Linking Gene, Brain, and Behavior: DRD4, Frontal Asymmetry, and Temperament

ABSTRACT— Gene-environment interactions involving exogenous environmental factors are known to shape behavior and personality development. Although gene-environment interactions involving endogenous environmental factors are hypothesized to play an equally important role, this conceptual approach has not been empirically applied in the study of early-developing temperament in humans. Here we report evidence for a gene- endo environment (i.e., resting frontal brain electroencephalogram, EEG, asymmetry) interaction in predicting child temperament. The dopamine D4 receptor (DRD4) gene (long allele vs. short allele) moderated the relation between resting frontal EEG asymmetry (left vs. right) at 9 months and temperament at 48 months. Children who exhibited left frontal EEG asymmetry at 9 months and who possessed the DRD4 long allele were significantly more soothable at 48 months than other children. Among children with right frontal EEG asymmetry at 9 months, those with the DRD4 long allele had significantly more difficulties focusing and sustaining attention at 48 months than those with the DRD4 short allele. Resting frontal EEG asymmetry did not influence temperament in the absence of the DRD4 long allele. We discuss how the interaction of genetic and endoenvironmental factors may confer risk and protection for different behavioral styles in children.     

Putative EEG measures of social anxiety: Comparing frontal alpha asymmetry and delta–beta cross-frequency correlation

The goal of the present study was to examine whether frontal alpha asymmetry and delta–beta cross-frequency correlation during resting state, anticipation, and recovery are electroencephalographic (EEG) measures of social anxiety. For the first time, we jointly examined frontal alpha asymmetry and delta–beta correlation during resting state and during a social performance task in high (HSA) versus low (LSA) socially anxious females. Participants performed a social performance task in which they first watched and evaluated a video of a peer, and then prepared their own speech. They believed that their speech would be videotaped and evaluated by a peer. We found that HSA participants showed significant negative delta–beta correlation as compared to LSA participants during both anticipation of and recovery from the stressful social situation. This negative delta–beta correlation might reflect increased activity in subcortical brain regions and decreased activity in cortical brain regions. As we hypothesized, no group differences in delta–beta correlation were found during the resting state. This could indicate that a certain level of stress is needed to find EEG measures of social anxiety. As for frontal alpha asymmetry, we did not find any group differences. The present frontal alpha asymmetry results are discussed in relation to the evident inconsistencies in the frontal alpha asymmetry literature. Together, our results suggest that delta–beta correlation is a putative EEG measure of social anxiety.     

Frontal Brain Electrical Activity in Shyness and Sociability

A number of studies have shown that shyness and sociability may be two independent personality traits that are distinguishable across a variety of measures and cultures. Utilizing recent frontal activation–emotion models as a theoretical framework, this study examined the pattern of resting frontal electroencephalographic (EEG) activity in undergraduates who self-reported high and low shyness and sociability. Analyses revealed that shyness was associated with greater relative right frontal EEG activity, whereas sociability was associated with greater relative left frontal EEG activity. Also, different combinations of shyness and sociability were distinguishable on the basis of resting frontal EEG power. Although high-shy/high-social and high-shy/low-social subjects both exhibited greater relative right frontal EEG activity, they differed significantly on EEG power in the left, but not right, frontal lead. High-shy/high-social subjects exhibited significantly less EEG power (i.e., more activity) in the left frontal lead compared with the high-shy/low-social subjects. These findings suggest that in distinguishing individual differences in personality and personality subtypes, it is important to consider not only frontal EEG asymmetry measures, but also the pattern of absolute EEG power in each frontal hemisphere.     

The relation between electroencephalogram asymmetry and attention biases to threat at baseline and under stress

Electroencephalogram (EEG) asymmetry in the alpha frequency band has been implicated in emotion processing and broad approach-withdrawal motivation systems. Questions remain regarding the cognitive mechanisms that may help elucidate the observed links between EEG asymmetry and patterns of socioemotional functioning. The current study observed frontal EEG asymmetry patterns at rest and under social threat among young adults (N = 45, M = 21.1 years). Asymmetries were, in turn, associated with performance on an emotion-face dot-probe attention bias task. Attention biases to threat have been implicated as potential causal mechanisms in anxiety and social withdrawal. Frontal EEG asymmetry at baseline did not predict attention bias patterns to angry or happy faces. However, increases in right frontal alpha asymmetry from baseline to the stressful speech condition were associated with vigilance to angry faces and avoidance of happy faces. The findings may reflect individual differences in the pattern of response (approach or withdrawal) with the introduction of a mild stressor. Comparison analyses with frontal beta asymmetry and parietal alpha asymmetry did not find similar patterns. Thus, the data may reflect the unique role of frontal regions, particularly the dorsolateral prefrontal cortex, in cognitive control and threat detection, coupled with ruminative processes associated with alpha activity.     

Resting frontal brain asymmetry predicts affective responses to films

This article assessed whether resting electroencephalographic (EEG) asymmetry in anterior regions of the brain can predict affective responses to emotion elicitors. Baseline EEG was recorded from 32 female adults, after which Ss viewed film clips preselected to elicit positive or negative affect. Resting alpha power asymmetry in the frontal region significantly predicted self-reported global negative affect in response to clips and predicted the difference between global positive and negative affect. Analyses of discrete emotions revealed a strong relation between frontal asymmetry and fear responses to films. Effects were independent of Ss mood ratings at the time at which baseline EEG was measured. Resting anterior asymmetry may be a state-independent index of the individual's predisposition to respond affectively.     

BIS/BAS scores are correlated with frontal EEG asymmetry in intrusive and withdrawn depressed mothers

Differences between different style‐depressed mothers, intrusive and withdrawn, were examined by the use of the Behavioral Inhibition and Activation Scales (BIS/BAS) and EEG activity from the mid‐frontal and parietal regions. Analyses revealed that withdrawn mothers had left frontal EEG hypoactivation, higher Behavior Inhibition (BIS), and lower Behavior Activation (BAS) scores than the intrusive mothers. Further analysis revealed that the BIS, the BAS reward and the BAS‐BIS difference scores were related to frontal EEG asymmetry and power scores. BIS scores were also related to the mothers' withdrawn interaction style, supporting the use of the BIS/BAS as a screening instrument to help identify intrusive and withdrawn depressed mothers. ©2001 Michigan Association for Infant Mental Health.     

Frontal brain asymmetry predicts infants' response to maternal separation

Examined whether certain features of infant temperament might be related to individual differences in the asymmetry of resting frontal activation. EEG was recorded from the left and right frontal and parietal scalp regions of 13 normal 10-month-old infants. Infant behavior was then observed during a brief period of maternal separation. Those infants who cried in response to maternal separation showed greater right frontal activation during the preceding baseline period compared with infants who did not cry. Frontal activation asymmetry may be a state-independent marker for individual differences in threshold of reactivity to stressful events and vulnerability to particular emotions.     

Maternal sensitivity and infant response to frustration: The moderating role of EEG asymmetry

Two hundred and thirty-three 5-month-old infants and their mothers participated in a study designed to examine the influence of maternal sensitivity and infant neurophysiology, as well as interactions between these, on infants’ regulatory behavior and reactivity to emotional challenge. Maternal sensitivity was measured during two mother–child free-play episodes prior to the challenge task. Infant neurophysiology was derived from a measure of resting EEG asymmetry collected during a baseline episode. Infant regulatory behaviors (mother orienting and distraction) and reactivity to challenge (negative affect) were assessed during an arm restraint procedure. Maternal sensitivity predicted mother-orienting behavior for all infants, regardless of baseline EEG asymmetry. Maternal sensitivity also predicted more distraction behaviors for infants with left frontal EEG asymmetry at baseline. In contrast, maternal sensitivity predicted more negative affect for infants with right frontal EEG asymmetry at baseline. These findings lend support for the hypothesis that maternal sensitivity and infant neurophysiological functioning interact to predict regulatory behavior and reactivity and are discussed in terms of the significance for understanding infant regulatory development in the first year of life.     

Implicit regulatory focus associated with asymmetrical frontal cortical activity

Regulatory focus theory identifies two separate motivational systems, promotion and prevention, that fulfill different regulatory needs and are differentially related to approach and avoidance. In the psychophysiological literature, approach- and avoidance-related emotions and motivational orientations have been linked to asymmetries in frontal cortical activity. In an effort to synthesize these literatures, we examined the relationship between an implicit assessment of chronic regulatory focus and an electroencephalographic (EEG) index of resting frontal cortical asymmetry. Results supported the hypothesis that promotion regulatory focus would be associated with greater left frontal activity, and prevention regulatory focus would be associated with greater right frontal activity. Discussion highlights how this synthesis may benefit theorizing of the relationship between regulatory focus, motivation, and emotion, and of the function of asymmetrical frontal cortical activity.     

Emotion-modulated performance and activity in left dorsolateral prefrontal cortex

Functional MRI (fMRI) was used to examine the relationship between processing of pleasant and unpleasant stimuli and activity in prefrontal cortex. Twenty volunteers identified the colors in which pleasant, neutral, and unpleasant words were printed. Pleasant words prompted more activity bilaterally in dorsolateral prefrontal cortex (DLPFC) than did unpleasant words. In addition, pleasant words prompted more activity in left than in right DLPFC. Response speed to pleasant words was correlated with DLPFC activity. These data directly link positive affect, enhanced performance, and prefrontal activity, providing some of the first fMRI evidence supporting models of emotional valence and frontal brain asymmetry based on electroencephalography (EEG).     

Proneness to hypomania/mania symptoms or depression symptoms and asymmetrical frontal cortical responses to an anger-evoking event

The behavioral approach system (BAS) reflects the propensity to respond to signals of reward, including stimuli associated with safety and goal-oriented attack (e.g., anger). Hypomania/mania has been posited to involve increased BAS activity. In contrast, depression has been posited to involve decreased BAS activity. Building on past research, which suggests that increased left frontal cortical activity is a neurophysiological index of BAS activity, the present research tested the hypotheses that proneness toward hypomania/mania symptoms would be related to increased relative left frontal activity and that proneness toward depression symptoms would be related to decreased relative left frontal activity in response to an anger-evoking event. Results from 67 individuals who had completed a measure of proneness toward these affective symptoms and were exposed to an anger-evoking event supported the hypotheses.     

Laboratory-induced learned helplessness attenuates approach motivation as indexed by posterior versus frontal theta activity

Research suggests that midline posterior versus frontal electroencephalographic (EEG) theta activity (PFTA) may reflect a novel neurophysiological index of approach motivation. Elevated PFTA has been associated with approach-related tendencies both at rest and during laboratory tasks designed to enhance approach motivation. PFTA is sensitive to changes in dopamine signaling within the fronto-striatal neural circuit, which is centrally involved in approach motivation, reward processing, and goal-directed behavior. To date, however, no studies have examined PFTA during a laboratory task designed to reduce approach motivation or goal-directed behavior. Considerable animal and human research supports the hypothesis put forth by the learned helplessness theory that exposure to uncontrollable aversive stimuli decreases approach motivation by inducing a state of perceived uncontrollability. Accordingly, the present study examined the effect of perceived uncontrollability (i.e., learned helplessness) on PFTA. EEG data were collected from 74 participants (mean age = 19.21 years; 40 females) exposed to either Controllable (n = 26) or Uncontrollable (n = 25) aversive noise bursts, or a No-Noise Condition (n = 23). In line with prediction, individuals exposed to uncontrollable aversive noise bursts displayed a significant decrease in PFTA, reflecting reduced approach motivation, relative to both individuals exposed to controllable noise bursts or the No-Noise Condition. There was no relationship between perceived uncontrollability and frontal EEG alpha asymmetry, another commonly used neurophysiological index of approach motivation. Results have implications for understanding the neurophysiology of approach motivation and establishing PFTA as a neurophysiological index of approach-related tendencies.     

Speech presentation cues moderate frontal EEG asymmetry in socially withdrawn young adults

Socially withdrawn individuals display solitary behavior across wide contexts with both unfamiliar and familiar peers. This tendency to withdraw may be driven by either past or anticipated negative social encounters. In addition, socially withdrawn individuals often exhibit right frontal electroencephalogram (EEG) asymmetry at baseline and when under stress. In the current study we examined shifts in frontal EEG activity in young adults (N=41) at baseline, as they viewed either an anxiety-provoking or a benign speech video, and as they subsequently prepared for their own speech. Results indicated that right frontal EEG activity increased, relative to the left, only for socially withdrawn participants exposed to the anxious video. These results suggest that contextual affective cues may prime an individual's response to stress, particularly if they illustrate or substantiate an anticipated negative event.     

ADHD Symptoms in Post-Institutionalized Children Are Partially Mediated by Altered Frontal EEG Asymmetry

Individual differences in the propensity for left versus right frontal electroencephalogram (EEG) asymmetry may underlie differences in approach/withdrawal tendencies and mental health deficits. Growing evidence suggests that early life adversity may shape brain development and contribute to the emergence of mental health problems. The present study examined frontal EEG asymmetry (FEA) following the transition to family care in children adopted internationally from institutional care settings between 15 and 36 months of age (N = 82; 46 female, 36 male). Two comparison groups were included: an international adoption control consisting of children adopted from foster care with little to no institutional deprivation (N = 45; 17 female, 28 male) and a post-adoption condition control consisting of children reared in birth families of the same education and income as the adoptive families (N = 48; 23 female, 25 male). Consistent with evidence of greater approach and impulsivity-related behavior problems in post-institutionalized (PI) children, PI status was associated with greater left FEA than found in the other two groups. In addition, left FEA served as a mediator between institutionalization and age 5 ADHD symptoms for girls. Age at adoption and other preadoption factors were examined with results suggesting that earlier adoption into a supportive family resulted in a more typical pattern of brain functioning. Findings support the idea that the capacity of brain activity to evidence typical functioning following perturbation may differ in relation to the timing of intervention and suggest that the earlier the intervention of adoption, the better.     

Resting Frontal EEG Asymmetry and Personality Traits: A Meta‐analysis

Frontal asymmetry has been widely used as a marker of emotion, motivation, and psychopathology. When assessed during the resting state, it is regarded as an index of trait approach and withdrawal motivation. However, the replicability of these associations with personality is currently unclear. The present meta‐analysis seeks to provide a comprehensive quantitative review of the relationship between personality traits and resting electroencephalographic (EEG) frontal asymmetry. We distinguished five personality clusters: extraversion, neuroticism, impulsivity, anger, and defensiveness. Data from 79 independent samples with overall 5700 participants were included in the meta‐analysis. The results revealed that less than 0.4% of the variance in extraversion and neuroticism could be explained by resting frontal asymmetry. Similarly, a small effect was observed for trait anger, and a small‐sized to medium‐sized effect was observed for defensiveness, although the number of studies was very low. No significant effect emerged for impulsivity. The effects were further reduced after adjustment for publication bias. Given some evidence for heterogeneity, sub‐traits were analysed, and methodological moderators were investigated. Based on the results, we conclude that the validity of resting frontal asymmetry as a marker for personality is not supported. Finally, recommendations are given to increase the replicability of frontal asymmetry research. © 2019 European Association of Personality Psychology     

Frontal brain electrical activity (EEG) distinguishes valence and intensity of musical emotions

Using recent regional brain activation/emotion models as a theoretical framework, we examined whether the pattern of regional EEG activity distinguished emotions induced by musical excerpts which were known to vary in affective valence (i.e., positive vs. negative) and intensity (i.e., intense vs. calm) in a group of undergraduates. We found that the pattern of asymmetrical frontal EEG activity distinguished valence of the musical excerpts. Subjects exhibited greater relative left frontal EEG activity to joy and happy musical excerpts and greater relative right frontal EEG activity to fear and sad musical excerpts. We also found that, although the pattern of frontal EEG asymmetry did not distinguish the intensity of the emotions, the pattern of overall frontal EEG activity did, with the amount of frontal activity decreasing from fear to joy to happy to sad excerpts. These data appear to be the first to distinguish valence and intensity of musical emotions on frontal electrocortical measures.     

Frontal brain asymmetry in restrained eaters

It is well known that the eating patterns that restrain chronic dieters (restrained eaters) can be disinhibited by anxiety, which in turn has been associated with relative right frontal brain activity in independent electroencephalographic (EEG) studies. Combining these two lines of evidence, the authors tested the hypothesis that chronic restrained eating is associated with relative right frontal asymmetry. Resting anterior brain asymmetry and self-reported measures of anxiety and depression were collected in 23 restrained and 32 unrestrained eaters. As hypothesized, groups differed in tonic frontal activity, with restrained eaters showing more relative right frontal activity. Furthermore, relative right frontal activity was associated with greater self-reported restraint. Right-sided prefrontal asymmetry may thus represent a diathesis associated with increased vulnerability toward restrained eating.     

Longitudinal stability of temperamental exuberance and social-emotional outcomes in early childhood

The goals of the current study were to investigate the stability of temperamental exuberance across infancy and toddlerhood and to examine the associations between exuberance and social-emotional outcomes in early childhood. The sample consisted of 291 4-month-olds followed at 9, 24, and 36 months and again at 5 years of age. Behavioral measures of exuberance were collected at 9, 24, and 36 months. At 36 months, frontal electroencephalogram (EEG) asymmetry was assessed. At 5 years, maternal reports of temperament and behavior problems were collected, as were observational measures of social behavior during an interaction with an unfamiliar peer in the laboratory. Latent profile analysis revealed a high, stable exuberance profile that was associated with greater ratings of 5-year externalizing behavior and surgency, as well as observed disruptive behavior and social competence with unfamiliar peers. These associations were particularly true for children who displayed left frontal EEG asymmetry. Multiple factors supported an approach bias for exuberant temperament but did not differentiate between adaptive and maladaptive social-emotional outcomes at 5 years of age.     

Anger style, psychopathology, and regional brain activity

Depression and anxiety often involve high levels of trait anger and disturbances in anger expression. Reported anger experience and outward anger expression have recently been associated with left-biased asymmetry of frontal cortical activity, assumed to reflect approach motivation. However, different styles of anger expression could presumably involve different brain mechanisms and/or interact with psychopathology to produce various patterns of brain asymmetry. The present study explored these issues by comparing resting regional electroencephalographic activity in participants high in trait anger who differed in anger expression style (high anger-in, high anger-out, both) and participants low in trait anger, with depression and anxiety systematically assessed. Trait anger, not anger-in or anger-out, predicted left-biased asymmetry at medial frontal EEG sites. The anger-in group reported higher levels of anxious apprehension than did the anger-out group. Furthermore, anxious apprehension moderated the relationship between trait anger, anger-in, and asymmetry in favor of the left hemisphere. Results suggest that motivational direction is not always the driving force behind the relationship of anger and left frontal asymmetry. Findings also support a distinction between anxious apprehension and anxious arousal.     

Frontal and parietal EEG asymmetries interact to predict attentional bias to threat

Frontal and parietal electroencephalographic (EEG) asymmetries mark vulnerability to depression and anxiety. Drawing on cognitive theories of vulnerability, we hypothesise that cortical asymmetries predict attention to threat. Participants completed a dot-probe task in which bilateral face displays were followed by lateralised targets at either short (300 ms) or long (1050 ms) SOA. We also measured N2pc to face onset as an index of early attentional capture. At long SOA only, frontal and parietal asymmetry interacted to predict attentional bias to angry faces. Those with leftward frontal asymmetry showed no attentional bias. Among those with rightward frontal asymmetry those with low right parietal activity showed vigilance for threat, and those with high right parietal activity showed avoidance. Asymmetry was not related to the N2pc or to attentional bias at the short SOA. Findings suggest that trait asymmetries reflect function in a fronto-parietal network that controls attention to threat.