory effort, but in a highly temporally-specific manner, which is best reflected by the rate of dilation in the moments just prior to stimulus onset

The Cost of Regulating Effort: Reward and Difficulty Cues With Longer Prediction Horizons Have a Stronger Impact on Performance

Many theories on cognitive effort start from the assumption that cognitive effort can be expended at will, and flexibly up- or down-regulated depending on expected task demand and rewards. However, while effort regulation has been investigated across a wide range of incentive conditions, few investigated the cost of effort regulation itself. Across four experiments, we studied the effects of reward expectancy and task difficulty on effort expenditure in a perceptual decision-making task (random-dot-motion) and a cognitive control task (colour-naming Stroop), and within each task comparted cues between short (cueing the next trial) and long (cueing the next six trials) prediction horizons. We found that participants used the cue information only when it was valid for multiple trials in a row. In the random-dot-motion task, a high reward expectancy resulted in better accuracy, especially in easy trials, but only with long prediction horizon. Similarly, in the Stroop task, the reward facilitation of reaction time was only observed after reward cues with a long prediction horizon. Together, our results indicate that people experience a cost to effort regulation, and that lower adjustment frequency can compensate for this cost