Neuronal Computation Underlying Inferential Reasoning in Humans and Mice.

Every day we make decisions critical for adaptation and survival. We repeat actions with known consequences. But we also draw on loosely related events to infer and imagine the outcome of entirely novel choices. These inferential decisions are thought to engage a number of brain regions; however, the underlying neuronal computation remains unknown. Here, we use a multi-day cross-species approach in humans and mice to report the functional anatomy and neuronal computation underlying inferential decisions. We show that during successful inference, the mammalian brain uses a hippocampal prospective code to forecast temporally structured learned associations. Moreover, during resting behavior, coactivation of hippocampal cells in sharp-wave/ripples represent inferred relationships that include reward, thereby "joining-the-dots" between events that have not been observed together but lead to profitable outcomes. Computing mnemonic links in this manner may provide an important mechanism to build a cognitive map that stretches beyond direct experience, thus supporting flexible behavior.

Think You Know How Smell Works? Sniff Again.

The sense of smell is mediated by GPCRs in the odorant receptor (OR) family. Greer et al. report a new family of odor detectors, MS4As, that have similar cellular localization and chemodetection ability as ORs but are not GPCRs and follow a strikingly different logic of odor coding at the periphery.

Language is primarily a tool for communication rather than thought.

Language is a defining characteristic of our species, but the function, or functions, that it serves has been debated for centuries. Here we bring recent evidence from neuroscience and allied disciplines to argue that in modern humans, language is a tool for communication, contrary to a prominent view that we use language for thinking. We begin by introducing the brain network that supports linguistic ability in humans. We then review evidence for a double dissociation between language and thought, and discuss several properties of language that suggest that it is optimized for communication. We conclude that although the emergence of language has unquestionably transformed human culture, language does not appear to be a prerequisite for complex thought, including symbolic thought. Instead, language is a powerful tool for the transmission of cultural knowledge; it plausibly co-evolved with our thinking and reasoning capacities, and only reflects, rather than gives rise to, the signature sophistication of human cognition.

Preserved neural dynamics across animals performing similar behaviour.

Animals of the same species exhibit similar behaviours that are advantageously adapted to their body and environment. These behaviours are shaped at the species level by selection pressures over evolutionary timescales. Yet, it remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of each individual. The overall organization of neural circuits is preserved across individuals1 because of their common evolutionarily specified developmental programme2-4. Such organization at the circuit level may constrain neural activity5-8, leading to low-dimensional latent dynamics across the neural population9-11. Accordingly, here we suggested that the shared circuit-level constraints within a species would lead to suitably preserved latent dynamics across individuals. We analysed recordings of neural populations from monkey and mouse motor cortex to demonstrate that neural dynamics in individuals from the same species are surprisingly preserved when they perform similar behaviour. Neural population dynamics were also preserved when animals consciously planned future movements without overt behaviour12 and enabled the decoding of planned and ongoing movement across different individuals. Furthermore, we found that preserved neural dynamics extend beyond cortical regions to the dorsal striatum, an evolutionarily older structure13,14. Finally, we used neural network models to demonstrate that behavioural similarity is necessary but not sufficient for this preservation. We posit that these emergent dynamics result from evolutionary constraints on brain development and thus reflect fundamental properties of the neural basis of behaviour.

Single-neuronal predictions of others' beliefs in humans.

Human social behaviour crucially depends on our ability to reason about others. This capacity for theory of mind has a vital role in social cognition because it enables us not only to form a detailed understanding of the hidden thoughts and beliefs of other individuals but also to understand that they may differ from our own1-3. Although a number of areas in the human brain have been linked to social reasoning4,5 and its disruption across a variety of psychosocial disorders6-8, the basic cellular mechanisms that underlie human theory of mind remain undefined. Here, using recordings from single cells in the human dorsomedial prefrontal cortex, we identify neurons that reliably encode information about others' beliefs across richly varying scenarios and that distinguish self- from other-belief-related representations. By further following their encoding dynamics, we show how these cells represent the contents of the others' beliefs and accurately predict whether they are true or false. We also show how they track inferred beliefs from another's specific perspective and how their activities relate to behavioural performance. Together, these findings reveal a detailed cellular process in the human dorsomedial prefrontal cortex for representing another's beliefs and identify candidate neurons that could support theory of mind.

Drop that pipette: science by design.

An unexpected collaboration between a synthetic biology lab at UCSF and a Palo Alto-based design firm is stirring up the way that research is conceived and conducted, by integrating innovation and "design thinking" into the scientific method.

Effect of cognitive load on time spent offline during wakefulness.

Humans continuously alternate between online attention to the current environment and offline attention to internally generated thought and imagery. This may be a fundamental feature of the waking brain, but remains poorly understood. Here, we took a data-driven approach to defining online and offline states of wakefulness, using machine learning methods applied to measures of sensory responsiveness, subjective report, electroencephalogram (EEG), and pupil diameter. We tested the effect of cognitive load on the structure and prevalence of online and offline states, hypothesizing that time spent offline would increase as cognitive load of an ongoing task decreased. We also expected that alternation between online and offline states would persist even in the absence of a cognitive task. As in prior studies, we arrived at a three-state model comprised of one online state and two offline states. As predicted, when cognitive load was high, more time was spent online. Also as predicted, the same three states were present even when participants were not performing a task. These observations confirm our method is successful at isolating seconds-long periods of offline time. Varying cognitive load may be a useful way to manipulate time spent in at least one of these offline states in future experimental studies.

Mind blanking is a distinct mental state linked to a recurrent brain profile of globally positive connectivity during ongoing mentation.

Mind blanking (MB) is a waking state during which we do not report any mental content. The phenomenology of MB challenges the view of a constantly thinking mind. Here, we comprehensively characterize the MB's neurobehavioral profile with the aim to delineate its role during ongoing mentation. Using functional MRI experience sampling, we show that the reportability of MB is less frequent, faster, and with lower transitional dynamics than other mental states, pointing to its role as a transient mental relay. Regarding its neural underpinnings, we observed higher global signal amplitude during MB reports, indicating a distinct physiological state. Using the time-varying functional connectome, we show that MB reports can be classified with high accuracy, suggesting that MB has a unique neural composition. Indeed, a pattern of global positive-phase coherence shows the highest similarity to the connectivity patterns associated with MB reports. We interpret this pattern's rigid signal architecture as hindering content reportability due to the brain's inability to differentiate signals in an informative way. Collectively, we show that MB has a unique neurobehavioral profile, indicating that nonreportable mental events can happen during wakefulness. Our results add to the characterization of spontaneous mentation and pave the way for more mechanistic investigations of MB's phenomenology.

Visual object categorization in infancy.

Humans make sense of the world by organizing things into categories. When and how does this process begin? We investigated whether real-world object categories that spontaneously emerge in the first months of life match categorical representations of objects in the human visual cortex. Using eye tracking, we measured the differential looking time of 4-, 10-, and 19-mo-olds as they looked at pairs of pictures belonging to eight animate or inanimate categories (human/nonhuman, faces/bodies, real-world size big/small, natural/artificial). Taking infants' looking times as a measure of similarity, for each age group, we defined a representational space where each object was defined in relation to others of the same or of a different category. This space was compared with hypothesis-based and functional MRI-based models of visual object categorization in the adults' visual cortex. Analyses across different age groups showed that, as infants grow older, their looking behavior matches neural representations in ever-larger portions of the adult visual cortex, suggesting progressive recruitment and integration of more and more feature spaces distributed over the visual cortex. Moreover, the results characterize infants' visual categorization as an incremental process with two milestones. Between 4 and 10 mo, visual exploration guided by saliency gives way to an organization according to the animate-inanimate distinction. Between 10 and 19 mo, a category spurt leads toward a mature organization. We propose that these changes underlie the coupling between seeing and thinking in the developing mind.

Mapping the neural mechanism that distinguishes between holistic thinking and analytic thinking.

Holistic and analytic thinking are two distinct modes of thinking used to interpret the world with relative preferences varying across cultures. While most research on these thinking styles has focused on behavioral and cognitive aspects, a few studies have utilized functional magnetic resonance imaging (fMRI) to explore the correlations between brain metrics and self-reported scale scores. Other fMRI studies used single holistic and analytic thinking tasks. As a single task may involve processing in spurious low-level regions, we used two different holistic and analytic thinking tasks, namely the frame-line task and the triad task, to seek convergent brain regions to distinguish holistic and analytic thinking using multivariate pattern analysis (MVPA). Results showed that brain regions fundamental to distinguish holistic and analytic thinking include the bilateral frontal lobes, bilateral parietal lobes, bilateral precentral and postcentral gyrus, bilateral supplementary motor areas, bilateral fusiform, bilateral insula, bilateral angular gyrus, left cuneus, and precuneus, left olfactory cortex, cingulate gyrus, right caudate and putamen. Our study maps brain regions that distinguish between holistic and analytic thinking and provides a new approach to explore the neural representation of cultural constructs. We provide initial evidence connecting culture-related brain regions with language function to explain the origins of cultural differences in cognitive styles.

Perceived plausibility modulates hippocampal activity in episodic counterfactual thinking.

Episodic counterfactual thinking (ECT) consists of imagining alternative outcomes to past personal events. Previous research has shown that ECT shares common neural substrates with episodic future thinking (EFT): our ability to imagine possible future events. Both ECT and EFT have been shown to critically depend on the hippocampus, and past research has explored hippocampal engagement as a function of the perceived plausibility of an imagined future event. However, the extent to which the hippocampus is modulated by perceived plausibility during ECT is unknown. In this study, we combine two functional magnetic resonance imaging datasets to investigate whether perceived plausibility modulates hippocampal activity during ECT. Our results indicate that plausibility parametrically modulates hippocampal activity during ECT, and that such modulation is confined to the left anterior portion of the hippocampus. Moreover, our results indicate that this modulation is positive, such that increased activity in the left anterior hippocampus is associated with higher ratings of ECT plausibility. We suggest that neither effort nor difficulty alone can account for these results, and instead suggest possible alternatives to explain the role of the hippocampus during the construction of plausible and implausible ECT.

Conscious but not thinking-Mind-blanks during visuomotor tracking: An fMRI study of endogenous attention lapses.

Attention lapses (ALs) are complete lapses of responsiveness in which performance is briefly but completely disrupted and during which, as opposed to microsleeps, the eyes remain open. Although the phenomenon of ALs has been investigated by behavioural and physiological means, the underlying cause of an AL has largely remained elusive. This study aimed to investigate the underlying physiological substrates of behaviourally identified endogenous ALs during a continuous visuomotor task, primarily to answer the question: Were the ALs during this task due to extreme mind-wandering or mind-blanks? The data from two studies were combined, resulting in data from 40 healthy non-sleep-deprived subjects (20M/20F; mean age 27.1 years, 20-45). Only 17 of the 40 subjects were used in the analysis due to a need for a minimum of two ALs per subject. Subjects performed a random 2-D continuous visuomotor tracking task for 50 and 20 min in Studies 1 and 2, respectively. Tracking performance, eye-video, and functional magnetic resonance imaging (fMRI) were recorded simultaneously. A human expert visually inspected the tracking performance and eye-video recordings to identify and categorise lapses of responsiveness as microsleeps or ALs. Changes in neural activity during 85 ALs (17 subjects) relative to responsive tracking were estimated by whole-brain voxel-wise fMRI and by haemodynamic response (HR) analysis in regions of interest (ROIs) from seven key networks to reveal the neural signature of ALs. Changes in functional connectivity (FC) within and between the key ROIs were also estimated. Networks explored were the default mode network, dorsal attention network, frontoparietal network, sensorimotor network, salience network, visual network, and working memory network. Voxel-wise analysis revealed a significant increase in blood-oxygen-level-dependent activity in the overlapping dorsal anterior cingulate cortex and supplementary motor area region but no significant decreases in activity; the increased activity is considered to represent a recovery-of-responsiveness process following an AL. This increased activity was also seen in the HR of the corresponding ROI. Importantly, HR analysis revealed no trend of increased activity in the posterior cingulate of the default mode network, which has been repeatedly demonstrated to be a strong biomarker of mind-wandering. FC analysis showed decoupling of external attention, which supports the involuntary nature of ALs, in addition to the neural recovery processes. Other findings were a decrease in HR in the frontoparietal network before the onset of ALs, and a decrease in FC between default mode network and working memory network. These findings converge to our conclusion that the ALs observed during our task were involuntary mind-blanks. This is further supported behaviourally by the short duration of the ALs (mean 1.7 s), which is considered too brief to be instances of extreme mind-wandering. This is the first study to demonstrate that at least the majority of complete losses of responsiveness on a continuous visuomotor task are, if not due to microsleeps, due to involuntary mind-blanks.

Effects of task context on EEG correlates of mind-wandering.

This study was designed to examine how mind-wandering and its neural correlates vary across tasks with different attentional demands, motivated by the context regulation hypothesis of mind-wandering. Participants (n = 59 undergraduates) completed the sustained attention to response task (SART) and the Stroop selective attention task in counterbalanced order while EEG was recorded. The tasks included experience-sampling probes to identify self-reported episodes of mind-wandering, along with retrospective reports. Participants reported more mind-wandering during the SART than the Stroop and during whichever task was presented second during the session, compared with first. Replicating previous findings, EEG data (n = 37 usable participants) indicated increased alpha oscillations during episodes of mind-wandering, compared with on-task episodes, for both the SART and Stroop tasks. ERP data, focused on the P2 component reflecting perceptual processing, found that mind-wandering was associated with increased P2 amplitudes during the Stroop task, counter to predictions from the perceptual decoupling theory. Overall, the study found that self-report and neural correlates of mind-wandering are sensitive to task context. This line of research can further the understanding of how mechanisms of mind-wandering are adapted to varied tasks and situations.

Thinking computationally in translational psychiatry. A commentary on Neville et al. (2024).

There is a growing focus on the computational aspects of psychiatric disorders in humans. This idea also is gaining traction in nonhuman animal studies. Commenting on a new comprehensive overview of the benefits of applying this approach in translational research by Neville et al. (Cognitive Affective & Behavioral Neuroscience 1-14, 2024), we discuss the implications for translational model validity within this framework. We argue that thinking computationally in translational psychiatry calls for a change in the way that we evaluate animal models of human psychiatric processes, with a shift in focus towards symptom-producing computations rather than the symptoms themselves. Further, in line with Neville et al.'s adoption of the reinforcement learning framework to model animal behaviour, we illustrate how this approach can be applied beyond simple decision-making paradigms to model more naturalistic behaviours.

The vmPFC-IPL functional connectivity as the neural basis of future self-continuity impacted procrastination: the mediating role of anticipated positive outcomes.

Procrastination is universally acknowledged as a problematic behavior with wide-ranging consequences impacting various facets of individuals' lives, including academic achievement, social accomplishments, and mental health. Although previous research has indicated that future self-continuity is robustly negatively correlated with procrastination, it remains unknown about the neural mechanisms underlying the impact of future self-continuity on procrastination. To address this issue, we employed a free construction approach to collect individuals' episodic future thinking (EFT) thoughts regarding specific procrastination tasks. Next, we conducted voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analysis to explore the neural substrates underlying future self-continuity. Behavior results revealed that future self-continuity was significantly negatively correlated with procrastination, and positively correlated with anticipated positive outcome. The VBM analysis showed a positive association between future self-continuity and gray matter volumes in the right ventromedial prefrontal cortex (vmPFC). Furthermore, the RSFC results indicated that the functional connectivity between the right vmPFC and the left inferior parietal lobule (IPL) was positively correlated with future self-continuity. More importantly, the mediation analysis demonstrated that anticipated positive outcome can completely mediate the relationship between the vmPFC-IPL functional connectivity and procrastination. These findings suggested that vmPFC-IPL functional connectivity might prompt anticipated positive outcome about the task and thereby reduce procrastination, which provides a new perspective to understand the relationship between future self-continuity and procrastination.

Ten simple rules for designing and conducting undergraduate replication projects.

Conducting a replication study is a valuable way for undergraduate students to learn about the scientific process and gain research experience. By promoting the evaluation of existing studies to confirm their reliability, replications play a unique, though often underappreciated, role in the scientific enterprise. Involving students early in this process can help make replication mainstream among the new generation of scientists. Beyond their benefit to science, replications also provide an invaluable learning ground for students, from encouraging the development of critical thinking to emphasizing the importance of details and honing research skills. In this piece, we outline 10 simple rules for designing and conducting undergraduate replication projects, from conceptualization to implementation and dissemination. We hope that these guidelines can help educators provide students with a meaningful and constructive pedagogical experience, without compromising the scientific value of the replication project, therefore ensuring robust, valuable contributions to our understanding of the world.

Expectations Versus Fantasies and Vaccine Hesitancy: How Suffering From COVID-19 Versus Suffering From Vaccines Interact.

BACKGROUND: Previous research on COVID-19 vaccination highlights future thoughts associated with possible Coronavirus infection and vaccine side effects as key predictors of vaccine hesitancy. Yet, research has focused on independent contributions of such future thoughts, neglecting their interactive aspects. PURPOSE: We examined whether thoughts about two possible COVID-related futures (suffering from COVID-19 and vaccine side effects) interactively predict vaccine hesitancy and vaccination behavior among unvaccinated and vaccinated people. Importantly, we compared two forms of future thinking: beliefs or expectations (likelihood judgments) versus fantasies (free thoughts and images describing future events). METHODS: In Study 1, we conducted a longitudinal study with an unvaccinated group (N = 210). We assessed expectations versus fantasies about the two COVID-related futures as predictors. As outcome variables, we measured vaccine hesitancy, and 9 weeks later we assessed information seeking and vaccine uptake. Study 2 was a cross-sectional study comparing vaccine hesitancy of an unvaccinated group (N = 307) to that of a vaccinated group (N = 311). RESULTS: Study 1 found that more negative fantasies about COVID-19 impact and less negative fantasies about vaccine side effects interactively predicted lower vaccine hesitancy and more vaccine-related behaviors among unvaccinated people; no such interaction was observed between respective expectations. Study 2 replicated these results of Study 1. Additionally, for vaccinated people, low expectations of negative COVID-19 impact and high expectations of negative vaccine impact interactively predicted higher vaccine hesitancy, whereas no such interaction was observed for respective fantasies. CONCLUSIONS: Research on vaccine hesitancy should explore interactions between future thinking about disease and about vaccine side effects. Importantly, there is much to be gained by distinguishing expectations versus fantasies: vaccination interventions aiming to boost vaccine uptake among unvaccinated people should tap into their negative future fantasies regarding both disease and vaccine side effects.

In two correlational studies, we investigated the relationship between future thoughts about two possible COVID-related futures­suffering from COVID-19 and vaccine side effects­and vaccine hesitancy. Prior research has emphasized thoughts about these potential risks as significant predictors of vaccine hesitancy but has focused on their independent contributions, neglecting their interactive nature. Our research examined the interaction between the thoughts about disease and those about vaccine side effects, highlighting the two forms of future thinking: expectations (likelihood judgments) and fantasies (free-flowing thoughts and images describing a future event). In a longitudinal study (Study 1) with an unvaccinated group, we found that more negative fantasies about COVID-19 disease and less negative fantasies about vaccine side effects interactively predicted lower vaccine hesitancy and more vaccination behavior. There was no interaction between the expectations. Study 2, a cross-sectional study comparing another unvaccinated sample to a vaccinated sample, revealed a divergent pattern in the two groups; negative fantasies, not expectations, interactively predicted vaccine hesitancy among unvaccinated people while expectations, not fantasies, did so among vaccinated people. The research suggests the importance of considering interactions between future thoughts about disease and vaccine side effects in understanding vaccine hesitancy and distinguishing expectations and fantasies.

Teleological reasoning bias is predicted by pupil dynamics: Evidence for the extensive integration account of bias in reasoning.

Teleological reasoning is the tendency for humans to see purpose and intentionality in natural phenomena when there is none. In this study, we assess three competing theories on how bias in reasoning arises by examining performance on a teleological reasoning task while measuring pupil size and response times. We replicate that humans (N = 45) are prone to accept false teleological explanations. Further, we show that errors on the teleological reasoning task are associated with slower response times, smaller baseline pupil size, and larger pupil dilations. The results are in line with the single-process extensive integration account and directly oppose predictions from dual-processing accounts. Lastly, by modeling responses with a drift-diffusion model, we find that larger baseline pupil size is associated with lower decision threshold and higher drift rate, whereas larger pupil dilations are associated with higher decision threshold and lower drift rate. The results highlight the role of neural gain and the Locus Coeruleus-Norepinephrine system in modulating evidence integration and bias in reasoning. Thus, teleological reasoning and susceptibility to bias likely arise due to extensive processing rather than through fast and effortless processing.

Taking time to compose thoughts with prefrontal schemata.

Under what conditions can prefrontal cortex direct the composition of brain states, to generate coherent streams of thoughts? Using a simplified Potts model of cortical dynamics, crudely differentiated into two halves, we show that once activity levels are regulated, so as to disambiguate a single temporal sequence, whether the contents of the sequence are mainly determined by the frontal or by the posterior half, or by neither, depends on statistical parameters that describe its microcircuits. The frontal cortex tends to lead if it has more local attractors, longer lasting and stronger ones, in order of increasing importance. Its guidance is particularly effective to the extent that posterior cortices do not tend to transition from state to state on their own. The result may be related to prefrontal cortex enforcing its temporally-oriented schemata driving coherent sequences of brain states, unlike the atemporal "context" contributed by the hippocampus. Modelling a mild prefrontal (vs. posterior) lesion offers an account of mind-wandering and event construction deficits observed in prefrontal patients.