Early Infant Prefrontal Cortical Microstructure Predicts Present and Future Emotionality.

BACKGROUND: High levels of infant negative emotionality (NE) and low positive emotionality (PE) predict future emotional and behavioral problems. The prefrontal cortex (PFC) supports emotional regulation, with each PFC subregion specializing in specific emotional processes. Neurite orientation dispersion and density imaging estimates microstructural integrity and myelination via the neurite density index (NDI) and dispersion via the orientation dispersion index (ODI), with potential to more accurately evaluate microstructural alterations in the developing brain. Yet, no study has used these indices to examine associations between PFC microstructure and concurrent or developing infant emotionality. METHODS: We modeled PFC subregional NDI and ODI at 3 months with caregiver-reported infant NE and PE at 3 months (n = 61) and at 9 months (n = 50), using multivariable and subsequent bivariate regression models. RESULTS: The most robust statistically significant findings were positive associations among 3-month rostral anterior cingulate cortex (ACC) ODI and caudal ACC NDI and concurrent NE, a positive association between 3-month lateral orbitofrontal cortex ODI and prospective NE, and a negative association between 3-month dorsolateral PFC ODI and concurrent PE. Multivariate models also revealed that other PFC subregional microstructure measures, as well as infant and caregiver sociodemographic and clinical factors, predicted infant 3- and 9-month NE and PE. CONCLUSIONS: Greater NDI and ODI, reflecting greater microstructural complexity, in PFC regions supporting salience perception (rostral ACC), decision making (lateral orbitofrontal cortex), action selection (caudal ACC), and attentional processes (dorsolateral PFC) might result in greater integration of these subregions with other neural networks and greater attention to salient negative external cues, thus higher NE and/or lower PE. These findings provide potential infant cortical markers of future psychopathology risk.

Prenatal stress and externalizing behaviors in childhood and adolescence: A systematic review and meta-analysis.

Accumulating evidence suggests that psychological distress during pregnancy is linked to offspring risk for externalizing outcomes (e.g., reactive/aggressive behaviors, hyperactivity, and impulsivity). Effect sizes across studies have varied widely, however, due to differences in study design and methodology, including control for the confounding continuation of distress in the postnatal period. Clarifying these inconsistencies is necessary to guide the precision of prevention efforts and inform public health policies. A meta-analysis was conducted with 55 longitudinal studies to investigate the association between prenatal psychological distress (anxiety, depression, and perceived stress) and offspring externalizing behaviors. Results revealed a significant but small effect (r = .160) of prenatal distress on externalizing behaviors. The magnitude of the prenatal effect size remained largely unchanged after adjusting for postnatal distress (r = .159), implicating a unique effect of psychological distress during the prenatal period in the etiology of externalizing behaviors. Moderation tests showed that prenatal effects did not vary based on type and timing of psychological distress during pregnancy. Greater instability of distress from prenatal to postnatal periods predicted larger effects. Prenatal effects were comparable across most externalizing outcomes, consistent with the common comorbidity of externalizing spectrum disorders, although effects appeared smaller for nonaggressive rule-breaking (vs. aggressive) behaviors. Significant associations persisted across all developmental periods, appearing slightly larger in early childhood. We discuss these results in the context of developmental and psychobiological theories of externalizing behavior, offer preliminary clinical and public health implications, and highlight directions for future research including the need for longitudinal studies with more racially and socioeconomically diverse families. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Early infant prefrontal gray matter volume is associated with concurrent and future infant emotionality.

High levels of infant negative emotionality (NE) are associated with emotional and behavioral problems later in childhood. Identifying neural markers of high NE as well as low positive emotionality (PE) in infancy can provide neural markers to aid early identification of vulnerability, and inform interventions to help delay or even prevent psychiatric disorders before the manifestation of symptoms. Prefrontal cortical (PFC) subregions support the regulation of NE and PE, with each PFC subregion differentially specializing in distinct emotional regulation processes. Gray matter (GM) volume measures show good test-retest reliability, and thus have potential use as neural markers of NE and PE. Yet, while studies showed PFC GM structural abnormalities in adolescents and young adults with affective disorders, few studies examined how PFC subregional GM measures are associated with NE and PE in infancy. We aimed to identify relationships among GM in prefrontal cortical subregions at 3 months and caregiver report of infant NE and PE, covarying for infant age and gender and caregiver sociodemographic and clinical variables, in two independent samples at 3 months (Primary: n = 75; Replication sample: n = 40) and at 9 months (Primary: n = 44; Replication sample: n = 40). In the primary sample, greater 3-month medial superior frontal cortical volume was associated with higher infant 3-month NE (p < 0.05); greater 3-month ventrolateral prefrontal cortical volume predicted lower infant 9-month PE (p < 0.05), even after controlling for 3-month NE and PE. GM volume in other PFC subregions also predicted infant 3- and 9-month NE and PE, together with infant demographic factors, caregiver age, and/or caregiver affective instability and anxiety. These findings were replicated in the independent sample. To our knowledge, this is the first study to determine in primary and replication samples associations among infant PFC GM volumes and concurrent and prospective NE and PE, and identify promising, early markers of future psychopathology risk.

Neural Network Functional Interactions Mediate or Suppress White Matter-Emotional Behavior Relationships in Infants.

BACKGROUND: Elucidating the neural basis of infant positive emotionality and negative emotionality can identify biomarkers of pathophysiological risk. Our goal was to determine how functional interactions among large-scale networks supporting emotional regulation influence white matter (WM) microstructural-emotional behavior relationships in 3-month-old infants. We hypothesized that microstructural-emotional behavior relationships would be differentially mediated or suppressed by underlying resting-state functional connectivity (rsFC), particularly between default mode network and central executive network structures. METHODS: The analytic sample comprised primary caregiver-infant dyads (52 infants [42% female, mean age at scan = 15.10 weeks]), with infant neuroimaging and emotional behavior assessments conducted at 3 months. Infant WM and rsFC were assessed by diffusion-weighted imaging/tractography and resting-state magnetic resonance imaging during natural, nonsedated sleep. The Infant Behavior Questionnaire-Revised provided measures of infant positive emotionality and negative emotionality. RESULTS: After significant WM-emotional behavior relationships were observed, multimodal analyses were performed using whole-brain voxelwise mediation. Results revealed that greater cingulum bundle volume was significantly associated with lower infant positive emotionality (ß = -0.263, p = .031); however, a pattern of lower rsFC between central executive network and default mode network structures suppressed this otherwise negative relationship. Greater uncinate fasciculus volume was significantly associated with lower infant negative emotionality (ß = -0.296, p = .022); however, lower orbitofrontal cortex-amygdala rsFC suppressed this otherwise negative relationship, while greater orbitofrontal cortex-central executive network rsFC mediated this relationship. CONCLUSIONS: Functional interactions among neural networks have an important influence on WM microstructural-emotional behavior relationships in infancy. These relationships can elucidate neural mechanisms that contribute to future behavioral and emotional problems in childhood.

Patterns of Infant Amygdala Connectivity Mediate the Impact of High Caregiver Affect on Reducing Infant Smiling: Discovery and Replication.

BACKGROUND: Behavioral research indicates that caregiver mood disorders and emotional instability in the early months following childbirth are associated with lower positive emotionality and higher negative emotionality in infants, but the neural mechanisms remain understudied. METHODS: Using resting-state functional connectivity as a measure of the functional architecture of the early infant brain, we aimed to determine the extent to which connectivity between the amygdala, a key region supporting emotional learning and perception, and large-scale neural networks mediated the association between caregiver affect and anxiety and early infant negative emotionality and positive emotionality. Two samples of infants (first sample: n = 58; second sample: n = 31) 3 months of age underwent magnetic resonance imaging during natural sleep. RESULTS: During infancy, greater resting-state functional connectivity between the amygdala and the salience network and, to a lesser extent, lower amygdala and executive control network resting-state functional connectivity mediated the effect of greater caregiver postpartum depression and trait anxiety on reducing infant smiling (familywise error-corrected p < .05). Furthermore, results from the first sample were replicated in the second, independent sample, to a greater extent for caregiver depression than for caregiver anxiety. CONCLUSIONS: We provide evidence of early objective neural markers that can help identify infants who are more likely to be at risk from, versus those who might be protected against, the deleterious effects of caregiver depression and anxiety and reduced positive emotionality.

Limbic white matter structural integrity at 3 months prospectively predicts negative emotionality in 9-month-old infants: a preliminary study.

BACKGROUND: Little is known about how early alterations in white matter relate to clinically relevant behaviors such as emotional dysregulation. Thus, our goal was to examine how the white matter structural integrity of key limbic (i.e., uncinate fasciculus and cingulum) and commissural (i.e., forceps minor) bundles in 3-month-old infants prospectively predicts emotional regulation behaviors at 9 months. METHODS: Three-month-old infants underwent multishell diffusion-weighted imaging. Following image processing, tractography was performed for each tract within each infant's native space (n=20). Measures of white matter integrity, including microstructure and morphology, were extracted from each tract. At 9 months, negative emotionality (NE) and positive emotionality (PE) were elicited using Laboratory Assessment of Temperament tasks. Elastic net regressions were performed for variable selection, which included white matter integrity variables from each of the 3 tracts, along with several covariates, including age, sex, use of public assistance, and the mother's depressive symptoms. Outcome variables were NE and PE composite scores evaluated in two separate models. RESULTS: Notably, following hierarchical regression using elastic net-selected variables, uncinate structural integrity was the most robust predictor of NE (ß=-0.631, p=0.005). LIMITATIONS: The sample size of our study is a limitation, however, as a preliminary study, our goal was to describe our findings to inform future, larger studies. CONCLUSIONS: Greater uncinate structural integrity predicted lower NE, suggesting that greater uncinate structural integrity at 3 months allows greater emotional regulation capacity at 9 months. To our knowledge, this is the first study to demonstrate prospective brain-to-emotional behavior relationships in infants.