The effects of parental presence on amygdala and mPFC activation during fear conditioning: An exploratory study.

Learning safe versus dangerous cues is crucial for survival. During development, parents can influence fear learning by buffering their children's stress response and increasing exploration of potentially aversive stimuli. Rodent findings suggest that these behavioral effects are mediated through parental presence modulation of the amygdala and medial prefrontal cortex (mPFC). Here, we investigated whether similar parental modulation of amygdala and mPFC during fear learning occurs in humans. Using a within-subjects design, behavioral (final N = 48, 6-17 years, mean = 11.61, SD = 2.84, 60% females/40% males) and neuroimaging data (final N = 39, 6-17 years, mean = 12.03, SD = 2.98, 59% females/41% males) were acquired during a classical fear conditioning task, which included a CS+ followed by an aversive noise (US; 75% reinforcement rate) and a CS-. Conditioning occurred once in physical contact with the participant's parent and once alone (order counterbalanced). Region of interest analyses examined the unconditioned stress response by BOLD activation to the US (vs. implicit baseline) and learning by activation to the CS+ (vs. CS-). Results showed that during US presentation, parental presence reduced the centromedial amygdala activity, suggesting buffering of the unconditioned stress response. In response to learned stimuli, parental presence reduced mPFC activity to the CS+ (relative to the CS-), although this result did not survive multiple comparisons' correction. These preliminary findings indicate that parents modulate amygdala and mPFC activity during exposure to unconditioned and conditioned fear stimuli, potentially providing insight into the neural mechanisms by which parents act as a social buffer during fear learning. RESEARCH HIGHLIGHTS: (1)This study used a within-participant experimental design to investigate how parental presence (vs. absence) affects youth's neural responses in a classical fear conditioning task. (2)Parental presence reduced the youth's centromedial amygdala activation to the unconditioned stimulus (US), suggesting parental buffering of the neural unconditioned response (UR). (3)Parental presence reduced the youth's mPFC activation to a conditioned threat cue (CS+) compared to a safety cue (CS-), suggesting possible parental modulation of fear learning.

Probing the content of affective semantic memory following caregiving-related early adversity.

Cognitive science has demonstrated that we construct knowledge about the world by abstracting patterns from routinely encountered experiences and storing them as semantic memories. This preregistered study tested the hypothesis that caregiving-related early adversities (crEAs) shape affective semantic memories to reflect the content of those adverse interpersonal-affective experiences. We also tested the hypothesis that because affective semantic memories may continue to evolve in response to later-occurring positive experiences, child-perceived attachment security will inform their content. The sample comprised 160 children (ages 6-12 at Visit 1; 87F/73 M), 66% of whom experienced crEAs (n = 105). At Visit 1, crEA exposure prior to study enrollment was operationalized as parental-reports endorsing a history of crEAs (abuse/neglect, permanent/significant parent-child separation); while child-reports assessed concurrent attachment security. A false memory task was administered online ∼2.5 years later (Visit 2) to probe the content of affective semantic memories-specifically attachment schemas. Results showed that crEA exposure (vs. no exposure) was associated with a higher likelihood of falsely endorsing insecure (vs. secure) schema scenes. Attachment security moderated the association between crEA exposure and insecure schema-based false recognition. Findings suggest that interpersonal-affective semantic schemas include representations of parent-child interactions that may capture the quality of one's own attachment experiences and that these representations shape how children remember attachment-relevant narrative events. Findings are also consistent with the hypothesis that these affective semantic memories can be modified by later experiences. Moving forward, the approach taken in this study provides a means of operationalizing Bowlby's notion of internal working models within a cognitive neuroscience framework. RESEARCH HIGHLIGHTS: Affective semantic memories representing insecure schema knowledge (child needs + needs-not-met) may be more salient, elaborated, and persistent among youths exposed to early caregiving adversity. All youths, irrespective of early caregiving adversity exposure, may possess affective semantic memories that represent knowledge of secure schemas (child needs + needs-met). Establishing secure relationships with parents following early-occurring caregiving adversity may attenuate the expression of insecure semantic memories, suggesting potential malleability. Affective semantic memories include schema representations of parent-child interactions that may capture the quality of one's own attachment experiences and shape how youths remember attachment-relevant events.

Preliminary examination of the effects of an early parenting intervention on amygdala-orbitofrontal cortex resting-state functional connectivity among high-risk children: A randomized clinical trial.

We examined the long-term causal effects of an evidence-based parenting program delivered in infancy on children's emotion regulation and resting-state functional connectivity (rs-fc) during middle childhood. Families were referred to the study by Child Protective Services (CPS) as part of a diversion from a foster care program. A low-risk group of families was also recruited. CPS-involved families were randomly assigned to receive the target (Attachment and Biobehavioral Catch-up, ABC) or a control intervention (Developmental Education for Families, DEF) before infants turned 2. Both interventions were home-based, manualized, and 10-sessions long. During middle childhood, children underwent a 6-min resting-state functional MRI scan. Amygdala seed-based rs-fc analysis was completed with intervention group as the group-level predictor of interest. Fifty-seven children (NABC = 21; NDEF = 17; NCOMP = 19; Mage = 10.02 years, range = 8.08-12.14) were scanned successfully. The DEF group evidenced negative left amygdala↔OFC connectivity, whereas connectivity was near zero in the ABC and comparison groups (ABCvsDEF: Cohen's d = 1.17). ABC may enhance high-risk children's regulatory neurobiology outcomes ∼8 years after the intervention was completed.

Pandemic beyond the virus: maternal COVID-related postnatal stress is associated with infant temperament.

BACKGROUND: Studies have shown that infant temperament varies with maternal psychosocial factors, in utero illness, and environmental stressors. We predicted that the pandemic would shape infant temperament through maternal SARS-CoV-2 infection during pregnancy and/or maternal postnatal stress. To test this, we examined associations among infant temperament, maternal prenatal SARS-CoV-2 infection, maternal postnatal stress, and postnatal COVID-related life disruptions. METHODS: We tested 63 mother-infant dyads with prenatal maternal SARS-CoV-2 infections and a comparable group of 110 dyads without infections. To assess postnatal maternal stress, mothers completed the Perceived Stress Scale 4 months postpartum and an evaluation of COVID-related stress and life disruptions 6 months postpartum. Mothers reported on infant temperament when infants were 6-months-old using the Infant Behavior Questionnaire-Revised (IBQ-R) Very Short Form. RESULTS: Maternal SARS-CoV-2 infection during pregnancy was not associated with infant temperament or maternal postnatal stress. Mothers with higher self-reported postnatal stress rated their infants lower on the Positive Affectivity/Surgency and Orienting/Regulation IBQ-R subscales. Mothers who reported greater COVID-related life disruptions rated their infants higher on the Negative Emotionality IBQ-R subscale. CONCLUSIONS: Despite no effect of prenatal maternal SARS-CoV-2 infection, stress and life disruptions incurred by the COVID-19 pandemic were associated with infant temperament at 6-months. IMPACT: SARS-CoV-2 infection during pregnancy is not associated with postnatal ratings of COVID-related life disruptions, maternal stress, or infant temperament. Postnatal ratings of maternal stress during the COVID-19 pandemic are associated with normative variation in maternal report of infant temperament at 6 months of age. Higher postnatal ratings of maternal stress are associated with lower scores on infant Positive Affectivity/Surgency and Orienting/Regulation at 6 months of age. Higher postnatal ratings of COVID-related life disruptions are associated with higher scores on infant Negative Emotionality at 6 months of age.

Associations between cortical thickness and anxious/depressive symptoms differ by the quality of early care.

A variety of childhood experiences can lead to anxious/depressed (A/D) symptoms. The aim of the present study was to explore the brain morphological (cortical thickness and surface area) correlates of A/D symptoms and the extent to which these phenotypes vary depending on the quality of the parenting context in which children develop. Structural magnetic resonance imaging (MRI) scans were acquired on 45 children with Child Protective Services (CPS) involvement due to risk of not receiving adequate care (high-risk group) and 25 children without CPS involvement (low-risk group) (rangeage = 8.08-12.14; Mage = 10.05) to assess cortical thickness (CT) and cortical surface area (SA). A/D symptoms were measured using the Child Behavioral Checklist. The association between A/D symptoms and CT, but not SA, differed by risk status such that high-risk children showed decreasing CT as A/D scores increased, whereas low-risk children showed increasing CT as A/D scores increased. This interaction was specific to CT in prefrontal, frontal, temporal, and parietal cortical regions. The groups had marginally different A/D scores, in the direction of higher risk being associated with lower A/D scores. Results suggest that CT correlates of A/D symptoms are differentially shaped by the quality of early caregiving experiences and should be distinguished between high- and low-risk children.

Amygdala responses to threat in violence-exposed children depend on trauma context and maternal caregiving.

Early life adversity (ELA) has been linked with increased arousal responses to threat, including increased amygdala reactivity. Effects of ELA on brain function are well recognized, and emerging evidence suggests that caregivers may influence how environmental stressors impact children's brain function. We investigated the hypothesis that positive interaction between mother and child can buffer against ELA effects on children's neural responses to threat, and related symptoms. N = 53 mother-child pairs (children ages 8-14 years) were recruited from an urban population at high risk for violence exposure. Maternal caregiving was measured using the Parenting Questionnaire and in a cooperation challenge task. Children viewed fearful and neutral face stimuli during functional magnetic resonance imaging. Children who experienced greater violence at home showed amygdala sensitization, whereas children experiencing more school and community violence showed amygdala habituation. Sensitization was in turn linked with externalizing symptoms. However, maternal warmth was associated with a normalization of amygdala sensitization in children, and fewer externalizing behaviors prospectively up to 1 year later. Findings suggested that the effects of violence exposure on threat-related neural circuitry depend on trauma context (inside or outside the home) and that primary caregivers can increase resilience.

Sensory processing challenges as a novel link between early caregiving experiences and mental health.

Early caregiving adversity (ECA) is associated with elevated psychological symptomatology. While neurobehavioral ECA research has focused on socioemotional and cognitive development, ECA may also increase risk for "low-level" sensory processing challenges. However, no prior work has compared how diverse ECA exposures differentially relate to sensory processing, or, critically, how this might influence psychological outcomes. We examined sensory processing challenges in 183 8-17-year-old youth with and without histories of institutional (orphanage) or foster caregiving, with a particular focus on sensory over-responsivity (SOR), a pattern of intensified responses to sensory stimuli that may negatively impact mental health. We further tested whether sensory processing challenges are linked to elevated internalizing and externalizing symptoms common in ECA-exposed youth. Relative to nonadopted comparison youth, both groups of ECA-exposed youth had elevated sensory processing challenges, including SOR, and also had heightened internalizing and externalizing symptoms. Additionally, we found significant indirect effects of ECA on internalizing and externalizing symptoms through both general sensory processing challenges and SOR, covarying for age and sex assigned at birth. These findings suggest multiple forms of ECA confer risk for sensory processing challenges that may contribute to mental health outcomes, and motivate continuing examination of these symptoms, with possible long-term implications for screening and treatment following ECA.

Effects of familiar music exposure on deliberate retrieval of remote episodic and semantic memories in healthy aging adults.

Familiar music facilitates memory retrieval in adults with dementia. However, mechanisms behind this effect, and its generality, are unclear because of a lack of parallel work in healthy aging. Exposure to familiar music enhances spontaneous recall of memories directly cued by the music, but it is unknown whether such effects extend to deliberate recall more generally - e.g., to memories not directly linked to the music being played. It is also unclear whether familiar music boosts recall of specific episodes versus more generalised semantic memories, or whether effects are driven by domain-general mechanisms (e.g., improved mood). In a registered report study, we examined effects of familiar music on deliberate recall in healthy adults ages 65-80 years (N = 75) by presenting familiar music from earlier in life, unfamiliar music, and non-musical audio clips across three sessions. After each clip, we assessed free recall of remote memories for pre-selected events. Contrary to our hypotheses, we found no effects of music exposure on recall of prompted events, though familiar music evoked spontaneous memories most often. These results suggest that effects of familiar music on recall may be limited to memories specifically evoked in response to the music (Preprint and registered report protocol at https://osf.io/kjnwd/).

Age-Related Increases in Posterior Hippocampal Granularity Are Associated with Remote Detailed Episodic Memory in Development.

Episodic memory is critical to human functioning. In adults, episodic memory involves a distributed neural circuit in which the hippocampus plays a central role. As episodic memory abilities continue to develop across childhood and into adolescence, studying episodic memory maturation can provide insight into the development and construction of these hippocampal networks, and ultimately clues to their function in adulthood. While past developmental studies have shown that the hippocampus helps to support memory in middle childhood and adolescence, the extent to which ongoing maturation within the hippocampus contributes to developmental change in episodic memory abilities remains unclear. In contrast, slower maturing regions, such as the PFC, have been suggested to be the neurobiological locus of memory improvements into adolescence. However, it is also possible that the methods used to detect hippocampal development during middle childhood and adolescence are not sensitive enough. Here, we examine how temporal covariance (or differentiation) in voxel representations within anterior and posterior hippocampus change with age to support the development of detailed recollection in male and female developing humans. We find age-related increases in the distinctiveness of temporal activation profiles in the posterior, but not anterior, hippocampus. Second, we show that this measure of granularity, when present during postencoding rest periods, correlates with the recall of detailed memories of preceding stimuli several weeks postencoding, suggesting that granularity may promote memory stabilization.SIGNIFICANCE STATEMENT Studying hippocampal maturation can provide insight into episodic memory development, as well as clues to episodic functioning in adulthood. Past work has shown evidence both for and against hippocampal contributions to age-related improvements in memory performance, but has relied heavily on univariate approaches (averaging activity across hippocampal voxels), which may not be sensitive to nuanced developmental change. Here we use a novel approach, examining time signatures in individual hippocampal voxels to reveal regionally specific (anterior vs posterior hippocampus) differences in the distinctiveness (granularity) of temporal activation profiles across development. Importantly, posterior hippocampus granularity during windows of putative memory stabilization was associated with long-term memory specificity. This suggests that the posterior hippocampus gradually builds the capacity to support detailed episodic recall.

Age-related change in task-evoked amygdala-prefrontal circuitry: A multiverse approach with an accelerated longitudinal cohort aged 4-22 years.

The amygdala and its connections with medial prefrontal cortex (mPFC) play central roles in the development of emotional processes. While several studies have suggested that this circuitry exhibits functional changes across the first two decades of life, findings have been mixed - perhaps resulting from differences in analytic choices across studies. Here we used multiverse analyses to examine the robustness of task-based amygdala-mPFC function findings to analytic choices within the context of an accelerated longitudinal design (4-22 years-old; N = 98; 183 scans; 1-3 scans/participant). Participants recruited from the greater Los Angeles area completed an event-related emotional face (fear, neutral) task. Parallel analyses varying in preprocessing and modeling choices found that age-related change estimates for amygdala reactivity were more robust than task-evoked amygdala-mPFC functional connectivity to varied analytical choices. Specification curves indicated evidence for age-related decreases in amygdala reactivity to faces, though within-participant changes in amygdala reactivity could not be differentiated from between-participant differences. In contrast, amygdala-mPFC functional connectivity results varied across methods much more, and evidence for age-related change in amygdala-mPFC connectivity was not consistent. Generalized psychophysiological interaction (gPPI) measurements of connectivity were especially sensitive to whether a deconvolution step was applied. Our findings demonstrate the importance of assessing the robustness of findings to analysis choices, although the age-related changes in our current work cannot be overinterpreted given low test-retest reliability. Together, these findings highlight both the challenges in estimating developmental change in longitudinal cohorts and the value of multiverse approaches in developmental neuroimaging for assessing robustness of results.