Morphological similarity of amygdala-ventral prefrontal pathways represents trait anxiety in younger and older adults.

Stronger amygdala-ventral prefrontal white matter connectivity has been associated with lower trait anxiety, possibly reflecting an increased capacity for efficient communication between the two regions. However, there are also reports arguing against this brain-anxiety association. To address these inconsistencies in the literature, we tested the possibility that idiosyncratic tract morphology may account for meaningful individual differences in trait anxiety, even among those with comparable microstructural integrity. Here, we adopted intersubject representational similarity analysis, an analytic framework that captures multivariate patterns of similarity, to analyze the morphological similarity of amygdala-ventral prefrontal pathways. Data drawn from the Leipzig Study for Mind-Body-Emotion Interactions dataset showed that younger adults (20 to 35 y of age) with low trait anxiety, in contrast to trait-anxious individuals, had consistently similar morphological configurations in their left amygdala-ventral prefrontal pathways. Additional tests on an independent sample of older adults (60 to 75 y of age) validated this finding. Our study reveals a generalizable pattern of brain-anxiety association that is embedded within the shared geometries between fiber tract morphology and trait anxiety data.

Adaptive-to-maladaptive gradient of emotion regulation tendencies are embedded in the functional-structural hybrid connectome.

BACKGROUND: Emotion regulation tendencies are well-known transdiagnostic markers of psychopathology, but their neurobiological foundations have mostly been examined within the theoretical framework of cortical-subcortical interactions. METHODS: We explored the connectome-wide neural correlates of emotion regulation tendencies using functional and diffusion magnetic resonance images of healthy young adults (N = 99; age 20-30; 28 females). We first tested the importance of considering both the functional and structural connectome through intersubject representational similarity analyses. Then, we employed a canonical correlation analysis between the functional-structural hybrid connectome and 23 emotion regulation strategies. Lastly, we sought to externally validate the results on a transdiagnostic adolescent sample (N = 93; age 11-19; 34 females). RESULTS: First, interindividual similarity of emotion regulation profiles was significantly correlated with interindividual similarity of the functional-structural hybrid connectome, more so than either the functional or structural connectome. Canonical correlation analysis revealed that an adaptive-to-maladaptive gradient of emotion regulation tendencies mapped onto a specific configuration of covariance within the functional-structural hybrid connectome, which primarily involved functional connections in the motor network and the visual networks as well as structural connections in the default mode network and the subcortical-cerebellar network. In the transdiagnostic adolescent dataset, stronger functional signatures of the found network were associated with higher general positive affect through more frequent use of adaptive coping strategies. CONCLUSIONS: Taken together, our study illustrates a gradient of emotion regulation tendencies that is best captured when simultaneously considering the functional and structural connections across the whole brain.

Altered Task-Evoked Corticolimbic Responsivity in Generalized Anxiety Disorder.

Generalized anxiety disorder (GAD) is marked by uncontrollable, persistent worry and exaggerated response to uncertainty. Here, we review and summarize the findings from the GAD literature that employs functional neuroimaging methods. In particular, the present review focuses on task-based blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. We find that select brain regions often regarded as a part of a corticolimbic circuit (e.g., amygdala, anterior cingulate cortex, prefrontal cortex) are consistently targeted for a priori hypothesis-driven analyses, which, in turn, shows varying degrees of abnormal BOLD responsivity in GAD. Data-driven whole-brain analyses show the insula and the hippocampus, among other regions, to be affected by GAD, depending on the task used in each individual study. Overall, while the heterogeneity of the tasks and sample size limits the generalizability of the findings thus far, some promising convergence can be observed in the form of the altered BOLD responsivity of the corticolimbic circuitry in GAD.

Amygdalostriatal coupling underpins positive but not negative coloring of ambiguous affect.

Humans routinely integrate affective information from multiple sources. For example, we rarely interpret an emotional facial expression devoid of context. In this paper, we describe the neural correlates of an affective computation that involves integrating multiple sources, by leveraging the ambiguity and subtle feature-based valence signals found in surprised faces. Using functional magnetic resonance imaging, participants reported the valence of surprised faces modulated by positive or negative sentences. Amygdala activity corresponded to the valence value assigned to each contextually modulated face, with greater activity reflecting more negative ratings. Amygdala activity did not track the valence of the faces or sentences per se. Moreover, the amygdala was functionally coupled with the nucleus accumbens only during face trials preceded by positive contextual cues. These data suggest 1) valence-related amygdala activity reflects the integrated valence values rather than the valence values of each individual component, and 2) amygdalostriatal coupling underpins positive but not negative coloring of ambiguous affect.

General functional connectivity: Shared features of resting-state and task fMRI drive reliable and heritable individual differences in functional brain networks.

Intrinsic connectivity, measured using resting-state fMRI, has emerged as a fundamental tool in the study of the human brain. However, due to practical limitations, many studies do not collect enough resting-state data to generate reliable measures of intrinsic connectivity necessary for studying individual differences. Here we present general functional connectivity (GFC) as a method for leveraging shared features across resting-state and task fMRI and demonstrate in the Human Connectome Project and the Dunedin Study that GFC offers better test-retest reliability than intrinsic connectivity estimated from the same amount of resting-state data alone. Furthermore, at equivalent scan lengths, GFC displayed higher estimates of heritability than resting-state functional connectivity. We also found that predictions of cognitive ability from GFC generalized across datasets, performing as well or better than resting-state or task data alone. Collectively, our work suggests that GFC can improve the reliability of intrinsic connectivity estimates in existing datasets and, subsequently, the opportunity to identify meaningful correlates of individual differences in behavior. Given that task and resting-state data are often collected together, many researchers can immediately derive more reliable measures of intrinsic connectivity through the adoption of GFC rather than solely using resting-state data. Moreover, by better capturing heritable variation in intrinsic connectivity, GFC represents a novel endophenotype with broad applications in clinical neuroscience and biomarker discovery.

Microstructural integrity of white matter moderates an association between childhood adversity and adult trait anger.

Amongst a number of negative life sequelae associated with childhood adversity is the later expression of a higher dispositional tendency to experience anger and frustration to a wide range of situations (i.e., trait anger). We recently reported that an association between childhood adversity and trait anger is moderated by individual differences in both threat-related amygdala activity and executive control-related dorsolateral prefrontal cortex (dlPFC) activity, wherein individuals with relatively low amygdala and high dlPFC activity do not express higher trait anger even when having experienced childhood adversity. Here, we examine possible structural correlates of this functional dynamic using diffusion magnetic resonance imaging data from 647 young adult men and women volunteers. Specifically, we tested whether the degree of white matter microstructural integrity as indexed by fractional anisotropy modulated the association between childhood adversity and trait anger. Our analyses revealed that higher microstructural integrity of multiple pathways was associated with an attenuated link between childhood adversity and adult trait anger. Amongst these pathways was the uncinate fasciculus (UF; ΔR 2 = 0.01), which not only provides a major anatomical link between the amygdala and prefrontal cortex but also is associated with individual differences in regulating negative emotion through top-down cognitive reappraisal. These findings suggest that higher microstructural integrity of distributed white matter pathways including but not limited to the UF may represent an anatomical foundation serving to buffer against the expression of childhood adversity as later trait anger, which is itself associated with multiple negative health outcomes.

Human Amygdala Tracks a Feature-Based Valence Signal Embedded within the Facial Expression of Surprise.

Human amygdala function has been traditionally associated with processing the affective valence (negative vs positive) of an emotionally charged event, especially those that signal fear or threat. However, this account of human amygdala function can be explained by alternative views, which posit that the amygdala might be tuned to either (1) general emotional arousal (activation vs deactivation) or (2) specific emotion categories (fear vs happy). Delineating the pure effects of valence independent of arousal or emotion category is a challenging task, given that these variables naturally covary under many circumstances. To circumvent this issue and test the sensitivity of the human amygdala to valence values specifically, we measured the dimension of valence within the single facial expression category of surprise. Given the inherent valence ambiguity of this category, we show that surprised expression exemplars are attributed valence and arousal values that are uniquely and naturally uncorrelated. We then present fMRI data from both sexes, showing that the amygdala tracks these consensus valence values. Finally, we provide evidence that these valence values are linked to specific visual features of the mouth region, isolating the signal by which the amygdala detects this valence information.SIGNIFICANCE STATEMENT There is an open question as to whether human amygdala function tracks the valence value of cues in the environment, as opposed to either a more general emotional arousal value or a more specific emotion category distinction. Here, we demonstrate the utility of surprised facial expressions because exemplars within this emotion category take on valence values spanning the dimension of bipolar valence (positive to negative) at a consistent level of emotional arousal. Functional neuroimaging data showed that amygdala responses tracked the valence of surprised facial expressions, unconfounded by arousal. Furthermore, a machine learning classifier identified particular visual features of the mouth region that predicted this valence effect, isolating the specific visual signal that might be driving this neural valence response.

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.

Computational meta-analysis of statistical parametric maps in major depression.

OBJECTIVE: Several neuroimaging meta-analyses have summarized structural brain changes in major depression using coordinate-based methods. These methods might be biased toward brain regions where significant differences were found in the original studies. In this study, a novel voxel-based technique is implemented that estimates and meta-analyses between-group differences in grey matter from individual MRI studies, which are then applied to the study of major depression. METHODS: A systematic review and meta-analysis of voxel-based morphometry studies were conducted comparing participants with major depression and healthy controls by using statistical parametric maps. Summary effect sizes were computed correcting for multiple comparisons at the voxel level. Publication bias and heterogeneity were also estimated and the excess of heterogeneity was investigated with metaregression analyses. RESULTS: Patients with major depression were characterized by diffuse bilateral grey matter loss in ventrolateral and ventromedial frontal systems extending into temporal gyri compared to healthy controls. Grey matter reduction was also detected in the right parahippocampal and fusiform gyri, hippocampus, and bilateral thalamus. Other areas included parietal lobes and cerebellum. There was no evidence of statistically significant publication bias or heterogeneity. CONCLUSIONS: The novel computational meta-analytic approach used in this study identified extensive grey matter loss in key brain regions implicated in emotion generation and regulation. Results are not biased toward the findings of the original studies because they include all available imaging data, irrespective of statistically significant regions, resulting in enhanced detection of additional areas of grey matter loss.

Heroes and villains: opposing narrative roles engage neural synchronization in the inferior frontal gyrus.

Neuroscientific studies have highlighted the role of the default mode network (DMN) in processing narrative information. Here, we examined whether the neural synchronization of the DMN tracked the appearances of protagonists and antagonists when viewing highly engaging, socially rich audiovisual narratives. Using inter-subject correlation analysis on two independent, publicly available movie-watching fMRI datasets, we computed whole-brain neural synchronization during the appearance of the protagonists and antagonists. Results showed that the inferior frontal gyrus (IFG) had higher ISC values during the appearance of the protagonists than the antagonists. Importantly, these findings were generalized in both datasets. We discuss the results in the context of information integration and emotional empathy, which are relevant to functions of the IFG. Our study presents generalizable evidence that the IFG show distinctive synchronization patterns due to differences in narrative roles.

Intrinsic functional connectivity of motor and heteromodal association cortex predicts individual differences in regulatory focus.

Regulatory focus theory (RFT) describes two cognitive-motivational systems for goal pursuit-the promotion and prevention systems-important for self-regulation and previously implicated in vulnerability to psychopathology. According to RFT, the promotion system is engaged in attaining ideal goals (e.g. hopes and dreams), whereas the prevention system is associated with accomplishing ought goals (e.g. duties and obligations). Prior task-based functional magnetic resonance imaging (fMRI) studies have mostly explored the mapping of these two systems onto the activity of a priori brain regions supporting motivation and executive control in both healthy and depressed adults. However, complex behavioral processes such as those guided by individual differences in regulatory focus are likely supported by widely distributed patterns of intrinsic functional connectivity. We used data-driven connectome-based predictive modeling to identify patterns of distributed whole-brain intrinsic network connectivity associated with individual differences in promotion and prevention system orientation in 1,307 young university volunteers. Our analyses produced a network model predictive of prevention but not promotion orientation, specifically the subjective experience of successful goal pursuit using prevention strategies. The predictive model of prevention success was highlighted by decreased intrinsic functional connectivity of both heteromodal association cortices in the parietal and limbic networks and the primary motor cortex. We discuss these findings in the context of strategic inaction, which drives individuals with a strong dispositional prevention orientation to inhibit their behavioral tendencies in order to shield the self from potential losses, thus maintaining the safety of the status quo but also leading to trade-offs in goal pursuit success.

Intersubject representational similarity analysis uncovers the impact of state anxiety on brain activation patterns in the human extrastriate cortex.

The current study used functional magnetic resonance imaging (fMRI) and showed that state anxiety modulated extrastriate cortex activity in response to emotionally-charged visual images. State anxiety and neuroimaging data from 53 individuals were subjected to an intersubject representational similarity analysis (ISRSA), wherein the geometries between neural and behavioral data were compared. This analysis identified the extrastriate cortex (fusiform gyrus and area MT) to be the sole regions whose activity patterns covaried with state anxiety. Importantly, we show that this brain-behavior association is revealed when treating state anxiety data as a multidimensional response pattern, rather than a single composite score. This suggests that ISRSA using multivariate distances may be more sensitive in identifying the shared geometries between self-report questionnaires and brain imaging data. Overall, our findings demonstrate that a transient state of anxiety may influence how visual information - especially those relevant to the valence dimension - is processed in the extrastriate cortex.

Tracking emotions from song lyrics: Analyzing 30 years of K-pop hits.

Emotions that are shared by a large number of people could broadly impact affective experiences at the individual level. Here, we used text mining on popular song lyrics-a cultural product that has been suggested to mirror emotions that many members of a society value and prefer-to track the changes in emotions over time. Morpheme frequency analysis and structural topic modeling on 2,962 hit K-pop songs from 1990 to 2019 showed converging evidence for increased positive emotional content and decreased negative emotional content embedded within the lyrics. This pattern of temporal shift in emotions aligned with rapid changes in South Korea in the past 30 years, notably a rise in individualism and ego orientation in a traditionally collectivistic culture, as well as economic growth. More generally, this study illustrates a strategy for tracking emotions that people value and prefer from large natural language data, supplementing existing methods such as self-reported surveys and laboratory experiments. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

On the relationship between the social brain, social connectedness, and wellbeing.

The emergence of social neuroscience in the past two decades has offered a useful neurocognitive framework for understanding human social behavior. Of importance, social neuroscience research aimed to provide mechanistic explanations for the established link between wellbeing and social behavioral phenomena-particularly those reflective of social connectedness. Here, we provide an overview of the relevant literature focusing on recent work using functional magnetic resonance imaging (fMRI). In general, fMRI research demonstrated that aspects of social connectedness that are known to either positively (e.g., social acceptance) or negatively (e.g., social isolation) impact wellbeing also modulated the activity of subcortical reward system accordingly. Similar modulatory influence was found for the activity of other brain regions such as the medial prefrontal cortex, which are typically regarded as components of the "social brain" that support a wide range of functions related to social cognition and behavior. Elucidating such individual differences in brain activity may shed light onto the neural underpinnings of the link between social connectedness and wellbeing.

Topographical similarity of cortical thickness represents generalized anxiety symptoms in adolescence.

Generalized anxiety disorder (GAD) is a common condition characterized by excessive and uncontrollable worry, along with its high comorbidity rates. Despite increasing efforts to identify the neural underpinnings of GAD, neuroimaging research using cortical thickness have yielded largely inconsistent results. To address this, we adopted an inter-subject representational similarity analysis framework to explore a potential nonlinear relationship between vertex-wise cortical thickness and generalized anxiety symptom severity. We utilized a sample of 120 adolescents (13-18 years of age) from the Healthy Brain Network dataset. Here, we found greater topographical resemblance among participants with heightened generalized anxiety symptoms in the left caudal anterior cingulate and pericalcarine cortex. These results were not driven by the effects of age, sex, ADHD diagnosis, and GAD diagnosis. Such associations were not observed when including a group of younger participants (11-12 years of age) for analyses, highlighting the importance of age range selection when considering the link between cortical thickness and anxiety. Our findings reveal a novel cortical thickness topography that represents generalized anxiety in adolescents, which is embedded within the shared geometries between generalized anxiety symptoms and cortical thickness.

Similarity in functional connectome architecture predicts teenage grit.

Grit is a personality trait that encapsulates the tendency to persevere and maintain consistent interest for long-term goals. While prior studies found that grit predicts positive behavioral outcomes, there is a paucity of work providing explanatory evidence from a neurodevelopmental perspective. Based on previous research suggesting the utility of the functional connectome (FC) as a developmental measure, we tested the idea that individual differences in grit might be, in part, rooted in brain development in adolescence and emerging adulthood (N = 64, 11-19 years of age). Our analysis showed that grit was associated with connectome stability across conditions and connectome similarity across individuals. Notably, inter-subject representational similarity analysis revealed that teenagers who were grittier shared similar FC architecture with each other, more so than those with lower grit. Our findings suggest that individuals with high levels of grit are more likely to exhibit a converging pattern of whole-brain functional connectivity, which may underpin subsequent beneficial behavioral outcomes.

Corticolimbic structural connectivity encapsulates real-world emotional reactivity and happiness.

Emotional reactivity to everyday events predicts happiness, but the neural circuits underlying this relationship remain incompletely understood. Here, we combined experience sampling methods and diffusion magnetic resonance imaging to examine the association among corticolimbic structural connectivity, real-world emotional reactivity and daily experiences of happiness from 79 young adults (35 females). Participants recorded momentary assessments of emotional and happiness experiences five times a day for a week, approximately 2 weeks after brain scanning. Model-based emotional reactivity scores, which index the degree to which moment-to-moment affective state varies with the occurrence of positive or negative events, were computed. Results showed that stronger microstructural integrity of the uncinate fasciculus and the external capsule was associated with both greater positive and negative emotional reactivity scores. The relationship between these fiber tracts and experienced happiness was explained by emotional reactivity. Importantly, this indirect effect was observed for emotional reactivity to positive but not negative real-world events. Our findings suggest that the corticolimbic circuits supporting socioemotional functions are associated with emotional reactivity and happiness in the real world.

Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest.

Anxiety is linked to compromised interactions between the amygdala and the dorsal and ventral medial prefrontal cortex (mPFC). While numerous task-based neuroimaging studies show that anxiety levels predict amygdala-mPFC connectivity and response magnitude, here we tested the hypothesis that anxiety would predict functional connectivity between these brain regions even during rest. Resting-state functional magnetic resonance imaging scans and self-reported measures of anxiety were acquired from healthy subjects. At rest, individuals with high anxiety were characterized by negatively correlated amygdala-ventral mPFC functional connectivity, while low anxious subjects showed positively correlated activity. Further, high anxious subjects showed amygdala-dorsal mPFC activity that was uncorrelated, while low anxious subjects showed negatively correlated activity. These data show that amygdala-mPFC connectivity at rest indexes normal individual differences in anxiety.

Structural connectome-based prediction of trait anxiety.

Neurobiological research on anxiety has shown that trait-anxious individuals may be characterized by weaker structural connectivity of the amygdala-prefrontal circuitry, representing a reduced capacity for efficient communication between the two brain regions. However, comparison of available studies has been inconsistent, possibly related to factors such as aging that influences both trait anxiety and structural connectivity of the brain. To help clarify the nature of brain-anxiety relationship, we applied a connectome-based predictive modeling framework on 148 diffusion-weighted imaging data from the Leipzig Study for Mind-Body Emotion Interactions dataset and identified multivariate patterns of whole-brain structural connectivity that predicted trait anxiety. Results showed that networks predictive of trait anxiety differed across age groups. Specifically, an isolated negative network, which shared overlapping features with the amygdala-prefrontal circuitry, was found in younger adults (20-30 years of age), whereas a widespread positive network highlighted by frontotemporal and frontolimbic connectivity was identified when both younger and older adults (20-80 years of age) were examined. No predictive network was observed when only older adults (30-80 years of age) were considered. Our findings highlight an important age-dependent effect on the structural connectome-based prediction of trait anxiety, supporting ongoing efforts to develop potential neural biomarkers of anxiety.