7-Tesla evidence for columnar and rostral-caudal organization of the human periaqueductal gray response in the absence of threat: a working memory study.

The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain-body communication, and is often studied for its role in "fight-or-flight" and "freezing" responses to threat. We used ultra-high field 7-Tesla fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function in humans during a working memory task (N = 87). Both mild and moderate cognitive demand elicited spatially similar patterns of whole brain BOLD response, and moderate cognitive demand elicited widespread BOLD increases above baseline in the brainstem. Notably, these brainstem increases were not significantly greater than those in the mild demand condition, suggesting that a subthreshold brainstem BOLD increase occurred for mild cognitive demand as well. PAG response was group-aligned and examined with subject-specific masks. In PAG, both mild and moderate demand elicited a well-defined response in ventrolateral PAG (vlPAG), a region thought to be functionally related to anticipated painful threat in humans and non-human animals-yet, the present task posed only the most minimal (if any) "threat", with the cognitive tasks used being approximately equivalent to remembering a phone number. These findings suggest that the PAG may play a more general role in visceromotor regulation, even in the absence of threat.Significance statement The periaqueductal gray (PAG) is thought to control survival-related behavior, and is typically studied using experiments that manipulate threat. Others have proposed that the PAG plays a more general role in bodily regulation, but studies examining PAG function outside of threat-based experimental contexts are rare. We used high-resolution fMRI to examine PAG response in humans during a working memory task, which involves minimal threat. Moderate cognitive demands elicited a well-defined response in ventrolateral PAG, a functional subregion thought to coordinate a "freezing" response to threat. A task where threat is minimal elicited a clear fMRI response in one of the most well-known survival circuits in the brain, which suggests the PAG supports a more general function in brain--body coordination.

In search of animal normativity: a framework for studying social norms in non-human animals.

Social norms - rules governing which behaviours are deemed appropriate or inappropriate within a given community - are typically taken to be uniquely human. Recently, this position has been challenged by a number of philosophers, cognitive scientists, and ethologists, who have suggested that social norms may also be found in certain non-human animal communities. Such claims have elicited considerable scepticism from norm cognition researchers, who doubt that any non-human animals possess the psychological capacities necessary for normative cognition. However, there is little agreement among these researchers about what these psychological prerequisites are. This makes empirical study of animal social norms difficult, since it is not clear what we are looking for and thus what should count as behavioural evidence for the presence (or absence) of social norms in animals. To break this impasse, we offer an approach that moves beyond contested psychological criteria for social norms. This approach is inspired by the animal culture research program, which has made a similar shift away from heavily psychological definitions of 'culture' to become organised around a cluster of more empirically tractable concepts of culture. Here, we propose an analogous set of constructs built around the core notion of a normative regularity, which we define as a socially maintained pattern of behavioural conformity within a community. We suggest methods for studying potential normative regularities in wild and captive primates. We also discuss the broader scientific and philosophical implications of this research program with respect to questions of human uniqueness, animal welfare and conservation.

A functional account of stimulation-based aerobic glycolysis and its role in interpreting BOLD signal intensity increases in neuroimaging experiments.

In aerobic glycolysis, oxygen is abundant, and yet cells metabolize glucose without using it, decreasing their ATP per glucose yield by 15-fold. During task-based stimulation, aerobic glycolysis occurs in localized brain regions, presenting a puzzle: why produce ATP inefficiently when, all else being equal, evolution should favor the efficient use of metabolic resources? The answer is that all else is not equal. We propose that a tradeoff exists between efficient ATP production and the efficiency with which ATP is spent to transmit information. Aerobic glycolysis, despite yielding little ATP per glucose, may support neuronal signaling in thin (< 0.5 µm), information-efficient axons. We call this the efficiency tradeoff hypothesis. This tradeoff has potential implications for interpretations of task-related BOLD "activation" observed in fMRI. We hypothesize that BOLD "activation" may index local increases in aerobic glycolysis, which support signaling in thin axons carrying "bottom-up" information, or "prediction error"-i.e., the BIAPEM (BOLD increases approximate prediction error metabolism) hypothesis. Finally, we explore implications of our hypotheses for human brain evolution, social behavior, and mental disorders.

Cortical and subcortical mapping of the allostatic-interoceptive system in the human brain: replication and extension with 7 Tesla fMRI.

The brain continuously anticipates the energetic needs of the body and prepares to meet those needs before they arise, a process called allostasis. In support of allostasis, the brain continually models the internal state of the body, a process called interoception. Using published tract-tracing studies in non-human animals as a guide, we previously identified a large-scale system supporting allostasis and interoception in the human brain with functional magnetic resonance imaging (fMRI) at 3 Tesla. In the present study, we replicated and extended this system in humans using 7 Tesla fMRI (N = 91), improving the precision of subgenual and pregenual anterior cingulate topography as well as brainstem nuclei mapping. We verified over 90% of the anatomical connections in the hypothesized allostatic-interoceptive system observed in non-human animal research. We also identified functional connectivity hubs verified in tract-tracing studies but not previously detected using 3 Tesla fMRI. Finally, we demonstrated that individuals with stronger fMRI connectivity between system hubs self-reported greater interoceptive awareness, building on construct validity evidence from our earlier paper. Taken together, these results strengthen evidence for the existence of a whole-brain system supporting interoception in the service of allostasis and we consider the implications for mental and physical health.

Improving the study of brain-behavior relationships by revisiting basic assumptions.

Neuroimaging research has been at the forefront of concerns regarding the failure of experimental findings to replicate. In the study of brain-behavior relationships, past failures to find replicable and robust effects have been attributed to methodological shortcomings. Methodological rigor is important, but there are other overlooked possibilities: most published studies share three foundational assumptions, often implicitly, that may be faulty. In this paper, we consider the empirical evidence from human brain imaging and the study of non-human animals that calls each foundational assumption into question. We then consider the opportunities for a robust science of brain-behavior relationships that await if scientists ground their research efforts in revised assumptions supported by current empirical evidence.

Assembly of Uranyl Peroxides from Ball Milled Solids.

Mechanochemistry enables transformations of highly insoluble materials such as uranium dioxide or the mineral studtite [(UO2)(O2)(H2O)2]·(H2O)2 into uranyl triperoxide compounds that can subsequently assemble into hydroxide-bridged uranyl peroxide dimers in the presence of lithium hydroxide. Dissolution of these solids in water yields uranyl peroxide nanoclusters including U24, Li24[(UO2)(O2)(OH)]24. Insoluble uranium solids can transform into highly soluble uranyl peroxide phases in the solid state with miniscule quantities of water. Such reactions are potentially applicable to uranium processing in the front and back end of the nuclear fuel cycle.

Interoception as modeling, allostasis as control.

The brain regulates the body by anticipating its needs and attempting to meet them before they arise - a process called allostasis. Allostasis requires a model of the changing sensory conditions within the body, a process called interoception. In this paper, we examine how interoception may provide performance feedback for allostasis. We suggest studying allostasis in terms of control theory, reviewing control theory's applications to related issues in physiology, motor control, and decision making. We synthesize these by relating them to the important properties of allostatic regulation as a control problem. We then sketch a novel formalism for how the brain might perform allostatic control of the viscera by analogy to skeletomotor control, including a mathematical view on how interoception acts as performance feedback for allostasis. Finally, we suggest ways to test implications of our hypotheses.

Allostasis as a core feature of hierarchical gradients in the human brain.

This paper integrates emerging evidence from two broad streams of scientific literature into one common framework: (a) hierarchical gradients of functional connectivity that reflect the brain's large-scale structural architecture (e.g., a lamination gradient in the cerebral cortex); and (b) approaches to predictive processing and one of its specific instantiations called allostasis (i.e., the predictive regulation of energetic resources in the service of coordinating the body's internal systems). This synthesis begins to sketch a coherent, neurobiologically inspired framework suggesting that predictive energy regulation is at the core of human brain function, and by extension, psychological and behavioral phenomena, providing a shared vocabulary for theory building and knowledge accumulation.

Allostasis refers to the process by which the brain anticipates the needs of the body and attempts to meet those needs before they arise, and is one specific instantiation of a broader predictive processing framework. In this perspective article, we propose that allostasis is a basic function of the human brain subserved by an intrinsic architecture composed of two hierarchical functional gradients. Our framework, based on a synthesis of multimodal and multiscale evidence across species, begins to sketch a coherent, neurobiologically inspired research program suggesting that predictive energy regulation is at the core of human brain function, and by extension, psychological and behavioral phenomena, providing a shared vocabulary for theory building and knowledge accumulation.

A human colliculus-pulvinar-amygdala pathway encodes negative emotion.

Animals must rapidly respond to threats to survive. In rodents, threat-related signals are processed through a subcortical pathway from the superior colliculus to the amygdala, a putative "low road" to affective behavior. This pathway has not been well characterized in humans. We developed a novel pathway identification framework that uses pattern recognition to identify connected neural populations and optimize measurement of inter-region connectivity. We first verified that the model identifies known thalamocortical pathways with high sensitivity and specificity in 7 T (n = 56) and 3 T (n = 48) fMRI experiments. Then we identified a human functional superior colliculus-pulvinar-amygdala pathway. Activity in this pathway encodes the intensity of normative emotional responses to negative images and sounds but not pleasant images or painful stimuli. These results provide a functional description of a human "low road" pathway selective for negative exteroceptive events and demonstrate a promising method for characterizing human functional brain pathways.

The sense of should: A biologically-based framework for modeling social pressure.

What is social pressure, and how could it be adaptive to conform to others' expectations? Existing accounts highlight the importance of reputation and social sanctions. Yet, conformist behavior is multiply determined: sometimes, a person desires social regard, but at other times she feels obligated to behave a certain way, regardless of any reputational benefit-i.e. she feels a sense of should. We develop a formal model of this sense of should, beginning from a minimal set of biological premises: that the brain is predictive, that prediction error has a metabolic cost, and that metabolic costs are prospectively avoided. It follows that unpredictable environments impose metabolic costs, and in social environments these costs can be reduced by conforming to others' expectations. We elaborate on a sense of should's benefits and subjective experience, its likely developmental trajectory, and its relation to embodied mental inference. From this individualistic metabolic strategy, the emergent dynamics unify social phenomenon ranging from status quo biases, to communication and motivated cognition. We offer new solutions to long-studied problems (e.g. altruistic behavior), and show how compliance with arbitrary social practices is compelled without explicit sanctions. Social pressure may provide a foundation in individuals on which societies can be built.

Theory of mind network activity is associated with metaethical judgment: An item analysis.

The theory of mind network (ToMN) is a set of brain regions activated by a variety of social tasks. Recent work has proposed that these associations with ToMN activity may relate to a common underlying computation: processing prediction error in social contexts. The present work presents evidence consistent with this hypothesis, using a fine-grained item analysis to examine the relationship between ToMN activity and variance in stimulus features. We used an existing dataset (consisting of statements about morals, facts, and preferences) to examine the variability in ToMN activity elicited by moral statements, using metaethical judgments (i.e. judgments of how objective/subjective morals are) as a proxy for their predictability/support by social consensus. Study 1 validated expected patterns of behavioral judgments in our stimuli set, and Study 2 associated by-stimulus estimates of metaethical judgment with ToMN activity, showing that ToMN activity was negatively associated with objective morals and positively associated with subjective morals. Whole brain analyses indicated that these associations were strongest in bilateral temporoparietal junction (TPJ). We also observed additional by-stimulus associations with ToMN, including positive associations with the presence of a person (across morals, facts, and preferences), a negative association with agreement (among morals only), and a positive association with mental state inference (in preferences only, across 3 independent measures and behavioral samples). We discuss these findings in the context of recent predictive processing models, and highlight how predictive models may facilitate new perspectives on both metaethics and the nature of distinctions between social domains (e.g. morals vs. preferences).

Beginning with biology: "Aspects of cognition" exist in the service of the brain's overall function as a resource-regulator.

Lieder and Griffiths rightly urge that computational cognitive models be constrained by resource usage, but they should go further. The brain's primary function is to regulate resource usage. As a consequence, resource usage should not simply select among algorithmic models of "aspects of cognition." Rather, "aspects of cognition" should be understood as existing in the service of resource management.

Examining the hierarchical nature of scene representations in memory.

How are scene representations stored in memory? Researchers have often posited that scene representations have a hierarchical structure with background elements providing a scaffold for more detailed foreground elements. To further investigate scene representation and the role of background and foreground information, we introduced a new stimulus set: chimera scenes, which have the central block of objects belonging to one scene category (foreground), and the surrounding structure belonging to another (background). We used a contextual cueing paradigm and emphasized the relative importance of each by having the target placed on either the background or foreground. In a transfer block, we found that though changes to the background were highly detrimental to search performance for background targets, search performance was only slightly affected by changes to either the foreground or the background for foreground targets. These results indicate that rather than a fixed hierarchy, the structure of scene representations are more aptly captured by a parallel model that stores information flexibly. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Not as distinct as you think: Reasons to doubt that morality comprises a unified and objective conceptual category.

That morality comprises a distinct and objective conceptual category is a critical claim for Stanford's target article. We dispute this claim. Statistical conclusions about a distinct moral domain were not justified in prior work, on account of the "stimuli-as-fixed-effects" fallacy. Furthermore, we have found that, behaviorally and neurally, morals share more in common with preferences than facts.

Examining overlap in behavioral and neural representations of morals, facts, and preferences.

Metaethical judgments refer to judgments about the information expressed by moral claims. Moral objectivists generally believe that moral claims are akin to facts, whereas moral subjectivists generally believe that moral claims are more akin to preferences. Evidence from developmental and social psychology has generally favored an objectivist view; however, this work has typically relied on few examples, and analyses have disallowed statistical generalizations beyond these few stimuli. The present work addresses whether morals are represented as fact-like or preference-like, using behavioral and neuroimaging methods, in combination with statistical techniques that can (a) generalize beyond our sample stimuli, and (b) test whether particular item features are associated with neural activity. Behaviorally, and contrary to prior work, morals were perceived as more preference-like than fact-like. Neurally, morals and preferences elicited common magnitudes and spatial patterns of activity, particularly within the dorsal-medial prefrontal cortex (DMPFC), a critical region for social cognition. This common DMPFC activity for morals and preferences was present across whole-brain conjunctions, and in individually localized functional regions of interest (targeting the theory of mind network). By contrast, morals and facts did not elicit any neural activity in common. Follow-up item analyses suggested that the activity elicited in common by morals and preferences was explained by their shared tendency to evoke representations of mental states. We conclude that morals are represented as far more subjective than prior work has suggested. This conclusion is consistent with recent theoretical research, which has argued that morality is fundamentally about regulating social relationships. (PsycINFO Database Record

Know thy enemy: Education about terrorism improves social attitudes toward terrorists.

Hatred of terrorists is an obstacle to the implementation of effective counterterrorism policies-it invites indiscriminate retaliation, whereas many of the greatest successes in counterterrorism have come from understanding terrorists' personal and political motivations. Drawing from psychological research, traditional prejudice reduction strategies are generally not well suited to the task of reducing hatred of terrorists. Instead, in 2 studies, we explored education's potential ability to reduce extreme negative attitudes toward terrorists. Study 1 compared students in a college course on terrorism (treatment) with wait-listed students, measuring prosocial attitudes toward a hypothetical terrorist. Initially, all students reported extremely negative attitudes; however, at the end of the semester, treatment students' attitudes were significantly improved. Study 2 replicated the effect within a sample of treatment and control classes drawn from universities across the United States. The present work was part of an ongoing research project, focusing on foreign policy and the perceived threat of terrorism; thus classes did not explicitly aim to reduce prejudice, making the effect of treatment somewhat surprising. One possibility is that learning about terrorists "crowds out" the initial pejorative associations-that is, the label terrorism may ultimately call more information to mind, diluting its initial negative associative links. Alternatively, students may learn to challenge how the label terrorist is being applied. In either case, learning about terrorism can decrease the extreme negative reactions it evokes, which is desirable if one wishes to implement effective counterterrorism policies. (PsycINFO Database Record

Acute and chronic stress exposure predicts 1-year recurrence in adult outpatients with residual depression symptoms following response to treatment.

BACKGROUND: One of the strongest predictors of depression recurrence in those who respond to treatment is the presence of residual depressive symptoms. Our goal was to examine stressful life event exposure as a mechanism of recurrence in previously depressed patients with residual depression symptoms. That is, we predicted that higher levels of residual symptoms will significantly predict exposure to acute life events that will then heighten prospective recurrence risk. METHODS: Participants included 68 adult outpatients with major depression (42 women; age 18-60) who completed a 12-month naturalistic follow-up after achieving remission in a 20-week randomized, open label trial of interpersonal psychotherapy, cognitive-behavioral therapy, or antidepressant medication. Depression recurrence was defined as the reemergence of an episode of major depression as determined by structured interview. Acute life events and chronic stressors were assessed at the end of follow-up using a contextual interview. RESULTS: Posttreatment depression scores significantly prospectively predicted an increased risk for recurrence, and acute life events in the follow-up period. Cox regression survival analyses modeling life events as time-dependent covariates showed that life event exposure mediated the relation of residual symptoms to recurrence even controlling for chronic stress. CONCLUSIONS: Our findings implicate residual symptoms in heightening depression recurrence risk through exposure to stressful life events. Depression recurrence adds significantly to the burden of the disorder. Therefore, rigorous follow-up of patients targeting the stressful context has the potential to prevent a lifelong pattern of illness.

Maternal history of depression is associated with enhanced theory of mind in depressed and nondepressed adult women.

Theory of mind forms the basis of social cognition and develops on a stereotyped ontogenetic timetable. Yet, there are individual differences in theory of mind that may be transmitted through genetic and/or environmental mechanisms. In the current study we examined the relation of maternal history of depression to individual differences in theory of mind in a sample of adult women. Sixty-one depressed women (23% with a positive maternal history of depression) and 30 non-depressed women (33% with a positive maternal history of depression) completed the 'Reading the Mind in the Eyes task', a test of theory of mind decoding. Women with a maternal history of depression performed better on the Eyes task than those without. Further, the younger the mother's onset of depression, the better the current probands' Eyes task performance. These results are consistent with a broader literature linking hypersensitive social cognition and depression risk. We discuss the potential clinical implications of our results.