Evaluating the effect of action-like video game play and of casual video game play on anxiety in adolescents with elevated anxiety: protocol for a multi-center, parallel group, assessor-blind, randomized controlled trial.

BACKGROUND: Adolescence is a critical period for the onset and maintenance of anxiety disorders, which raises the importance of intervening early; one possibility of doing so is via digital interventions. Within that research field, at least two important research paths have been explored in the past years. On the one hand, the anxiolytic effect of casual video games has been tested as such gaming activity may distract away from anxious thoughts through the induction of flow and redirection of attention toward the game and thus away of anxious thoughts. On the other hand, the bidirectional link between weak attentional control and higher anxiety has led to the design of interventions aiming at improving attentional control such as working memory training studies. Taking stock that another genre of gaming, action video games, improves attentional control, game-based interventions that combines cognitive training and action-like game features would seem relevant. This three-arm randomized controlled trial aims to evaluate the feasibility and the efficacy of two video game interventions to document how each may potentially alleviate adolescent anxiety-related symptoms when deployed fully on-line. METHODS: The study aims to recruit 150 individuals, 12 to 14 years of age, with high levels of anxiety as reported by the parents' online form of the Screen for Child Anxiety Related Disorders questionnaire. This trial contrasts a child-friendly, "action-like" video game designed to improve attentional control abilities in a progressive and stepwise manner (Eco-Rescue), a casual puzzle video game selected to act as a positive distraction tool (Bejeweled) and finally a control group with no assigned training intervention to control for possible test-retest effects (No-training). Participants will be assigned randomly to one of the three study arms. They will be assessed for main (anxiety) and secondary outcomes (attentional control, affective working memory) at three time points, before training (T1), one week after the 6-week training (T2) and four months after completing the training (T3). DISCUSSION: The results will provide evidence for the feasibility and the efficacy of two online video game interventions at improving mental health and emotional well-being in adolescents with high levels of anxiety. This project will contribute unique knowledge to the field, as few studies have examined the effects of video game play in the context of digital mental health interventions for adolescents. TRIAL REGISTRATION: The trial is registered on ClinicalTrials.gov (NCT05923944, June 20, 2023).

Enhanced late positive potential to conditioned threat cue during delayed extinction in anxious youth.

BACKGROUND: Deficits in threat learning relate to anxiety symptoms. Since several anxiety disorders arise in adolescence, impaired adolescent threat learning could contribute to adolescent changes in risk for anxiety. This study compared threat learning among anxious and non-anxious youth using self-reports, peripheral psychophysiology measures, and event-related potentials. Because exposure therapy, the first-line treatment for anxiety disorders, is largely based on principles of extinction learning, the study also examined the link between extinction learning and treatment outcomes among anxious youth. METHODS: Clinically anxious (n = 28) and non-anxious (n = 33) youth completed differential threat acquisition and immediate extinction. They returned to the lab a week later to complete a threat generalization test and a delayed extinction task. Following these two experimental visits, anxious youth received exposure therapy for 12 weeks. RESULTS: Anxious as compared to non-anxious youth demonstrated elevated cognitive and physiological responses across acquisition and immediate extinction learning, as well as greater threat generalization. In addition, anxious youth showed enhanced late positive potential response to the conditioned threat cue compared to the safety cue during delayed extinction. Finally, aberrant neural response during delayed extinction was associated with poorer treatment outcomes. CONCLUSIONS: The study emphasizes differences between anxious and non-anxious youth in threat learning processes and provides preliminary support for a link between neural processing during delayed extinction and exposure-based treatment outcome in pediatric anxiety.

Induced error-related theta activity, not error-related negativity, predicts task performance as well as anxiety and worry during real-life stress in a youth sample.

OBJECTIVE: The study examined differences between induced error-related theta activity (4-7 Hz) and error-related negativity (ERN) in youth and their unique associations with task performance as well as anxiety and worry during real-life stress a year later. We hypothesized that induced theta, but not the ERN, would predict task performance. We also hypothesized that induced theta would predict less anxiety and worries during situational stress a year later, while ERN would predict more anxiety and worries. METHOD: Participants included 76 children aged 8-13 years who completed a flanker task while electroencephalogram (EEG) and behavioral data (t0 ) were collected. Approximately 1 year later (t1 ), during the first COVID-19 lockdown, 40 families from the original sample completed a battery of online questionnaires to assess the children's stress-related symptoms (anxiety, negative emotions and worries). We employed an analytical method that allowed us to differentiate between induced error-related theta and the evoked ERN. RESULTS: Induced error-related theta, but not ERN, was associated with behavioral changes during the task, such as post-error speeding. Furthermore, induced error-related theta, but not ERN, was prospectively associated with less anxiety, worries, and fewer negative emotions a year later during COVID-19 lockdown. CONCLUSIONS: Findings suggest ERN and error-related theta are dissociable processes reflecting error monitoring in youth. Specifically, induced error-related theta is more robustly associated with changes in behavior in the laboratory and with less anxiety and worries in real-world settings.

Looking fear in the face: Adults but not adolescents gaze at social threat during observational learning.

Observational threat learning is an indirect pathway to learn about what is safe versus dangerous. Visual gaze patterns may be an important measure to understand the underlying mechanisms of social threat learning. However, little research has considered this type of learning or attention allocation during observational learning, and even less has examined it across development. The study examined visual gaze patterns during observational threat acquisition amongst adolescents and adults. Ninety-three adolescents (13-17 years) and 78 adults (18-34 years) underwent a differential observational acquisition task by watching a video wherein a learning model was presented with colored bells. One bell (conditioned stimulus, CS+) was associated with an electric stimulation to the learning model's arm (social unconditioned stimulus, social US), while the other bell was not (CS-). Eye tracking was used during each trial. First, all participants, regardless of age, fixated longer on the face of the learning model when the CS+ was presented than when the CS- was presented. Second, adolescents averted their gaze from the learning model's face when the learning model received an electrical stimulation, whereas adults fixated more on the learning model's face when the stimulation was administered. Finally, adolescents understood the CS+-US contingency less than adults, stemming from the different gaze pattern for the age groups to the social US. Results replicate previous findings in adults and extend them to adolescents, emphasizing the importance of the learning model's facial expressions in conveying information on what is safe versus dangerous in the environment. Moreover, results showed developmental differences in gaze patterns during observational threat learning; this translated into poorer understanding of the CS+-US association amongst adolescents.

Observational extinction reduces fear and its retention among adolescents and adults.

Observational fear learning has been notably understudied in fear learning research, especially the potential benefits of observational extinction. Additionally, no studies have investigated observational extinction during adolescence, a key developmental stage for the emergence of anxiety disorders. This study compared observational and direct fear extinction following observational fear acquisition among adolescents and adults. Participants underwent differential observational fear acquisition. Next, participants underwent one of three fear extinctions: (1) observational extinction, (2) direct extinction, (3) no-extinction. Thereafter, participants underwent a US reminder and finally, a direct exposure test. Skin conductance response (SCR), self-reported fear, and risk assessment were measured. Differential observational fear acquisition was demonstrated by both age groups across all measures. During extinction, the observational and direct extinction groups did not differ in differential extinction, however, during the US reminder the observational group exhibited higher SCR compared to the direct group, but not the no-extinction group. Finally, during the direct exposure test, the no-extinction group showed greater differential risk assessment and higher SCR compared to the observational and direct groups. Additionally, adolescents showed poorer discrimination between the CSs compared to adults. Observational extinction successfully reduced fear and its retention amongst youth and adults pointing to the potential benefit of vicarious exposure therapy.

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.

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. They then returned to the lab after 7-10 days to complete an extinction recall task that also assessed threat generalization. Results indicated that more severe overall anxiety was associated with greater cognitive and physiological threat responses during acquisition, extinction, and extinction recall. During acquisition and extinction, all anxiety dimensions manifested greater cognitive threat responses, while panic, separation anxiety, and social anxiety symptoms, but not generalized anxiety, were related to heightened physiological threat responses. In contrast, when we assessed generalization of cognitive threat responses, we found only generalized anxiety symptoms were associated with greater threat response generalization. The study provides preliminary evidence of specificity in threat responses during threat learning across youth with different anxiety symptoms.

Fear learning, avoidance, and generalization are more context-dependent for adults than adolescents.

This study examined developmental differences in contextual and perceptual generalization of fear and avoidance learning. Adults (N = 39) and adolescents (N = 44) completed differential fear acquisition wherein each conditional stimulus (CS) appeared in a background context. In the dangerous context, one stimulus (CS+) predicted an aversive sound, and the other stimulus (CS-) did not. In the safe context, the aversive sound was never administered with either CS. During fear generalization, participants were presented with three generalization stimuli (GSs), ranging on a perceptual continuum from threat to safety stimuli, in both contexts. Participants then completed avoidance conditioning and avoidance generalization phases, allowing them to actively avoid the upcoming aversive sound by pressing an avoidance button. Developmental differences emerged in threat perception, physiological arousal, avoidance behavior, and eye movements during contextual fear learning and generalization. Adolescents showed less discrimination between stimuli and contexts than adults, resulting primarily from their elevated fear responses to safety and generalized stimuli. Developmental differences in fear learning should be further explored in future research, as they could explain why adolescence is a sensitive developmental period for anxiety.

Watch and Learn: Vicarious Threat Learning across Human Development.

Vicarious threat learning is an important pathway in learning about safety and danger in the environment and is therefore critical for survival. It involves learning by observing another person's (the demonstrator) fearful responses to threat and begins as early as infancy. The review discusses the literature on vicarious threat learning and infers how this learning pathway may evolve over human development. We begin by discussing the methods currently being used to study observational threat learning in the laboratory. Next, we focus on the social factors influencing vicarious threat learning; this is followed by a review of vicarious threat learning among children and adolescents. Finally, we examine the neural mechanisms underpinning vicarious threat learning across human development. To conclude, we encourage future research directions that will help elucidate how vicarious threat learning emerges and how it relates to the development of normative fear and pathological anxiety.

Return of fear following extinction in youth: An event-related potential study.

The ability to learn to differentiate safety from danger matures gradually, particularly when such learning occurs over an extended time period. And yet, most research on fear learning examines the early phases of such learning and mainly in adults. The current study examined fear conditioning and extinction, as well as one form of extended learning, return of fear (ROF). Thirty-three typically developing children (age range: 7-14 years) completed fear conditioning and extinction; self-reports and psychophysiological indices were measured at this point. Two weeks later, children completed a ROF test (n = 23), and event-related potentials (ERPs) were recorded. Results indicated successful fear acquisition and extinction. Moreover, participants reported greater fear of the conditioned stimulus (CS+) than the safety stimulus (CS-) in the ROF test 2 weeks later. In electrophysiology data, ROF manifested as a larger late positive potential (LPP) response to the CS+ than the CS-. Finally, these differences in LPP responses were positively correlated with poorer extinction, as indicated by the GSR responses 2 weeks earlier. This is the first ERP study to demonstrate ROF in children. The LPP measure may index an interplay between inhibitory and excitatory brain-related processes underlying the long-term effects of fear learning.

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.

Effects of the COVID19 Pandemic on Transgender and Gender Non-Conforming Adolescents' Mental Health.

We assessed the effects of the COVID19 lockdown on the mental health of transgender and gender non-conforming (TGN) youth (n = 18) vs cisgender youth (29 males; 29 females). Coronavirus Health Impact Survey (CRISIS) and Emotion Regulation Questionnaire were used in an online study. No group differences were found in demographic variables and exposure to COVID19. Negative emotions/feeling increased for all groups. Cisgender youth reported using more adaptive emotion regulation strategies than TGN youth. While the lockdown similarly affected TGN and cisgender youth, the former showed elevated levels of symptomatology and fewer adaptive emotional regulation strategies.

Using a novel paradigm to examine observational fear-learning across development.

BACKGROUND: Fear-learning through observing others begins early in life. Yet, most observational fear-learning research has focused on adults. The current study used a novel developmentally appropriate observational fear conditioning paradigm to examine differences in observational fear-learning among children, adolescents, and adults. METHOD: Thirty-six typically developing children, 41 typically developing adolescents, and 40 adults underwent differential observational fear conditioning followed by a direct exposure test. Skin conductance response (SCR) and self-reported fear were measured. RESULTS: Successful differential observational fear-learning was demonstrated in all three age groups as indexed by SCR, yet developmental differences emerged. Children showed overall higher physiological arousal during acquisition compared to adolescents and adults. Additionally, children reported less differential fear and were less successful at reporting the conditioned stimulus-unconditioned stimulus contingency compared to adolescents and adults. Finally, adolescents tended to overgeneralize their fear compared with adults. CONCLUSIONS: This is the first study to compare observational fear-learning among children, adolescents, and adults. The novel task effectively induced observational fear-learning, particularly among adolescents and adults. Findings revealed developmental differences that have both theoretical and clinical implications.

Effects of increased attention allocation to threat and safety stimuli on fear extinction and its recall.

BACKGROUND AND OBJECTIVES: Attention plays an important role in the treatment of anxiety. Increased attention to threat has been shown to yield improved treatment outcomes in anxious patients following exposure-based therapy. This study examined whether increasing attention to learned stimuli during fear extinction, an experimental analogue for exposure-based treatments, could improve extinction learning and its maintenance. METHODS: Sixty-five healthy adults were randomized into experimental or control conditions. All completed a differential fear conditioning task. During extinction, a subtle attentional manipulation was implemented in the experimental group, designed to increase participants' attention to both threat and safety cues. Three days later, an extinction recall test was conducted using the original cues and two perceptually similar morphs. RESULTS: Fear conditioning was achieved in both behavioral and psychophysiological measures. In addition, between-group differences emerged during extinction. The experimental group exhibited increased attention to stimuli and lower fear responses in physiological measure than the control group. Similarly, during extinction recall, the experimental group exhibited lower startle responses than the control group. Last, across groups, attending to the safety cue during extinction was associated with lower self-reported risk of the two generalization morphs displayed during extinction recall. LIMITATIONS: Skin conductance response (SCR) was not measured during extinction recall. Future research should include both SCR and additional generalization morphs so as to allow for the examination of more subtle individual differences. CONCLUSIONS: Results indicate that the attentional manipulation increased attention allocation to stimuli during extinction; this, in turn, affected fear-related physiological response.

High avoidance despite low fear of a second-order conditional stimulus.

This study examined avoidance learning using a second-order threat conditioning paradigm. Participants completed fear acquisition wherein a second-order threat cue (preCS+) was paired with a threat cue (CS+) followed by an aversive sound (US); another stimulus was never associated with the US (CS-). During avoidance conditioning, participants could press a button when the preCS + or the CS- was presented, preventing upcoming events. During response prevention and extinction, the avoidance button was removed. Avoidance persistence was then examined in the absence of the actual threat. Results revealed that although the preCS+ and CS- elicited low levels of fear following Pavlovian fear acquisition, during avoidance conditioning, participants showed more avoidance of the preCS+ than the CS-. They also reported the preCS+ as more dangerous than the CS-. Following extinction, participants returned to actively avoid the preCS+ and rated it as more dangerous than the CS-. Finally, the association between avoidance learning and persistence of avoidance was mediated by self-reported threat expectancy during extinction. Our findings suggest avoidance behavior can be triggered by low levels of experienced fear, and this avoidance may play a role in the development and maintenance of threat beliefs.

The effects of age and trait anxiety on avoidance learning and its generalization.

Avoidance is an important self-protective behavior, but excessive avoidance is maladaptive and a core feature of anxiety disorders. Given that several of these disorders emerge in adolescence, maladaptive avoidance learning might be a risk factor in subsequent psychopathology. The current study investigated the effects of age and trait anxiety on avoidance learning and related processes. Adults and youth completed a differential fear-conditioning task. Thereafter, during avoidance conditioning, participants learned to press a button cancelling an upcoming aversive sound. Next, during extinction, no aversive sound was presented, and the avoidance button was removed. Last, in the generalization test, a series of morphs ranging in similarity from the safety cue to the danger cue were presented, and the avoidance button was reintroduced. Self-reported safety-danger ratings and skin conductance responses were collected. Developmental differences emerged in safety-danger ratings during avoidance conditioning; while adults exhibited a gradual decrease in differential danger ratings, among youth, this response was moderated by trait anxiety levels. Following extinction, participants returned to avoid the danger cue and perceptually similar morphs. Moreover, avoidance response to some generalized stimuli was associated with trait anxiety levels. These findings highlight the importance of examining avoidance learning in relation to anxiety symptoms throughout development.

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.

Levels of early-childhood behavioral inhibition predict distinct neurodevelopmental pathways to pediatric anxiety.

BACKGROUND: Anxiety symptoms gradually emerge during childhood and adolescence. Individual differences in behavioral inhibition (BI), an early-childhood temperament, may shape developmental paths through which these symptoms arise. Cross-sectional research suggests that level of early-childhood BI moderates associations between later anxiety symptoms and threat-related amygdala-prefrontal cortex (PFC) circuitry function. However, no study has characterized these associations longitudinally. Here, we tested whether level of early-childhood BI predicts distinct evolving associations between amygdala-PFC function and anxiety symptoms across development. METHODS: Eighty-seven children previously assessed for BI level in early childhood provided data at ages 10 and/or 13 years, consisting of assessments of anxiety and an fMRI-based dot-probe task (including threat, happy, and neutral stimuli). Using linear-mixed-effects models, we investigated longitudinal changes in associations between anxiety symptoms and threat-related amygdala-PFC connectivity, as a function of early-childhood BI. RESULTS: In children with a history of high early-childhood BI, anxiety symptoms became, with age, more negatively associated with right amygdala-left dorsolateral-PFC connectivity when attention was to be maintained on threat. In contrast, with age, low-BI children showed an increasingly positive anxiety-connectivity association during the same task condition. Behaviorally, at age 10, anxiety symptoms did not relate to fluctuations in attention bias (attention bias variability, ABV) in either group; by age 13, low-BI children showed a negative anxiety-ABV association, whereas high-BI children showed a positive anxiety-ABV association. CONCLUSIONS: Early-childhood BI levels predict distinct neurodevelopmental pathways to pediatric anxiety symptoms. These pathways involve distinct relations among brain function, behavior, and anxiety symptoms, which may inform diagnosis and treatment.

Fear conditioning and extinction in anxious and non-anxious youth: A meta-analysis.

Fear conditioning and extinction have been implicated in the etiology and maintenance of anxiety disorders. Most fear conditioning studies have been conducted with adult samples and the few published developmental studies in clinically anxious youth have yielded inconsistent results. The aim of the current review was to use meta-analysis to examine possible differences in fear conditioning and extinction in clinically anxious and non-anxious youth. Seven fear conditioning studies were included in the analysis, with a total of 160 clinically anxious and 166 non-anxious youth. All the studies included in the meta-analysis used a differential conditioning paradigm with at least one or more of the primary dependent variables: self-reported fear, skin conductance response (SCR) and fear potentiated startle (FPS). Similar differential fear acquisition and extinction patterns were observed in anxious and non-anxious individuals. However, anxious youth exhibited stronger fear responses to individual stimuli compared to their non-anxious counterparts. Results in clinically anxious youth resemble those reported in previous studies with clinically anxious adults. Importantly, due to the small number of fear learning studies conducted among youth, these results should be interpreted with caution. Further research is needed so as to better understand fear acquisition and extinction processes in developmental populations. In addition, future studies should focus on other fear-related learning processes such as differences in return of fear, retrieval of fear memory and more subtle differences in fear generalization.