AlphaFold predictions are valuable hypotheses and accelerate but do not replace experimental structure determination.

Artificial intelligence-based protein structure prediction methods such as AlphaFold have revolutionized structural biology. The accuracies of these predictions vary, however, and they do not take into account ligands, covalent modifications or other environmental factors. Here, we evaluate how well AlphaFold predictions can be expected to describe the structure of a protein by comparing predictions directly with experimental crystallographic maps. In many cases, AlphaFold predictions matched experimental maps remarkably closely. In other cases, even very high-confidence predictions differed from experimental maps on a global scale through distortion and domain orientation, and on a local scale in backbone and side-chain conformation. We suggest considering AlphaFold predictions as exceptionally useful hypotheses. We further suggest that it is important to consider the confidence in prediction when interpreting AlphaFold predictions and to carry out experimental structure determination to verify structural details, particularly those that involve interactions not included in the prediction.

Trends in U.S. public confidence in science and opportunities for progress.

In recent years, many questions have been raised about whether public confidence in science is changing. To clarify recent trends in the public's confidence and factors that are associated with these feelings, an effort initiated by the National Academies' Strategic Council for Research Excellence, Integrity, and Trust (the Strategic Council) analyzed findings from multiple survey research organizations. The Strategic Council's effort, which began in 2022, found that U.S. public confidence in science, the scientific community, and leaders of scientific communities is high relative to other civic, cultural, and governmental institutions for which researchers regularly collect such data. However, confidence in these institutions has fallen during the previous 5 years. Science's decline, while real, is similar to or less than that in the other groups. A recent study goes into greater detail by exploring public views of science. From these data, we observe that many of the surveyed U.S. public question the extent to which scientists share their values or overcome personal biases when presenting conclusions. At the same time, large majorities agree on certain types of actions that they want scientists to take. For example, 84% respond that it is "somewhat important" or "very important" for scientists to disclose their funders. Ninety-two percent (92%) offer the same responses to scientists "being open to changing their minds based on new evidence." Collectively, these data clarify how the U.S. public views science and scientists. They also suggest actions that can affect public confidence in science and scientists in the years to come.

Two views on the cognitive brain.

Cognition can be defined as computation over meaningful representations in the brain to produce adaptive behaviour. There are two views on the relationship between cognition and the brain that are largely implicit in the literature. The Sherringtonian view seeks to explain cognition as the result of operations on signals performed at nodes in a network and passed between them that are implemented by specific neurons and their connections in circuits in the brain. The contrasting Hopfieldian view explains cognition as the result of transformations between or movement within representational spaces that are implemented by neural populations. Thus, the Hopfieldian view relegates details regarding the identity of and connections between specific neurons to the status of secondary explainers. Only the Hopfieldian approach has the representational and computational resources needed to develop novel neurofunctional objects that can serve as primary explainers of cognition.

Spine dynamics in the brain, mental disorders and artificial neural networks.

In the brain, most synapses are formed on minute protrusions known as dendritic spines. Unlike their artificial intelligence counterparts, spines are not merely tuneable memory elements: they also embody algorithms that implement the brain's ability to learn from experience and cope with new challenges. Importantly, they exhibit structural dynamics that depend on activity, excitatory input and inhibitory input (synaptic plasticity or 'extrinsic' dynamics) and dynamics independent of activity ('intrinsic' dynamics), both of which are subject to neuromodulatory influences and reinforcers such as dopamine. Here we succinctly review extrinsic and intrinsic dynamics, compare these with parallels in machine learning where they exist, describe the importance of intrinsic dynamics for memory management and adaptation, and speculate on how disruption of extrinsic and intrinsic dynamics may give rise to mental disorders. Throughout, we also highlight algorithmic features of spine dynamics that may be relevant to future artificial intelligence developments.

Rewarding cognitive effort increases the intrinsic value of mental labor.

Current models of mental effort in psychology, behavioral economics, and cognitive neuroscience typically suggest that exerting cognitive effort is aversive, and people avoid it whenever possible. The aim of this research was to challenge this view and show that people can learn to value and seek effort intrinsically. Our experiments tested the hypothesis that effort-contingent reward in a working-memory task will induce a preference for more demanding math tasks in a transfer phase, even though participants were aware that they would no longer receive any reward for task performance. In laboratory Experiment 1 (n = 121), we made reward directly contingent on mobilized cognitive effort as assessed via cardiovascular measures (ß-adrenergic sympathetic activity) during the training task. Experiments 2a to 2e (n = 1,457) were conducted online to examine whether the effects of effort-contingent reward on subsequent demand seeking replicate and generalize to community samples. Taken together, the studies yielded reliable evidence that effort-contingent reward increased participants' demand seeking and preference for the exertion of cognitive effort on the transfer task. Our findings provide evidence that people can learn to assign positive value to mental effort. The results challenge currently dominant theories of mental effort and provide evidence and an explanation for the positive effects of environments appreciating effort and individual growth on people's evaluation of effort and their willingness to mobilize effort and approach challenging tasks.

Phasic, Event-Related Transcutaneous Auricular Vagus Nerve Stimulation Modifies Behavioral, Pupillary, and Low-Frequency Oscillatory Power Responses.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed to activate the locus ceruleus-noradrenaline (LC-NA) system. However, previous studies failed to find consistent modulatory effects of taVNS on LC-NA biomarkers. Previous studies suggest that phasic taVNS may be capable of modulating LC-NA biomarkers such as pupil dilation and alpha oscillations. However, it is unclear whether these effects extend beyond pure sensory vagal nerve responses. Critically, the potential of the pupillary light reflex as an additional taVNS biomarker has not been explored so far. Here, we applied phasic active and sham taVNS in 29 subjects (16 female, 13 male) while they performed an emotional Stroop task (EST) and a passive pupil light reflex task (PLRT). We recorded pupil size and brain activity dynamics using a combined Magnetoencephalography (MEG) and pupillometry design. Our results show that phasic taVNS significantly increased pupil dilation and performance during the EST. During the PLRT, active taVNS reduced and delayed pupil constriction. In the MEG, taVNS increased frontal-midline theta and alpha power during the EST, whereas occipital alpha power was reduced during both the EST and PLRT. Our findings provide evidence that phasic taVNS systematically modulates behavioral, pupillary, and electrophysiological parameters of LC-NA activity during cognitive processing. Moreover, we demonstrate for the first time that the pupillary light reflex can be used as a simple and effective proxy of taVNS efficacy. These findings have important implications for the development of noninvasive neuromodulation interventions for various cognitive and clinical applications.SIGNIFICANCE STATEMENT taVNS has gained increasing attention as a noninvasive neuromodulation technique and is widely used in clinical and nonclinical research. Nevertheless, the exact mechanism of action of taVNS is not yet fully understood. By assessing physiology and behavior in a response conflict task in healthy humans, we demonstrate the first successful application of a phasic, noninvasive vagus nerve stimulation to improve cognitive control and to systematically modulate pupillary and electrophysiological markers of the noradrenergic system. Understanding the mechanisms of action of taVNS could optimize future clinical applications and lead to better treatments for mental disorders associated with noradrenergic dysfunction. In addition, we present a new taVNS-sensitive pupillary measure representing an easy-to-use biomarker for future taVNS studies.

Resting-state effective connectivity is systematically linked to reappraisal success of high- and low-intensity negative emotions.

Emotion regulation is a process by which individuals modulate their emotional responses to cope with different environmental demands, for example, by reappraising the emotional situation. Here, we tested whether effective connectivity of a reappraisal-related neural network at rest is predictive of successfully regulating high- and low-intensity negative emotions in an emotion-regulation task. Task-based and resting-state functional magnetic resonance imaging (rs-fMRI) data of 28 participants were collected using ultra-high magnetic field strength at 7 Tesla during three scanning sessions. We used spectral dynamic causal modeling (spDCM) on the rs-fMRI data within brain regions modulated by emotion intensity. We found common connectivity patterns for both high- and low-intensity stimuli. Distinctive effective connectivity patterns in relation to low-intensity stimuli were found from frontal regions connecting to temporal regions. Reappraisal success for high-intensity stimuli was predicted by additional connections within the vlPFC and from temporal to frontal regions. Connectivity patterns at rest predicting reappraisal success were generally more pronounced for low-intensity stimuli, suggesting a greater role of stereotyped patterns, potentially reflecting preparedness, when reappraisal was relatively easy to implement. The opposite was true for high-intensity stimuli, which might require a more flexible recruitment of resources beyond what is reflected in resting state connectivity patterns. Resting-state effective connectivity emerged as a robust predictor for successful reappraisal, revealing both shared and distinct network dynamics for high- and low-intensity stimuli. These patterns signify specific preparatory states associated with heightened vigilance, attention, self-awareness, and goal-directed cognitive processing, particularly during reappraisal for mitigating the emotional impact of external stimuli. Our findings hold potential implications for understanding psychopathological alterations in brain connectivity related to affective disorders.

Rapid runtime learning by curating small datasets of high-quality items obtained from memory.

We propose the "runtime learning" hypothesis which states that people quickly learn to perform unfamiliar tasks as the tasks arise by using task-relevant instances of concepts stored in memory during mental training. To make learning rapid, the hypothesis claims that only a few class instances are used, but these instances are especially valuable for training. The paper motivates the hypothesis by describing related ideas from the cognitive science and machine learning literatures. Using computer simulation, we show that deep neural networks (DNNs) can learn effectively from small, curated training sets, and that valuable training items tend to lie toward the centers of data item clusters in an abstract feature space. In a series of three behavioral experiments, we show that people can also learn effectively from small, curated training sets. Critically, we find that participant reaction times and fitted drift rates are best accounted for by the confidences of DNNs trained on small datasets of highly valuable items. We conclude that the runtime learning hypothesis is a novel conjecture about the relationship between learning and memory with the potential for explaining a wide variety of cognitive phenomena.

Electrophysiological correlates of face and object perception: A comparative analysis of 2D laboratory and virtual reality conditions.

Human face perception is a specialized visual process with inherent social significance. The neural mechanisms reflecting this intricate cognitive process have evolved in spatially complex and emotionally rich environments. Previous research using VR to transfer an established face perception paradigm to realistic conditions has shown that the functional properties of face-sensitive neural correlates typically observed in the laboratory are attenuated outside the original modality. The present study builds on these results by comparing the perception of persons and objects under conventional laboratory (PC) and realistic conditions in VR. Adhering to established paradigms, the PC- and VR modalities both featured images of persons and cars alongside standard control images. To investigate the individual stages of realistic face processing, response times, the typical face-sensitive N170 component, and relevant subsequent components (L1, L2; pre-, post-response) were analyzed within and between modalities. The between-modality comparison of response times and component latencies revealed generally faster processing under realistic conditions. However, the obtained N170 latency and amplitude differences showed reduced discriminative capacity under realistic conditions during this early stage. These findings suggest that the effects commonly observed in the lab are specific to monitor-based presentations. Analyses of later and response-locked components showed specific neural mechanisms for identification and evaluation are employed when perceiving the stimuli under realistic conditions, reflected in discernible amplitude differences in response to faces and objects beyond the basic perceptual features. Conversely, the results do not provide evidence for comparable stimulus-specific perceptual processing pathways when viewing pictures of the stimuli under conventional laboratory conditions.

The path of dishonesty: identification of mental processes with electrical neuroimaging.

Much research finds that lying takes longer than truth-telling. Yet, the source of this response time difference remains elusive. Here, we assessed the spatiotemporal evolution of electrical brain activity during honesty and dishonesty in 150 participants using a sophisticated electrical neuroimaging approach-the microstate approach. This uniquely positioned us to identify and contrast the entire chain of mental processes involved during honesty and dishonesty. Specifically, we find that the response time difference is the result of an additional late-occurring mental process, unique to dishonest decisions, interrupting the antecedent mental processing. We suggest that this process inhibits the activation of the truth, thus permitting the execution of the lie. These results advance our understanding of dishonesty and clarify existing theories about the role of increased cognitive load. More broadly, we demonstrate the vast potential of our approach to illuminate the temporal organization of mental processes involved in decision-making.

Anxiety disrupts performance monitoring: integrating behavioral, event-related potential, EEG microstate, and sLORETA evidence.

Anxiety impacts performance monitoring, though theory and past research are split on how and for whom. However, past research has often examined either trait anxiety in isolation or task-dependent state anxiety and has indexed event-related potential components, such as the error-related negativity or post-error positivity (Pe), calculated at a single node during a limited window of time. We introduced 2 key novelties to this electroencephalography research to examine the link between anxiety and performance monitoring: (i) we manipulated antecedent, task-independent, state anxiety to better establish the causal effect; (ii) we conducted moderation analyses to determine how state and trait anxiety interact to impact performance monitoring processes. Additionally, we extended upon previous work by using a microstate analysis approach to isolate and sequence the neural networks and rapid mental processes in response to error commission. Results showed that state anxiety disrupts response accuracy in the Stroop task and error-related neural processes, primarily during a Pe-related microstate. Source localization shows that this disruption involves reduced activation in the dorsal anterior cingulate cortex and compensatory activation in the right lateral prefrontal cortex, particularly among people high in trait anxiety. We conclude that antecedent anxiety is largely disruptive to performance monitoring.

Quantifying the contribution of subject and group factors in brain activation.

Research in neuroscience often assumes universal neural mechanisms, but increasing evidence points toward sizeable individual differences in brain activations. What remains unclear is the extent of the idiosyncrasy and whether different types of analyses are associated with different levels of idiosyncrasy. Here we develop a new method for addressing these questions. The method consists of computing the within-subject reliability and subject-to-group similarity of brain activations and submitting these values to a computational model that quantifies the relative strength of group- and subject-level factors. We apply this method to a perceptual decision-making task (n = 50) and find that activations related to task, reaction time, and confidence are influenced equally strongly by group- and subject-level factors. Both group- and subject-level factors are dwarfed by a noise factor, though higher levels of smoothing increases their contributions relative to noise. Overall, our method allows for the quantification of group- and subject-level factors of brain activations and thus provides a more detailed understanding of the idiosyncrasy levels in brain activations.

Mental Time Travel as Self-Affirmation.

ACADEMIC ABSTRACT: This article integrates and advances the scope of research on the role of mental time travel in bolstering the self. We propose that imagining the self in the future (prospection) or in the past (retrospection) highlights central and positive self-aspects. Thus, bringing to mind one's future or past broadens the perceived bases of self-integrity and offers a route to self-affirmation. In reviewing corresponding research programs on self-prospection and nostalgia, we illustrate that mental time travel serves to affirm the self in terms of self-esteem, coherence, and control. Mental time travel could be implemented as a source of self-affirmation for facilitating coping and behavior change in several domains such as relationships, health, education, and organizational contexts. PUBLIC ABSTRACT: People can mentally travel to their future or to their past. When people imagine what they will be like in the future, or what they were like in the past, they tend to think about themselves in terms of the important and positive attributes that they possess. Thinking about themselves in such an affirming way expands and consolidates their self-views. This broader image of themselves can increase self-esteem (the extent to which one likes who they are), coherence (the extent to which one perceives life as meaningful), and control (the extent to which one feels capable of initiating and pursuing goals or effecting desirable outcomes). Mental time travel, then, has favorable or affirming consequences for one's self-views. These consequences can be harnessed to modify one's behavior in such life domains as relationships, health, education, and work.

Failing professional practice placements in allied health: What do we understand about the student experience? A scoping review.

Professional practice placements are an essential component of allied health and nursing programs. Whilst most students pass these placements, a small percentage of students will fail or be at risk of failing. Supporting students undergoing a failing experience is a time critical, time consuming, emotional and resource-heavy task which is often undertaken by key university staff and impacts all stakeholders. Whilst several studies have provided insight into this experience from the educator and/or university perspective, this scoping review aimed to identify the students' experience of failing or nearly failing a professional practice experience. Following Arskey and O'Malley's framework for scoping reviews, 24 papers were included in this review. This review generated six themes including the reasons for failure, how failure looks and feels, how supports, service and strategies influence the student experience of failure, the importance of communication, relationships and organisational culture, the impact infrastructure and policies have, and the consequences of failure. The outcomes of this scoping review highlighted three key characteristics of the research to date: (a) the student voice is still largely missing; (b) the student perspective is distinctly different to that of other stakeholders; and (c) the interventions used appear not to be student-informed or student-led. Better understanding this experience from the student's perspective could create a more sustainable practice education environment by designing and implementing more effective supports, services or strategies that reduce the overall impact a failing experience has on students and key stakeholders.

The role of environmental contextual cues in sequence learning: evidence from a virtual maze context.

Studies on sequence learning usually focus on single, isolated stimuli that are presented sequentially. For example, in the serial reaction time (RT) task, stimuli are either presented in a predictable sequence or in a random sequence, and better performance with the predictable sequence is taken as evidence for sequence-specific learning. Yet, little is known about the role of environmental context cues in sequence learning. If the target stimuli are embedded in a meaningful context, would this facilitate learning by providing helpful contextual associations or would it hinder learning by adding distracting stimuli? This question was examined in two studies. A pilot study compared sequence learning in a virtual maze with a horizontal vs. vertical maze context, in which arrow stimuli guide spatial lever movement responses that resulted in a corresponding virtual transport on the screen. The results showed only overall somewhat better performance with the vertical maze compared to the horizontal maze, but general practice effects and sequence-specific learning effects were the same for both contexts. The main study compared sequence learning with a maze context to sequence learning of arrows without a maze context. The results showed significantly better learning with maze context than without context. These data suggest that the maze context facilitated sequence learning by inducing a meaningful spatial representation ("mental map") similar to that formed in wayfinding.

Differences in motor imagery abilities in active and sedentary individuals: new insights from backward-walking imagination.

Evidence has shown that imagining a complex action, like backward-walking, helps improve the execution of the gesture. Despite this, studies in sport psychology have provided heterogeneous results on the use of motor imagery (MI) to improve performance. We aimed to fill this gap by analyzing how sport experience influences backward-walking MI processes in a sample of young women (n = 41, mean age = 21 ± 2.2) divided into Active and Sedentary. All participants were allocated to two randomized mental chronometric tasks, in which they had first to imagine and then execute forward-walking (FW) and backward-walking (BW). The Isochrony Efficiency measured the difference between imagination and execution times in both conditions (FW and BW). Moreover, we analyzed the ability to vividly imagine FW and BW within various perspectives in both groups through the Vividness of Movement Imagery Questionnaire (VMIQ-2). Findings showed that active individuals performed better in the BW imagery task when compared to sedentary ones (F1,39 = 4.98; p = 0.03*), while there were no differences between groups in the FW imagery task (F1,39 = .10; p = 0.75). Further, VMIQ-2 had evidenced that the ability to imagine backward is influenced by perspective used. Specifically, the use of internal visual imagery (IVI) led to worse Isochrony Efficiency (t32,25 = 2.16; p = 0.04*), while the use of kinesthetic imagery (KIN) led to better Isochrony Efficiency (t32,25 = - 2.34; p = 0.03*). These results suggest a close relation between motor experience and complex motor imagery processes and open new insights for studying these mental processes.

Dynamite plots in surgical research over 10 years: a meta-study using machine-learning analysis.

PURPOSE: Bar charts of numerical data, often known as dynamite plots, are unnecessary and misleading. Their tendency to alter the perception of mean's position through the within-the-bar bias and their lack of information on the distribution of the data are two of numerous reasons. The machine learning tool, Barzooka, can be used to rapidly screen for different graph types in journal articles.We aim to determine the proportion of original research articles using dynamite plots to visualize data, and whether there has been a change in their use over time. METHODS: Original research articles in nine surgical fields of research were sampled based on MeSH terms and then harvested using the Python-based biblio-glutton-harvester tool. After harvesting, they were analysed using Barzooka. Over 40 000 original research articles were included in the final analysis. The results were adjusted based on previous validation data with 95% confidence bounds. Kendall τ coefficient with the Mann-Kendall test for significance was used to determine the trend of dynamite plot use over time. RESULTS: Eight surgical fields of research showed a statistically significant decrease in use of dynamite plots over 10 years. Oral and maxillofacial surgery showed no significant trend in either direction. In 2022, use of dynamite plots, dependent on field and 95% confidence bounds, ranges from ~30% to 70%. CONCLUSION: Our results show that the use of dynamite plots in surgical research has decreased over time; however, use remains high. More must be done to understand this phenomenon and educate surgical researchers on data visualization practices.

Can we get human nature right?

Few questions in science are as controversial as human nature. At stake is whether our basic concepts and emotions are all learned from experience, or whether some are innate. Here, I demonstrate that reasoning about innateness is biased by the basic workings of the human mind. Psychological science suggests that newborns possess core concepts of "object" and "number." Laypeople, however, believe that newborns are devoid of such notions but that they can recognize emotions. Moreover, people presume that concepts are learned, whereas emotions (along with sensations and actions) are innate. I trace these beliefs to two tacit psychological principles: intuitive dualism and essentialism. Essentialism guides tacit reasoning about biological inheritance and suggests that innate traits reside in the body; per intuitive dualism, however, the mind seems ethereal, distinct from the body. It thus follows that, in our intuitive psychology, concepts (which people falsely consider as disembodied) must be learned, whereas emotions, sensations, and emotions (which are considered embodied) are likely innate; these predictions are in line with the experimental results. These conclusions do not speak to the question of whether concepts and emotions are innate, but they suggest caution in its scientific evaluation.

Metacognitive evaluation of postdecisional perceptual representations.

Perceptual confidence is thought to arise from metacognitive processes that evaluate the underlying perceptual decision evidence. We investigated whether metacognitive access to perceptual evidence is constrained by the hierarchical organization of visual cortex, where high-level representations tend to be more readily available for explicit scrutiny. We found that the ability of human observers to evaluate their confidence did depend on whether they performed a high-level or low-level task on the same stimuli, but was also affected by manipulations that occurred long after the perceptual decision. Confidence in low-level perceptual decisions degraded with more time between the decision and the response cue, especially when backward masking was present. Confidence in high-level tasks was immune to backward masking and benefitted from additional time. These results can be explained by a model assuming confidence heavily relies on postdecisional internal representations of visual stimuli that degrade over time, where high-level representations are more persistent.

Promoting a more diverse and inclusive research workforce through the research scholars program.

BACKGROUND: Novel and comprehensive approaches are needed to address shortcomings in the diversity and inclusiveness of the scientific workforce. In response to this need and informed by multiple programs and data sources, we created the Research Scholars Program (RSP). The RSP is a yearlong program for early-career faculty with an overall objective to overcome barriers to the academic success, retention, progression, and promotion of groups underrepresented in biomedical and behavioral research. The goal of the RSP is to increase research confidence and productivity, build a supportive research community, and reduce isolation by providing personal and group research enrichment to junior faculty through professional development, mentorship, and networking. METHODS: We adapted evidence-based approaches for our institutional context and vetted the RSP across our campus. The resulting RSP consists of three main elements: (1) five levels of Mosaic Mentorship; (2) group and tailored professional development programming; and (3) scientific and social networking. To determine the potential of the RSP to improve research confidence critical to success, we used a modified shortened version of the Clinical Research Appraisal Inventory (CRAI-12) to assess participants' confidence in performing a variety of research tasks before and after program participation. We collected information about retention, promotion, and grants submitted and awarded. Additionally, we conducted semi-structured exit interviews with each scholar after program participation to identify programmatic strengths and areas for improvement. Data for Cohorts 1 and 2 (N = 12) were analyzed. RESULTS: Our assessment finds, with one exception, increasing confidence in participants' research skills across all items, ranging from 0.4 (4.7%) to 2.6 (40.6%). In their exit interviews, the Research Scholars (RS) described their improved productivity and increased sense of belonging and support from others. Research Scholars noted numerous components of the RSP as strengths, including the Mosaic Mentorship model, professional development programming, and opportunities for both informal and formal interactions. Respondents identified time pressure, a lack of feedback, and unclear expectations of the various mentorship roles as areas in which the program can improve. CONCLUSION: Preliminary findings indicate that the RSP is successful in building the research confidence of underrepresented and disadvantaged early-career faculty. While this report focuses on the development and protocol of the RSP, additional cohorts and data will provide the evidence base to support dissemination as a national model of research professional development. Such programming is critical to ensure sustainable support structures, institutional networks, infrastructure, and resources that will improve discovery and equity through inclusive excellence.