Seven 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 T fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function during a working memory task (N = 87). Both mild and moderate cognitive demands elicited spatially similar patterns of whole-brain blood oxygenation level-dependent (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. Subject-specific masks were group aligned to examine PAG response. In PAG, both mild and moderate demands elicited a well-defined response in ventrolateral PAG, a region thought to be functionally related to anticipated painful threat in humans and nonhuman animals-yet, the present task posed only the most minimal (if any) "threat," with the cognitive tasks used being approximately as challenging as 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.

The impact of sociality and affective valence on brain activation: A meta-analysis.

Thirty years of neuroimaging reveal the set of brain regions consistently associated with pleasant and unpleasant affect in humans-or the neural reference space for valence. Yet some of humans' most potent affective states occur in the context of other humans. Prior work has yet to differentiate how the neural reference space for valence varies as a product of the sociality of affective stimuli. To address this question, we meta-analyzed across 614 social and non-social affective neuroimaging contrasts, summarizing the brain regions that are consistently activated for social and non-social affective information. We demonstrate that across the literature, social and non-social affective stimuli yield overlapping activations within regions associated with visceromotor control, including the amygdala, hypothalamus, anterior cingulate cortex and insula. However, we find that social processing differs from non-social affective processing in that it involves additional cortical activations in the medial prefrontal and posterior cingulum that have been associated with mentalizing and prediction. A Bayesian classifier was able to differentiate unpleasant from pleasant affect, but not social from non-social affective states. Moreover, it was not able to classify unpleasantness from pleasantness at the highest levels of sociality. These findings suggest that highly social scenarios may be equally salient to humans, regardless of their valence.

Neural effects of antidepressant medication and psychological treatments: a quantitative synthesis across three meta-analyses.

BACKGROUND: Influential theories predict that antidepressant medication and psychological therapies evoke distinct neural changes. AIMS: To test the convergence and divergence of antidepressant- and psychotherapy-evoked neural changes, and their overlap with the brain's affect network. METHOD: We employed a quantitative synthesis of three meta-analyses (n = 4206). First, we assessed the common and distinct neural changes evoked by antidepressant medication and psychotherapy, by contrasting two comparable meta-analyses reporting the neural effects of these treatments. Both meta-analyses included patients with affective disorders, including major depressive disorder, generalised anxiety disorder and panic disorder. The majority were assessed using negative-valence tasks during neuroimaging. Next, we assessed whether the neural changes evoked by antidepressants and psychotherapy overlapped with the brain's affect network, using data from a third meta-analysis of affect-based neural activation. RESULTS: Neural changes from psychotherapy and antidepressant medication did not significantly converge on any region. Antidepressants evoked neural changes in the amygdala, whereas psychotherapy evoked anatomically distinct changes in the medial prefrontal cortex. Both psychotherapy- and antidepressant-related changes separately converged on regions of the affect network. CONCLUSIONS: This supports the notion of treatment-specific brain effects of antidepressants and psychotherapy. Both treatments induce changes in the affect network, but our results suggest that their effects on affect processing occur via distinct proximal neurocognitive mechanisms of action.

Functional Involvement of Human Periaqueductal Gray and Other Midbrain Nuclei in Cognitive Control.

Recent theoretical advances have motivated the hypothesis that the periaqueductal gray (PAG) participates in behaviors that involve changes in the autonomic control of visceromotor activity, including during cognitively demanding tasks. We used ultra-high-field (7 tesla) fMRI to measure human brain activity at 1.1 mm resolution while participants completed a working memory task. Consistent with prior work, participants were less accurate and responded more slowly with increasing memory load-signs of increasing task difficulty. Whole-brain fMRI analysis revealed increased activity in multiple cortical areas with increasing working memory load, including frontal and parietal cortex, dorsal cingulate, supplementary motor area, and anterior insula. Several dopamine-rich midbrain nuclei, such as the substantia nigra and ventral tegmental area, also exhibited load-dependent increases in activation. To investigate PAG involvement during cognitive engagement, we developed an automated method for segmenting and spatially normalizing the PAG. Analyses using cross-validated linear support vector machines showed that the PAG discriminated high versus low working memory load conditions with 95% accuracy in individual subjects based on activity increases in lateral and ventrolateral PAG. Effect sizes in the PAG were comparable in magnitude to those in many of the cortical areas. These findings suggest that cognitive control is not only associated with cortical activity in the frontal and parietal lobes, but also with increased activity in the subcortical PAG and other midbrain regions involved in the regulation of autonomic nervous system function.SIGNIFICANCE STATEMENT Functional neuroimaging in humans has shown that cognitive control engages multiple corticostriatal networks and brainstem nuclei, but theoretical advances suggest that the periaqueductal gray (PAG) should also be engaged during cognitively demanding tasks. Recent advances in ultra-high-field fMRI provided an opportunity to obtain the first evidence that increased activation of intermediate and rostral portions of lateral and ventrolateral PAG columns in humans is modulated by cognitive load. These findings suggest that cognitive control is not solely mediated by activity in the cortex, but that midbrain structures important for autonomic regulation also play a crucial role in higher-order cognition.

The influence of fear on risk taking: a meta-analysis.

A common finding in the study of emotion and decision making is the tendency for fear and anxiety to decrease risk taking. The current meta-analysis summarises the strength and variability of this effect in the extant empirical literature. Our analysis of 136 effect sizes, derived from 68 independent samples and 9,544 participants, included studies that experimentally manipulated fear or measured naturally varying levels of fear or anxiety in both clinical and non-clinical samples, and studies measuring risky decision making and risk estimation. A multilevel random effects model estimated a small to moderate average effect size (r = 0.22), such that fear was related to decreased risky decision making and increased risk estimation. There was also high heterogeneity in the effect sizes. Moderator analyses showed that effect sizes were greater when risk tasks used tangible (e.g. monetary) outcomes and when studies used clinically anxious participants. However, there also remained considerable variability in effect sizes, the sources of which remain unknown. We posit several potential factors that may contribute to observed variability in this effect for future study, including factors concerning both the nature of fear experience and the risk taking context.

The Brain Basis of Positive and Negative Affect: Evidence from a Meta-Analysis of the Human Neuroimaging Literature.

The ability to experience pleasant or unpleasant feelings or to represent objects as "positive" or "negative" is known as representing hedonic "valence." Although scientists overwhelmingly agree that valence is a basic psychological phenomenon, debate continues about how to best conceptualize it scientifically. We used a meta-analysis of 397 functional magnetic resonance imaging (fMRI) and positron emission tomography studies (containing 914 experimental contrasts and 6827 participants) to test 3 competing hypotheses about the brain basis of valence: the bipolarity hypothesis that positive and negative affect are supported by a brain system that monotonically increases and/or decreases along the valence dimension, the bivalent hypothesis that positive and negative affect are supported by independent brain systems, and the affective workspace hypothesis that positive and negative affect are supported by a flexible set of valence-general regions. We found little evidence for the bipolar or bivalent hypotheses. Findings instead supported the hypothesis that, at the level of brain activity measurable by fMRI, valence is flexibly implemented across instances by a set of valence-general limbic and paralimbic brain regions.

Emotions in "Black and White" or Shades of Gray? How We Think About Emotion Shapes Our Perception and Neural Representation of Emotion.

The demands of social life often require categorically judging whether someone's continuously varying facial movements express "calm" or "fear," or whether one's fluctuating internal states mean one feels "good" or "bad." In two studies, we asked whether this kind of categorical, "black and white," thinking can shape the perception and neural representation of emotion. Using psychometric and neuroimaging methods, we found that (a) across participants, judging emotions using a categorical, "black and white" scale relative to judging emotions using a continuous, "shades of gray," scale shifted subjective emotion perception thresholds; (b) these shifts corresponded with activity in brain regions previously associated with affective responding (i.e., the amygdala and ventral anterior insula); and (c) connectivity of these regions with the medial prefrontal cortex correlated with the magnitude of categorization-related shifts. These findings suggest that categorical thinking about emotions may actively shape the perception and neural representation of the emotions in question.

A Bayesian model of category-specific emotional brain responses.

Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories--fear, anger, disgust, sadness, or happiness--is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches.

Identification of discrete functional subregions of the human periaqueductal gray.

The midbrain periaqueductal gray (PAG) region is organized into distinct subregions that coordinate survival-related responses during threat and stress [Bandler R, Keay KA, Floyd N, Price J (2000) Brain Res 53 (1):95-104]. To examine PAG function in humans, researchers have relied primarily on functional MRI (fMRI), but technological and methodological limitations have prevented researchers from localizing responses to different PAG subregions. We used high-field strength (7-T) fMRI techniques to image the PAG at high resolution (0.75 mm isotropic), which was critical for dissociating the PAG from the greater signal variability in the aqueduct. Activation while participants were exposed to emotionally aversive images segregated into subregions of the PAG along both dorsal/ventral and rostral/caudal axes. In the rostral PAG, activity was localized to lateral and dorsomedial subregions. In caudal PAG, activity was localized to the ventrolateral region. This shifting pattern of activity from dorsal to ventral PAG along the rostrocaudal axis mirrors structural and functional neurobiological observations in nonhuman animals. Activity in lateral and ventrolateral subregions also grouped with distinct emotional experiences (e.g., anger and sadness) in a factor analysis, suggesting that each subregion participates in distinct functional circuitry. This study establishes the use of high-field strength fMRI as a promising technique for revealing the functional architecture of the PAG. The techniques developed here also may be extended to investigate the functional roles of other brainstem nuclei.

Distinct regions of prefrontal cortex are associated with the controlled retrieval and selection of social information.

Research in social neuroscience has uncovered a social knowledge network that is particularly attuned to making social judgments. However, the processes that are being performed by both regions within this network and those outside of this network that are nevertheless engaged in the service of making a social judgment remain unclear. To help address this, we drew upon research in semantic memory, which suggests that making a semantic judgment engages 2 distinct control processes: A controlled retrieval process, which aids in bringing goal-relevant information to mind from long-term stores, and a selection process, which aids in selecting the information that is goal-relevant from the information retrieved. In a neuroimaging study, we investigated whether controlled retrieval and selection for social information engage distinct portions of both the social knowledge network and regions outside this network. Controlled retrieval for social information engaged an anterior ventrolateral portion of the prefrontal cortex, whereas selection engaged both the dorsomedial prefrontal cortex and temporoparietal junction within the social knowledge network. These results suggest that the social knowledge network may be more involved with the selection of social information than the controlled retrieval of it and incorporates lateral prefrontal regions in accessing memory for making social judgments.

More than labels: neural representations of emotion words are widely distributed across the brain.

Although emotion words such as "anger," "disgust," "happiness," or "pride" are often thought of as mere labels, increasing evidence points to language as being important for emotion perception and experience. Emotion words may be particularly important for facilitating access to the emotion concepts. Indeed, deficits in semantic processing or impaired access to emotion words interfere with emotion perception. Yet, it is unclear what these behavioral findings mean for affective neuroscience. Thus, we examined the brain areas that support processing of emotion words using representational similarity analysis of functional magnetic resonance imaging data (N = 25). In the task, participants saw 10 emotion words (e.g. "anger," "happiness") while in the scanner. Participants rated each word based on its valence on a continuous scale ranging from 0 (Pleasant/Good) to 1 (Unpleasant/Bad) scale to ensure they were processing the words. Our results revealed that a diverse range of brain areas including prefrontal, midline cortical, and sensorimotor regions contained information about emotion words. Notably, our results overlapped with many regions implicated in decoding emotion experience by prior studies. Our results raise questions about what processes are being supported by these regions during emotion experience.

Fear-related psychophysiological patterns are situation and individual dependent: A Bayesian model comparison approach.

Is there a universal mapping of physiology to emotion, or do these mappings vary substantially by person or situation? Psychologists, philosophers, and neuroscientists have debated this question for decades. Most previous studies have focused on differentiating emotions on the basis of accompanying autonomic responses using analytical approaches that often assume within-category homogeneity. In the present study, we took an alternative approach to this question. We determined the extent to which the relationship between subjective experience and autonomic reactivity generalizes across, or depends upon, the individual and situation for instances of a single emotion category, specifically, fear. Electrodermal activity and cardiac activity-two autonomic measures that are often assumed to show robust relationships with instances of fear-were recorded while participants reported fear experience in response to dozens of fear-evoking videos related to three distinct situations: spiders, heights, and social encounters. We formally translated assumptions from diverse theoretical models into a common framework for model comparison analyses. Results exceedingly favored a model that assumed situation-dependency in the relationship between fear experience and autonomic reactivity, with subject variance also significant but constrained by situation. Models that assumed generalization across situations and/or individuals performed much worse by comparison. These results call into question the assumption of generalizability of autonomic-subjective mappings across instances of fear, as required in translational research from nonhuman animals to humans, and advance a situated approach to understanding the autonomic correlates of fear experience. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Fluency generating emotion words correlates with verbal measures but not emotion regulation, alexithymia, or depressive symptoms.

How do you feel? To answer this question, one must first think of potential emotion words before choosing the best fit. However, we have little insight into how the ability to rapidly bring to mind emotion words-emotion fluency-relates to emotion functioning or general verbal abilities. In this study, we measured emotion fluency by counting how many emotion words participants could generate in 60 s. Participants (N = 151 in 2011-2012) also completed a behavioral measure of verbal fluency (i.e., how many words starting with "P" or "J" participants could produce in 60 s), a cognitive reappraisal emotion regulation task, and emotion functioning questionnaires. In preregistered analyses, we found that participants produced more negative emotion words than positive words and more positive words than neutral words in the emotion fluency task. As hypothesized, emotion fluency was positively related to verbal fluency, but contrary to hypotheses, emotion fluency was not related to self-reported or task-based emotion functioning (e.g., alexithymia, depression, and emotion regulation ability). As such, in community samples, emotion fluency may reflect general cognitive abilities rather than processes crucial to emotional well-being. While emotion fluency as measured here does not track indices of well-being, future research is needed to investigate potential contexts in which verbal fluency for emotion words may be key to emotion regulation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

Sinful pleasures and pious woes? Using fMRI to examine evaluative and hedonic emotion knowledge.

Traditionally, lust and pride have been considered pleasurable, yet sinful in the West. Conversely, guilt is often considered aversive, yet valuable. These emotions illustrate how evaluations about specific emotions and beliefs about their hedonic properties may often diverge. Evaluations about specific emotions may shape important aspects of emotional life (e.g. in emotion regulation, emotion experience and acquisition of emotion concepts). Yet these evaluations are often understudied in affective neuroscience. Prior work in emotion regulation, affective experience, evaluation/attitudes and decision-making point to anterior prefrontal areas as candidates for supporting evaluative emotion knowledge. Thus, we examined the brain areas associated with evaluative and hedonic emotion knowledge, with a focus on the anterior prefrontal cortex. Participants (N = 25) made evaluative and hedonic ratings about emotion knowledge during functional magnetic resonance imaging (fMRI). We found that greater activity in the medial prefrontal cortex (mPFC), ventromedial PFC (vmPFC) and precuneus was associated with an evaluative (vs hedonic) focus on emotion knowledge. Our results suggest that the mPFC and vmPFC, in particular, may play a role in evaluating discrete emotions.

Using citation network analysis to enhance scholarship in psychological science: A case study of the human aggression literature.

Researchers cannot keep up with the volume of articles being published each year. In order to develop adequate expertise in a given field of study, students and early career scientists must be strategic in what they decide to read. Here we propose using citation network analysis to characterize the literature topology of a given area. We used the human aggression literature as our example. Our citation network analysis identified 15 research communities on aggression. The five largest communities were: "media and video games", "stress, traits and aggression", "rumination and displaced aggression", "role of testosterone", and "social aggression". We examined the growth of these research communities over time, and we used graph theoretic approaches to identify the most influential papers within each community and the "bridging" articles that linked distinct communities to one another. Finally, we also examined whether our citation network analysis would help mitigate gender bias relative to focusing on total citation counts. The percentage of articles with women first authors doubled when identifying influential articles by community structure versus citation count. Our approach of characterizing literature topologies using citation network analysis may provide a valuable resource for psychological scientists by outlining research communities and their growth over time, identifying influential papers within each community (including bridging papers), and providing opportunities to increase gender equity in the field.

A Computational Neural Model for Mapping Degenerate Neural Architectures.

Degeneracy in biological systems refers to a many-to-one mapping between physical structures and their functional (including psychological) outcomes. Despite the ubiquity of the phenomenon, traditional analytical tools for modeling degeneracy in neuroscience are extremely limited. In this study, we generated synthetic datasets to describe three situations of degeneracy in fMRI data to demonstrate the limitations of the current univariate approach. We describe a novel computational approach for the analysis referred to as neural topographic factor analysis (NTFA). NTFA is designed to capture variations in neural activity across task conditions and participants. The advantage of this discovery-oriented approach is to reveal whether and how experimental trials and participants cluster into task conditions and participant groups. We applied NTFA on simulated data, revealing the appropriate degeneracy assumption in all three situations and demonstrating NTFA's utility in uncovering degeneracy. Lastly, we discussed the importance of testing degeneracy in fMRI data and the implications of applying NTFA to do so.

Identifying the what, why, and how of an observed action: an fMRI study of mentalizing and mechanizing during action observation.

Humans commonly understand the unobservable mental states of others by observing their actions. Embodied simulation theories suggest that this ability may be based in areas of the fronto-parietal mirror neuron system, yet neuroimaging studies that explicitly investigate the human ability to draw mental state inferences point to the involvement of a “mentalizing" system consisting of regions that do not overlap with the mirror neuron system. For the present study, we developed a novel action identification paradigm that allowed us to explicitly investigate the neural bases of mentalizing observed actions. Across repeated viewings of a set of ecologically valid video clips of ordinary human actions, we manipulated the extent to which participants identified the unobservable mental states of the actor (mentalizing) or the observable mechanics of their behavior (mechanizing). Although areas of the mirror neuron system did show an enhanced response during action identification, its activity was not significantly modulated by the extent to which the observers identified mental states. Instead, several regions of the mentalizing system, including dorsal and ventral aspects of medial pFC, posterior cingulate cortex, and temporal poles, were associated with mentalizing actions, whereas a single region in left lateral occipito-temporal cortex was associated with mechanizing actions. These data suggest that embodied simulation is insufficient to account for the sophisticated mentalizing that human beings are capable of while observing another and that a different system along the cortical midline and in anterior temporal cortex is involved in mentalizing an observed action.

At the Neural Intersection Between Language and Emotion.

What role does language play in emotion? Behavioral research shows that emotion words such as "anger" and "fear" alter emotion experience, but questions still remain about mechanism. Here, we review the neuroscience literature to examine whether neural processes associated with semantics are also involved in emotion. Our review suggests that brain regions involved in the semantic processing of words: (i) are engaged during experiences of emotion, (ii) coordinate with brain regions involved in affect to create emotions, (iii) hold representational content for emotion, and (iv) may be necessary for constructing emotional experience. We relate these findings with respect to four theoretical relationships between language and emotion, which we refer to as "non-interactive," "interactive," "constitutive," and "deterministic." We conclude that findings are most consistent with the interactive and constitutive views with initial evidence suggestive of a constitutive view, in particular. We close with several future directions that may help test hypotheses of the constitutive view.

Emotion Naming Impedes Both Cognitive Reappraisal and Mindful Acceptance Strategies of Emotion Regulation.

Friends and therapists often encourage people in distress to say how they feel (i.e., name their emotions) with the hope that identifying their emotions will help them cope. Although lay and some psychological theories posit that emotion naming should facilitate subsequent emotion regulation, there is little research directly testing this question. Here, we report on two experimental studies that test how naming the emotions evoked by aversive images impacts subsequent regulation of those emotions. In study 1 (N = 80), participants were randomly assigned into one of four between-subjects conditions in which they either (i) passively observed aversive images, (ii) named the emotions that these images made them feel, (iii) regulated their emotions by reappraising the meaning of images, or (iv) both named and regulated their emotions. Analyses of self-reported negative affect revealed that emotion naming impeded emotion regulation via reappraisal. Participants who named their emotions before reappraising reported feeling worse than those who regulated without naming. Study 2 (N = 60) replicated these findings in a within-participants design, demonstrated that emotion naming also impeded regulation via mindful acceptance, and showed that observed effects were unrelated to a measure of social desirability, thereby mitigating the concern of experimenter demand. Together, these studies show that the impact of emotion naming on emotion regulation opposes common intuitions: instead of facilitating emotion regulation via reappraisal or acceptance, constructing an instance of a specific emotion category by giving it a name may "crystalize" one's affective experience and make it more resistant to modification. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00036-y.