David W. Haley

Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU

Data from animal models indicate that neonatal stress or pain can permanently alter subsequent behavioral and/or physiological reactivity to stressors. However, cumulative effects of pain related to acute procedures in the neonatal intensive care unit (NICU) on later stress and/or pain reactivity has received limited attention. The objective of this study is to examine relationships between prior neonatal pain exposure (number of skin breaking procedures), and subsequent stress and pain reactivity in preterm infants in the NICU. Eighty‐seven preterm infants were studied at 32 (±1 weeks) postconceptional age (PCA). Infants who received analgesia or sedation in the 72 h prior to each study, or any postnatal dexamethasone, were excluded. Outcomes were infant responses to two different stressors studied on separate days in a repeated measures randomized crossover design: (1) plasma cortisol to stress of a fixed series of nursing procedures; (2) behavioral (Neonatal Facial Coding System; NFCS) and cardiac reactivity to pain of blood collection. Among infants born ≤28 weeks gestational age (GA), but not 29–32 weeks GA, higher cumulative neonatal procedural pain exposure was related to lower cortisol response to stress and to lower facial (but not autonomic) reactivity to pain, at 32 weeks PCA, independent of early illness severity and morphine exposure since birth. Repeated neonatal procedural pain exposure among neurodevelopmentally immature preterm infants was associated with down‐regulation of the hypothalamic–pituitary–adrenal axis, which was not counteracted with morphine. Differential effects of early pain on development of behavioral, physiologic and hormonal systems warrant further investigation.

Infant Stress and Parent Responsiveness: Regulation of Physiology and Behavior During Still-Face and Reunion

This study examined infant response and recovery from a social challenge and parent responses. Behavioral and physiological responses were measured from forty-three 5- and 6-month-olds infants during a modified still-face procedure that used an additional still-face reunion sequence. Results confirm the hypothesis that infants of more responsive parents show more regulation than infants of less responsive parents. Infants of more responsive parents showed greater regulation of heart rate and negative affect during the final episode of the procedure than infants of less responsive parents. In addition, this procedure elicited a cortisol response (from .22 microg/dl to .31 microg/dl). Findings suggest important links between parent behavior and infant stress reactivity and regulation.

Cortisol, contingency learning, and memory in preterm and full-term infants

Cortisol plays an important role in learning and memory. An inverted-U shaped function has been proposed to account for the positive and negative effects of cortisol on cognitive performance and memory in adults, such that too little or too much impair but moderate amounts facilitate performance. Whether such relationships between cortisol and mental function apply to early infancy, when cortisol secretion, learning, and memory undergo rapid developmental changes, is unknown. We compared relationships between learning/memory and cortisol in preterm and full-term infants and examined whether a greater risk for adrenal insufficiency associated with prematurity produces differential cortisol-memory relationships. Learning in three-month old (corrected for gestational age) preterm and full-term infants was evaluated using a conjugate reinforcement mobile task. Memory was tested by repeating the same task 24h later. Salivary cortisol samples were collected before and 20 min after the presentation of the mobile. We found that preterm infants had lower cortisol levels and smaller cortisol responses than full-term infants. This is consistent with relative adrenal insufficiency reported in the neonatal period. Infants who showed increased cortisol levels from 0 to 20 min on Day 1 had significantly better memory, regardless of prematurity, than infants who showed decreased cortisol levels.

Contingency Learning and Reactivity in Preterm and Full-Term Infants at 3 Months.

Learning difficulties in preterm infants are thought to reflect impairment in arousal regulation. We examined relationships among gestational age, learning speed, and behavioral and physiological reactivity in 55 preterm and 49 full-term infants during baseline, contingency, and nonreinforcement phases of a conjugate mobile paradigm at 3 months corrected age. For all infants, negative affect, looking duration, and heart rate levels increased during contingency and nonreinforcement phases, whereas respiratory sinus arrhythmia (RSA, an index of parasympathetic activity) decreased and cortisol did not change. Learners showed greater RSA suppression and less negative affect than nonlearners. This pattern was particularly evident in the preterm group. Overall, preterm infants showed less learning, spent less time looking at the mobile, and had lower cortisol levels than full-term infants. Preterm infants also showed greater heart rate responses to contingency and dampened heart rate responses to nonreinforcement compared to full-term infants. Findings underscore differences in basal and reactivity measures in preterm compared to full-term infants and suggest that the capacity to regulate parasympathetic activity during a challenge enhances learning in preterm infants.

Physiological correlates of memory recall in infancy: vagal tone, cortisol, and imitation in preterm and full-term infants at 6 months

We examined the role of physiological regulation (heart rate, vagal tone, and salivary cortisol) in short-term memory in preterm and full-term 6-month-old infants. Using a deferred imitation task to evaluate social learning and memory recall, an experimenter modeled three novel behaviors (removing, shaking, and replacing a glove) on a puppet. Infants were tested immediately after being shown the behaviors as well as following a 10-min delay. We found that greater suppression of vagal tone was related to better memory recall in full-term infants tested immediately after the demonstration as well as in preterm infants tested later after a 10-min delay. We also found that preterm infants showed greater coordination of physiology (i.e., tighter coupling of vagal tone, heart rate, and cortisol) at rest and during retrieval than full-term infants. These findings provide new evidence of the important links between changes in autonomic activity and memory recall in infancy. They also raise the intriguing possibility that social learning, imitation behavior, and the formation of new memories are modulated by autonomic activity that is coordinated differently in preterm and full-term infants.

Relationship disruption stress in human infants: A validation study with experimental and control groups

The current study examined whether the psychological stress of the still-face (SF) task (i.e. stress resulting from a parents unresponsiveness) is a valid laboratory stress paradigm for evaluating infant cortisol reactivity. Given that factors external to the experimental paradigm, such as arriving at a new place, may cause an elevation in cortisol secretion; we tested the hypothesis that infants would show a cortisol response to the SF task but not to a normal FF task (control). Saliva was collected for cortisol measurement from 6-month-old infants (n = 31) randomly assigned to either a repeated SF task or to a continuous FF task. Parent–infant dyads were videotaped. Salivary cortisol concentration was measured at baseline, 20, and 30 min after the start of the procedure. Infant salivary cortisol concentrations showed a significant increase over time for the SF task but not for the FF task. The results provide new evidence that the repeated SF task provides a psychological challenge that is due to the SF condition rather than to some non-task related factor; these results provide internal validity for the paradigm. The study offers new insight into the role of parent–infant interactions in the activation of the infant stress response system.

Infant anticipatory stress

In humans, anticipatory stress involves activation of the limbic–hypothalamic–pituitary–adrenal axis, which releases stress hormones such as cortisol in response to an impending stressor. Conditioning of the stress response to anticipate and prepare for future challenges is a hallmark of adaptation. It is unknown whether human infants in the first year of life have developed the neural circuitry to support the anticipation of stressful events in an attachment context. Here, we show that human infants at six months of age produce an anticipatory stress response, as indicated by the release of stress hormones, when re-exposed after 24 h to a context in which they demonstrated a stress response to a disruption in the parent–infant relationship. Although infant stress response (cortisol elevation) was greater to the stressful event (parent unresponsiveness) than to the second exposure to the stress context (room, chair, presence of parent and experimenter, etc.), it was greater in the stress group than in the control group on both days. Results suggest that human infants have the capacity to produce an anticipatory stress response that is based on expectations about how their parents will treat them in a specific context.

Infant cries rattle adult cognition

The attention-grabbing quality of the infant cry is well recognized, but how the emotional valence of infant vocal signals affects adult cognition and cortical activity has heretofore been unknown. We examined the effects of two contrasting infant vocalizations (cries vs. laughs) on adult performance on a Stroop task using a cross-modal distraction paradigm in which infant distractors were vocal and targets were visual. Infant vocalizations were presented before (Experiment 1) or during each Stroop trial (Experiment 2). To evaluate the influence of infant vocalizations on cognitive control, neural responses to the Stroop task were obtained by measuring electroencephalography (EEG) and event-related potentials (ERPs) in Experiment 1. Based on the previously demonstrated existence of negative arousal bias, we hypothesized that cry vocalizations would be more distracting and invoke greater conflict processing than laugh vocalizations. Similarly, we expected participants to have greater difficulty shifting attention from the vocal distractors to the target task after hearing cries vs. after hearing laughs. Behavioral results from both experiments showed a cry interference effect, in which task performance was slower with cry than with laugh distractors. Electrophysiology data further revealed that cries more than laughs reduced attention to the task (smaller P200) and increased conflict processing (larger N450), albeit differently for incongruent and congruent trials. Results from a correlation analysis showed that the amplitudes of P200 and N450 were inversely related, suggesting a reciprocal relationship between attention and conflict processing. The findings suggest that cognitive control processes contribute to an attention bias to infant signals, which is modulated in part by the valence of the infant vocalization and the demands of the cognitive task. The findings thus support the notion that infant cries elicit a negative arousal bias that is distracting; they also identify, for the first time, the neural dynamics underlying the unique influence that infant cries and laughs have on cognitive control.

Children’s autonomic nervous system activity while transgressing: Relations to guilt feelings and aggression.

Despite the well-established protective functions of guilt across childhood, its underlying physiological mechanisms have received little attention. We used latent difference scores (LDS) to model changes in children’s (N = 267; 4- and 8-year-olds, 51% girls) skin conductance (SC) and respiratory sinus arrhythmia (RSA) while they imagined themselves committing antisocial acts. We then tested if their later reports of guilt, caregiver-reported aggressive behavior, and age were associated with these physiological changes. For 8-year-olds, changes in RSA leading up to and during transgressions were uniquely associated with the intensity of guilt feelings after transgressions. Eight-year-olds with higher guilt were rated lower in aggression, although children’s physiology and aggression were not directly related. We discuss how fluctuations in physiology while transgressing may prepare children to mount adaptive guilt responses afterward and—more broadly—implications for understanding the mechanisms behind guilt and related behavior in early and middle childhood.

The special status of sad infant faces: age and valence differences in adults’ cortical face processing

Abstract Understanding the relative and joint prioritization of age- and valence-related face characteristics in adults’ cortical face processing remains elusive because these two characteristics have not been manipulated in a single study of neural face processing. We used electroencephalography to investigate adults’ P1, N170, P2 and LPP responses to infant and adult faces with happy and sad facial expressions. Viewing infant vs adult faces was associated with significantly larger P1, N170, P2 and LPP responses, with hemisphere and/or participant gender moderating this effect in select cases. Sad faces were associated with significantly larger N170 responses than happy faces. Sad infant faces were associated with significantly larger N170 responses in the right hemisphere than all other combinations of face age and face valence characteristics. We discuss the relative and joint neural prioritization of infant face characteristics and negative facial affect, and their biological value as distinct caregiving and social cues.