Beyond Increasing Sample Sizes: Optimizing Effect Sizes in Neuroimaging Research on Individual Differences.

Linking neurobiology to relatively stable individual differences in cognition, emotion, motivation, and behavior can require large sample sizes to yield replicable results. Given the nature of between-person research, sample sizes at least in the hundreds are likely to be necessary in most neuroimaging studies of individual differences, regardless of whether they are investigating the whole brain or more focal hypotheses. However, the appropriate sample size depends on the expected effect size.

The Organization of Anxiety Symptoms Along the Threat Imminence Continuum.

Pathological anxiety is highly prevalent, impairing, and often chronic. Yet, despite considerable research, mechanistic understanding of anxiety and its translation to clinical practice remain limited. Here, we first highlight two foundational complications that contribute to this gap: a reliance on a phenomenology-driven definition of pathological anxiety in neurobiological mechanistic research, and a limited understanding of the chronicity of anxiety symptom expression.

A preliminary study of threat-anticipatory responding in Latina youth: associations with age, anxiety, and cortical thickness.

Variation in prefrontal cortex neuroanatomy has been previously associated with elevated physiological responses to anticipated aversive events. The extent to which such associations extend beyond the specific ecology of treatment-seeking youth from upper-middle socioeconomic backgrounds is unknown. The current study tests the replicability of neuroanatomical correlates of anticipatory responding and the moderating roles of age and anxiety severity in a community sample of Latina girls, a historically underrepresented group exhibiting high levels of untreated anxiety.

Threat Appraisal and Pediatric Anxiety: Proof of Concept of a Latent Variable Approach.

Elevated threat appraisal is a postulated neurodevelopmental mechanism of anxiety disorders. However, laboratory-assessed threat appraisals are task-specific and subject to measurement error. We utilized latent variable analysis to integrate youth's self-reported threat appraisals across different experimental tasks; we next examined associations with pediatric anxiety as well as behavioral and psychophysiological task indices.

Using mobile eye-tracking to evaluate gaze behavior during a speech in pediatric anxiety disorders.

Background: Altered gaze in social settings is a hallmark of social anxiety; however, little research directly examines gaze in anxiety-provoking contexts among youth with anxiety disorders, limiting mechanistic insight into pediatric anxiety. The present study leveraged mobile eye-tracking technology to examine gaze behavior during a naturalistic stressor in a clinical developmental sample.

Methods: Sixty-one youth (ages 8-17 years; 28 with anxiety disorders, 33 non-anxious controls) completed a naturalistic social stress task (public speaking in front of a videotaped classroom audience) while wearing eye-tracking glasses.

Late positive potential reveals sustained threat contingencies despite extinction in adolescents but not adults.

Background: Major theories link threat learning processes to anxiety symptoms, which typically emerge during adolescence. While this developmental stage is marked by substantial maturation of the neural circuity involved in threat learning, research directly examining adolescence-specific patterns of neural responding during threat learning is scarce. This study compared adolescents and adults in acquisition and extinction of conditioned threat responses assessed at the cognitive, psychophysiological, and neural levels, focusing on the late positive potential (LPP), an event-related potential (ERP) component indexing emotional valence.

How adverse childhood experiences get under the skin: A systematic review, integration and methodological discussion on threat and reward learning mechanisms.

Adverse childhood experiences (ACEs) are a major risk factor for the development of multiple psychopathological conditions, but the mechanisms underlying this link are poorly understood. Associative learning encompasses key mechanisms through which individuals learn to link important environmental inputs to emotional and behavioral responses. ACEs may impact the normative maturation of associative learning processes, resulting in their enduring maladaptive expression manifesting in psychopathology.

Eye-tracking measurement of attention bias to social threat among youth: A replication and extension study.

Attentional bias to social threat cues has been linked to heightened anxiety and irritability in youth. Yet, inconsistent methodology has limited replication and led to mixed findings. The current study aims to 1) replicate and extend two previous pediatric studies demonstrating a relationship between negative affectivity and attentional bias to social threat and 2) examine the test-retest reliability of an eye-tracking paradigm among a subsample of youth.

Normalization of Fronto-Parietal Activation by Cognitive-Behavioral Therapy in Unmedicated Pediatric Patients With Anxiety Disorders.

Objective: Anxiety disorders are prevalent among youths and are often highly impairing. Cognitive-behavioral therapy (CBT) is an effective first-line treatment. The authors investigated the brain mechanisms associated with symptom change following CBT.

The free-viewing matrix task: A reliable measure of attention allocation in psychopathology.

Aberrant attention allocation has been implicated in the etiology and maintenance of a range of psychopathologies. However, three decades of research, relying primarily on manual response-time tasks, have been challenged on the grounds of poor reliability of its attention bias indices. Here, in a large, multisite, international study we provide reliability information for a new eye-tracking-based measure of attention allocation and its relation to psychopathology and age.

Development of Neural Mechanisms Underlying Threat Processing: Associations With Childhood Social Reticence and Adolescent Anxiety.

Background: Social reticence in early childhood is characterized by shy and anxiously avoidant behavior, and it confers risk for pediatric anxiety disorders later in development. Aberrant threat processing may play a critical role in this association between early reticent behavior and later psychopathology. The goal of this longitudinal study is to characterize developmental trajectories of neural mechanisms underlying threat processing and relate these trajectories to associations between early-childhood social reticence and adolescent anxiety.

Understanding anxiety symptoms as aberrant defensive responding along the threat imminence continuum.

Threat-anticipatory defensive responses have evolved to promote survival in a dynamic world. While inherently adaptive, aberrant expression of defensive responses to potential threat could manifest as pathological anxiety, which is prevalent, impairing, and associated with adverse outcomes. Extensive translational neuroscience research indicates that normative defensive responses are organized by threat imminence, such that distinct response patterns are observed in each phase of threat encounter and orchestrated by partially conserved neural circuitry.

Consensus design of a calibration experiment for human fear conditioning.

Fear conditioning is a widely used laboratory model to investigate learning, memory, and psychopathology across species. The quantification of learning in this paradigm is heterogeneous in humans and psychometric properties of different quantification methods can be difficult to establish. To overcome this obstacle, calibration is a standard metrological procedure in which well-defined values of a latent variable are generated in an established experimental paradigm.

Attention Training as a Low-Intensity Treatment for Concerning Anxiety in Clinic-Referred Youth.

Although youth anxiety treatment research has focused largely on severe and impairing anxiety levels, even milder anxiety levels, including levels that do not meet full criteria for a diagnosis, can be impairing and cause for concern. There is a need to develop and test viable treatments for these concerning anxiety levels to improve functioning and reduce distress. We present findings from a randomized controlled efficacy trial of attention bias modification treatment (ABMT) and attention control training (ACT) for youths with concerning anxiety levels.

Fear-potentiated startle reveals diminished threat extinction in pathological anxiety.

Background: Major theories propose that perturbed threat learning is central to pathological anxiety, but empirical support is inconsistent. Failures to detect associations with anxiety may reflect limitations in quantifying conditioned responses to anticipated threat, and hinder translation of theory into empirical work. In prior work, we could not detect threat-specific anxiety effects on states of conditioned threat using psychophysiology in a large sample of patients and healthy comparisons.

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).

Family accommodation in pediatric anxiety: Relations with avoidance and self-efficacy.

Pediatric anxiety disorders are common, impairing, and chronic when not effectively treated. A growing body of research implicates family accommodation in the maintenance of pediatric anxiety. The present study aimed to quantify previously untested relations among family accommodation and two theoretically linked constructs: avoidance and self-efficacy.

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).

Unique associations between conditioned cognitive and physiological threat responses and facets of anxiety symptomatology in youth.

This study examined associations between anxiety symptomatology and cognitive and physiological threat responses during threat learning in a large sample of children and adolescents. Anxiety symptomatology severity along different dimensions (generalized anxiety, separation anxiety, social anxiety, and panic symptoms) was measured using parental and self-reports. Participants completed differential threat acquisition and extinction using an age-appropriate threat conditioning task.

Reliability of task-evoked neural activation during face-emotion paradigms: Effects of scanner and psychological processes.

Assessing and improving test-retest reliability is critical to efforts to address concerns about replicability of task-based functional magnetic resonance imaging. The current study uses two statistical approaches to examine how scanner and task-related factors influence reliability of neural response to face-emotion viewing. Forty healthy adult participants completed two face-emotion paradigms at up to three scanning sessions across two scanners of the same build over approximately 2 months.

A checklist for assessing the methodological quality of concurrent tES-fMRI studies (ContES checklist): a consensus study and statement.

Low-intensity transcranial electrical stimulation (tES), including alternating or direct current stimulation, applies weak electrical stimulation to modulate the activity of brain circuits. Integration of tES with concurrent functional MRI (fMRI) allows for the mapping of neural activity during neuromodulation, supporting causal studies of both brain function and tES effects. Methodological aspects of tES-fMRI studies underpin the results, and reporting them in appropriate detail is required for reproducibility and interpretability.

Threat imminence reveals links among unfolding of anticipatory physiological response, cortical-subcortical intrinsic functional connectivity, and anxiety.

Excessive expression of fear responses in anticipation of threat occurs in anxiety, but understanding of underlying pathophysiological mechanisms is limited. Animal research indicates that threat-anticipatory defensive responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from basic neuroscience research in animals on threat imminence could guide mechanistic research in humans mapping abnormal function in this circuitry to aberrant defensive responses in pathological anxiety.

Neural correlates of extinguished threat recall underlying the commonality between pediatric anxiety and irritability.

Background: Anxiety and irritability frequently co-occur in youth and are mediated by aberrant threat responses. However, empirical evidence on neural mechanisms underlying this co-occurrence is limited. To address this, we apply data-driven latent phenotyping to data from a prior report of a well-validated threat extinction recall fMRI paradigm.