Neuronal correlates of metacognition in primate frontal cortex

Humans are metacognitive: they monitor and control their cognition. Our hypothesis was that neuronal correlates of metacognition reside in the same brain areas responsible for cognition, including frontal cortex. Recent work demonstrated that nonhuman primates are capable of metacognition, so we recorded from single neurons in the frontal eye field, dorsolateral prefrontal cortex, and supplementary eye field of monkeys (Macaca mulatta) that performed a metacognitive visual-oculomotor task. The animals made a decision and reported it with a saccade, but received no immediate reward or feedback. Instead, they had to monitor their decision and bet whether it was correct. Activity was correlated with decisions and bets in all three brain areas, but putative metacognitive activity that linked decisions to appropriate bets occurred exclusively in the SEF. Our results offer a survey of neuronal correlates of metacognition and implicate the SEF in linking cognitive functions over short periods of time.     

Ruthless reductionism and social cognition

Social cognition appears to present phenomena that "ruthlessly reductive" molecular and cellular neuroscience cannot fruitfully investigate or explain. This is because the causes of such phenomena are distal and external not only to the molecular machinery of individual neurons, but to individual brains. However, the "reductionist's epiphany" insists that to the extent that we understand the specific molecular mechanisms that underlie phenomena upon which most or all social cognition depends, we can be sure that molecular mechanisms for the broader phenomena can be found using standard experimental methods from molecular and cellular cognition. Furthermore, social recognition memory consolidation is required for virtually all types of social cognition, and its specific molecular mechanisms have now been uncovered experimentally. These same molecular mechanisms obtain across a wide variety of divergent species (from invertebrates to vertebrates). Thus we can expect to find the molecular mechanisms of the broader social cognitive functions that must "plug into" these specific molecular mechanisms, despite these functions' typically distal, external initial causes. This conclusion rests on explicit scientific facts, not just on some vague philosophical commitment to physicalism about mind.     

Social neuroscience of disgust

Disgust can be thought of as an affective system that has evolved to detect signs of pathogens, parasite and toxins as well as to stimulate behaviors that reduce the risk of their acquisition. Disgust incorporates social cognitive mechanisms to regulate exposure to and, or anticipate and avoid exposure to pathogens and toxins. Social cognition entails the acquisition of social information about others (ie, social recognition) and from others (ie, social learning). This involves recognizing and assessing other individuals and the pathogen/parasite/contamination/toxin threat they pose and deciding about when and how to interact with and, or avoid them. Social cognition provides a frame‐work for examining the expression of disgust and the associated neurobiological mechanisms. Here, we briefly consider the relations between social cognition and pathogen/parasite/toxin avoidance behaviors. We briefly discuss aspects of: (1) the odor mediated social recognition of actual and potentially infected individuals and the impact of parasite/pathogen threat on disgust mate and social partner choice; (2) the roles of “out‐groups” (strangers, unfamiliar individuals) and “in‐groups” (familiar individuals) in the expression of disgust and pathogen avoidance behaviors; (3) individual and social learning of disgust and empathy for disgust; (4) toxin elicited disgust and anticipatory disgust; (5) the neurobiological mechanisms, and in particular the roles of the nonapeptide, oxytocin and estrogenic mechanism associated with social cognition and the expression of disgust. These findings on the social neuroscience of disgust have a direct bearing on our understanding of the roles of disgust in shaping human and nonhuman social behavior.     

Nonsocial and social cognition in schizophrenia: current evidence and future directions

Cognitive impairment in schizophrenia involves a broad array of nonsocial and social cognitive domains. It is a core feature of the illness, and one with substantial implications for treatment and prognosis. Our understanding of the causes, consequences and interventions for cognitive impairment in schizophrenia has grown substantially in recent years. Here we review a range of topics, including: a) the types of nonsocial cognitive, social cognitive, and perceptual deficits in schizophrenia; b) how deficits in schizophrenia are similar or different from those in other disorders; c) cognitive impairments in the prodromal period and over the lifespan in schizophrenia; d) neuroimaging of the neural substrates of nonsocial and social cognition, and e) relationships of nonsocial and social cognition to functional outcome. The paper also reviews the considerable efforts that have been directed to improve cognitive impairments in schizophrenia through novel psychopharmacology, cognitive remediation, social cognitive training, and alternative approaches. In the final section, we consider areas that are emerging and have the potential to provide future insights, including the interface of motivation and cognition, the influence of childhood adversity, metacognition, the role of neuroinflammation, computational modelling, the application of remote digital technology, and novel methods to evaluate brain network organization. The study of cognitive impairment has provided a way to approach, examine and comprehend a wide range of features of schizophrenia, and it may ultimately affect how we define and diagnose this complex disorder.     

Self-Knowledge Dim-Out: Stress Impairs Metacognitive Accuracy

Modulation of frontal lobes activity is believed to be an important pathway trough which the hypothalamic-pituitary-adrenal (HPA) axis stress response impacts cognitive and emotional functioning. Here, we investigate the effects of stress on metacognition, which is the ability to monitor and control one''s own cognition. As the frontal lobes have been shown to play a critical role in metacognition, we predicted that under activation of the HPA axis, participants should be less accurate in the assessment of their own performances in a perceptual decision task, irrespective of the effect of stress on the first order perceptual decision itself. To test this prediction, we constituted three groups of high, medium and low stress responders based on cortisol concentration in saliva in response to a standardized psycho-social stress challenge (the Trier Social Stress Test). We then assessed the accuracy of participants'' confidence judgments in a visual discrimination task. As predicted, we found that high biological reactivity to stress correlates with lower sensitivity in metacognition. In sum, participants under stress know less when they know and when they do not know.     

Testing the Cognition of the Forgotten Colobines: A First Look at Golden Snub-Nosed Monkeys (Rhinopithecus roxellana)

Although our understanding of primate cognition is growing rapidly, little is known about the cognition of colobines. Here we report the results of a set of 5 experiments on colobine cognition using 17 golden snub-nosed monkeys (Rhinopithecus roxellana). These monkeys are folivores that form multilevel societies with groups of hundreds of individuals and relatively high fission–fusion dynamics. We investigated their sensitivity to human social cues and ability to inhibit impulsive behavioral responses. In three sociocognitive experiments we found that, like most other primates, they follow the gaze direction of a human demonstrator but there is no evidence that they use others’ social cues in a cooperative task to locate hidden food or in a competitive task to steal forbidden food. In two inhibitory control experiments, we found that the monkeys showed a low level of inhibitory control, comparable to that of other folivorous primates. These results suggest that phylogeny and folivory might have been important in shaping the cognition of golden snub-nosed monkeys. Moreover, this species’ large group size and relatively high fission–fusion dynamics may not have imposed a significant social challenge to their cognition, as social interactions occur mainly within basic social units.     

Occurrence and social structure of Baird's beaked whales,Berardius bairdii,in the Commander Islands,Russia

The social structure of Baird's beaked whales is completely unstudied, and it is unknown if either females or males form long‐term social associations or occur in stable groups. In this paper we summarize our observations of individually identified animals over the span of 6 yr to provide insight on their long‐term social structure. We have identified 122 whales, with 28 of them encountered three times or more and thus included in the analysis of social structure. We found that the whales exhibited nonrandom patterns of social associations with some individuals preferentially associating with each other. Whales with more scarred skin had higher maximum association coefficients, which indicates that older animals and/or males were more inclined to form stable associations. Cluster analysis with a modularity test for gregariousness divided the whales into four clusters. Whales from the same clusters did not always occur together, but some individuals retained stable associations over several years. The strength of social relationships decayed over periods of months, with between‐year relationships showing little deviation from what would be expected if association was random. Generally these findings do not correspond to a stable society with fixed groups but instead suggest a fission‐fusion society with some stable alliances.     

Social cognition

Social cognition concerns the various psychological processes that enable individuals to take advantage of being part of a social group. Of major importance to social cognition are the various social signals that enable us to learn about the world. Such signals include facial expressions, such as fear and disgust, which warn us of danger, and eye gaze direction, which indicate where interesting things can be found. Such signals are particularly important in infant development. Social referencing, for example, refers to the phenomenon in which infants refer to their mothers' facial expressions to determine whether or not to approach a novel object. We can learn a great deal simply by observing others. Much of this signalling seems to happen automatically and unconsciously on the part of both the sender and the receiver. We can learn to fear a stimulus by observing the response of another, in the absence of awareness of that stimulus. By contrast, learning by instruction, rather than observation, does seem to depend upon awareness of the stimulus, since such learning does not generalize to situations where the stimulus is presented subliminally. Learning by instruction depends upon a meta-cognitive process through which both the sender and the receiver recognize that signals are intended to be signals. An example would be the 'ostensive' signals that indicate that what follows are intentional communications. Infants learn more from signals that they recognize to be instructive. I speculate that it is this ability to recognize and learn from instructions rather than mere observation which permitted that advanced ability to benefit from cultural learning that seems to be unique to the human race.     

Role of social cognition in post‐traumatic stress disorder: A review and meta‐analysis

Social functioning is a key component of recovery after a potentially traumatic experience, and the buffering role of the social support in trauma resilience and recovery has been very well documented. Factors contributing to resilience and recovery are notable because although most people will experience a traumatic event during their lifetimes, only 6% to 10% are diagnosed with post‐traumatic stress disorder (PTSD). The relationship between an individual and their social environment is determined both by the quality of the social environment itself, and by the individual's perception and understanding of information conveyed by the other people around them. However, little research has considered the contribution of these internal social cognitive processes to PTSD risk or resilience. The current review draws on the existing literature on social cognitive functioning in trauma exposure and PTSD, identifying key questions and themes for future research. We utilized a meta‐analytic approach to assess the evidence for alterations in social cognition in PTSD, finding a consistent large deficit in social cognitive performance in PTSD groups relative to trauma‐exposed and healthy controls. We then reviewed the literature on the interaction of genes and the social environment, supporting the hypothesis that social cognitive deficits are a preexisting risk factor for PTSD. Finally, we reviewed relevant neuroimaging findings, which suggest that alterations in social cognition affect the perception of threat cues in PTSD. Overall, research on social cognition and PTSD is still emerging, but existing findings suggest this is an important and understudied area for the understanding of PTSD.     

Nerve growth factor (NGF) loop 4 dimeric mimetics activate ERK and AKT and promote NGF-like neurotrophic effects

Previous work indicating that nerve growth factor (NGF) protein loops 2 and 4 interact with TrkA receptors raise the possibility that small molecule mimetics corresponding to TrkA-interacting domains that have NGF agonist activity can be developed. We applied our previously developed strategy of dimeric peptidomimetics to address the hypothesis that loop 4 small molecule dimeric mimetics would activate TrkA-related signal transduction and mimic NGF neurotrophic effects in a structure-specific manner. A loop 4 cyclized peptide dimer demonstrated NGF-like neurotrophic activity, whereas peptides with scrambled sequence, added or substituted residues, or cyclized in monomeric form were inactive. Activity was blocked by the TrkA inhibitors K252a and AG879 but not by NGF p75 receptor blocking antibody. Dimeric, but not monomeric, peptides partially blocked NGF activity. This profile was consistent with that of a NGF partial agonist. ERK and AKT phosphorylation was stimulated only by biologically active peptides and was blocked by K252a. The ERK inhibitor U0126 blocked the neurite- but not the survival-promoting activity of both NGF and active peptide. These studies support the proof of concept that small molecule NGF loop 4 mimetics can activate NGF signaling pathways and can mimic death-preventing and neurite-promoting effects of NGF. This finding will guide the rational design of NGF single-domain mimetics and contribute to elucidating NGF signal transduction mechanisms.     

Rings and ribbons in protein structures: Characterization using helical parameters and Ramachandran plots for repeating dipeptides

Helical parameters displayed on a Ramachandran plot allow peptide structures with successive residues having identical main chain conformations to be studied. We investigate repeating dipeptide main chain conformations and present Ramachandran plots encompassing the range of possible structures. Repeating dipeptides fall into the categories: rings, ribbons, and helices. Partial rings occur in the form of “nests” and “catgrips”; many nests are bridged by an oxygen atom hydrogen bonding to the main chain NH groups of alternate residues, an interaction optimized by the ring structure of the nest. A novel recurring feature is identified that we name unpleated β, often situated at the ends of a β‐sheet strand. Some are partial rings causing the polypeptide to curve gently away from the sheet; some are straight. They lack β‐pleat and almost all incorporate a glycine. An example is the first glycine in the GxxxxGK motif of P‐loop proteins. Ribbons in repeating dipeptides can be either flat, as seen in repeated type II and type II′ β‐turns, or twisted, as in multiple type I and type I′ β‐turns. Hexa‐ and octa‐peptides in such twisted ribbons occur frequently in proteins, predominantly with type I β‐turns, and are the same as the “β‐bend ribbons” hitherto identified only in short peptides. One is seen in the GTPase‐activating protein for Rho in the active, but not the inactive, form of the enzyme. It forms a β‐bend ribbon, which incorporates the catalytic arginine, allowing its side chain guanidino group to approach the active site and enhance enzyme activity. Proteins 2014; 82:230–239. © 2013 Wiley Periodicals, Inc.     

Activity: Structure,Genesis, and Units of Analysis

One of the most remarkable events in Soviet psychology in the second half of the '70s was the discussion of the problem of the relationship between communication and activity [8,13,18,19,21,23]. We considered the following approach to the problem, which we here present in its most general form, the most constructive: Communication and activity are undoubtedly interrelated; but communication (in contrast to perception, memory, etc.) is not usefully regarded as simply one type of activity as it is analyzed in terms of Leont'ev's paradigm activity—action—operation, motive—goal—condition. This approach to the problem is useful primarily for advancing the theory of activity: it points sharply to the very essential point, insufficiently developed in the theory of activity, that analysis of social environments and the mechanisms of human activity is both collective and individual.     

The future of future-oriented cognition in non-humans: theory and the empirical case of the great apes

One of the most contested areas in the field of animal cognition is non-human future-oriented cognition. We critically examine key underlying assumptions in the debate, which is mainly preoccupied with certain dichotomous positions, the most prevalent being whether or not ‘real’ future orientation is uniquely human. We argue that future orientation is a theoretical construct threatening to lead research astray. Cognitive operations occur in the present moment and can be influenced only by prior causation and the environment, at the same time that most appear directed towards future outcomes. Regarding the current debate, future orientation becomes a question of where on various continua cognition becomes ‘truly’ future-oriented. We question both the assumption that episodic cognition is the most important process in future-oriented cognition and the assumption that future-oriented cognition is uniquely human. We review the studies on future-oriented cognition in the great apes to find little doubt that our closest relatives possess such ability. We conclude by urging that future-oriented cognition not be viewed as expression of some select set of skills. Instead, research into future-oriented cognition should be approached more like research into social and physical cognition.     

A cross-culture,cross-gender comparison of perspective taking mechanisms

Being able to judge another person''s visuo-spatial perspective is an essential social skill, hence we investigated the generalizability of the involved mechanisms across cultures and genders. Developmental, cross-species, and our own previous research suggest that two different forms of perspective taking can be distinguished, which are subserved by two distinct mechanisms. The simpler form relies on inferring another''s line-of-sight, whereas the more complex form depends on embodied transformation into the other''s orientation in form of a simulated body rotation. Our current results suggest that, in principle, the same basic mechanisms are employed by males and females in both, East-Asian (EA; Chinese) and Western culture. However, we also confirmed the hypothesis that Westerners show an egocentric bias, whereas EAs reveal an other-oriented bias. Furthermore, Westerners were slower overall than EAs and showed stronger gender differences in speed and depth of embodied processing. Our findings substantiate differences and communalities in social cognition mechanisms across genders and two cultures and suggest that cultural evolution or transmission should take gender as a modulating variable into account.     

Distributed Cognition: An Ectoderm-Centric Perspective

Distributed cognition is widely recognized as an approach to the study of all cognition. It identifies the distribution of cognitive processes between persons and technology, among people, and across time in the development of the social and material contexts for thinking. This paper suggests an ectoderm-centric perspective as the basis for distributed cognition, and in so doing redefines distributed cognition as the ability of an organism to interact with its environment for the purpose of satisfying its most basic physiological (internal and external) and social needs in order to survive and sustain itself. Underlying this ectoderm-centric perspective is a proposed theory of reactive and interactive learning.     

Activity-dependent regulation of synaptic size in Drosophila neuromuscular junctions

One of the fundamental questions in neural development is how neurons form synapses of the appropriate size for the efficient transfer of information across neural circuits. Here we investigated the mechanisms that bring about the size correlation between synapses and postsynaptic cells during development of Drosophila neuromuscular junctions (NMJs). To do this, we made use of a unique system in which two neighboring muscles (M6 and M7) are innervated by the same neurons. In mature NMJs, synaptic size on M6 is normally larger than that on M7, in accordance with the difference in muscle volume; this ensures the same extent of contraction of both muscles, and we refer to this correspondence as "matching". We found that matching was apparent in larvae 8 h after hatching, but not in newly hatched larvae despite the difference in muscle volume. When sensory inputs were suppressed by the expression of tetanus toxin in sensory neurons, matching did not occur, although synapses were able to grow. Matching was also suppressed by the inhibition of motoneuronal activity. These results suggest that matching is induced by regulating the rate of synaptic growth on M6 and M7 in an experience- and activity-dependent manner. It seems most likely that retrograde signals from the postsynaptic to the presynaptic cell convey the information about muscle cell size. We thus examined whether a candidate of retrograde signaling in NMJs, BMP signaling, is involved in matching. However, there was no effect on matching in BMP type II receptor gene mutants, suggesting that other experience-driven mechanisms besides BMP signaling are involved in the proper development of synapses.     

Social Cognition Deficits and Psychopathic Traits in Young People Seeking Mental Health Treatment

Antisocial behaviours and psychopathic traits place an individual at risk for criminality, mental illness, substance dependence, and psychosocial dysfunction. Social cognition deficits appear to be associated with psychopathic traits and are believed to contribute to interpersonal dysfunction. Most research investigating the relationship of these traits with social cognition has been conducted either in children or adult forensic settings. We investigated whether psychopathic traits were associated with social cognition in 91 young people presenting for mental healthcare (aged between 15 and 25 years). Participants completed symptom severity measures, neuropsychological tests, the Reading the Mind in the Eyes Test of social cognition (RMET), and the Antisocial Process Screening Device (APSD) to assess psychopathic personality traits. Correlation analyses showed poorer social cognition was associated with greater psychopathic traits (r = −.36, p = .01). Interestingly, social cognition performance predicted unique variance in concurrent psychopathic personality traits above gender, IQ sustained attention, and working memory performance. These findings suggest that social cognitive impairments are associated with psychopathic tendencies in young people presenting for community mental healthcare. Research is needed to establish the directionality of this relationship and to determine whether social cognition training is an effective treatment amongst young people with psychopathic tendencies.     

Explaining distortions in metacognition with an attractor network model of decision uncertainty

Metacognition is the ability to reflect on, and evaluate, our cognition and behaviour. Distortions in metacognition are common in mental health disorders, though the neural underpinnings of such dysfunction are unknown. One reason for this is that models of key components of metacognition, such as decision confidence, are generally specified at an algorithmic or process level. While such models can be used to relate brain function to psychopathology, they are difficult to map to a neurobiological mechanism. Here, we develop a biologically-plausible model of decision uncertainty in an attempt to bridge this gap. We first relate the model’s uncertainty in perceptual decisions to standard metrics of metacognition, namely mean confidence level (bias) and the accuracy of metacognitive judgments (sensitivity). We show that dissociable shifts in metacognition are associated with isolated disturbances at higher-order levels of a circuit associated with self-monitoring, akin to neuropsychological findings that highlight the detrimental effect of prefrontal brain lesions on metacognitive performance. Notably, we are able to account for empirical confidence judgements by fitting the parameters of our biophysical model to first-order performance data, specifically choice and response times. Lastly, in a reanalysis of existing data we show that self-reported mental health symptoms relate to disturbances in an uncertainty-monitoring component of the network. By bridging a gap between a biologically-plausible model of confidence formation and observed disturbances of metacognition in mental health disorders we provide a first step towards mapping theoretical constructs of metacognition onto dynamical models of decision uncertainty. In doing so, we provide a computational framework for modelling metacognitive performance in settings where access to explicit confidence reports is not possible.     

Canonical and Alternative MAPK Signaling

The archetype of MAPK cascade activation is somewhat challenged by the most recent discovery of unexpected phosphorylation patterns, alternative activation mechanisms and sub-cellular localization, in various members of this protein kinase family. In particular, activation by autophosphorylation pathways has now been described for the three best understood MAPK subgroups: ERK1/2; JNK1/2 and p38α/β. Also, a form of dosage compensation between homologues has been shown to occur in the case of ERK1/2 and JNK1/2. In this paper we summarize the MAPK activation pathway, with an emphasis on non-canonical examples. We use this information to propose a model for MAPK signal transduction that considers a cross-talk between MAPKs with different activation loop sequence motifs and unique C-terminal extensions. We highlight the occurrence of non-canonical substrate specificity during MAPK auto-activation, in strong connection with MAPK homo- and hetero-dimerization events.