Pre-scan state anxiety is associated with greater right amygdala-hippocampal response to fearful versus happy faces among trait-anxious Latina girls.

BACKGROUND: Unfamiliarity with academic research may contribute to higher levels of anticipatory state anxiety about affective neuroimaging tasks. Children with high trait anxiety display differences in brain response to fearful facial affect compared to non-anxious youth, but little is known about the influence of state anxiety on this association. Because reduced engagement in scientific research and greater mistrust among minoritized groups may lead to systematic differences in pre-scan state anxiety, it is crucial to understand the neural correlates of state anxiety during emotion processing so as to disambiguate sources of individual differences. METHODS: The present study probed the interactive effects of pre-scan state anxiety, trait anxiety, and emotional valence (fearful vs. happy faces) on neural activation during implicit emotion processing in a community sample of 46 preadolescent Latina girls (8-13 years). RESULTS: Among girls with mean and high levels of trait anxiety, pre-scan state anxiety was associated with greater right amygdala-hippocampal and left inferior parietal lobe response to fearful faces relative to happy faces. CONCLUSIONS: Anticipatory state anxiety in the scanning context may cause children with moderate and high trait anxiety to be hypervigilant to threats, further compounding the effects of trait anxiety. Neuroimaging researchers should control for state anxiety so that systematic differences in brain activation resulting from MRI apprehension are not misleadingly attributed to demographic or environmental characteristics.

Longitudinal Change in Adolescent Depression and Anxiety Symptoms from before to during the COVID-19 Pandemic.

This study aimed to examine changes in depression and anxiety symptoms from before to during the first 6 months of the COVID-19 pandemic in a sample of 1,339 adolescents (9-18 years old, 59% female) from three countries. We also examined if age, race/ethnicity, disease burden, or strictness of government restrictions moderated change in symptoms. Data from 12 longitudinal studies (10 U.S., 1 Netherlands, 1 Peru) were combined. Linear mixed effect models showed that depression, but not anxiety, symptoms increased significantly (median increase = 28%). The most negative mental health impacts were reported by multiracial adolescents and those under 'lockdown' restrictions. Policy makers need to consider these impacts by investing in ways to support adolescents' mental health during the pandemic.

Neural responding during uncertain threat anticipation in pediatric anxiety.

Excessive fear responses to uncertain threat are a key feature of anxiety disorders (ADs), though most mechanistic work considers adults. As ADs onset in childhood and confer risk for later psychopathology, we sought to identify conditions of uncertain threat that distinguish 8-17-year-old youth with AD (n = 19) from those without AD (n = 33), and assess test-retest reliability of such responses in a companion sample of healthy adults across three sites (n = 19). In an adapted uncertainty of threat paradigm, visual cues parametrically signaled threat of aversive stimuli (fear faces) in 25 % increments (0 %, 25 %, 50 %, 100 %), while participants underwent functional magnetic resonance imaging (fMRI). We compared neural response elicited by cues signaling different degrees of probability regarding the subsequent delivery of fear faces. Overall, youth displayed greater engagement of bilateral inferior parietal cortex, fusiform gyrus, and lingual gyrus during uncertain threat anticipation in general. Relative to healthy youth, AD youth exhibited greater activation in ventrolateral prefrontal cortex (vlPFC)/BA47 during uncertain threat anticipation in general. Further, AD differed from healthy youth in scaling of ventral striatum/sgACC activation with threat probability and attenuated flexibility of responding during parametric uncertain threat. Complementing these results, significant, albeit modest, cross-site test-retest reliability in these regions was observed in an independent sample of healthy adults. While preliminary due to a small sample size, these findings suggest that during uncertainty of threat, AD youth engage vlPFC regions known to be involved in fear regulation, response inhibition, and cognitive control. Findings highlight the potential of isolating neural correlates of threat anticipation to guide treatment development and translational work in youth.

Anxiety symptoms and puberty interactively predict lower cingulum microstructure in preadolescent Latina girls.

Preadolescence is a period of increased vulnerability for anxiety, especially among Latina girls. Reduced microstructure (fractional anisotropy; FA) of white matter tracts between limbic and prefrontal regions may underlie regulatory impairments in anxiety. However, developmental research on the association between anxiety and white matter microstructure is mixed, possibly due to interactive influences with puberty. In a sample of 39 Latina girls (8-13 years), we tested whether pubertal stage moderated the association between parent- and child-reported anxiety symptoms and FA in the cingulum and uncinate fasciculus. Parent- but not child-reported anxiety symptoms predicted lower cingulum FA, and this effect was moderated by pubertal stage, such that this association was only significant for prepubertal girls. Neither anxiety nor pubertal stage predicted uncinate fasciculus FA. These findings suggest that anxiety is associated with disruptions in girls' cingulum white matter microstructure and that this relationship undergoes maturational changes during puberty.

School-aged children with higher anxiety symptoms show greater correspondence between subjective negative emotions and autonomic arousal.

Individuals exhibit variability in the degree of correspondence between autonomic and subjective indicators of emotional experience. The current study examined whether convergence between autonomic arousal and negative emotions during emotion-inducing story vignettes is associated with internalizing symptoms in school-aged children. A diverse sample of 97 children aged 8 to 12 years participated in this study in which they reported on their anxiety and depression. Children's electrodermal activity was assessed while they read vignettes depicting children experiencing sadness and fear. Participants also reported on their emotional reaction to the vignettes. Children's anxiety and electrodermal activity to fear vignettes were associated only at high levels, but not mean or low levels, of self-reported negative emotions to fear vignettes. These findings suggest that hyperawareness, in which self-reported negative emotionality is high when physiological reactivity is also high, is associated with greater risk for anxiety, but not depression, during middle childhood.

A practical guide for researchers and reviewers using the ABCD Study and other large longitudinal datasets.

As the largest longitudinal study of adolescent brain development and behavior to date, the Adolescent Brain Cognitive Development (ABCD) Study® has provided immense opportunities for researchers across disciplines since its first data release in 2018. The size and scope of the study also present a number of hurdles, which range from becoming familiar with the study design and data structure to employing rigorous and reproducible analyses. The current paper is intended as a guide for researchers and reviewers working with ABCD data, highlighting the features of the data (and the strengths and limitations therein) as well as relevant analytical and methodological considerations. Additionally, we explore justice, equity, diversity, and inclusion efforts as they pertain to the ABCD Study and other large-scale datasets. In doing so, we hope to increase both accessibility of the ABCD Study and transparency within the field of developmental cognitive neuroscience.

Computational modeling of threat learning reveals links with anxiety and neuroanatomy in humans.

Influential theories implicate variations in the mechanisms supporting threat learning in the severity of anxiety symptoms. We use computational models of associative learning in conjunction with structural imaging to explicate links among the mechanisms underlying threat learning, their neuroanatomical substrates, and anxiety severity in humans. We recorded skin-conductance data during a threat-learning task from individuals with and without anxiety disorders (N=251; 8-50 years; 116 females). Reinforcement-learning model variants quantified processes hypothesized to relate to anxiety: threat conditioning, threat generalization, safety learning, and threat extinction. We identified the best-fitting models for these processes and tested associations among latent learning parameters, whole-brain anatomy, and anxiety severity. Results indicate that greater anxiety severity related specifically to slower safety learning and slower extinction of response to safe stimuli. Nucleus accumbens gray-matter volume moderated learning-anxiety associations. Using a modeling approach, we identify computational mechanisms linking threat learning and anxiety severity and their neuroanatomical substrates.

Equity, diversity, and inclusion in developmental neuroscience: Practical lessons from community-based participatory research.

Exclusion of racialized minorities in neuroscience directly harms communities and potentially leads to biased prevention and intervention approaches. As magnetic resonance imaging (MRI) and other neuroscientific techniques offer progressive insights into the neurobiological underpinnings of mental health research agendas, it is incumbent on us as researchers to pay careful attention to issues of diversity and representation as they apply in neuroscience research. Discussions around these issues are based largely on scholarly expert opinion without actually involving the community under study. In contrast, community-engaged approaches, specifically Community-Based Participatory Research (CBPR), actively involve the population of interest in the research process and require collaboration and trust between community partners and researchers. This paper outlines a community-engaged neuroscience approach for the development of our developmental neuroscience study on mental health outcomes in preadolescent Latina youth. We focus on "positionality" (the multiple social positions researchers and the community members hold) and "reflexivity" (the ways these positions affect the research process) as conceptual tools from social sciences and humanities. We propose that integrating two unique tools: a positionality map and Community Advisory Board (CAB) into a CBPR framework can counter the biases in human neuroscience research by making often invisible-or taken-for-granted power dynamics visible and bolstering equitable participation of diverse communities in scientific research. We discuss the benefits and challenges of incorporating a CBPR method in neuroscience research with an illustrative example of a CAB from our lab, and highlight key generalizable considerations in research design, implementation, and dissemination that we hope are useful for scholars wishing to take similar approaches.

Paternal expressed emotion influences psychobiological indicators of threat and safety learning in daughters: A preliminary study.

This preliminary study examined the association of children's anxiety, paternal expressed emotion (EE), and their interaction with psychophysiological indices of children's threat and safety learning. Participants included 24 father-daughter dyads. Daughters (ages 8-13 years, 100% Latina) self-reported their anxiety levels and completed a differential threat conditioning and extinction paradigm, during which psychophysiological responding was collected. Fathers completed a Five-Minute Speech Sample, from which paternal EE (i.e., criticism, emotional overinvolvement) was assessed. Anxiety-dependent associations emerged between paternal EE and individual differences in daughters' psychophysiological responding to safety signals during threat conditioning. Paternal EE was positively associated with psychophysiological responding to safety in daughters with high and mean, but not low, levels of anxiety. Although previous work suggests that chronic harsh maternal parenting is a potential risk factor for children's general threat and safety learning, these preliminary findings implicate milder forms of negative parenting behavior in fathers, particularly for highly anxious children.

Social relevance modulates multivariate neural representations of threat generalization in children and adults.

Few studies have examined threat generalization across development and no developmental studies have compared the generalization of social versus nonsocial threat, making it difficult to identify contextual factors that contribute to threat learning across development. The present study assessed youth and adults' multivoxel neural representations of social versus nonsocial threat stimuli. Twenty adults (Mage  = 25.7 ± 4.9) and 16 youth (Mage  = 14.1 ± 1.7) completed two conditioning and extinction recall paradigms: one social and one nonsocial paradigm. Three weeks after conditioning, participants underwent a functional magnetic resonance imaging extinction recall task that presented the extinguished threat cue (CS+), a safety cue (CS-), and generalization stimuli (GS) consisting of CS-/CS+ blends. Across age groups, neural activity patterns and self-reported fear and memory ratings followed a linear generalization gradient for social threat stimuli and a quadratic generalization gradient for nonsocial threat stimuli, indicating enhanced threat/safety discrimination for social relative to nonsocial threat stimuli. The amygdala and ventromedial prefrontal cortex displayed the greatest neural pattern differentiation between the CS+ and GS/CS-, reinforcing their role in threat learning and extinction recall. Contrary to predictions, age did not influence threat representations. These findings highlight the importance of the social relevance of threat on generalization across development.

Social skills moderate the time-varying association between aggression and peer rejection among children with and without ADHD.

Although childhood aggression is typically associated with peer rejection, some children concurrently employ coercive and socially skilled behavior and successfully avoid negative peer outcomes. However, research on children's dual use of coercive and social behavior has largely employed cross-sectional designs with nonclinical populations and, as a result, little is known about the covariation of aggression with social skills, particularly among high-risk samples. We directly addressed this limitation by testing childhood aggression and social skills as separate time-varying predictors of prospective change in peer rejection in a sample of children with and without attention-deficit/hyperactivity disorder (ADHD). Two hundred and two 5-10-year-old children (M = 7.9 years, SD = 1.2) with and without ADHD were followed prospectively for 6 years. Key constructs, including children's overt aggression, social skills, and peer rejection, were collected at each of the three waves using multiple methods and informants. Controlling for demographic factors and time-varying ADHD symptoms, longitudinal change in child-, parent-, and teacher-reported aggression positively predicted prospective change in parent- and teacher-reported peer rejection. Importantly, predictions were moderated by parent- and teacher-reported social skills, such that aggression inversely predicted peer rejection for children with high social skills. These results demonstrate that social skills meaningfully alter trajectories of peer rejection predicted from cross-time variation in aggression. We discuss the theoretical and empirical implications of these findings within a developmental psychopathology framework, including recommendations for directions for future research.

Threat-anticipatory psychophysiological response is enhanced in youth with anxiety disorders and correlates with prefrontal cortex neuroanatomy.

Background: Threat anticipation engages neural circuitry that has evolved to promote defensive behaviours; perturbations in this circuitry could generate excessive threat-anticipation response, a key characteristic of pathological anxiety. Research into such mechanisms in youth faces ethical and practical limitations. Here, we use thermal stimulation to elicit pain-anticipatory psychophysiological response and map its correlates to brain structure among youth with anxiety and healthy youth. Methods: Youth with anxiety (n = 25) and healthy youth (n = 25) completed an instructed threat-anticipation task in which cues predicted nonpainful or painful thermal stimulation; we indexed psychophysiological response during the anticipation and experience of pain using skin conductance response. High-resolution brain-structure imaging data collected in another visit were available for 41 participants. Analyses tested whether the 2 groups differed in their psychophysiological cue-based pain-anticipatory and pain-experience responses. Analyses then mapped psychophysiological response magnitude to brain structure. Results: Youth with anxiety showed enhanced psychophysiological response specifically during anticipation of painful stimulation (b = 0.52, p = 0.003). Across the sample, the magnitude of psychophysiological anticipatory response correlated negatively with the thickness of the dorsolateral prefrontal cortex (pFWE < 0.05); psychophysiological response to the thermal stimulation correlated positively with the thickness of the posterior insula (pFWE < 0.05). Limitations: Limitations included the modest sample size and the cross-sectional design. Conclusion: These findings show that threat-anticipatory psychophysiological response differentiates youth with anxiety from healthy youth, and they link brain structure to psychophysiological response during pain anticipation and experience. A focus on threat anticipation in research on anxiety could delineate relevant neural circuitry.

Divergence in cortical representations of threat generalization in affective versus perceptual circuitry in childhood: Relations with anxiety.

Children at risk for anxiety display elevated threat sensitivity and may inaccurately classify safe stimuli as threatening, a process known as overgeneralization. Little is known about whether such overgeneralization might stem from altered sensory representations of stimuli resembling threat, especially in youth. Here we implement representational similarity analysis of fMRI data to examine the similarity of neural representations of threat versus ambiguous or safe stimuli in threat and perceptual neurocircuitry among children at varying levels of anxiety traits. Three weeks after completing threat conditioning and extinction, children underwent an fMRI extinction recall task, during which they viewed the extinguished threat cue (CS+), safety cue (CS-) and generalization stimuli (GS) consisting of CS-/CS+ blends. Multivoxel BOLD signal patterns were measured in seven regions of interest: four affective areas (ventromedial prefrontal cortex (vmPFC), anterior insular cortex (AIC), dorsomedial prefrontal cortex (dmPFC), and amygdala) and three perceptual areas (inferior temporal cortex (ITC) and visual areas V1 and V4). Compared to low anxious children, children with high trait anxiety evidenced less neural pattern differentiation between the CS+ and similar GS, particularly in the vmPFC. Together, these results demonstrate the utility of multivariate neuroimaging approaches in arbitrating the relative contributions of perceptual versus affective sources to threat generalization.

Anticipatory Threat Responding: Associations With Anxiety, Development, and Brain Structure.

BACKGROUND: While translational theories link neurodevelopmental changes in threat learning to pathological anxiety, findings from studies in patients inconsistently support these theories. This inconsistency may reflect difficulties in studying large patient samples with wide age ranges using consistent methods. A dearth of imaging data in patients further limits translational advances. We address these gaps through a psychophysiology and structural brain imaging study in a large sample of patients across the lifespan. METHODS: A total of 351 participants (8-50 years of age; 209 female subjects; 195 healthy participants and 156 medication-free, treatment-seeking patients with anxiety) completed a differential threat conditioning and extinction paradigm that has been validated in pediatric and adult populations. Skin conductance response indexed psychophysiological response to conditioned (CS+, CS-) and unconditioned threat stimuli. Structural magnetic resonance imaging data were available for 250 participants. Analyses tested anxiety and age associations with psychophysiological response in addition to associations between psychophysiology and brain structure. RESULTS: Regardless of age, patients and healthy comparison subjects demonstrated comparable differential threat conditioning and extinction. The magnitude of skin conductance response to both conditioned stimulus types differentiated patients from comparison subjects and covaried with dorsal prefrontal cortical thickness; structure-response associations were moderated by anxiety and age in several regions. Unconditioned responding was unrelated to anxiety and brain structure. CONCLUSIONS: Rather than impaired threat learning, pathological anxiety involves heightened skin conductance response to potential but not immediately present threats; this anxiety-related potentiation of anticipatory responding also relates to variation in brain structure. These findings inform theoretical considerations by highlighting anticipatory response to potential threat in anxiety.

The psychobiology of emotional development: The case for examining sociocultural processes.

Psychobiological techniques to assess emotional responding have revolutionized the field of emotional development in recent decades by equipping researchers with the tools to quantify children's emotional reactivity and regulation more directly than behavioral approaches allow. Knowledge gained from the incorporation of methods spanning levels of analysis has been substantial, yet many open questions remain. In this prospective review, we (a) describe the major conceptual and empirical advances that have resulted from this methodological innovation, and (b) lay out a case for what we view as the most pressing challenge for the next decades of research into the psychobiology of emotional development: focusing empirical efforts toward understanding the implications of the broader sociocultural contexts in which children develop that shape the psychobiology of emotion. Thus, this review integrates previous knowledge about the psychobiology of emotion with a forward-looking set of recommendations for incorporating sociocultural processes into future investigations.

Anticipatory Effects on Perceived Pain: Associations With Development and Anxiety.

OBJECTIVE: Naturalistic studies suggest that expectation of adverse experiences such as pain exerts particularly strong effects on anxious youth. In healthy adults, expectation influences the experience of pain. The current study uses experimental methods to compare the effects of expectation on pain among adults, healthy youth, and youth with an anxiety disorder. METHODS: Twenty-three healthy adults, 20 healthy youth, and 20 youth with an anxiety disorder underwent procedures in which auditory cues were paired with noxious thermal stimulation. Through instructed conditioning, one cue predicted low-pain stimulation and the other predicted high-pain stimulation. At test, each cue was additionally followed by a single temperature calibrated to elicit medium pain ratings. We compared cue-based expectancy effects on pain across the three groups, based on cue effects on pain elicited on medium heat trials. RESULTS: Across all groups, as expected, participants reported greater pain with increasing heat intensity (ß = 2.29, t(41) = 29.94, p < .001). Across all groups, the critical medium temperature trials were rated as more painful in the high- relative to low-expectancy condition (ß = 1.72, t(41) = 10.48, p < .001). However, no evidence of between-group differences or continuous associations with age or anxiety was observed. CONCLUSIONS: All participants showed strong effects of expectancy on pain. No influences of development or anxiety arose. Complex factors may influence associations among anxiety, development, and pain reports in naturalistic studies. Such factors may be identified using experiments that employ more complex, yet controlled manipulations of expectancy or assess neural correlates of expectancy.

Anxiety symptoms and children's eye gaze during fear learning.

BACKGROUND: The eye region of the face is particularly relevant for decoding threat-related signals, such as fear. However, it is unclear if gaze patterns to the eyes can be influenced by fear learning. Previous studies examining gaze patterns in adults find an association between anxiety and eye gaze avoidance, although no studies to date examine how associations between anxiety symptoms and eye-viewing patterns manifest in children. The current study examined the effects of learning and trait anxiety on eye gaze using a face-based fear conditioning task developed for use in children. METHODS: Participants were 82 youth from a general population sample of twins (aged 9-13 years), exhibiting a range of anxiety symptoms. Participants underwent a fear conditioning paradigm where the conditioned stimuli (CS+) were two neutral faces, one of which was randomly selected to be paired with an aversive scream. Eye tracking, physiological, and subjective data were acquired. Children and parents reported their child's anxiety using the Screen for Child Anxiety Related Emotional Disorders. RESULTS: Conditioning influenced eye gaze patterns in that children looked longer and more frequently to the eye region of the CS+ than CS- face; this effect was present only during fear acquisition, not at baseline or extinction. Furthermore, consistent with past work in adults, anxiety symptoms were associated with eye gaze avoidance. Finally, gaze duration to the eye region mediated the effect of anxious traits on self-reported fear during acquisition. CONCLUSIONS: Anxiety symptoms in children relate to face-viewing strategies deployed in the context of a fear learning experiment. This relationship may inform attempts to understand the relationship between pediatric anxiety symptoms and learning.

A developmental analysis of threat/safety learning and extinction recall during middle childhood.

The current study examined developmental changes in fear learning and generalization in 54 healthy 5-10-year old children using a novel fear conditioning paradigm. In this task, the conditioned stimuli (CS+/CS-) were two blue and yellow colored cartoon bells, and the unconditioned stimulus was an unpleasant loud alarm sound presented with a red cartoon bell. Physiological and subjective data were acquired. Three weeks after conditioning, 48 of these participants viewed the CS-, CS+, and morphed images resembling the CS+. Participants made threat-safety discriminations while appraising threat and remembering the CS+. Although no age-related differences in fear learning emerged, patterns of generalization were qualified by child age. Older children demonstrated better discrimination between the CS+ and CS morphs than younger age groups and also reported more fear to stimuli resembling the CS+ than younger children. Clinical implications and future directions are discussed.

Brain response to viewing others being harmed in children with conduct disorder symptoms.

BACKGROUND: Deficient empathic processing is thought to foster conduct disorder (CD). It is important to determine the extent to which neural response associated with perceiving harm to others predicts CD symptoms and callous disregard for others. METHODS: A total of 107 9- to 11-year-old children (52 female) were recruited from pediatric and mental health clinics, representing a wide range of CD symptoms. Children were scanned with functional magnetic resonance imaging while viewing brief video clips of persons being harmed intentionally or accidentally. RESULTS: Perceiving harm evoked increased hemodynamic response in the anterior insula (aINS), anterior cingulate cortex (ACC), amygdala, periaqueductal gray (PAG), caudate, and inferior parietal lobe (IPL) across all participants. Intentionally caused, relative to unintentional harm was associated with greater activity in the aINS, amygdala, and temporal pole. There was an inverse association of number of CD symptoms with right posterior insula in both the Harm > No Harm and the Intentional > Unintentional Harm contrasts. Furthermore, an inverse association between callousness and posterior insula activation was found in the Harm > No Harm contrast, with the opposite pattern for reactive aggression scores. An interaction revealed a stronger association in girls between CD symptoms and the right posterior superior temporal sulcus (pSTS) in the Intentional Harm versus Unintentional Harm contrast. CONCLUSIONS: Children with greater CD and callousness exhibit dampened hemodynamic response to viewing others being harmed in the insula, a region which plays a key role in empathy and emotional awareness. Sex differences in the neural correlates of CD were observed.