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.

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.

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.

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.

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.

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.

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.

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.

Quantifying Motor Experience in the Infant Brain: EEG Power, Coherence, and Mu Desynchronization.

The emergence of new motor skills, such as reaching and walking, dramatically changes how infants engage with the world socially and cognitively. Several examples of how motor experience can cascade into cognitive and social development have been documented, yet a significant knowledge gap remains in our understanding of whether these observed behavioral changes are accompanied by underlying neural changes. We propose that electroencephalography (EEG) measures such as power, coherence, and mu desynchronization are optimal tools to quantify motor experience in the infant brain. In this mini-review, we will summarize existing infant research that has separately assessed the relation between motor, cognitive, or social development with coherence, power, or mu desynchronization. We will discuss how the reviewed neural changes seen in seemingly separate developmental domains may be linked based on existing behavioral evidence. We will further propose that power, coherence, and mu desynchronization be used in research exploring the links between motor experience and cognitive and social development.

Contextual startle responses moderate the relation between behavioral inhibition and anxiety in middle childhood.

Behavioral inhibition (BI), a temperament characterized in early childhood by wariness and avoidance of novelty, is a risk factor for anxiety disorders. An enhanced startle response has been observed in adolescents characterized with BI in childhood, particularly when they also manifest concurrent symptoms of anxiety. However, no prior study has examined relations among BI, startle responsivity, and anxiety in a prospective manner. Data for the present study were from a longitudinal study of infant temperament. Maternal reports and observations of BI were assessed at ages 2 and 3. At age 7, participants completed a startle procedure, while electromyography was collected, where participants viewed different colors on a screen that were associated with either the delivery of an aversive stimulus (i.e., puff of air to the larynx; threat cue) or the absence of the aversive stimulus (i.e., safety cue). Parental reports of child anxiety were collected when children were 7 and 9 years of age. Results revealed that startle responses at age 7 moderated the relation between early BI and 9-year anxiety. These findings provide insight into one potential mechanism that may place behaviorally inhibited children at risk for anxiety.

A new biomarker to examine the role of hippocampal function in the development of spatial reorientation in children: a review.

Spatial navigation is an adaptive skill that involves determining the route to a particular goal or location, and then traveling that path. A major component of spatial navigation is spatial reorientation, or the ability to reestablish a sense of direction after being disoriented. The hippocampus is known to be critical for navigating, and has more recently been implicated in reorienting in adults, but relatively little is known about the development of the hippocampus in relation to these large-scale spatial abilities in children. It has been established that, compared to school-aged children, preschool children tend to perform poorly on certain spatial reorientation tasks, suggesting that their hippocampi may not be mature enough to process the demands of such a task. Currently, common techniques used to examine underlying brain activity, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), are not suitable for examining hippocampal development in young children. In the present paper, we argue instead for the use of eyeblink conditioning (EBC), a relatively under-utilized, inexpensive, and safe method that is easy to implement in developing populations. In addition, EBC has a well defined neural circuitry, which includes the hippocampus, making it an ideal tool to indirectly measure hippocampal functioning in young children. In this review, we will evaluate the literature on EBC and its relation to hippocampal development, and discuss the possibility of using EBC as an objective measure of associative learning in relation to large-scale spatial skills. We support the use of EBC as a way to indirectly access hippocampal function in typical and atypical populations in order to characterize the neural substrates associated with the development of spatial reorientation abilities in early childhood. As such, EBC is a potential, simple biomarker for success in tasks that require the hippocampus, including spatial reorientation.

Associations between infant temperament, maternal stress, and infants' sleep across the first year of life.

Effects of temperament and maternal stress on infant sleep behaviors were explored longitudinally. Negative temperament was associated with sleep problems, and with longer sleep latency and night wakefulness, whereas maternal stress was associated with day sleep duration, suggesting infant and maternal characteristics affect sleep differentially.

Eyeblink conditioning: a non-invasive biomarker for neurodevelopmental disorders.

Eyeblink conditioning (EBC) is a classical conditioning paradigm typically used to study the underlying neural processes of learning and memory. EBC has a well-defined neural circuitry, is non-invasive, and can be employed in human infants shortly after birth making it an ideal tool to use in both developing and special populations. In addition, abnormalities in the cerebellum, a region of the brain highly involved in EBC, have been implicated in a number of neurodevelopmental disorders including autism spectrum disorders (ASDs). In the current paper, we review studies that have employed EBC as a biomarker for several neurodevelopmental disorders including fetal alcohol syndrome, Down syndrome, fragile X syndrome, attention deficit/hyperactivity disorder, dyslexia, specific language impairment, and schizophrenia. In addition, we discuss the benefits of using such a tool in individuals with ASD.

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.

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.

Effects of negative temperament on 5-month-old infants' behavior during the still-face paradigm.

Five-month-old infants characterized as low or high on temperamental negativity participated with their mothers in the still-face paradigm. Compared to low negative infants, high negative infants displayed greater negative engagement during reunion suggesting that infant temperament significantly contributes to individual differences in the still-face effect.