Multiomic foundations of human prefrontal cortex tissue function.

The prefrontal cortex (PFC) is a region of the brain that in humans is involved in the production of higher-order functions such as cognition, emotion, perception, and behavior. Neurotransmission in the PFC produces higher-order functions by integrating information from other areas of the brain. At the foundation of neurotransmission, and by extension at the foundation of higher-order brain functions, are an untold number of coordinated molecular processes involving the DNA sequence variants in the genome, RNA transcripts in the transcriptome, and proteins in the proteome. These "multiomic" foundations are poorly understood in humans, perhaps in part because most modern studies that characterize the molecular state of the human PFC use tissue obtained when neurotransmission and higher-order brain functions have ceased (i.e., the postmortem state). Here, analyses are presented on data generated for the Living Brain Project (LBP) to investigate whether PFC tissue from individuals with intact higher-order brain function has characteristic multiomic foundations. Two complementary strategies were employed towards this end. The first strategy was to identify in PFC samples obtained from living study participants a signature of RNA transcript expression associated with neurotransmission measured intracranially at the time of PFC sampling, in some cases while participants performed a task engaging higher-order brain functions. The second strategy was to perform multiomic comparisons between PFC samples obtained from individuals with intact higher-order brain function at the time of sampling (i.e., living study participants) and PFC samples obtained in the postmortem state. RNA transcript expression within multiple PFC cell types was associated with fluctuations of dopaminergic, serotonergic, and/or noradrenergic neurotransmission in the substantia nigra measured while participants played a computer game that engaged higher-order brain functions. A subset of these associations - termed the "transcriptional program associated with neurotransmission" (TPAWN) - were reproduced in analyses of brain RNA transcript expression and intracranial neurotransmission data obtained from a second LBP cohort and from a cohort in an independent study. RNA transcripts involved in TPAWN were found to be (1) enriched for RNA transcripts associated with measures of neurotransmission in rodent and cell models, (2) enriched for RNA transcripts encoded by evolutionarily constrained genes, (3) depleted of RNA transcripts regulated by common DNA sequence variants, and (4) enriched for RNA transcripts implicated in higher-order brain functions by human population genetic studies. In PFC excitatory neurons of living study participants, higher expression of the genes in TPAWN tracked with higher expression of RNA transcripts that in rodent PFC samples are markers of a class of excitatory neurons that connect the PFC to deep brain structures. TPAWN was further reproduced by RNA transcript expression patterns differentiating living PFC samples from postmortem PFC samples, and significant differences between living and postmortem PFC samples were additionally observed with respect to (1) the expression of most primary RNA transcripts, mature RNA transcripts, and proteins, (2) the splicing of most primary RNA transcripts into mature RNA transcripts, (3) the patterns of co-expression between RNA transcripts and proteins, and (4) the effects of some DNA sequence variants on RNA transcript and protein expression. Taken together, this report highlights that studies of brain tissue obtained in a safe and ethical manner from large cohorts of living individuals can help advance understanding of the multiomic foundations of brain function.

Dopamine and serotonin in human substantia nigra track social context and value signals during economic exchange.

Dopamine and serotonin are hypothesized to guide social behaviours. In humans, however, we have not yet been able to study neuromodulator dynamics as social interaction unfolds. Here, we obtained subsecond estimates of dopamine and serotonin from human substantia nigra pars reticulata during the ultimatum game. Participants, who were patients with Parkinson's disease undergoing awake brain surgery, had to accept or reject monetary offers of varying fairness from human and computer players. They rejected more offers in the human than the computer condition, an effect of social context associated with higher overall levels of dopamine but not serotonin. Regardless of the social context, relative changes in dopamine tracked trial-by-trial changes in offer value-akin to reward prediction errors-whereas serotonin tracked the current offer value. These results show that dopamine and serotonin fluctuations in one of the basal ganglia's main output structures reflect distinct social context and value signals.

Noradrenaline tracks emotional modulation of attention in human amygdala.

The noradrenaline (NA) system is one of the brain's major neuromodulatory systems; it originates in a small midbrain nucleus, the locus coeruleus (LC), and projects widely throughout the brain.1,2 The LC-NA system is believed to regulate arousal and attention3,4 and is a pharmacological target in multiple clinical conditions.5,6,7 Yet our understanding of its role in health and disease has been impeded by a lack of direct recordings in humans. Here, we address this problem by showing that electrochemical estimates of sub-second NA dynamics can be obtained using clinical depth electrodes implanted for epilepsy monitoring. We made these recordings in the amygdala, an evolutionarily ancient structure that supports emotional processing8,9 and receives dense LC-NA projections,10 while patients (n = 3) performed a visual affective oddball task. The task was designed to induce different cognitive states, with the oddball stimuli involving emotionally evocative images,11 which varied in terms of arousal (low versus high) and valence (negative versus positive). Consistent with theory, the NA estimates tracked the emotional modulation of attention, with a stronger oddball response in a high-arousal state. Parallel estimates of pupil dilation, a common behavioral proxy for LC-NA activity,12 supported a hypothesis that pupil-NA coupling changes with cognitive state,13,14 with the pupil and NA estimates being positively correlated for oddball stimuli in a high-arousal but not a low-arousal state. Our study provides proof of concept that neuromodulator monitoring is now possible using depth electrodes in standard clinical use.

Causal role of a neural system for separating and selecting multidimensional social cognitive information.

People are multi-faceted, typically good at some things but bad at others, and a critical aspect of social judgement is the ability to focus on those traits relevant for the task at hand. However, it remains unknown how the brain supports such context-dependent social judgement. Here, we examine how people represent multidimensional individuals, and how the brain extracts relevant information and filters out irrelevant information when comparing individuals within a specific dimension. Using human fMRI, we identify distinct neural representations in dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI) supporting separation and selection of information for context-dependent social judgement. Causal evaluation using non-invasive brain stimulation shows that AI disruption alters the impact of relevant information on social comparison, whereas dmPFC disruption only affects the impact of irrelevant information. This neural circuit is distinct from the one supporting integration across, as opposed to separation of, different features of a multidimensional cognitive space.

Identifying cultural differences in metacognition.

Some aspects of human metacognition, such as the ability to consciously evaluate our beliefs and decisions, are hypothesized to be culturally acquired. However, direct evidence for this claim is lacking. As an initial step toward answering this question, here we examine differences in metacognitive performance between populations matched for occupation (students), income, demographics and general intelligence but drawn from 2 distinct cultural milieus (Beijing, China and London, U.K.). Chinese participants showed more efficient metacognitive evaluation of perceptual decision-making task performance compared to U.K. participants. These differences manifested in boosts to postdecisional processing following error trials, despite no differences in first-order performance. In a second experiment, we directly replicate these findings and show that a metacognitive advantage generalizes to a task that replaces postdecision evidence with equivalent social advice. Together, our results are consistent with a proposal that metacognitive capacity is shaped via sociocultural interactions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neurocomputational mechanisms of confidence in self and others.

Computing confidence in one's own and others' decisions is critical for social success. While there has been substantial progress in our understanding of confidence estimates about oneself, little is known about how people form confidence estimates about others. Here, we address this question by asking participants undergoing fMRI to place bets on perceptual decisions made by themselves or one of three other players of varying ability. We show that participants compute confidence in another player's decisions by combining distinct estimates of player ability and decision difficulty - allowing them to predict that a good player may get a difficult decision wrong and that a bad player may get an easy decision right. We find that this computation is associated with an interaction between brain systems implicated in decision-making (LIP) and theory of mind (TPJ and dmPFC). These results reveal an interplay between self- and other-related processes during a social confidence computation.

Distinct neurocomputational mechanisms support informational and socially normative conformity.

A change of mind in response to social influence could be driven by informational conformity to increase accuracy, or by normative conformity to comply with social norms such as reciprocity. Disentangling the behavioural, cognitive, and neurobiological underpinnings of informational and normative conformity have proven elusive. Here, participants underwent fMRI while performing a perceptual task that involved both advice-taking and advice-giving to human and computer partners. The concurrent inclusion of 2 different social roles and 2 different social partners revealed distinct behavioural and neural markers for informational and normative conformity. Dorsal anterior cingulate cortex (dACC) BOLD response tracked informational conformity towards both human and computer but tracked normative conformity only when interacting with humans. A network of brain areas (dorsomedial prefrontal cortex (dmPFC) and temporoparietal junction (TPJ)) that tracked normative conformity increased their functional coupling with the dACC when interacting with humans. These findings enable differentiating the neural mechanisms by which different types of conformity shape social changes of mind.

Cultural differences in neurocognitive mechanisms underlying believing.

Believing as a fundamental mental process influences other cognitive/affective processes and behavior. However, it is unclear whether believing engages distinct neurocognitive mechanisms in people with different cultural experiences. We addressed this issue by scanning Chinese and Danish adults using functional MRI during believing judgments on personality traits of oneself and a celebrity. Drift diffusion model analyses of behavioral performances revealed that speed/quality of information acquisition varied between believing judgments on positive and negative personality traits in Chinese but not in Danes. Chinese adopted a more conservative strategy of decision-making during celebrity- than self-believing judgments whereas an opposite pattern was observed in Danes. Non-decisional processes were longer for celebrity- than for self-believing in Danes but not in Chinese. Believing judgments activated the medial prefrontal cortex (mPFC) in both cultural groups but elicited stronger left anterior insular and ventral frontal activations in Chinese. Greater mPFC activity in Chinese was associated with longer duration of non-decision processes during believing-judgments, which predicted slower retrieval of self-related information in a memory test. Greater mPFC activity in Danes, however, was associated with a less degree of adopting a conservative strategy during believing judgments, which predicted faster retrieval of self-related information. Our findings highlight different neurocognitive processes engaged in believing between individuals from East Asian and Western cultures.

Sub-second Dopamine and Serotonin Signaling in Human Striatum during Perceptual Decision-Making.

Recent animal research indicates that dopamine and serotonin, neuromodulators traditionally linked to appetitive and aversive processes, are also involved in sensory inference and decisions based on such inference. We tested this hypothesis in humans by monitoring sub-second striatal dopamine and serotonin signaling during a visual motion discrimination task that separates sensory uncertainty from decision difficulty in a factorial design. Caudate nucleus recordings (n = 4) revealed multi-scale encoding: in three participants, serotonin tracked sensory uncertainty, and, in one participant, both dopamine and serotonin tracked deviations from expected trial transitions within our factorial design. Putamen recordings (n = 1) supported a cognition-action separation between caudate nucleus and putamen-a striatal sub-division unique to primates-with both dopamine and serotonin tracking decision times. These first-of-their-kind observations in the human brain reveal a role for sub-second dopamine and serotonin signaling in non-reward-based aspects of cognition and action.

Private-public mappings in human prefrontal cortex.

A core feature of human cognition is an ability to separate private states of mind - what we think or believe - from public actions - what we say or do. This ability is central to successful social interaction - with different social contexts often requiring different mappings between private states and public actions in order to minimise conflict and facilitate communication. Here we investigated how the human brain supports private-public mappings, using an interactive task which required subjects to adapt how they communicated their confidence about a perceptual decision to the social context. Univariate and multivariate analysis of fMRI data revealed that a private-public distinction is reflected in a medial-lateral division of prefrontal cortex - with lateral frontal pole (FPl) supporting the context-dependent mapping from a private sense of confidence to a public report. The concept of private-public mappings provides a promising framework for understanding flexible social behaviour.

Knowing Ourselves Together: The Cultural Origins of Metacognition.

Metacognition - the ability to represent, monitor and control ongoing cognitive processes - helps us perform many tasks, both when acting alone and when working with others. While metacognition is adaptive, and found in other animals, we should not assume that all human forms of metacognition are gene-based adaptations. Instead, some forms may have a social origin, including the discrimination, interpretation, and broadcasting of metacognitive representations. There is evidence that each of these abilities depends on cultural learning and therefore that cultural selection might shape human metacognition. The cultural origins hypothesis is a plausible and testable alternative that directs us towards a substantial new programme of research.

Human noise blindness drives suboptimal cognitive inference.

Humans typically make near-optimal sensorimotor judgements but show systematic biases when making more cognitive judgements. Here we test the hypothesis that, while humans are sensitive to the noise present during early sensory encoding, the "optimality gap" arises because they are blind to noise introduced by later cognitive integration of variable or discordant pieces of information. In six psychophysical experiments, human observers judged the average orientation of an array of contrast gratings. We varied the stimulus contrast (encoding noise) and orientation variability (integration noise) of the array. Participants adapted near-optimally to changes in encoding noise, but, under increased integration noise, displayed a range of suboptimal behaviours: they ignored stimulus base rates, reported excessive confidence in their choices, and refrained from opting out of objectively difficult trials. These overconfident behaviours were captured by a Bayesian model blind to integration noise. Our study provides a computationally grounded explanation of human suboptimal cognitive inference.

Group decision-making is optimal in adolescence.

Group decision-making is required in early life in educational settings and central to a well-functioning society. However, there is little research on group decision-making in adolescence, despite the significant neuro-cognitive changes during this period. Researchers have studied adolescent decision-making in 'static' social contexts, such as risk-taking in the presence of peers, and largely deemed adolescent decision-making 'sub-optimal'. It is not clear whether these findings generalise to more dynamic social contexts, such as the discussions required to reach a group decision. Here we test the optimality of group decision-making at different stages of adolescence. Pairs of male pre-to-early adolescents (8 to 13 years of age) and mid-to-late adolescents (14 to 17 years of age) together performed a low-level, perceptual decision-making task. Whenever their individual decisions differed, they were required to negotiate a joint decision. While there were developmental differences in individual performance, the joint performance of both adolescent groups was at adult levels (data obtained from a previous study). Both adolescent groups achieved a level of joint performance expected under optimal integration of their individual information into a joint decision. Young adolescents' joint, but not individual, performance deteriorated over time. The results are consistent with recent findings attesting to the competencies, rather than the shortcomings, of adolescent social behaviour.

Who gains more: Experts or novices? The benefits of interaction under numerical uncertainty.

Interacting to reach a shared decision is an omnipresent component of human collaboration. We explored the interaction between dyads of individuals with different levels of expertise. The members of the dyads completed a number line task privately, jointly and privately again. In the joint condition, dyad members shared their private estimates and then negotiated a joint estimate. Both dyad members averaged their private individual estimates to determine joint estimates, thereby showing a strong equality bias. Their performance in the joint condition exceeded the performance of the dyad's best estimator, demonstrating interaction benefit, only when the dyad members had similar levels of expertise and when the averaged dyad performance was sufficiently accurate. At the end of the task, participants rated their level and their partner's level of competence. Participants were accurate in classifying themselves as the expert or the novice within the dyad. Nevertheless, novices tended to overestimate their ability as they admitted to being less competent but only slightly worse than their expert partner. Experts, instead, believed themselves to be more competent but were humble and considered their performance only marginally better than their partner's. Overall, these results have important implications for settings in which people with different levels of expertise interact. (PsycINFO Database Record

Distinct encoding of decision confidence in human medial prefrontal cortex.

Our confidence in a choice and the evidence pertaining to a choice appear to be inseparable. However, an emerging computational consensus holds that the brain should maintain separate estimates of these quantities for adaptive behavioral control. We have devised a psychophysical task to decouple confidence in a perceptual decision from both the reliability of sensory evidence and the relation of such evidence with respect to a choice boundary. Using human fMRI, we found that an area in the medial prefrontal cortex, the perigenual anterior cingulate cortex (pgACC), tracked expected performance, an aggregate signature of decision confidence, whereas neural areas previously proposed to encode decision confidence instead tracked sensory reliability (posterior parietal cortex and ventral striatum) or boundary distance (presupplementary motor area). Supporting that information encoded by pgACC is central to a subjective sense of decision confidence, we show that pgACC activity does not simply covary with expected performance, but is also linked to within-subject and between-subject variation in explicit confidence estimates. Our study is consistent with the proposal that the brain maintains choice-dependent and choice-independent estimates of certainty, and sheds light on why dysfunctional confidence often emerges following prefrontal lesions and/or degeneration.

Making better decisions in groups.

We review the literature to identify common problems of decision-making in individuals and groups. We are guided by a Bayesian framework to explain the interplay between past experience and new evidence, and the problem of exploring the space of hypotheses about all the possible states that the world could be in and all the possible actions that one could take. There are strong biases, hidden from awareness, that enter into these psychological processes. While biases increase the efficiency of information processing, they often do not lead to the most appropriate action. We highlight the advantages of group decision-making in overcoming biases and searching the hypothesis space for good models of the world and good solutions to problems. Diversity of group members can facilitate these achievements, but diverse groups also face their own problems. We discuss means of managing these pitfalls and make some recommendations on how to make better group decisions.

"Is voice a marker for Autism spectrum disorder? A systematic review and meta-analysis".

Individuals with Autism Spectrum Disorder (ASD) tend to show distinctive, atypical acoustic patterns of speech. These behaviors affect social interactions and social development and could represent a non-invasive marker for ASD. We systematically reviewed the literature quantifying acoustic patterns in ASD. Search terms were: (prosody OR intonation OR inflection OR intensity OR pitch OR fundamental frequency OR speech rate OR voice quality OR acoustic) AND (autis* OR Asperger). Results were filtered to include only: empirical studies quantifying acoustic features of vocal production in ASD, with a sample size >2, and the inclusion of a neurotypical comparison group and/or correlations between acoustic measures and severity of clinical features. We identified 34 articles, including 30 univariate studies and 15 multivariate machine-learning studies. We performed meta-analyses of the univariate studies, identifying significant differences in mean pitch and pitch range between individuals with ASD and comparison participants (Cohen's d of 0.4-0.5 and discriminatory accuracy of about 61-64%). The multivariate studies reported higher accuracies than the univariate studies (63-96%). However, the methods used and the acoustic features investigated were too diverse for performing meta-analysis. We conclude that multivariate studies of acoustic patterns are a promising but yet unsystematic avenue for establishing ASD markers. We outline three recommendations for future studies: open data, open methods, and theory-driven research. Autism Res 2017, 10: 384-407. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Doubly Bayesian Analysis of Confidence in Perceptual Decision-Making.

Humans stand out from other animals in that they are able to explicitly report on the reliability of their internal operations. This ability, which is known as metacognition, is typically studied by asking people to report their confidence in the correctness of some decision. However, the computations underlying confidence reports remain unclear. In this paper, we present a fully Bayesian method for directly comparing models of confidence. Using a visual two-interval forced-choice task, we tested whether confidence reports reflect heuristic computations (e.g. the magnitude of sensory data) or Bayes optimal ones (i.e. how likely a decision is to be correct given the sensory data). In a standard design in which subjects were first asked to make a decision, and only then gave their confidence, subjects were mostly Bayes optimal. In contrast, in a less-commonly used design in which subjects indicated their confidence and decision simultaneously, they were roughly equally likely to use the Bayes optimal strategy or to use a heuristic but suboptimal strategy. Our results suggest that, while people's confidence reports can reflect Bayes optimal computations, even a small unusual twist or additional element of complexity can prevent optimality.

Equality bias impairs collective decision-making across cultures.

We tend to think that everyone deserves an equal say in a debate. This seemingly innocuous assumption can be damaging when we make decisions together as part of a group. To make optimal decisions, group members should weight their differing opinions according to how competent they are relative to one another; whenever they differ in competence, an equal weighting is suboptimal. Here, we asked how people deal with individual differences in competence in the context of a collective perceptual decision-making task. We developed a metric for estimating how participants weight their partner's opinion relative to their own and compared this weighting to an optimal benchmark. Replicated across three countries (Denmark, Iran, and China), we show that participants assigned nearly equal weights to each other's opinions regardless of true differences in their competence-even when informed by explicit feedback about their competence gap or under monetary incentives to maximize collective accuracy. This equality bias, whereby people behave as if they are as good or as bad as their partner, is particularly costly for a group when a competence gap separates its members.