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.

Neuronal sequences in population bursts encode information in human cortex.

Neural coding has traditionally been examined through changes in firing rates and latencies in response to different stimuli1-5. However, populations of neurons can also exhibit transient bursts of spiking activity, wherein neurons fire in a specific temporal order or sequence6-8. The human brain may utilize these neuronal sequences within population bursts to efficiently represent information9-12, thereby complementing the well-known neural code based on spike rate or latency. Here we examined this possibility by recording the spiking activity of populations of single units in the human anterior temporal lobe as eight participants performed a visual categorization task. We find that population spiking activity organizes into bursts during the task. The temporal order of spiking across the activated units within each burst varies across stimulus categories, creating unique stereotypical sequences for individual categories as well as for individual exemplars within a category. The information conveyed by the temporal order of spiking activity is separable from and complements the information conveyed by the units' spike rates or latencies following stimulus onset. Collectively, our data provide evidence that the human brain contains a complementary code based on the neuronal sequence within bursts of population spiking to represent information.

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.

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.

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.

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.

Differences in the neural correlates of schizophrenia with positive and negative formal thought disorder in patients with schizophrenia in the ENIGMA dataset.

Formal thought disorder (FTD) is a clinical key factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, the relationship between FTD symptom dimensions and patterns of regional brain volume loss in schizophrenia remains to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles by enrolling a large multi-site cohort acquired by the ENIGMA Schizophrenia Working Group (752 schizophrenia patients and 1256 controls), to unravel the neuroanatomy of FTD in schizophrenia and using virtual histology tools on implicated brain regions to investigate the cellular basis. Based on the findings of previous clinical and neuroimaging studies, we decided to separately explore positive, negative and total formal thought disorder. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but positive and negative FTD demonstrated a dissociation: negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD also showed associations with microglial cell types. These results provide an important step towards linking FTD to brain structural changes and their cellular underpinnings, providing an avenue for a better mechanistic understanding of this syndrome.

Coupled changes between ruminating thoughts and resting-state brain networks during the transition into adulthood.

Perseverative negative thoughts, known as rumination, might arise from emotional challenges and preclude mental health when transitioning into adulthood. Due to its multifaceted nature, rumination can take several ruminative response styles, that diverge in manifestations, severity, and mental health outcomes. Still, prospective ruminative phenotypes remain elusive insofar. Longitudinal study designs are ideal for stratifying ruminative response styles, especially with resting-state functional MRI whose setup naturally elicits people's ruminative traits. Here, we considered self-rated questionnaires on rumination and psychopathology, along with resting-state functional MRI data in 595 individuals assessed at age 18 and 22 from the IMAGEN cohort. We conducted independent component analysis to characterize eight single static resting-state functional networks in each subject and session and furthermore conducted a dynamic analysis, tackling the time variations of functional networks during the entire scanning time. We then investigated their longitudinal mediation role between changes in three ruminative response styles (reflective pondering, brooding, and depressive rumination) and changes in internalizing and co-morbid externalizing symptoms. Four static and two dynamic networks longitudinally differentiated these ruminative styles and showed complemental sensitivity to internalizing and co-morbid externalizing symptoms. Among these networks, the right frontoparietal network covaried with all ruminative styles but did not play any mediation role towards psychopathology. The default mode, the salience, and the limbic networks prospectively stratified these ruminative styles, suggesting that maladaptive ruminative styles are associated with altered corticolimbic function. For static measures, only the salience network played a longitudinal causal role between brooding rumination and internalizing symptoms. Dynamic measures highlighted the default-mode mediation role between the other ruminative styles and co-morbid externalizing symptoms. In conclusion, we identified the ruminative styles' psychometric and neural outcome specificities, supporting their translation into applied research on young adult mental healthcare.

The relationships among metacognitive functions, sleep-related thought-control strategies and sleep quality: A mediation analysis.

In the context of sleep disturbances, increasing evidence suggests a critical role of sleep-related dysfunctional metacognitive activity, including metacognitive control of intrusive thoughts in the pre-sleep period. Although the relationship between sleep-related thought-control strategies and poor sleep quality is well recognized, the possible contribution of general metacognitive functioning within this relation is still unclear. In this study, we performed a mediation analysis to examine the role of thought-control strategies on the relationship between metacognitive abilities and sleep quality in individuals with different self-reported sleep characteristics. Two-hundred and forty-five individuals participated in the study. Participants completed the Pittsburgh Sleep Quality Index, the Thought Control Questionnaire Insomnia-Revised, and the Metacognition Self-Assessment Scale to evaluate sleep quality, thought-control strategies and metacognitive functions, respectively. The results showed that worry strategy in the pre-sleep period mediates the relationship between metacognitive functions and sleep quality. Particularly, the ability to understand one's mental states and mastery functions could be the two metacognitive domains primarily involved in the dysfunctional metacognitive thought-control activity responsible for reduced sleep quality. The observed effect suggests that inadequate metacognitive functioning is associated with poor sleep quality in healthy subjects via the mediation of dysfunctional worry strategy. These findings suggest the potential relevance of clinical interventions to enhance specific metacognitive abilities, with the aim to promote more functional strategies for managing cognitive and emotional processes during the pre-sleep period.

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.

Pathways From Spatial Skills to Mathematics: The Roles of Gender and Fluid Reasoning.

There are contentious and persistent gender differences reported in some measures of spatial skills, particularly mental rotation and, to a lesser extent, perspective-taking, which may have an impact on mathematics success. Furthermore, pathways between spatial skills and mathematics may be mediated by other cognitive factors, such as fluid reasoning. Participants (N = 320, age range 8-12 years) completed measures of mental rotation, perspective-taking, fluid reasoning, and mathematics. Regression analyses were conducted to assess the mediation effect of fluid reasoning on the relations between mental rotation and perspective-taking, and mathematics. Moderated mediation was performed to assess the effects of gender and age on these relations. Mental rotation and perspective-taking both predicted performance in mathematics for the overall sample, and fluid reasoning was found to partially mediate these relations. For mental rotation, gender moderated the mediation model, with mental rotation directly predicting performance in mathematics for males but not females. The mediation model for perspective-taking and mathematics was not moderated by gender. Although a predictor of performance, age did not moderate any of the reported relations. These findings suggest that gender differences in some spatial skills, such as mental rotation, may extend to the pathways linking the skills to mathematics. Although mental rotation may be predictive of mathematics performance for boys, the same might not be so for girls. Extrinsic spatial skills, such as perspective-taking, offer new pathways to explore in the growing body of work examining the links between spatial reasoning and mathematics.

Default mode network electrophysiological dynamics and causal role in creative thinking.

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally directed cognition. The present study employs stereo-EEG in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by a stronger increase in gamma band power (30-70 Hz) coupled with lower theta band power (4-8 Hz). The difference in activity between the two networks was especially strong during the mind wandering task. Within the DMN, we found that the tasks showed different dynamics, with the alternate uses task engaging the DMN more during the initial stage of the task, and mind wandering in the later stage. Gamma power changes were mainly driven by lateral DMN sites, while theta power displayed task-specific effects. During alternate uses task, theta changes did not show spatial differences within the DMN, while mind wandering was associated to an early lateral and late dorsomedial DMN engagement. Furthermore, causal manipulations of DMN regions using direct cortical stimulation preferentially decreased the originality of responses in the alternative uses task, without affecting fluency or mind wandering. Our results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in divergent thinking. These findings shed light on the neural constructs supporting different forms of cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts.

Personality Moderates Intra-Individual Variability in EEG Microstates and Spontaneous Thoughts.

Variability in brain activity that persists after accounting for overt behavioral and physiological states is often considered noise and controlled as a covariate in research. However, studying intra-individual variability in brain function can provide valuable insights into the dynamic nature of the brain. To explore this, we conducted a study on 43 participants analyzing the EEG microstate dynamics and self-reported spontaneous mental activity during five-minute resting-state recordings on two separate days with a twenty days average delay between recordings. Our results showed that the associations between EEG microstates and spontaneous cognition significantly changed from one day to another. Moreover, microstate changes were associated with changes in spontaneous cognition. Specifically, inter-day changes in Verbal thoughts about Others and future Planning were positively related to bottom-up sensory network-related microstate changes and negatively associated with top-down, attention, and salience network-related microstates. In addition, we find that personality traits are related to inter-day changes in microstates and spontaneous thoughts. Specifically, extraversion, neuroticism, agreeableness, and openness to experience moderated the relationship between inter-day changes in EEG microstates and spontaneous thoughts. Our study provides valuable information on the dynamic changes in the EEG microstate-spontaneous cognition organization, which could be essential for developing interventions and treatments for neuropsychiatric disorders.