Toward a mechanistic understanding of the role of error monitoring and memory in social anxiety.

Cognitive models state that social anxiety (SA) involves biased cognitive processing that impacts what is learned and remembered within social situations, leading to the maintenance of SA. Neuroscience work links SA to enhanced error monitoring, reflected in error-related neural responses arising from mediofrontal cortex (MFC). Yet, the role of error monitoring in SA remains unclear, as it is unknown whether error monitoring can drive changes in memory, biasing what is learned or remembered about social situations. Motivated by the longer-term goal of identifying mechanisms implicated in SA, in the current study we developed and validated a novel paradigm for probing the role of error-related MFC theta oscillations (associated with error monitoring) and incidental memory biases in SA. Electroencephalography (EEG) data were collected while participants completed a novel Face-Flanker task, involving presentation of task-unrelated, trial-unique faces behind target/flanker arrows on each trial. A subsequent incidental memory assessment evaluated memory biases for error events. Severity of SA symptoms were associated with greater error-related theta synchrony over MFC, as well as between MFC and sensory cortex. Social anxiety also was positively associated with incidental memory biases for error events. Moreover, greater error-related MFC-sensory theta synchrony during the Face-Flanker predicted subsequent incidental memory biases for error events. Collectively, the results demonstrate the potential of a novel paradigm to elucidate mechanisms underlying relations between error monitoring and SA.

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.

Social versus non-social behavioral inhibition: Differential prediction from early childhood of long-term psychosocial outcomes.

Behavioral inhibition (BI) is a temperamental style characterized by cautious and fearful behaviors in novel situations. The present multi-method, longitudinal study examined whether young children's observed and parent-reported BI in social versus non-social contexts predicts different long-term psychosocial outcomes. Participants (N = 279) were drawn from a longitudinal study of socioemotional development. BI in social contexts ("social BI") was measured via children's observed wariness toward unfamiliar adults and peers at 24 and 36 months and parents' reports of children's social fear/shyness at 24, 36, and 48 months. BI in non-social contexts ("non-social BI") was measured via children's observed fearful responses to masks and novel toys, and parents' reports of children's distress to non-social novelty at 9 months and non-social fear at 48 months. At 15 years, anxiety was assessed via adolescent- and parent-reports, and global internalizing and externalizing problems were assessed via parent-reports. Confirmatory factor analysis showed that a two-factor model fit the BI data significantly better than a single-factor model, providing evidence for the dissociation of BI in social versus non-social contexts. Social BI was uniquely associated with adolescent social anxiety, whereas non-social BI was specifically associated with adolescent separation anxiety. Neither social BI nor non-social BI predicted global internalizing and externalizing problems, providing evidence for the specific relations between BI and anxiety problems. Together, these results suggest that young children's inhibited responses in social versus non-social situations predict different subtypes of anxiety problems in adolescence, highlighting the multifaceted nature of BI and the divergent trajectories of different anxiety problems.

Electrophysiological correlates of inhibitory control in children: Relations with prenatal maternal risk factors and child psychopathology.

Inhibitory control plays an important role in children's cognitive and socioemotional development, including their psychopathology. It has been established that contextual factors such as socioeconomic status (SES) and parents' psychopathology are associated with children's inhibitory control. However, the relations between the neural correlates of inhibitory control and contextual factors have been rarely examined in longitudinal studies. In the present study, we used both event-related potential (ERP) components and time-frequency measures of inhibitory control to evaluate the neural pathways between contextual factors, including prenatal SES and maternal psychopathology, and children's behavioral and emotional problems in a large sample of children (N = 560; 51.75% females; Mage = 7.13 years; Rangeage = 4-11 years). Results showed that theta power, which was positively predicted by prenatal SES and was negatively related to children's externalizing problems, mediated the longitudinal and negative relation between them. ERP amplitudes and latencies did not mediate the longitudinal association between prenatal risk factors (i.e., prenatal SES and maternal psychopathology) and children's internalizing and externalizing problems. Our findings increase our understanding of the neural pathways linking early risk factors to children's psychopathology.

Age-related trends in aperiodic EEG activity and alpha oscillations during early- to middle-childhood.

Age-related structural and functional changes that occur during brain development are critical for cortical development and functioning. Previous electroencephalography (EEG) and magnetoencephalography (MEG) studies have highlighted the utility of power spectra analyses and have uncovered age-related trends that reflect perceptual, cognitive, and behavioural states as well as their underlying neurophysiology. The aim of the current study was to investigate age-related change in aperiodic and periodic alpha activity across a large sample of pre- and school-aged children (N = 502, age range 4 -11-years-of-age). Power spectra were extracted from baseline EEG recordings (eyes closed, eyes open) for each participant and parameterized into aperiodic activity to derive the offset and exponent parameters and periodic alpha oscillatory activity to derive the alpha peak frequency and the associated power estimates. Multilevel models were run to investigate age-related trends and condition-dependent changes for each of these measures. We found quadratic age-related effects for both the aperiodic offset and exponent. In addition, we observed increases in periodic alpha peak frequency as a function of age. Aperiodic measures and periodic alpha power were larger in magnitude during eyes closed compared to the eyes open baseline condition. Taken together, these results advance our understanding of the maturational patterns/trajectories of brain development during early- to middle-childhood.

Context and domain matter: the error-related negativity in peer presence predicts fear of negative evaluation, not global social anxiety, in adolescents.

BACKGROUND: Social anxiety symptoms are most likely to emerge during adolescence, a developmental window marked by heightened concern over peer evaluation. However, the neurocognitive mechanism(s) underlying adolescent social anxiety remain unclear. Emerging work points to the error-related negativity (ERN) as a potential neural marker of exaggerated self/error-monitoring in social anxiety, particularly for errors committed in front of peers. However, social anxiety symptoms are marked by heterogeneity and it remains unclear exactly what domain(s) of social anxiety symptoms are associated with ERN variation in peer presence, particularly within the adolescent period. METHODS: To advance and deepen the mechanistic understanding of the ERN's putative role as a neural marker for social anxiety in adolescence, we leveraged a social manipulation procedure and assessed a developmentally salient domain of social anxiety during adolescence - fear of negative evaluation (FNE). Adolescents residing in Hanzhong, a small city in the southwestern region of mainland China, had EEG recorded while performing a flanker task, twice (peer presence/absence); FNE, as well as global social anxiety symptoms, was assessed. RESULTS: Overall ERN increases in peer presence. FNE specifically, but not global levels of social anxiety symptoms, predicted ERN in peer presence. CONCLUSIONS: These data are the first demonstration that the ERN relates to a specific domain of social anxiety in adolescents, as well as the first evidence of such relations within a non-WEIRD (Western, Educated, Industrialized, Rich and Democratic) sample. Results have important implications for theory and research into adolescent social anxiety.

Annual Research Review: Developmental pathways linking early behavioral inhibition to later anxiety.

Behavioral Inhibition is a temperament identified in the first years of life that enhances the risk for development of anxiety during late childhood and adolescence. Amongst children characterized with this temperament, only around 40 percent go on to develop anxiety disorders, meaning that more than half of these children do not. Over the past 20 years, research has documented within-child and socio-contextual factors that support differing developmental pathways. This review provides a historical perspective on the research documenting the origins of this temperament, its biological correlates, and the factors that enhance or mitigate risk for development of anxiety. We review as well, research findings from two longitudinal cohorts that have identified moderators of behavioral inhibition in understanding pathways to anxiety. Research on these moderators has led us to develop the Detection and Dual Control (DDC) framework to understand differing developmental trajectories among behaviorally inhibited children. In this review, we use this framework to explain why and how specific cognitive and socio-contextual factors influence differential pathways to anxiety versus resilience.

Development of auditory change-detection and attentional capture, and their relation to inhibitory control.

EEG methods offer a promising approach to study the development of attention or attention-related processes such as change-detection and attentional capture. However, the development of these attention processes from early to middle childhood is not well understood. In the current study, we utilized a passive three-stimulus oddball paradigm to examine age-related changes in auditory change-detection and attentional capture in a large sample of children across childhood (N = 475; 249 female, 226 male; Mage  = 6.71; SDage  = 2.22; Rangeage  = 4.01-11.5 years). Conventional ERP analyses revealed no age-related changes in change detection (mismatch negativity) and attentional capture (P3a) components, but we observed age-related reductions in late automatic processing of auditory change (late discriminative negativity). However, when utilizing time-frequency analyses, we observed developmental increases in frontocentral signal strength (power) and consistency (inter-trial phase synchrony) in delta and theta bands in response to novel sounds. Such frontocentral delta/theta responses have been linked in prior work to cognitive control. To further examine this possibility, we examined relations with inhibitory control. Results revealed that increased consistency in theta in response to novel sounds was related to improved inhibitory control. Together, our results advance our understanding of the development of attention in childhood. Moreover, they demonstrate the contributions of time-frequency approaches to studying neurocognitive development. Finally, our results highlight the utility of neuroimaging paradigms that have low cognitive and motor demands to study the development of psychological processes.

Multimodal study of the neural sources of error monitoring in adolescents and adults.

The ability to monitor performance during a goal-directed behavior differs among children and adults in ways that can be measured with several tasks and techniques. As well, recent work has shown that individual differences in error monitoring moderate temperamental risk for anxiety and that this moderation changes with age. We investigated age differences in neural responses linked to performance monitoring using a multimodal approach. The approach combined functional MRI and source localization of event-related potentials (ERPs) in 12-year-old, 15-year-old, and adult participants. Neural generators of two components related to performance and error monitoring, the N2 and ERN, lay within specific areas of fMRI clusters. Whereas correlates of the N2 component appeared similar across age groups, age-related differences manifested in the location of the generators of the ERN component. The dorsal anterior cingulate cortex (dACC) was the predominant source location for the 12-year-old group; this area manifested posteriorly for the 15-year-old and adult groups. A fMRI-based ROI analysis confirmed this pattern of activity. These results suggest that changes in the underlying neural mechanisms are related to developmental changes in performance monitoring.

Family-based care buffers the stress sensitizing effect of early deprivation on executive functioning difficulties in adolescence.

We examined whether family care following early-life deprivation buffered the association between stressful life events (SLEs) and executive functioning (EF) in adolescence. In early childhood, 136 institutionally reared children were randomly assigned to foster care or care-as-usual; 72 never-institutionalized children served as a comparison group. At age 16 years, adolescents (n = 143; 54% female; 67.1% Romanian) self-reported recent SLEs, completed a battery of memory and EF tasks, and completed a go/nogo task in which mediofrontal theta power (MFTP) was measured using electroencephalogram. More independent SLEs predicted lower EF and more dependent SLEs predicted lower MFTP, but only among adolescents with prolonged early deprivation. Findings provide preliminary evidence that family care following early deprivation may facilitate resilience against stress during adolescence on EF.

Infant temperament prospectively predicts general psychopathology in childhood.

Recent models of psychopathology suggest the presence of a general factor capturing the shared variance among all symptoms along with specific psychopathology factors (e.g., internalizing and externalizing). However, few studies have examined predictors that may serve as transdiagnostic risk factors for general psychopathology from early development. In the current study we examine, for the first time, whether observed and parent-reported infant temperament dimensions prospectively predict general psychopathology as well as specific psychopathology dimensions (e.g., internalizing and externalizing) across childhood. In a longitudinal cohort (N = 291), temperament dimensions were assessed at 4 months of age. Psychopathology symptoms were assessed at 7, 9, and 12 years of age. A bifactor model was used to estimate general, internalizing, and externalizing psychopathology factors. Across behavioral observations and parent-reports, higher motor activity in infancy significantly predicted greater general psychopathology in mid to late childhood. Moreover, low positive affect was predictive of the internalizing-specific factor. Other temperament dimensions were not related with any of the psychopathology factors after accounting for the general psychopathology factor. The results of this study suggest that infant motor activity may act as an early indicator of transdiagnostic risk. Our findings inform the etiology of general psychopathology and have implications for the early identification for children at risk for psychopathology.

Time-frequency dynamics of error monitoring in childhood: An EEG study.

Error monitoring allows individuals to monitor and adapt their behavior by detecting errors. Error monitoring is thought to develop throughout childhood and adolescence. However, most of this evidence comes from studies in late childhood and adolescence utilizing event-related potentials (ERPs). The current study utilizes time-frequency (TF) and connectivity analyses to provide a comprehensive examination of age-related changes in error-monitoring processes across early childhood (N = 326; 50.9% females; 4-9 years). ERP analyses indicated the presence of the error-related negativity (ERN) and error positivity (Pe) across all ages. Results showed no error-specific age-related changes in the ERN and the Pe. However, TF analyses suggested error-related frontocentral responses in delta and theta signal strength (power), delta consistency (intertrial phase synchrony), and delta synchrony (interchannel phase synchrony) between frontrocentral and frontolateral clusters-all of which increased with age. Additionally, the current study examines the reliability and effect size estimates of the ERP and TF measures. For most measures, more trials were needed to achieve acceptable reliability than what is commonly used in the psychophysiological literature. Resources to facilitate the measurement and reporting of reliability are provided. Overall, findings highlight the utility of TF analyses and provide useful information for future studies examining the development of error monitoring.

Inhibitory control and set shifting describe different pathways from behavioral inhibition to socially anxious behavior.

Individuals with a behaviorally inhibited (BI) temperament are more likely to develop social anxiety. However, the mechanisms by which socially anxious behavior emerges from BI are unclear. Variation in different forms of top-down control, specifically executive functions (EF), may play distinct roles and characterize differential pathways to social anxiety. Here 291 children were assessed for BI in toddlerhood (ages 2 and 3), parent-reported inhibitory control and set shifting during middle childhood (age 7), and multidimensional assessment of socially anxious behavior completed during late childhood and early adolescence (ages 9 and 12). Structural equation modeling revealed that early variation in BI predicted the development of socially anxious behavior through either higher levels of parent-reported inhibitory control or lower levels of parent-reported set shifting. These data reinforce the notion that top-down control does not uniformly influence relations between temperament and socially anxious behavior. These data suggest novel approaches to thinking about the role of EFs and social anxiety outcomes as children approach adolescence.

The influence of social motivation on neural correlates of cognitive control in girls.

Motivation influences cognitive control, particularly in childhood and adolescence. Previous work finds that the error-related negativity (ERN), an event-related potential (ERP) linked to cognitive control following errors, is influenced by social motivation. However, it is unclear whether the influences of social motivation on the ERN extend to stimulus-locked neural correlates of cognitive control. This study reexamines how social motivation influences cognitive control in adolescence by exploring motivational influences on two stimulus-locked ERPs; the N2 and P3. Adolescent girls (8-17 years of age) completed a flanker task under two different conditions. In the social condition, girls were led to believe that they were evaluated by a peer during a flanker task. In the nonsocial condition, girls completed a flanker task while evaluated by a computer. Results revealed that all girls exhibited a larger P3 in social as compared to nonsocial contexts, whereas the N2 was not different between contexts. In addition, the largest P3 enhancements were observed among younger girls. These findings suggest that social motivation influences some ERP components related to cognitive control, and such influences change across development. Additionally, findings suggest the importance of including multiple ERPs when interpreting the functional significance of motivation on cognitive control.

Contrasting time and frequency domains: ERN and induced theta oscillations differentially predict post-error behavior.

The present study investigated the neural dynamics of error processing in both the time and frequency domains, as well as associated behavioral phenomena, at the single-trial level. We used a technique that enabled us to separately investigate the evoked and induced aspects of the EEG signal (Cohen & Donner, 2013, Journal of Neurophysiology, 110[12], 2752-2763). We found that at the single-trial level, while the (evoked) error-related negativity (ERN) predicted only post-error slowing (PES)-and only when errors occurred on incongruent trials-induced frontal midline theta power served as a robust predictor of both PES and post-error accuracy (PEA) regardless of stimulus congruency. Mediation models of both electrophysiological indices demonstrated that although the relationship between theta and PEA was mediated by PES, there was not a relationship between the ERN and PEA. Our data suggest that although the ERN and frontal midline theta index functionally related underlying cognitive processes, they are not simply the same process manifested in different domains. In addition, our findings are consistent with the adaptive theory of post-error slowing, as PES was positively associated with post-error accuracy at the single-trial level. More generally, our study provides additional support for the inclusion of a time-frequency approach to better understand the role of medial frontal cortex in action monitoring.

Changes in working memory influence the transition from reactive to proactive cognitive control during childhood.

Cognitive control develops rapidly over the first decade of life, with one of the dominant changes being a transition from reliance on 'as-needed' control (reactive control) to a more planful, sustained form of control (proactive control). Although the emergence of proactive control is important for mature behavior, we know little about how this transition takes place, the neural correlates of this transition, and whether development of executive functions influences the ability to adopt a proactive control strategy. This study addresses these questions, focusing on the transition from reactive to proactive control in a cross-sectional sample of 79 children-forty-one 5-year-olds and thirty-eight 9-year-olds. Children completed an adapted version of the AX-Continuous Performance Task while electroencephalography was recorded and a standardized executive function battery was administered. Results revealed 5-year-olds predominantly employed reactive strategies, whereas 9-year-olds used proactive strategies. Use of proactive control was predicted by working memory ability, above and beyond other executive functions. Moreover, when enacting proactive control, greater increases in neural activity underlying working memory updating were observed; links between working memory ability and proactive control strategy use were mediated by such neural activity. These results provide convergent evidence that the transition from reactive to proactive control may be dependent on age-related changes in neurocognitive indices of working memory and that working memory may influence adopting a proactive control strategy.

Relations between catechol-O-methyltransferase Val158Met genotype and inhibitory control development in childhood.

The Val158Met rs4680 single-nucleotide polymorphism (SNP) at the catechol-O-methyltransferase (COMT) gene, primarily involved in dopamine breakdown within prefrontal cortex, has shown relations with inhibitory control (IC) in both adults and children. However, little is known about how COMT genotype relates to developmental trajectories of IC throughout childhood. Here, our study explored the effects of the COMT genotype (Val/Val, Val/Met, and Met/Met) on IC trajectories between the ages of 5 and 10 years. Children (n = 222) completed a Go/Nogo task at ages 5, 7, and 10; IC was characterized using signal detection theory to examine IC performance (d') and response strategy (RS) (criterion). COMT genotype was not related to initial levels of IC performance and RS at age 5 or change in RS from ages 5 to 10. In contrast, COMT genotype was related to change in IC performance between 5 and 10 years. While Val/Val children did not differ from Val/Met children in development of IC performance, children with the Met/Met genotype exhibited more rapid development of IC performance when compared with Val/Met peers. These results suggest that COMT genotype modulates the development of IC performance in middle childhood.

Mu rhythm desynchronization is specific to action execution and observation: Evidence from time-frequency and connectivity analysis.

Mu desynchronization is the attenuation of EEG power in the alpha frequency range recorded over central scalp locations thought to reflect motor cortex activation. Mu desynchronization during observation of an action is believed to reflect mirroring system activation in humans. However, this notion has recently been questioned because, among other reasons, the potential contamination of mu rhythm and occipital alpha activity induced by attention processes following presentation of visual stimuli in observation conditions. This study examined the validity of mu desynchronization as a measure of mirroring system activation in infants and further investigated the pattern of functional connectivity between the central and occipital regions during execution and observation of movement. EEG was recorded while 46 9-month-old infants executed grasping actions and observed an experimenter grasping. Current source density (CSD) was applied to EEG data and, time-frequency and connectivity analyses were performed in CSD transformed data. Mu desynchronization was evident over central regions during both execution and observation of movements. Independent alpha desynchronization over occipital region was also present in both conditions. The connectivity analyses revealed that central-occipital areas were functionally more connected compared to other areas of the brain during observation of movements. Collectively, the results demonstrate the validity of mu desynchronization as an index of infant mirroring system activity and support the proposal of a functional connection between distinct mirroring and attention processes during observation of action.

Adolescent cognitive control, theta oscillations, and social observation.

Theta oscillations (4-8 Hz) provide an organizing principle of cognitive control, allowing goal-directed behavior. In adults, theta power over medial-frontal cortex (MFC) underlies conflict/error monitoring, whereas theta connectivity between MFC and lateral-frontal regions reflects cognitive control recruitment. However, prior work has not separated theta responses that occur before and immediately after a motor response, nor explained how medial-lateral connectivity drives different kinds of control behaviors. Theta's role during adolescence, a developmental window characterized by a motivation-control mismatch also remains unclear. As social observation is known to influence motivation, this might be a particularly important context for studying adolescent theta dynamics. Here, adolescents performed a flanker task alone or under social observation. Focusing first on the nonsocial context, we parsed cognitive control into dissociable subprocesses, illustrating how theta indexes distinct components of cognitive control working together dynamically to produce goal-directed behavior. We separated theta power immediately before/after motor responses, identifying behavioral links to conflict monitoring and error monitoring, respectively. MFC connectivity was separated before/after responses and behaviorally-linked to reactive and proactive control, respectively. Finally, distinct forms of post-error control were dissociated, based on connectivity with rostral/caudal frontal cortex. Social observation was found to exclusively upregulate theta measures indexing post-response error monitoring and proactive control, as opposed to conflict monitoring and reactive control. Linking adolescent cognitive control to theta oscillations provides a bridge between non-invasive recordings in humans and mechanistic studies of neural oscillations in animal models; links to social observation provide insight into the motivation-control interactions that occur during adolescence.

Development of inhibitory control during childhood and its relations to early temperament and later social anxiety: unique insights provided by latent growth modeling and signal detection theory.

BACKGROUND: Children with the temperament of behavioral inhibition (BI) face increased risk for social anxiety. However, not all children with BI develop anxiety symptoms. Inhibitory control (IC) has been suggested as a moderator of the pathway between BI and social anxiety. This study uses longitudinal data to characterize development of IC and tests the hypothesis that IC moderates associations between early BI and later social anxiety symptoms. METHODS: Children completed a Go/Nogo task at ages 5, 7, and 10 years as part of a longitudinal study of BI (measured at 2-3 years) and social anxiety symptoms (measured at 12 years). To assess IC development, response strategy (criterion) and inhibitory performance (d') were characterized using signal detection theory. Latent growth models were used to characterize the development of IC and examine relations among BI, IC parameters, and social anxiety symptoms. RESULTS: IC response strategy did not change between 5 and 10 years of age, whereas IC performance improved over time. BI scores in toddlerhood predicted neither initial levels (intercept) nor changes (slope) in IC response strategy or IC performance. However, between ages 5 and 10, rate of change in IC performance, but not response strategy, moderated relations between BI and later parent-reported social anxiety symptoms. Specifically, greater age-related improvements in IC performance predicted higher levels of social anxiety in high BI children. CONCLUSIONS: IC development in childhood occurs independent of BI levels. However, rapid increases in IC performance moderate risk for social anxiety symptoms in children with BI. Implications for theory and practice are discussed.