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.     

Withdrawn and intrusive maternal interaction style and infant frontal EEG asymmetry shifts in infants of depressed and non-depressed mothers

The effects of maternal interaction style (intrusive/withdrawn) on the development of brain electrical activity were studied in infants of depressed and non-depressed mothers shortly after birth and again at 3-6 months of age. Infants of depressed mothers exhibited significantly greater relative right frontal EEG activation than infants of non-depressed mothers. Infants of depressed withdrawn mothers exhibited greater relative right frontal EEG activation than infants of depressed intrusive mothers. Furthermore, while infants of depressed mothers with intrusive interaction styles showed a shift towards greater relative left frontal EEG activation from birth to 3-6 months, infants of depressed mothers with withdrawn interaction styles showed a shift towards greater relative right frontal EEG activation.     

Relations between behavioral reactivity at 4 months and attachment classification at 14 months in a selected sample

Attachment at 14 months of age was examined in a sample of infants who had been selected for high or low levels of positive or negative affective reactivity and motor activity at 4 months of age. The type of early emotional reactivity was not clearly associated with attachment security or insecurity. The proposal of Belsky and Rovine [Belsky, J., & Rovine, M. (1987). Temperament and attachment security in the strange situation: An empirical rapprochement. Child Development, 58, 787–795] that infants classified as B3/B4 or C1/C2 are temperamentally more negatively reactive than those classified as A1/A2 or B1/B2 was supported. Compared with infants who showed high levels of positive affect and infants who scored low on affective reactivity, infants who showed high levels of negative affect in response to stimulation at 4 months of age were significantly more likely to be classified as B3/B4 or C1/C2 in the Strange Situation at 14 months of age. These findings are discussed in the context of prior inconsistent findings about the relations between temperament and groups of attachment sub-classifications. The role of different methods of assessing temperament and the importance of selected samples in clarifying such relations is discussed.     

Ordinary variations in maternal caregiving influence human infants' stress reactivity

ABSTRACT— We sought to extend earlier work by examining whether there are ordinary variations in human maternal caregiving behavior (MCB) that are related to stress reactivity in infants. We observed 185 mother-infant dyads and used standard coding systems to identify variations in caregiving behavior. We then created two extreme groups and found that infants receiving low-quality MCB showed more fearfulness, less positive joint attention, and greater right frontal electroencephalographic asymmetry than infants receiving high-quality MCB. Group differences in stress reactivity were not a result of measured infant temperament. However, infants receiving low-quality MCB manifested significantly more negative affect during caregiving activities than did infants receiving high-quality MCB. The results suggest that ordinary variations in MCB may influence the expression of neural systems involved in stress reactivity in human infants.     

Development of frontal electroencephalogram (EEG) and heart rate (ECG) responses to affective musical stimuli during the first 12 months of post-natal life

We examined the development of infants' regional electrocortical (EEG) and heart rate (ECG) responses to affective musical stimuli during the first 12 months of post-natal life. Separate groups of infants were seen at 3 (n=33), 6 (n=42), 9 (n=52), and 12 (n=40) months of age at which time regional EEG and ECG responses were continuously recorded during a baseline condition and during the presentation of three orchestral pieces that were known to vary in affective valence and intensity (happy, sad, fear). Overall, there were two important findings. First, we found that although the overall amount of EEG 4-8 Hz power increased between 3 and 12 months, the distribution of EEG power changed across age, with the younger infants (3- and 6-month-olds) showing no difference between frontal and parietal regions, but the older infants (9- and 12-month-olds) showing relatively more activation at frontal than at parietal sites. This development likely reflects the maturation of frontal lobe function. Second, we found that the presentation of affective music significantly increased brain activity at 3 months of age, had seemingly little effect at 6 and 9 months, and significantly attenuated brain activity at 12 months. Findings suggest that there is a clear developmental change in the effect of music on brain activity in the first year, with music having a "calming" influence on infants by the end of the first year of life.     

Right frontal EEG asymmetry and behavioral inhibition in infants of depressed mothers

Recent studies have shown associations between maternal psychopathology and inhibited behaviors in infants. Moreover, physiological factors have been identified as affecting the continuity of behavioral inhibition across childhood. The purpose of the present study was to examine electroencephalogram (EEG) activity and inhibited behavior in 12-month-old infants of depressed versus non-depressed and mothers. Repeated measures MANOVAs indicated that the infants of mothers with stable psychopathology had greater relative right frontal EEG asymmetry, a pattern that typically accompanies greater negative affect and greater withdrawal behaviors. Infants of affectively ill mothers also showed more proximal behaviors toward a stranger and a novel toy than infants of well mothers, but fewer non-proximal behaviors toward their mothers. These results are discussed within a framework of behavioral inhibition for infants exposed to early psychopathologies in their mothers.     

Infant frontal EEG asymmetry moderates the association between maternal behavior and toddler negative affectivity

Relatively little work has examined potential interactions between child intrinsic factors and extrinsic environmental factors in the development of negative affect in early life. This work is important because high levels of early negative affectivity have been associated with difficulties in later childhood adjustment. We examined associations between infant frontal electroencephalogram (EEG), maternal parenting behaviors, and children’s negative affect across the first two years of life. Infant baseline frontal EEG asymmetry was measured at 5 months; maternal sensitivity and intrusiveness were observed during mother-child interaction at 5 and 24 months; and mothers provided reports of toddler negative affect at 24 months. Results indicated that maternal sensitive behaviors at 5 months were associated with less negative affect at 24 months, but only for infants with left frontal EEG asymmetry. Similarly, maternal sensitive behaviors at 24 months were associated with less toddler negative affect at 24 months, but only for infants with left frontal EEG asymmetry. In contrast, maternal intrusive behaviors at 5- and 24-months were associated with greater toddler negative affect, but only for infants with right frontal EEG asymmetry at 5-months. Findings suggest that levels of negative affect in toddlers may be at least partially a result of interactions between children’s own early neurophysiological functioning and maternal behavior during everyday interactions with children in the first two years of life.     

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.     

Targeting adolescent mothers with depressive symptoms for early intervention

Infants of mothers with depressive symptoms show developmental delays if symptoms persist over the first 6 months of the infant's life, thus highlighting the importance of identifying those mothers for early intervention. In Study 1, mothers with depressive symptoms (n = 160) and mothers without depressive symptoms (n = 100) and their infants were monitored to identify variables from the first 3 months that predict which mothers would still be symptomatic at 6 months. A "dysregulation" profile was noted for the infants of depressed mothers, including lower Brazelton scores, more indeterminate sleep, and elevated norepinephrine, epinephrine, and dopamine levels at the neonatal period, and greater right frontal EEG activation, lower vagal tone, and negative interactions at the 3- and 6-month periods. A group of maternal variables from the neonatal and 3-month assessments accounted for 51% of the variance in the mothers' continuing depressive symptoms. These variables included greater right frontal EEG activation, lower vagal tone, and less positive interactions at 3 months, and elevated norepinephrine, serotonin, and cortisol levels at the neonatal stage. In Study 2, a similar sample of mothers with depressive symptoms (n = 160) and without depressive symptoms (n = 100) was recruited and followed to 3 months. Those symptomatic mothers who had values above (or below) the median (depending on the negative direction) on the predictor variables identified in Study 1 (taken from the first 3 months) were then randomly assigned to an intervention or a control group at 3 months. These groups were then compared with each other, as well as with the group without depressive symptoms, at 6 and 12 months. The intervention, conducted from 3 to 6 months, consisted of free day care for the infants and a rehab program (social, educational, and vocational) plus several mood induction interventions for the mothers, including relaxation therapy, music mood induction, massage therapy, and mother-infant interaction coaching. Although the mothers who received the intervention continued to have more depressive symptoms than did the nondepressed mothers, their interactions significantly improved and their biochemical values and vagal tone normalized. Their infants also showed more positive interations, better growth, fewer pediatric complications, and normalized biochemical values, and by 12 months their mental and motor scores were better than those of the infants in the control group.     

Corrected and uncorrected Bayley scores: Longitudinal developmental patterns in low and high birth weight preterm infants

In this study, we longitudinally investigated developmental changes in very low birth weight (VLBW, less than 1500 gms), in higher birth weight (HBW, 1500–2000 gms) preterm, and in full-term (FT) infants. We also investigated changes in their caretaking home environment. The subjects were 20 VLBW, 39 HBW, and 24 FT infants who participated in an intervention study. Blind independent assessments were performed at 4, 8, 12, and 16 months corrected age using the Bayley mental and motor scales, both corrected for prematurity and uncorrected, the Infant and Toddler temperament questionnaires, and the Caldwell Home Observation for Measurement of the Environment inventory (HOME). The VLBW infants obtained the lowest mental (77) and motor (77) uncorrected scores, which were significantly different from the mental and motor scores of the HBW (94 and 89, respectively) and of the FT (115 and 109, respectively) infants. Mental and motor uncorrected scores were significantly lower at 4 months than at 8, 12, and 16 months. By 12 months, the uncorrected scores of the HBW infants no longer differed from the FT ones, and by 16 months only the difference between the FT and the VLBW was significant. The corrected mental and motor scores yielded no significant group or age differences. Post hoc analysis of an interaction in the motor scores yielded significantly higher scores for the FT than for the VLBW group at the last assessment. Overall, the VLBW infants were more passive and less intense than were either HBW or FT infants. In general, the home environment of the VLBW infants was significantly less stimulating and responsive than was the home environment of the FT and HBW infants. These results are discussed in terms of vulnerability of the VLBW preterm infants to developmental deficits and the difficulties their parents experience in their caretaking role.     

Electrophysiological responses to auditory novelty in temperamentally different 9‐month‐old infants

Behavioral reactivity to novel stimuli in the first half‐year of life has been identified as a key aspect of early temperament and a significant precursor of approach and withdrawal tendencies to novelty in later infancy and early childhood. The current study examines the neural signatures of reactivity to novel auditory stimuli in 9‐month‐old infants in relation to prior temperamental reactivity. On the basis of the assessment of behavioral reactivity scores at 4 months of age, infants were classified into groups of high negatively reactive and high positively reactive infants. Along with an unselected control group, these groups of temperamentally different infants were given a three‐stimulus auditory oddball task at 9 months of age which employed frequent standard and infrequent deviant tones as well as a set of complex novel sounds. In comparison to high positively reactive and control infants, high negatively reactive infants displayed increased amplitude of a positive slow wave in the ERP response to deviant tones compared to standard tones. In contrast, high positively reactive infants showed a larger novelty P3 to the complex novel sounds. Results are discussed in terms of optimal levels of novelty for temperamentally different infants.     

Electroencephalogram and heart rate measures of working memory at 5 and 10 months of age

We recorded electroencephalogram (EEG; 6-9 Hz) and heart rate (HR) from infants at 5 and 10 months of age during baseline and performance on the looking A-not-B task of infant working memory (WM). Longitudinal baseline-to-task comparisons revealed WM-related increases in EEG power (all electrodes) and EEG coherence (medial frontal-occipital electrode pairs) at both ages. WM-related decreases in HR were only present at 5 months, and WM-related increases in EEG coherence became more localized by 10 months. Regression analyses revealed that baseline-to-task changes in psychophysiology accounted for variability in WM performance at 10 but not 5 months. HR and EEG power (medial frontal and lateral frontal electrodes) were unique predictors of variability in 10-month WM performance. These findings are discussed in relation to frontal lobe development and represent the first comprehensive longitudinal analysis of age-related changes in the behavioral and psychophysiological correlates of WM.     

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.     

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.     

Postnatal maternal symptoms of depression and child emotion dysregulation: The mediation role of infant EEG alpha asymmetry

In a community-based sample of 104 infants and their mothers, we hypothesized a pathway from postnatal maternal symptoms of depression to child emotion dysregulation, and tested at 6 months of age the mediation role of alpha asymmetry at frontal and parietal sites. We recorded infant resting-state EEG at 6 months of age. Child emotion dysregulation was measured at 24 months by the Child Behavior Checklist Dysregulation Profile derived from the CBCL 1½-5. Maternal depression symptoms were scored 6 months after the delivery by the Anxious/Depressed scale of the Adult Self-Report. We used structural equation modeling to test the mediation model from maternal depression symptoms to child emotion dysregulation mediated by frontal and parietal alpha asymmetry. The mediation model provided an excellent fit to the data [χ2(3) = 3.088, p = .378; RMSEA = .017, CFI = .1.00; SRMR = 0.040] and explained 23.3% of the variance in child emotion dysregulation. The indirect path via parietal alpha asymmetry was significant (β = .065; SE = .033; 95% CI = .001–.139; p = .048), i.e. greater levels of maternal depression symptoms predicted left parietal alpha asymmetry, which predicted higher levels of child emotion dysregulation. The direct effect, i.e. the pathway linking maternal depression symptoms and child emotion dysregulation above and beyond the indirect effects, was also significant. We found evidence for a partial mediation role of left parietal alpha asymmetry in a longitudinal pathway from postnatal maternal symptoms of depression to child emotion dysregulation, providing support for left parietal asymmetry as an index of biological vulnerability to emotion dysregulation in the first years of life.     

The ontogenesis of lateralized behavior in the domestic cat, Felis silvestris catus

For the first time, the development of paw preferences in the domestic cat, Felis silvestris catus, is explored. Twelve cats were tested at ages 12 weeks, 6 months, and 1 year on a challenge requiring them to use one of their paws to retrieve food. To control for repeated testing of the same cats at different ages, the subjects' paw preferences were compared with those of cats tested just once, at 6 months (n = 11) or 1 year (n = 14) of age. Analysis revealed a significant effect of age on the distribution of cats' paw preferences. Cats were significantly more likely to be ambilateral than paw preferent at 12 weeks and at 6 months but more likely to display a lateral bias in paw use at 1 year. There was a significant positive correlation between cats' paw preferences at 6 months and at 1 year. Lateralized behavior was strongly sex related. Females had a greater preference for using their right paw; males were significantly more inclined to adopt their left. Analysis revealed no significant difference in the direction or strength of paw preferences of cats tested longitudinally or cross-sectionally at 6 months or 1 year of age. Findings indicate that cats develop paw preferences by 1 year and hint at a relative stability in preferred paw use over time. The strong sex effect observed strengthens the case for the influence of a biological mechanism in the emergence of motor asymmetry in cats.     

Frontal EEG asymmetry and premenstrual dysphoric symptomatology

Resting frontal electroencephalographic (EEG) asymmetry has been hypothesized to tap a diathesis toward depression or other emotion-related psychopathology. Frontal EEG asymmetry was assessed in college women who reported high (n = 12) or low (n = 11) levels of premenstrual negative affect. Participants were assessed during both the follicular and the late luteal phases of the menstrual cycle. Women reporting low premenstrual dysphoric symptomatology exhibited greater relative left frontal activity at rest than did women high in premenstrual dysphoric symptomatology, an effect that was not qualified by phase of cycle. Although women with extreme levels of symptomatology were assessed, the question of whether such symptoms qualified for premenstrual dysphoric disorder criteria was not assessed. These results are consistent with a diathesis-stress model for premenstrual dysphoric symptomatology.     

Infant responses and the physical environment

A longitudinal study of infants ( n =23) from 6 to 13 months was made to explore infants' responses to objects high on complexity and responsiveness compared to low-scored ones, and whether the high-scored objects were preferred. Further, it was explored to what extent individual differences of the infants represent a source of variation. The results showed that more than 50% of the total variance was accounted for by differences in object qualities, and about 25% by individual differences. High-scored objects were significantly more often preferred compared to low-scored ones irrespective of age.     

Depression, anxiety, and resting frontal EEG asymmetry: a meta-analytic review

Emotion-related disturbances, such as depression and anxiety, have been linked to relative right-sided resting frontal electroencephalograph (EEG) asymmetry among adults and infants of afflicted mothers. However, a somewhat inconsistent pattern of findings has emerged. A meta-analysis was undertaken to (a) evaluate the magnitude of effects across EEG studies of resting frontal asymmetry and depression, anxiety, and comorbid depression and anxiety and (b) determine whether certain moderator variables could help reconcile inconsistent findings. Moderate effects of similar magnitude were obtained for the depression and anxiety studies, whereas a smaller effect emerged for comorbid studies. Three moderating variables predicted effect sizes: (a) Shorter EEG recording periods were associated with larger effects among adults, (b) different operationalizations of depression yielded effects of marginally different magnitudes, and (c) younger infant samples showed larger effects than older ones. The current data support a link between resting frontal EEG asymmetry and depression and anxiety and provide a partial account of inconsistent findings across studies.     

Massage and music therapies attenuate frontal EEG asymmetry in depressed adolescents

EEG asymmetry, specifically greater relative right frontal activation, is associated with negative affect. Depressed adults show stable patterns of this asymmetry. The present study assessed the effects of massage therapy and music therapy on frontal EEG asymmetry in depressed adolescents. Thirty adolescents with greater relative right frontal EEG activation and symptoms of depression were given either massage therapy (n = 14) or music therapy (n = 16). EEG was recorded for three-minute periods before, during, and after therapy. Frontal EEG asymmetry was significantly attenuated during and after the massage and music sessions.