Differential methylation of OPRK1 in borderline personality disorder is associated with childhood trauma.

According to a growing body of neurobiological evidence, the core symptoms of borderline personality disorder (BPD) may be linked to an opioidergic imbalance between the hedonic and stimulatory activity of mu opioid receptors (MOR) and the reward system inhibiting effects of kappa opioid receptors (KOR). Childhood trauma (CT), which is etiologically relevant to BPD, is also likely to lead to epigenetic and neurobiological adaptations by extensive activation of the stress and endogenous opioid systems. In this study, we investigated the methylation differences in the promoter of the KOR gene (OPRK1) in subjects with BPD (N = 47) and healthy controls (N = 48). Comparing the average methylation rates of regulatorily relevant subregions (specified regions CGI-1, CGI-2, EH1), we found no differences between BPD and HC. Analyzing individual CG nucleotides (N = 175), we found eight differentially methylated CG sites, all of which were less methylated in BPD, with five showing highly interrelated methylation rates. This differentially methylated region (DMR) was found on the falling slope (5') of the promoter methylation gap, whose effect is enhanced by the DMR hypomethylation in BPD. A dimensional assessment of the correlation between disease severity and DMR methylation rate revealed DMR hypomethylation to be negatively associated with BPD symptom severity (measured by BSL-23). Finally, analyzing the influence of CT on DMR methylation, we found DMR hypomethylation to correlate with physical and emotional neglect in childhood (quantified by CTQ). Thus, the newly identified DMR may be a biomarker of the risks caused by CT, which likely epigenetically contribute to the development of BPD.

Moral decision-making in context: Behavioral and neural processes underlying allocations based on need, merit, and equality.

How to fairly allocate goods is a key issue of social decision-making. Extensive research demonstrates that people do not selfishly maximize their own benefits, but instead also consider how others are affected. However, most accounts of the psychological processes underlying fairness-related behavior implicitly assume that assessments of fairness are somewhat stable. In this paper, we present results of a novel task, the Re-Allocation Game, in which two players receive an allocation determined by the computer and, on half of the trials, one player has the subsequent possibility to change this allocation. Importantly, prior to the receipt of the allocation, players were shown either their respective financial situations, their respective performance on a previous simple task, or random information, while being scanned using functional neuroimaging. As expected, our results demonstrate when given the opportunity, participants allocated on average almost half the money to anonymous others. However, our findings further show that participants used the provided information in a dynamic manner, revealing the underlying principle based on which people re-allocate money - namely based on merit, need, or equality - switches dynamically. On the neural level, we identified activity in the right and left dorsolateral prefrontal cortices related to context-independent inequity and context-dependent fairness information respectively when viewing the computer-generated allocations. At the same time, activity in the temporoparietal and precuneus represented these different types of fairness-related information in adjacent and partially overlapping clusters. Finally, we observed that the activity pattern in the precuneus and putamen was most clearly related to participants' subsequent re-allocation decisions. Together, our findings suggest that participants judge an allocation as fair or unfair using a network associated with cognitive control and theory-of-mind, while dynamically switching between what might constitute a fair allocation in a particular context.

Entering into a self-regulated learning mode prevents detrimental effects of feedback removal on memory.

Incentives can decrease performance by undermining intrinsic motivation. How such an interplay of external reinforcers and internal self-regulation influences memory processes, however, is less known. Here, we investigated their interaction on memory performance while learning the meaning of new-words from their context. Specifically, participants inferred congruent meanings of new-words from semantic context (congruent trials) or lack of congruence (incongruent trials), while receiving external feedback in the first or second half of trials only. Removing feedback during learning of congruent word meanings lowered subsequent recognition rates a day later, whereas recognition remained high in the group, which received feedback only in the second half. In contrast, feedback did not substantially alter recognition rates for learning that new-words had no congruent meanings. Our findings suggest that external reinforcers can selectively impair memories if internal self-regulated processes are not already established, but whether they do so depends on what is being learned (specific word-meanings vs. unspecific incongruence). This highlights the relevance of self-regulated learning in education to support stable memory formation.

Seeing and extrapolating motion trajectories share common informative activation patterns in primary visual cortex.

The natural environment is dynamic and moving objects become constantly occluded, engaging the brain in a challenging completion process to estimate where and when the object might reappear. Although motion extrapolation is critical in daily life-imagine crossing the street while an approaching car is occluded by a larger standing vehicle-its neural underpinnings are still not well understood. While the engagement of low-level visual cortex during dynamic occlusion has been postulated, most of the previous group-level fMRI-studies failed to find evidence for an involvement of low-level visual areas during occlusion. In this fMRI-study, we therefore used individually defined retinotopic maps and multivariate pattern analysis to characterize the neural basis of visible and occluded changes in motion direction in humans. To this end, participants learned velocity-direction change pairings (slow motion-upwards; fast motion-downwards or vice versa) during a training phase without occlusion and judged the change in stimulus direction, based on its velocity, during a following test phase with occlusion. We find that occluded motion direction can be predicted from the activity patterns during visible motion within low-level visual areas, supporting the notion of a mental representation of motion trajectory in these regions during occlusion.

Expectations in the Ultimatum Game: Distinct Effects of Mean and Variance of Expected Offers.

Being treated fairly by others is an important need in everyday life. Experimentally, fairness can be studied using the Ultimatum Game, where the decision to reject a low, but non-zero offer is seen as a way to punish the other player for an unacceptable offer. The canonical explanation of such behavior is inequity aversion: people prefer equal outcomes over personal gains. However, there is abundant evidence that people's decision to reject a low offer can be changed by contextual factors and their emotional state, which cannot be explained by the inequity aversion model. Here, we expand a recent alternative explanation: rejections are driven by deviations from expectations: the larger the difference between the actual offer and the expected offer, the more likely one is to reject the offer. Specifically, we provided participants with explicit information on what kind of offers to expect using histograms depicting distribution of offers given in a previous experiment by the same proposers. Crucially, we showed four different distributions, manipulating both the mean and the variance of these expected sets of offers. We found that 50% of our participants clearly and systematically changed their behavior as a function of their expectations (11% followed the standard-economic model of pure self-interest and 39% where not distinguishable from the inequity-aversion model). Using a logistic mixed-model analysis, we found that the mean and variance differently affect the decision to reject an offer. Specifically, the mean expected offer affected the threshold of what offers are acceptable, while the expected variance of offers changed how strict participants were about this threshold. Together, these results suggest that social expectations have a more complex nature as current theories propose.

The memory for time and space differentially engages the proximal and distal parts of the hippocampal subfields CA1 and CA3.

A well-accepted model of episodic memory involves the processing of spatial and non-spatial information by segregated pathways and their association within the hippocampus. However, these pathways project to distinct proximodistal levels of the hippocampus. Moreover, spatial and non-spatial subnetworks segregated along this axis have been recently described using memory tasks with either a spatial or a non-spatial salient dimension. Here, we tested whether the concept of segregated subnetworks and the traditional model are reconcilable by studying whether activity within CA1 and CA3 remains segregated when both dimensions are salient, as is the case for episodes. Simultaneously, we investigated whether temporal or spatial information bound to objects recruits similar subnetworks as items or locations per se, respectively. To do so, we studied the correlations between brain activity and spatial and/or temporal discrimination ratios in proximal and distal CA1 and CA3 by detecting Arc RNA in mice. We report a robust proximodistal segregation in CA1 for temporal information processing and in both CA1 and CA3 for spatial information processing. Our results suggest that the traditional model of episodic memory and the concept of segregated networks are reconcilable, to a large extent and put forward distal CA1 as a possible "home" location for time cells.

Predicting the other in cooperative interactions.

Recent research has shown that a collection of neurons in dorsal anterior cingulate cortex of rhesus monkeys may specifically encode the choice selection of an interaction partner. This raises interesting and important questions as to the nature of Theory of Mind processes in social interactive decision-making, with potential societal implications.