Challenge accepted: uncovering the role of rare genetic variants in Alzheimer’s disease

The search for rare variants in Alzheimer’s disease (AD) is usually deemed a high-risk - high-reward situation. The challenges associated with this endeavor are real. Still, the application of genome-wide technologies to large numbers of cases and controls or to small, well-characterized families has started to be fruitful.Rare variants associated with AD have been shown to increase risk or cause disease, but also to protect against the development of AD. All of these can potentially be targeted for the development of new drugs.Multiple independent studies have now shown associations of rare variants in NOTCH3, TREM2, SORL1, ABCA7, BIN1, CLU, NCK2, AKAP9, UNC5C, PLCG2, and ABI3 with AD and suggested that they may influence disease via multiple mechanisms. These genes have reported functions in the immune system, lipid metabolism, synaptic plasticity, and apoptosis. However, the main pathway emerging from the collective of genes harboring rare variants associated with AD is the Aβ pathway. Associations of rare variants in dozens of other genes have also been proposed, but have not yet been replicated in independent studies. Replication of this type of findings is one of the challenges associated with studying rare variants in complex diseases, such as AD. In this review, we discuss some of these primary challenges as well as possible solutions.Integrative approaches, the availability of large datasets and databases, and the development of new analytical methodologies will continue to produce new genes harboring rare variability impacting AD. In the future, more extensive and more diverse genetic studies, as well as studies of deeply characterized families, will enhance our understanding of disease pathogenesis and put us on the correct path for the development of successful drugs.

Comprehensive meta-analysis of associations between temperament and character traits in Cloninger’s psychobiological theory and mental disorders

Objective To explore the relationship between temperament and character traits in Cloninger’s psychobiological theory and mental disorders. Methods: A systematic literature search was conducted of five international databases for all articles published in English between January 1990 and April 2019 (PROSPERO-CRD42019133214). Owing to heterogeneity, pooled estimates of correlations for personality disorders and standardized mean differences for case–control studies related to other mental disorders were calculated using the random-effects method. Results The pooled effect sizes obtained from 149 studies showed that high harm avoidance (related to 22/24 diagnostic categories), low self-directedness (21/23), low cooperativeness (17/23), high self-transcendence (14/23), low reward dependence (11/24), high novelty-seeking (10/24), low novelty-seeking (7/24), high persistence (2/23), low persistence (2/23) and high reward dependence (2/24) were related to psychopathology. Conclusions All traits provided unique psychobiological tools for differential diagnosis of mental disorders. However, high harm avoidance and low self-directedness played a canonical role in psychopathology. Despite the study limitations, additional studies are warranted to evaluate the differential diagnoses suggested by the present model.

The Value of Seismic Data in Conventional and Unconventional Fields

The paper illustrates the value of seismic data in different environments after assessing the benefits and costs of processes such as seismic acquisition, seismic processing and seismic interpretation. Global examples from conventional and unconventional fields are discussed to show how seismic data plays a significant role in determining low-risk and high-reward wells and also eliminating the high-risk and low-reward wells. This paper shows an example of a conventional field in the state of Kansas, USA, where the net present value (NPV) increased by more than 17 times when 3D seismic data was acquired, while in an unconventional field the commercial success rate rose from 30% to 70% due to 3D seismic acquisition. However, two offshore fields in the Republic of Trinidad and Tobago are discussed to show that the NPV as impacted by advanced seismic processing was more than 111 ($M). Another example comes from Viking Field, a conventional field in Canada, where the NPV was increased from 3800 ($M) to 5000 ($M) when the seismic data was re-processed. Furthermore, the value of investing in seismic data was investigated and quantified by comparing two synthetically modeled scenarios in Saudi Arabia. Overall, the four examples from North America, Central America and Saudi Arabia illustrate that investment in seismic data has a positive impact on both conventional and unconventional fields. That provides strong evidence to encourage more investments in geophysical technologies.

Flower Color as Predictor for Nectar Reward Quantity in an Alpine Flower Community

Entomophilous plants have evolved colorful floral displays to attract flower visitors to achieve pollination. Although many insects possess innate preferences for certain colors, the underlying proximate and ultimate causes for this behavior are still not well understood. It has been hypothesized that the floral rewards, e.g., sugar content, of plants belonging to a particular color category correlate with the preference of the flower visitors. However, this hypothesis has been tested only for a subset of plant communities worldwide. Bumble bees are the most important pollinators in alpine environments and show a strong innate preference for (bee) “UV-blue” and “blue” colors. We surveyed plants visited by bumble bees in the subalpine and alpine zones (>1,400 m a.s.l.) of the Austrian Alps and measured nectar reward and spectral reflectance of the flowers. We found that the majority of the 105 plant samples visited by bumble bees fall into the color categories “blue” and “blue-green” of a bee-specific color space. Our study shows that color category is only a weak indicator for nectar reward quantity; and due to the high reward variance within and between categories, we do not consider floral color as a reliable signal for bumble bees in the surveyed habitat. Nevertheless, since mean floral reward quantity differs between categories, naïve bumble bees may benefit from visiting flowers that fall into the innately preferred color category during their first foraging flights.

In for a penny, in for a pound: examining motivated memory through the lens of retrieved context models

When people encounter items that they believe will help them gain reward, they later remember them better than others. A recent model of emotional memory, the emotional context maintenance and retrieval model (eCMR), predicts that these effects would be stronger when stimuli that predict high and low reward can compete with each other during both encoding and retrieval. We tested this prediction in two experiments. Participants were promised £1 for remembering some pictures, but only a few pence for remembering others. Their recall of the content of the pictures they saw was tested after 1 min and, in experiment 2, also after 24 h. Memory at the immediate test showed effects of list composition. Recall of stimuli that predicted high reward was greater than of stimuli that predicted lower reward, but only when high- and low-reward items were studied and recalled together, not when they were studied and recalled separately. More high-reward items in mixed lists were forgotten over a 24-h retention interval compared with items studied in other conditions, but reward did not modulate the forgetting rate, a null effect that should be replicated in a larger sample. These results confirm eCMR's predictions, although further research is required to compare that model against alternatives.

Reward Rapidly Enhances Visual Perception

Rewards exert a deep influence on our cognition and behavior. Here, we used a paradigm in which reward information was provided at either encoding or retrieval of a brief, masked stimulus to show that reward can also rapidly modulate perceptual encoding of visual information. Experiment 1 ( n = 30 adults) showed that participants’ response accuracy was enhanced when a to-be-encoded grating signaled high reward relative to low reward, but only when the grating was presented very briefly and participants reported that they were not consciously aware of it. Experiment 2 ( n = 29 adults) showed that there was no difference in participants’ response accuracy when reward information was instead provided at the stage of retrieval, ruling out an explanation of the reward-modulation effect in terms of differences in motivated retrieval. Taken together, our findings provide behavioral evidence consistent with a rapid reward modulation of visual perception, which may not require consciousness.

Cognitive performance in pain is predicted by effort, not goal desire

Background Pain’s disruptive effects on cognition are well documented. The seminal goal-pursuit account of pain suggests that cognitive disruption is less likely if participants are motivated to attended to a focal goal and not a pain goal. Objectives Existing theory is unclear about the conceptualisation and operationalisation of ‘focal goal’. This study aims to clarify how goals should be conceptualised and further seeks to test the theory of the goal-pursuit account. Methods In a pre-registered laboratory experiment, 56 participants completed an arithmetic task in high-reward/low-reward and pain/control conditions. Pain was induced via cold-water immersion. Results High levels of reported effort exertion predicted cognitive-task performance, whereas desire for rewards did not. Post-hoc analyses further suggest that additional effort in the pain condition compensated for pain’s disruptive effects, but when this extra effort was not exerted, performance deficits were observed in pain, compared to control, conditions. Conclusion Results suggest that ‘motivation’, or commitment to a focal goal, is best understood as effort exertion and not as a positive desire to achieve a goal. These results solidify existing theory and aid researchers in operationalising these constructs.

What I Have Learned . . . in My Journey as a Scholar

This chapter allows for a reflection on the many lessons learned as an organizational behavior scholar. On the topic of doing rigorous, reliable, and relevant research, the focus is on the importance of organizational life eliciting interesting and relevant research ideas, the upside and downside of “high risk/high reward” research, how to “go big” theoretically, how to “go big” in methods, and the importance of realism and specific lessons learned in conducting both lab and field studies. Other topics such as learnings about working most effectively with coauthors, including addressing authorship issues candidly and upfront are addressed as well. Importantly addressing how having a full and balanced life is not only helpful in its own right but is helpful to one’s career is discussed. Last, just as importantly are the things to learn not to do, such as not holding on too long to projects that are not salvageable, not being a disagreeable reviewer, not looking to saying no to new opportunities. Indeed learning to try to actually say yes (judiciously). Ultimately the chapter exhorts scholar to be kinder to ourselves, and ends with the hope that these learnings from this author’s journey will spark ideas, offer insights, and help in the journeys of other scholars.

Reward Expectation Differentially Modulates Global and Local Spatial Working Memory Accuracy

Although it has been suggested that reward expectation affects the performance of spatial working memory tasks, controversial results have been found in previous experiments. Hence, it is still unclear to what extent reward expectation has an effect on working memory. To clarify this question, a memory-guided saccade task was applied, in which participants were instructed to retain and reconstruct a temporospatial sequence of four locations by moving their eyes in each trial. The global- and local-level spatial working memory accuracies were calculated to determine the reward effect on the global and local level of processing in spatial working memory tasks. Although high reward expectation enhanced the encoding of spatial information, the percentage of trials in which the cued location was correctly fixated decreased with increment of reward expectation. The reconstruction of the global temporospatial sequence was enhanced by reward expectation, whereas the local reconstruction performance was not affected by reward. Furthermore, the improvements in local representations of uncued locations and local sequences were at the cost of the representation of cued locations. The results suggest that the reward effect on spatial working memory is modulated by the level of processing, which supports the flexible resource theory during maintenance.

Temptation shapes dishonesty and can alter working memory

This study shows that participants tend to remember an ambiguous, directional cue as biased towards stimuli associated with a high reward that can be attained dishonestly. Participants saw eight digits presented in a circular arrangement. On some trials, they were asked to report the digit (“Target Digit”) indicated by a jittery cue that was slightly biased in the direction of another digit (“Second Cued Digit”), which was either higher or lower than the Target Digit. Participants were paid based on the reported digit (higher digits meant higher pay) and not based on the accuracy of their report. In this setting, they could make self-serving mistakes by dishonestly reporting the Second Cued Digit when it was higher than the Target Digit. Replicating prior work, participants frequently made such self-serving mistakes. On other trials, after the digits disappeared, participants were asked to reproduce the direction of the jittery cue, without receiving any pay. Results showed that that participants’ reports of the cue were more biased toward high-rewarding digits than low-rewarding digits. This research provides preliminary evidence of a link between attention, dishonesty, and memory, offering an important constraint for theories in behavioral ethics.