In the face of ambiguity: intrinsic brain organization in development predicts one's bias toward positivity or negativity.

Exacerbated negativity bias, including in responses to ambiguity, represents a common phenotype of internalizing disorders. Individuals differ in their propensity toward positive or negative appraisals of ambiguity. This variability constitutes one's valence bias, a stable construct linked to mental health. Evidence suggests an initial negativity in response to ambiguity that updates via regulatory processes to support a more positive bias. Previous work implicates the amygdala and prefrontal cortex, and regions of the cingulo-opercular system, in this regulatory process. Nonetheless, the neurodevelopmental origins of valence bias remain unclear. The current study tests whether intrinsic brain organization predicts valence bias among 119 children and adolescents (6 to 17 years). Using whole-brain resting-state functional connectivity, a machine-learning model predicted valence bias (r = 0.20, P = 0.03), as did a model restricted to amygdala and cingulo-opercular system features (r = 0.19, P = 0.04). Disrupting connectivity revealed additional intra-system (e.g. fronto-parietal) and inter-system (e.g. amygdala to cingulo-opercular) connectivity important for prediction. The results highlight top-down control systems and bottom-up perceptual processes that influence valence bias in development. Thus, intrinsic brain organization informs the neurodevelopmental origins of valence bias, and directs future work aimed at explicating related internalizing symptomology.

Specialized late cingulo-opercular network activation elucidates the mechanisms underlying decisions about ambiguity.

Cortical task control networks, including the cingulo-opercular (CO) network play a key role in decision-making across a variety of functional domains. In particular, the CO network functions in a performance reporting capacity that supports successful task performance, especially in response to errors and ambiguity. In two studies testing the contribution of the CO network to ambiguity processing, we presented a valence bias task in which masked clearly and ambiguously valenced emotional expressions were slowly revealed over several seconds. This slow reveal task design provides a window into the decision-making mechanisms as they unfold over the course of a trial. In the main study, the slow reveal task was administered to 32 young adults in the fMRI environment and BOLD time courses were extracted from regions of interest in three control networks. In a follow-up study, the task was administered to a larger, online sample (n = 81) using a more extended slow reveal design with additional unmasking frames. Positive judgments of surprised faces were uniquely accompanied by slower response times and strong, late activation in the CO network. These results support the initial negativity hypothesis, which posits that the default response to ambiguity is negative and positive judgments are associated with a more effortful controlled process, and additionally suggest that this controlled process is mediated by the CO network. Moreover, ambiguous trials were characterized by a second CO response at the end of the trial, firmly placing CO function late in the decision-making process.

Think again: the role of reappraisal in reducing negative valence bias.

Stimuli such as surprised faces are ambiguous in that they are associated with both positive and negative outcomes. Interestingly, people differ reliably in whether they evaluate these and other ambiguous stimuli as positive or negative, and we have argued that a positive evaluation relies in part on a biasing of the appraisal processes via reappraisal. To further test this idea, we conducted two studies to evaluate whether increasing the cognitive accessibility of reappraisal through a brief emotion regulation task would lead to an increase in positive evaluations of ambiguity. Supporting this prediction, we demonstrated that cuing reappraisal, but not in three other forms of emotion regulation (Study 1a-d; n = 120), increased positive evaluations of ambiguous faces. In a sign of robustness, we also found that the effect of reappraisal generalised from ambiguous faces to ambiguous scenes (Study 2; n = 34). Collectively, these findings suggest that reappraisal may play a key role in determining responses to ambiguous stimuli. We discuss these findings in the context of affective flexibility, and suggest that valence bias (i.e. the tendency to evaluate ambiguity more positively or negatively) represents a novel approach to measuring implicit emotion regulation.

Reappraisal-related downregulation of amygdala BOLD activation occurs only during the late trial window.

During cognitive reappraisal, an individual reinterprets the meaning of an emotional stimulus to regulate the intensity of their emotional response. Prefrontal cortex activity has been found to support reappraisal and is putatively thought to downregulate the amygdala response to these stimuli. The timing of these regulation-related responses during the course of a trial, however, remains poorly understood. In the current fMRI study, participants were instructed to view or reappraise negative images and then rate how negative they felt following each image. The hemodynamic response function was estimated in 11 regions of interest for the entire time course of the trial including image viewing and rating. Notably, within the amygdala there was no evidence of downregulation in the early (picture viewing) window of the trial, only in the late (rating) window, which also correlated with a behavioral measure of reappraisal success. With respect to the prefrontal regions, some (e.g., inferior frontal gyrus) showed reappraisal-related activation in the early window, whereas others (e.g., middle frontal gyrus) showed increased activation primarily in the late window. These results highlight the temporal dynamics of different brain regions during emotion regulation and suggest that the amygdala response to negative images need not be immediately dampened to achieve successful cognitive reappraisal.

Interpersonal emotion regulation mitigates the link between trait neuroticism and a more negative valence bias.

Emerging research suggests that trait neuroticism is associated with enhanced attention to and perception of negative emotional stimuli, increasing the risk for multiple forms of psychopathology including depression and anxiety. However, modifiable factors such as certain forms of emotion regulation have the potential to weaken this association. In a large sample (N = 1252), we investigated the link between neuroticism and valence bias in response to stimuli that have the potential for both positive and negative interpretations and examined the moderating role of interpersonal emotion regulation. Primary tests of hypotheses demonstrated that increased neuroticism was associated with a more negative valence bias in response to ambiguity, but only for individuals who are less likely to rely on interpersonal resources to regulate negative affect. Supplemental analyses suggest that this moderation effect of interpersonal emotion regulation might depend on the nature of the stimuli, and that regulation of positive emotions-not just negative affect-can also contribute to a less negative valence bias. Taken together, results suggest that individuals who are high in neuroticism, but consistently rely on interpersonal relationships to regulate their emotions, are better able to override the bias toward negativity that can occur when appraising ambiguity.

Probabilistic mapping of human functional brain networks identifies regions of high group consensus.

Many recent developments surrounding the functional network organization of the human brain have focused on data that have been averaged across groups of individuals. While such group-level approaches have shed considerable light on the brain's large-scale distributed systems, they conceal individual differences in network organization, which recent work has demonstrated to be common and widespread. This individual variability produces noise in group analyses, which may average together regions that are part of different functional systems across participants, limiting interpretability. However, cost and feasibility constraints may limit the possibility for individual-level mapping within studies. Here our goal was to leverage information about individual-level brain organization to probabilistically map common functional systems and identify locations of high inter-subject consensus for use in group analyses. We probabilistically mapped 14 functional networks in multiple datasets with relatively high amounts of data. All networks show "core" (high-probability) regions, but differ from one another in the extent of their higher-variability components. These patterns replicate well across four datasets with different participants and scanning parameters. We produced a set of high-probability regions of interest (ROIs) from these probabilistic maps; these and the probabilistic maps are made publicly available, together with a tool for querying the network membership probabilities associated with any given cortical location. These quantitative estimates and public tools may allow researchers to apply information about inter-subject consensus to their own fMRI studies, improving inferences about systems and their functional specializations.

Exploring valence bias as a metric for frontoamygdalar connectivity and depressive symptoms in childhood.

Negativity bias is a core feature of depression that is associated with dysfunctional frontoamygdalar connectivity; this pathway is associated with emotion regulation and sensitive to neurobiological change during puberty. We used a valence bias task (ratings of emotional ambiguity) as a potential early indicator of depression risk and differences in frontoamygdalar connectivity. Previous work using this task demonstrated that children normatively have a negative bias that attenuates with maturation. Here, we test the hypothesis that persistence of this negativity bias as maturation ensues may reveal differences in emotion regulation development, and may be associated with increased risk for depression. In children aged 6-13 years, we tested the moderating role of puberty on relationships between valence bias, depressive symptoms, and frontoamygdalar connectivity. A negative bias was associated with increased depressive symptoms for those at more advanced pubertal stages (within this sample) and less regulatory frontoamygdalar connectivity, whereas a more positive bias was associated with more regulatory connectivity patterns. These data suggest that with maturation, individual differences in positivity biases and associated emotion regulation circuitry confer a differential risk for depression. Longitudinal work is necessary to determine the directionality of these effects and explore the influence of early life events.

The dynamic process of ambiguous emotion perception.

Everyday social interactions hinge on our ability to resolve uncertainty in nonverbal cues. For example, although some facial expressions (e.g. happy, angry) convey a clear affective meaning, others (e.g. surprise) are ambiguous, in that their meaning is determined by the context. Here, we used mouse-tracking to examine the underlying process of resolving uncertainty. Previous work has suggested an initial negativity, in part via faster response times for negative than positive ratings of surprise. We examined valence categorizations of filtered images in order to compare faster (low spatial frequencies; LSF) versus more deliberate processing (high spatial frequencies; HSF). When participants categorised faces as "positive", they first exhibited a partial attraction toward the competing ("negative") response option, and this effect was exacerbated for HSF than LSF faces. Thus, the effect of response conflict due to an initial negativity bias was exaggerated for HSF faces, likely because these images allow for greater deliberation than the LSFs. These results are consistent with the notion that more positive categorizations are characterised by an initial attraction to a default, negative response.

Dorsal Anterior Cingulate, Medial Superior Frontal Cortex, and Anterior Insula Show Performance Reporting-Related Late Task Control Signals.

The cingulo-opercular network (including the dorsal anterior cingulate and bilateral anterior insula) shows 3 distinct task-control signals across a wide variety of tasks, including trial-related signals that appear to come online at or near the end of the trial. Previous work suggests that there are separable responses in this network for errors and ambiguity, implicating multiple types of processing units within these regions. Using a unique paradigm, we directly show that these separable responses withhold activity to the end of the trial, in the service of reporting performance back into the task set. Participants performed a slow reveal task where images were presented behind a black mask which was gradually degraded, and they pressed a button when they could recognize the object that was being revealed. A behavioral pilot was used to identify ambiguous stimuli. We found interactive effects of accuracy and ambiguity, which suggests that these regions are computing and utilizing information, at one time, about both types of performance indices. Importantly, we showed a relationship between cingulo-opercular activity and behavioral performance, suggesting a role for these regions in performance reporting, per se. We discuss these results in the context of task control.

Tasks Driven by Perceptual Information Do Not Recruit Sustained BOLD Activity in Cingulo-Opercular Regions.

Sustained blood oxygen level dependent (BOLD) signal in the dorsal anterior cingulate cortex/medial superior frontal cortex (dACC/msFC) and bilateral anterior insula/frontal operculum (aI/fO) is found in a broad majority of tasks examined and is believed to function as a putative task set maintenance signal. For example, a meta-analysis investigating task-control signals identified the dorsal anterior cingulate cortex and anterior insula as exhibiting sustained activity across a variety of task types. Re-analysis of tasks included in that meta-analysis showed exceptions, suggesting that tasks where the information necessary to determine a response was present in the stimulus (i.e., perceptually driven) does not show strong sustained cingulo-opercular activity. In a new experiment, we tested the generality of this observation while addressing alternative explanations about sustained cingulo-opercular activity (including task difficulty and verbal vs. non-verbal task demands). A new, difficult, perceptually driven task was compared with 2 new tasks that depended on information beyond that provided by the stimulus. The perceptually driven task showed a lack of cingulo-opercular activity in contrast to the 2 newly constructed tasks. This finding supports the idea that sustained cingulo-opercular activity contributes to maintenance of task set in only a subset of tasks.

All in the first glance: first fixation predicts individual differences in valence bias.

Surprised expressions are interpreted as negative by some people, and as positive by others. When compared to fearful expressions, which are consistently rated as negative, surprise and fear share similar morphological structures (e.g. widened eyes), but these similarities are primarily in the upper part of the face (eyes). We hypothesised, then, that individuals would be more likely to interpret surprise positively when fixating faster to the lower part of the face (mouth). Participants rated surprised and fearful faces as either positive or negative while eye movements were recorded. Positive ratings of surprise were associated with longer fixation on the mouth than negative ratings. There were also individual differences in fixation patterns, with individuals who fixated the mouth earlier exhibiting increased positive ratings. These findings suggest that there are meaningful individual differences in how people process faces.

Spatial and temporal characteristics of error-related activity in the human brain.

A number of studies have focused on the role of specific brain regions, such as the dorsal anterior cingulate cortex during trials on which participants make errors, whereas others have implicated a host of more widely distributed regions in the human brain. Previous work has proposed that there are multiple cognitive control networks, raising the question of whether error-related activity can be found in each of these networks. Thus, to examine error-related activity broadly, we conducted a meta-analysis consisting of 12 tasks that included both error and correct trials. These tasks varied by stimulus input (visual, auditory), response output (button press, speech), stimulus category (words, pictures), and task type (e.g., recognition memory, mental rotation). We identified 41 brain regions that showed a differential fMRI BOLD response to error and correct trials across a majority of tasks. These regions displayed three unique response profiles: (1) fast, (2) prolonged, and (3) a delayed response to errors, as well as a more canonical response to correct trials. These regions were found mostly in several control networks, each network predominantly displaying one response profile. The one exception to this "one network, one response profile" observation is the frontoparietal network, which showed prolonged response profiles (all in the right hemisphere), and fast profiles (all but one in the left hemisphere). We suggest that, in the place of a single localized error mechanism, these findings point to a large-scale set of error-related regions across multiple systems that likely subserve different functions.

Developmental changes in the organization of functional connections between the basal ganglia and cerebral cortex.

The basal ganglia (BG) comprise a set of subcortical nuclei with sensorimotor, cognitive, and limbic subdivisions, indicative of functional organization. BG dysfunction in several developmental disorders suggests the importance of the healthy maturation of these structures. However, few studies have investigated the development of BG functional organization. Using resting-state functional connectivity MRI (rs-fcMRI), we compared human child and adult functional connectivity of the BG with rs-fcMRI-defined cortical systems. Because children move more than adults, customized preprocessing, including volume censoring, was used to minimize motion-induced rs-fcMRI artifact. Our results demonstrated functional organization in the adult BG consistent with subdivisions previously identified in anatomical tracing studies. Group comparisons revealed a developmental shift in bilateral posterior putamen/pallidum clusters from preferential connectivity with the somatomotor "face" system in childhood to preferential connectivity with control/attention systems (frontoparietal, ventral attention) in adulthood. This shift was due to a decline in the functional connectivity of these clusters with the somatomotor face system over development, and no change with control/attention systems. Applying multivariate pattern analysis, we were able to reliably classify individuals as children or adults based on BG-cortical system functional connectivity. Interrogation of the features driving this classification revealed, in addition to the somatomotor face system, contributions by the orbitofrontal, auditory, and somatomotor hand systems. These results demonstrate that BG-cortical functional connectivity evolves over development, and may lend insight into developmental disorders that involve BG dysfunction, particularly those involving motor systems (e.g., Tourette syndrome).

Separable responses to error, ambiguity, and reaction time in cingulo-opercular task control regions.

The dorsal anterior cingulate (dACC), along with the closely affiliated anterior insula/frontal operculum, have been demonstrated to show three types of task control signals across a wide variety of tasks. One of these signals, a transient signal that is thought to represent performance feedback, shows greater activity to error than correct trials. Other work has found similar effects for uncertainty/ambiguity or conflict, though some argue that dACC activity is, instead, modulated primarily by other processes more reflected in reaction time. Here, we demonstrate that, rather than a single explanation, multiple information processing operations are crucial to characterizing the function of these brain regions, by comparing operations within a single paradigm. Participants performed two tasks in an fMRI experimental session: (1) deciding whether or not visually presented word pairs rhyme, and (2) rating auditorily presented single words as abstract or concrete. A pilot was used to identify ambiguous stimuli for both tasks (e.g., word pair: BASS/GRACE; single word: CHANGE). We found greater cingulo-opercular activity for errors and ambiguous trials than clear/correct trials, with a robust effect of reaction time. The effects of error and ambiguity remained when reaction time was regressed out, although the differences decreased. Further stepwise regression of response consensus (agreement across participants for each stimulus; a proxy for ambiguity) decreased differences between ambiguous and clear trials, but left error-related differences almost completely intact. These observations suggest that trial-wise responses in cingulo-opercular regions monitor multiple performance indices, including accuracy, ambiguity, and reaction time.

Associations of state and chronic loneliness with interpretation bias: The role of internalizing symptoms.

Loneliness is common and, while generally transient, persists in up to 22% of the population. The rising prevalence and adverse impacts of chronic loneliness highlight the need to understand its underlying mechanisms. Evolutionary models of loneliness suggest that chronically lonely individuals demonstrate negative interpretation biases towards social information. It may also be that such biases are exacerbated by momentary increases in state loneliness, or elevated anxiety or depression. Yet, little research has tested these possibilities. The current study aimed to advance understandings of loneliness by examining associations of chronic loneliness with individual differences in negative interpretation bias for social (relative to non-social) stimuli, and testing whether these associations change in the context of increased state loneliness and current levels of anxiety and depressive symptoms. These aims were explored in 591 participants who completed an interpretation bias task before and after undergoing a state loneliness induction. Participants also self-reported chronic loneliness, anxiety, and depression. Linear mixed models indicated that only state (but not chronic) loneliness was associated with more positive interpretations of non-social stimuli, with greater anxiety and depressive symptoms predicting more negative interpretations. Implications of these findings for present theoretical models of loneliness are discussed.

Proposing a model whereby negative valence bias increases the risk for more severe dysphoric posttraumatic stress disorder and depression symptomology.

Experiencing trauma increases risk for posttraumatic stress disorder (PTSD) and depression, and individuals who experience psychopathology after a traumatic event often experience symptoms from both disorders. Because a tendency to view events in a more negative light and a propensity toward threat appraisals are risk factors for both PTSD and depression, negative valence bias-a tendency to appraise emotional ambiguity as having a more negative (less positive) meaning-may be a transdiagnostic risk factor. In other words, we expect individuals with a negative valence bias experience greater PTSD and depression symptoms. We measured valence bias and self-reported PTSD and depression symptoms in a sample of college students in 2021 (n = 287; 72.5% reported experiencing trauma). Although valence bias was not associated with PTSD symptoms as a whole, we found in our exploratory model that more negative bias was associated with greater dysphoria-related PTSD symptoms and greater depression symptoms (indirect effect p = .03). Thus, we propose a model whereby a more negative valence bias contributes to increased susceptibility for maladaptive stress responses, which may be associated with greater likelihood of symptoms of dysphoria-related PTSD and depression. These findings suggest that valence bias represents a transdiagnostic affective risk factor, warranting future research examining the impacts of bias-altering interventions (e.g., mindfulness-based treatments) as a means for managing symptoms in individuals with heightened dysphoria-related PTSD and/or depression symptoms. Additionally, in post hoc analyses it emerged that Latinx participants displayed a more negative valence bias, indicating the need for more research in diverse samples. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Concussion-Related Disruptions to Hub Connectivity in the Default Mode Network Are Related to Symptoms and Cognition.

Concussions present with a myriad of symptomatic and cognitive concerns; however, the relationship between these functional disruptions and the underlying changes in the brain are not yet well understood. Hubs, or brain regions that are connected to many different functional networks, may be specifically disrupted after concussion. Given the implications in concussion research, we quantified hub disruption within the default mode network (DMN) and between the DMN and other brain networks. We collected resting-state functional magnetic resonance imaging data from collegiate student-athletes (n = 44) at three time points: baseline (before beginning their athletic season), acute post-injury (approximately 48h after a diagnosed concussion), and recovery (after starting return-to-play progression, but before returning to contact). We used self-reported symptoms and computerized cognitive assessments collected across similar time points to link these functional connectivity changes to clinical outcomes. Concussion resulted in increased connectivity between regions within the DMN compared with baseline and recovery, and this post-injury connectivity was more positively related to symptoms and more negatively related to visual memory performance compared with baseline and recovery. Further, concussion led to decreased connectivity between DMN hubs and visual network non-hubs relative to baseline and recovery, and this post-injury connectivity was more negatively related to somatic symptoms and more positively related to visual memory performance compared with baseline and recovery. Relationships between functional connectivity, symptoms, and cognition were not significantly different at baseline versus recovery. These results highlight a unique relationship between self-reported symptoms, visual memory performance, and acute functional connectivity changes involving DMN hubs after concussion in athletes. This may provide evidence for a disrupted balance of within- and between-network communication highlighting possible network inefficiencies after concussion. These results aid in our understanding of the pathophysiological disruptions after concussion and inform our understanding of the associations between disruptions in brain connectivity and specific clinical presentations acutely post-injury.

Two common and distinct forms of variation in human functional brain networks.

The cortex has a characteristic layout with specialized functional areas forming distributed large-scale networks. However, substantial work shows striking variation in this organization across people, which relates to differences in behavior. While most previous work treats individual differences as linked to boundary shifts between the borders of regions, here we show that cortical 'variants' also occur at a distance from their typical position, forming ectopic intrusions. Both 'border' and 'ectopic' variants are common across individuals, but differ in their location, network associations, properties of subgroups of individuals, activations during tasks, and prediction of behavioral phenotypes. Border variants also track significantly more with shared genetics than ectopic variants, suggesting a closer link between ectopic variants and environmental influences. This work argues that these two dissociable forms of variation-border shifts and ectopic intrusions-must be separately accounted for in the analysis of individual differences in cortical systems across people.

Neural responses to ambiguity involve domain-general and domain-specific emotion processing systems.

Extant research has examined the process of decision making under uncertainty, specifically in situations of ambiguity. However, much of this work has been conducted in the context of semantic and low-level visual processing. An open question is whether ambiguity in social signals (e.g., emotional facial expressions) is processed similarly or whether a unique set of processors come on-line to resolve ambiguity in a social context. Our work has examined ambiguity using surprised facial expressions, as they have predicted both positive and negative outcomes in the past. Specifically, whereas some people tended to interpret surprise as negatively valenced, others tended toward a more positive interpretation. Here, we examined neural responses to social ambiguity using faces (surprise) and nonface emotional scenes (International Affective Picture System). Moreover, we examined whether these effects are specific to ambiguity resolution (i.e., judgments about the ambiguity) or whether similar effects would be demonstrated for incidental judgments (e.g., nonvalence judgments about ambiguously valenced stimuli). We found that a distinct task control (i.e., cingulo-opercular) network was more active when resolving ambiguity. We also found that activity in the ventral amygdala was greater to faces and scenes that were rated explicitly along the dimension of valence, consistent with findings that the ventral amygdala tracks valence. Taken together, there is a complex neural architecture that supports decision making in the presence of ambiguity: (a) a core set of cortical structures engaged for explicit ambiguity processing across stimulus boundaries and (b) other dedicated circuits for biologically relevant learning situations involving faces.

Surprise as an Emotion: A Response to Ortony.

We write in response to an article published in this journal by Andrew Ortony titled "Are All 'Basic Emotions' Emotions? A Problem for the (Basic) Emotions Construct." The author claimed that "for all its elevated status as a basic emotion, surprise fails to satisfy the minimal requirements that [he] proposed for something to be an emotion, and if it is not an emotion, it cannot possibly be a basic emotion." Although we acknowledge the concerns brought forth by Ortony, we respectfully disagree with his conclusion about surprise. To make a case against the assertion that surprise is valence-free, we summarize an extensive body of work showing that surprise is indeed valenced-in a specific manner (i.e., ambiguously valenced)-and that it meets all of Ortony's criteria for an emotion. In other words, rather than being described as neither positive nor negative, this emotion is either positive or negative. We consider the data with respect to surprise as a basic emotion, and we dispute the definitions of basic emotions as "widely divergent." Future work is needed to continue defining an emotion, and a basic emotion, but we believe this is a worthy effort toward shaping a still evolving field.