Neurite density of the hippocampus is associated with trace eyeblink conditioning latency in 4- to 6-year-olds.

Limited options exist to evaluate the development of hippocampal function in young children. Research has established that trace eyeblink conditioning (EBC) relies on a functional hippocampus. Hence, we set out to investigate whether trace EBC is linked to hippocampal structure, potentially serving as a valuable indicator of hippocampal development. Our study explored potential associations between individual differences in hippocampal volume and neurite density with trace EBC performance in young children. We used onset latency of conditioned responses (CR) and percentage of conditioned responses (% CR) as measures of hippocampal-dependent associative learning. Using a sample of typically developing children aged 4 to 6 years (N = 30; 14 girls; M = 5.70 years), participants underwent T1- and diffusion-weighted MRI scans and completed a 15-min trace eyeblink conditioning task conducted outside the MRI. % CR and CR onset latency were calculated based on all trials involving tone-puff presentations and tone-alone trials. Findings revealed a connection between greater left hippocampal neurite density and delayed CR onset latency. Children with higher neurite density in the left hippocampus tended to blink closer to the onset of the unconditioned stimulus, indicating that structural variations in the hippocampus were associated with more precise timing of conditioned responses. No other relationships were observed between hippocampal volume, cerebellum volume or neurite density, hippocampal white matter connectivity and any EBC measures. Preliminary results suggest that trace EBC may serve as a straightforward yet innovative approach for studying hippocampal development in young children and populations with atypical development.

Volumetric development of hippocampal subfields and hippocampal white matter connectivity: Relationship with episodic memory.

The hippocampus is a complex structure composed of distinct subfields. It has been central to understanding neural foundations of episodic memory. In the current cross-sectional study, using a large sample of 830, 3- to 21-year-olds from a unique, publicly available dataset we examined the following questions: (1) Is there elevated grey matter volume of the hippocampus and subfields in late compared to early development? (2) How does hippocampal volume compare with the rest of the cerebral cortex at different developmental stages? and (3) What is the relation between hippocampal volume and connectivity with episodic memory performance? We found hippocampal subfield volumes exhibited a nonlinear relation with age and showed a lag in volumetric change with age when compared to adjacent cortical regions (e.g., entorhinal cortex). We also observed a significant reduction in cortical volume across older cohorts, while hippocampal volume showed the opposite pattern. In addition to age-related differences in gray matter volume, dentate gyrus/cornu ammonis 3 volume was significantly related to episodic memory. We did not, however, find any associations with episodic memory performance and connectivity through the uncinate fasciculus, fornix, or cingulum. The results are discussed in the context of current research and theories of hippocampal development and its relation to episodic memory.

Using hippocampal-dependent eyeblink conditioning to predict individual differences in spatial reorientation strategies in 3- to 6-year-olds.

The hippocampus is a subcortical structure in the medial temporal lobe involved in cognitive functions such as spatial navigation and reorientation, episodic memory, and associative learning. While much is understood about the role of hippocampal function in learning and memory in adults, less is known about the relations between the hippocampus and the development of these cognitive skills in young children due to the limitations of using standard methods (e.g., MRI) to examine brain structure and function in developing populations. This study used hippocampal-dependent trace eyeblink conditioning (EBC) as a feasible approach to examine individual differences in hippocampal functioning as they relate to spatial reorientation and episodic memory performance in young children. Three- to six-year-old children (N = 50) completed tasks that measured EBC, spatial reorientation, and episodic memory, as well as non-hippocampal-dependent processing speed abilities. Results revealed that when age was held constant, individual differences in EBC performance were significantly related to individual differences in performance on the spatial reorientation test, but not on the episodic memory or processing speed tests. When the relations between hippocampal-dependent EBC and different reorientation strategies were explored, it was found that individual differences in hippocampal function predicted the use of geometric information for reorienting in space as opposed to a combined strategy that uses both geometric information and salient visual cues. The utilization of eyeblink conditioning to examine hippocampal function in young populations and its implications for understanding the dissociation between spatial reorientation and episodic memory development are discussed.

On the causes of early life experience effects: evaluating the role of mom.

Early life experiences are thought to have long-lasting effects on cognitive, emotional, and social function during adulthood. Changes in neuroendocrine function, particularly the hypothalamic-pituitary-adrenal (HPA) axis, contribute to these systems-level behavioral effects. In searching for causal mechanisms underlying these early experience effects, pioneering research has demonstrated an important role for maternal care in offspring development, and this has led to two persistent ideas that permeate current research and thinking: first, environmental impact on the developing infant is mediated through maternal care behavior; second, the more care that a mother provides, the better off her offspring. While a good beginning, the reality is likely more complex. In this review, we critically examine these ideas and propose a computationally-motivated theoretical framework, and within this framework, we consider evidence supporting a hypothesis of maternal modulation. These findings may inform policy decisions in the context of child health and development.

Maternal modulation of novelty effects on physical development.

Familiarity to the mother and the novelty afforded by the postnatal environment are two contrasting sources of neonatal influence. One hypothesis regarding their relationship is the maternal modulation hypothesis, which predicts that the same neonatal stimulation may have different effects depending on the maternal context. Here we tested this hypothesis using physical development, indexed by body weight, as an endpoint and found that, among offspring of mothers with a high initial swim-stress-induced corticosterone (CORT) response, neonatal novelty exposure induced an enhancement in early growth, and among offspring with mothers of a low initial CORT response, the same neonatal stimulation induced an impairment. At an older age, a novelty-induced increase in body weight was also found among offspring of mothers with high postnatal care reliability and a novelty-induced reduction found among offspring of mothers with low care reliability. These results support a maternal modulation of early stimulation effects on physical development and demonstrate that the maternal influence originates from multiple instead of any singular sources. These results (i) significantly extend the findings of maternal modulation from the domain of cognitive development to the domain of physical development; (ii) offer a unifying explanation for a previously inconsistent literature regarding early stimulation effects on body weight; and (iii) highlight the notion that the early experience effect involves no causal primacy but higher order interactions among the initial triggering events and subsequent events involving a multitude of maternal and nonmaternal influences.

Identification of emotional facial expressions among behaviorally inhibited adolescents with lifetime anxiety disorders.

The current study examined differences in emotion expression identification between adolescents characterised with behavioural inhibition (BI) in childhood with and without a lifetime history of anxiety disorder. Participants were originally assessed for BI during toddlerhood and for social reticence during childhood. During adolescence, participants returned to the laboratory and completed a facial emotion identification task and a clinical psychiatric interview. Results revealed that behaviorally inhibited adolescents with a lifetime history of anxiety disorder displayed a lower threshold for identifying fear relative to anger emotion expressions compared to non-anxious behaviorally inhibited adolescents and non-inhibited adolescents with or without anxiety. These findings were specific to behaviorally inhibited adolescents with a lifetime history of social anxiety disorder. Thus, adolescents with a history of both BI and anxiety, specifically social anxiety, are more likely to differ from other adolescents in their identification of fearful facial expressions. This offers further evidence that perturbations in the processing of emotional stimuli may underlie the aetiology of anxiety disorders.

Individual differences in fear potentiated startle in behaviorally inhibited children.

Behavioral inhibition (BI) is a temperament characterized during early childhood by increased fearfulness to novelty, social reticence to unfamiliar peers, and heightened risk for the development of anxiety. Heightened startle responses to safety cues have been found among behaviorally inhibited adolescents who have an anxiety disorder suggesting that this measure may serve as a biomarker for the development of anxiety amongst this risk population. However, it is unknown if these aberrant startle patterns emerge prior to the manifestation of anxiety in this temperament group. The current study examined potentiated startle in 7-year-old children characterized with BI early in life. High behaviorally inhibited children displayed increased startle magnitude to safety cues, particularly during the first half of the task, and faster startle responses compared to low behaviorally inhibited children. These findings suggest that aberrant startle responses are apparent in behaviorally inhibited children during early childhood prior to the onset of a disorder and may serve as a possible endophenotype for the development of anxiety.

Neonatal novelty-induced persistent enhancement in offspring spatial memory and the modulatory role of maternal self-stress regulation.

Development of spatial memory in the rat is influenced by both maternal and nonmaternal aspects of the postnatal environment. Yet it remains poorly understood how these two aspects of the postnatal environment interact to program offspring cognitive development. By considering the joint influence of neonatal environmental novelty and maternal self-stress regulation on the development of spatial memory function in Long-Evans hooded rats, we show a persistent neonatal novelty-induced enhancement in spatial reference and working memory functions among the same individual offspring from juvenility to adulthood and a contrasting transient maternal modulatory influence on this novelty-related enhancement present during only juvenility. Specifically, at and only at juvenility, for mothers with good self-stress regulation as indexed by a low circulating basal corticosterone level, offspring showed a novelty-induced enhancement in spatial memory function, whereas for mothers with poor self-stress regulation, indexed by a high basal corticosterone level, offspring showed little enhancement or even small impairments. These findings indicate that maternal and nonmaternal postnatal environments exert separate but interacting influences on offspring cognitive development and support a maternal modulation model of cognitive development that considers maternal self-stress regulation as an important factor among the multitude of maternal influences.

The role of attentional shifting in the relation between error monitoring and anxiety in youth.

The error-related negativity (ERN), a well-established neural marker of anxiety, reflects enhanced attention to internal threat signals. While attention to threat plays a crucial role in the development and maintenance of anxiety, it is unclear how attentional control influences the ERN-anxiety association. To address this, 37 youths (Mage = 10.89 years) completed self-report measures of attentional control and anxiety symptoms. To obtain ERN amplitude, youth completed a flanker task while simultaneous EEG was collected. Attentional control, specifically attentional shifting rather than focusing, moderated the relation between ERN amplitude and anxiety. Youth who displayed smaller neural responses to making an error and higher ability to shift attention experienced lower levels of anxiety, relative to those who exhibited larger neural responses to making an error or lower attention-shifting ability. These findings highlight that response magnitude to internal threat and ability to flexibly shift attention may jointly contribute to anxiety in youth.

One-month-old human infants learn about the social world while they sleep.

Although infants display preferences for social stimuli early in their lives, we know relatively little about the mechanisms of infant learning about the social world. In the current set of studies, 1-month-old infants underwent an adapted eyeblink conditioning paradigm to examine learning to both 'social' and non-social cues. While infants were asleep, they were presented with either a 'social' stimulus (a female voice) or one of two non-social stimuli (tone or backward voice) followed by an airpuff presented to the eyelid. Infants in the experimental groups displayed increased learning across trials, regardless of stimulus type. However, infants conditioned to the 'social' stimulus showed increased learning compared to infants conditioned to either of the non-social stimuli. These results suggest a mechanism by which learning about the social world occurs early in life and the power of ecologically valid cues in facilitating that learning.

Repetitive negative thinking and depressive symptoms are differentially related to response inhibition: The influence of non-emotional, socio-emotional, and self-referential stimuli.

Identifying transdiagnostic correlates of response inhibition deficits is important for understanding risk for internalizing disorders. Little work has compared the relationships between internalizing symptoms and repetitive negative thinking (RNT) with response inhibition across non-emotional and emotional domains, and no work has compared these relationships for inhibition of socio-emotional relative to self-referential stimuli. Undergraduate students (N = 71, 18.44 ± 0.71 years) selected on extremes of internalizing symptoms completed the Perseverative Thinking Questionnaire (PTQ) and a Go/No-Go paradigm using non-emotional stimuli, other individuals' sad facial expressions, and participants' own sad facial expressions. Participants exhibited more commission errors for sad facial expressions than non-emotional trials, though commission errors for others' and participants' own sad facial expressions did not differ. Depressive symptoms were associated with poorer inhibition of non-emotional stimuli; however, PTQ scores were associated with more successful inhibition of non-emotional stimuli. Our results provide evidence that transdiagnostic RNT as assessed by the PTQ may be related to better inhibition in non-emotional domains, but negative emotional stimuli may interfere with successful inhibition for those with high RNT, while depressive symptoms were linked to poorer inhibition of non-emotional stimuli. These findings have implications for internalizing disorders, which often are accompanied by RNT.

Ordinary variations in human maternal caregiving in infancy and biobehavioral development in early childhood: A follow-up study.

Rodent models of early caregiving find that pups reared by dams providing low levels of early stimulation subsequently display heightened stress reactivity and social aggression. We examined these effects in humans by investigating the effects of early caregiving on markers of biobehavioral development at ages 2 and 3 years. This study extended the findings reported by Hane and Fox (Hane and Fox [2006] Psychol. Sci. 17: 550-556) in which 185 mothers and infants were observed and scored for variations in maternal caregiving behavior (MCB) at age 9 months. Relative to young children who received high-quality MCB in infancy, those who received low-quality MCB showed significantly higher socially inhibited behavior with adults, right frontal electroencephalographam (EEG) asymmetry, aggressive play, and maternal reported internalizing behavior problems and anger proneness. These effects were independent of early temperamental reactivity. Results parallel rodent models and demonstrate that ordinary variations in MCB influence stress reactivity and social behavior in young children.

Childhood wayfinding experience explains sex and individual differences in adult wayfinding strategy and anxiety.

BACKGROUND: Anyone who has ever found themselves lost while driving in an unfamiliar neighborhood or forgotten where they parked their car can appreciate the importance of being able to navigate their environment. Navigation, or wayfinding, is a large-scale spatial ability that involves keeping track of the relative positions of objects and features in space, which allows for determining the path to a goal location. Early experiences shape spatial skill development, and research finds sex differences in spatial behaviors from preschool through adulthood, with males consistently outperforming females. The basis for sex differences in spatial aptitude is still debated, but explanations include differences in childhood spatial experience, the use of strategies for solving large-scale spatial problems, and spatial anxiety. The current study seeks to understand childhood wayfinding factors that may influence sex and individual differences in wayfinding strategies and wayfinding anxiety in adulthood. METHOD: One hundred fifty-nine undergraduate psychology students reported their childhood wayfinding experience (i.e., time spent outside, distance traveled), current use of wayfinding strategies (i.e., route strategy, orientation strategy), and current wayfinding anxiety and general anxiety levels. RESULTS: Independent samples t tests revealed that, compared with females, males reported spending more time outside and traveling farther distances as children, having less current wayfinding anxiety and route strategy use, and having more current orientation strategy use. Mediation analyses found that distance traveled, but not time spent outdoors, during childhood mediated sex differences in route strategy use and wayfinding anxiety in adults, even when controlling for general anxiety. Furthermore, when controlling for participant sex and general anxiety, current wayfinding anxiety mediated the relationship between distance traveled during childhood and route strategy use in adults. CONCLUSION: The current findings provide potential environmental explanations for sex and individual differences in large-scale spatial behaviors, including wayfinding. Specifically, sex differences in early wayfinding experience may explain why males and females develop different strategies for navigating and different levels of wayfinding anxiety. Furthermore, regardless of sex, allowing children to explore and navigate their outdoor environments away from home may help lessen their fears about navigating and, in turn, improve the strategies they choose to traverse unfamiliar territories.

Role of attention in the regulation of fear and anxiety.

Emotion regulation makes use of specific aspects of attention and executive functions that are critical for the development of adaptive social functioning, and perturbations in these processes can result in maladaptive behavior and psychopathology. Both involuntary and voluntary attention processes have been examined at both the behavioral and the neural levels and are implicated in the maintenance of fearful or anxious behaviors. However, relatively little is known about how these attention processes come to influence emotional behavior across development. The current review summarizes the extant literature on the links between voluntary and involuntary attention processes and the role that these attention processes have in the etiology, maintenance, and regulation of anxious behavior.

Attention to novelty in behaviorally inhibited adolescents moderates risk for anxiety.

BACKGROUND: Individual differences in specific components of attention contribute to behavioral reactivity and regulation. Children with the temperament of behavioral inhibition (BI) provide a good context for considering the manner in which certain components of attention shape behavior. Infants and children characterized as behaviorally inhibited manifest signs of heightened orienting to novelty. The current study considers whether this attention profile moderates risk for clinical anxiety disorders among adolescents with a history of BI. METHODS: Participants were assessed at multiple time points for BI, beginning in early childhood. At adolescence, event-related potentials (ERPs) were recorded during a three-stimulus auditory novelty oddball task, which employed frequent standard and infrequent deviant tones as well as a set of complex, novel sounds. Clinical diagnosis was carried out using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). P3 and mismatch negativity (MMN) components were examined at midline frontal, central, and parietal electrode sites. RESULTS: Individuals who displayed high levels of BI during childhood and increased P3 amplitude to novelty in adolescence were more likely to have a history of anxiety disorders compared to behaviorally inhibited adolescents with lower P3 amplitudes. Groups did not differ on measures of MMN. CONCLUSIONS: Increased neural responses to novelty moderate risk for anxiety disorders amongst individuals with a history of BI.

Neural Correlates of Attentional Processing of Threat in Youth with and without Anxiety Disorders.

Late-stage attentional processing of threatening stimuli, quantified through event-related potentials (ERPs), differentiates youth with and without anxiety disorders. It is unknown whether early-stage attentional processing of threatening stimuli differentiates these groups. Examining both early and late stage attentional processes in youth may advance knowledge and enhance efforts to identify biomarkers for translational prevention and treatment research. Twenty-one youth with primary DSM-IV-TR anxiety disorders (10 males, ages 8-15 years) and 21 typically developing Controls (15 males, ages 8-16 years) completed a dot probe task while electroencephalography (EEG) was recorded, and ERPs were examined. Youth with anxiety disorders showed significantly larger (more positive) P1 amplitudes for threatening stimuli than for neutral stimuli, and Controls showed the opposite pattern. Youth with anxiety showed larger (more negative) N170 amplitudes compared with Controls. Controls showed significantly larger (more positive) P2 and P3 amplitudes, regardless of stimuli valence, compared with youth with anxiety disorders. ERPs observed during the dot probe task indicate youth with anxiety disorders display distinct neural processing during early stage attentional orienting and processing of faces; this was not the case for Controls. Such results suggest these ERP components may have potential as biomarkers of anxiety disorders in youth.

Does intention matter? Relations between parent pointing, infant pointing, and developing language ability.

Infants' pointing is associated with concurrent and later language development. The communicative intention behind the point-i.e., imperative versus declarative-can affect both the nature and strength of these associations, and is therefore a critical factor to consider. Parents' pointing is associated with both infant pointing and infant language; however, less work has examined the intent behind parents' points. We explore relations between parents' and infants' pointing at the level of communicative intention, and examine how pointing relates to concurrent and longitudinal infant language skills. In a sample of 52 mother-infant dyads, we measured mother and infant pointing at infant age 12-months, and infant expressive and receptive language at 12-, 18-, and 24-months. We found that mothers produced points with a variety of intentions, however we did not find relations between mother and infant pointing within the different communicative intentions. Replicating previous research, infant declarative pointing was related both concurrently and longitudinally to their language ability. Mothers' declarative pointing was related to their infants' concurrent language, while their imperative pointing was not. Further, there was an interaction between parent and infant declarative pointing, such that the positive relation between parents' declarative pointing and their infants' concurrent receptive language was present only for those infants who were also producing declarative points themselves. Findings suggest that parents' declarative pointing may support both their infants' early word learning and, perhaps, provides a model for their infant to begin using points as well. This study constitutes an important initial exploration of these relations.

Exploring Infant Gesture and Joint Attention as Related Constructs and as Predictors of Later Language.

In infancy, use of gesture and the ability to engage in joint attention with others both predict later language development. Conceptually, gesture and joint attention abilities may reflect a similar underlying social communicative skill. However, these abilities are often studied separately. Despite the fact that gesture is often used in episodes of joint attention, little is known about the degree to which measures of gesture use and joint attention ability are associated with one another or how they similarly, or differentially, predict children's language abilities. Participants in the current study were 53 infants. At 12-months, multiple measures of infants' gesture use were gleaned from a free-play interaction with a parent. Infants' responding to and initiating joint attention were measured via the Early Social-Communicative Scales (ESCS, Mundy et al., 2003). Infants' expressive and receptive language was measured at 24-months with the Mullen Scales of Early Learning (Mullen, 1995). A factor analysis including gesture and joint attention measures indicated that at 12-months joint attention, particularly responding to joint attention, reflects a similar underlying construct with infant gesture use, yet they uniquely predict later language ability.

Individual differences in non-clinical maternal depression impact infant affect and behavior during the still-face paradigm across the first year.

Maternal depression can significantly impact mothers' sensitivity to their infants' needs as well as infants' social and emotional development. The still-face paradigm (SFP) is widely used to assess infants' understanding of the contingency between their own behavior and that of their caregivers, as well as infants' ability to self-regulate arousal levels during sudden changes in maternal responsiveness. Infants of clinically depressed mothers display blunted levels of negative affect compared to infants of non-depressed mothers during the still-face (SF) phase. However, little is known about whether individual differences in elevated, non-clinical levels of maternal depression similarly affect mother-infant interactions. The current study examines the longitudinal effects of non-clinical maternal depression on infant and maternal behaviors during the SFP. Infants (N=63) were assessed at 5 and 9 months and maternal depression was assessed at 5 months using the Beck Depression Inventory (BDI). Infants of mothers with elevated levels of depression displayed less negative engagement during the SF phase compared to infants of mothers with lower levels of depression. This effect was present at 5 months, but not at 9 months. Findings demonstrate that non-clinical levels of maternal depressive symptomatology can have a significant impact on infants' affective regulation during the first half of the first year of life, but this does not necessarily have a long-lasting influence later in infancy. Interventions may want to target mothers with non-clinical depression to promote healthy infant social and emotional development.