A longitudinal study on the association between trait mindfulness and maternal bonding across the perinatal period.

AIMS/BACKGROUND: The mother-to-infant is important for healthy child development. The current study focused on the association between maternal trait mindfulness and the course of maternal bonding from pregnancy to one year postpartum. DESIGN/METHODS: Women participating in a prospective perinatal cohort study (n = 1003) completed online questionnaires on maternal bonding (Pre- and Post-natal Bonding Scale) at 28 weeks of pregnancy, and at 8 weeks, 6 months and 12 months postpartum. At 20 weeks of pregnancy, women completed the Three Facet Mindfulness Questionnaire - Short Form. Multilevel analyses were used to analyse 1) changes in maternal bonding over time and 2) the relationship of these changes with different facets of trait mindfulness measured once during pregnancy. Demographics, obstetrics, and depressive symptoms were controlled for. RESULTS: Results showed that maternal bonding first increased from pregnancy to 8 weeks postpartum and then remained relatively stable throughout the first-year postpartum. On average, women with high scores on acting with awareness and non-judging also scored higher on maternal bonding, but demonstrated a smaller increase in maternal bonding scores over time when compared to women with medium and low scores on these mindfulness facets. Furthermore, non-reacting was also positively associated with the level of maternal bonding but was not related to the course of bonding over time. The main effects of non-reacting and non-judging were not significant after adjusting for covariates. Depressive symptoms and a high educational level were negatively associated with bonding. CONCLUSION: Mindfulness-based interventions may be helpful in supporting expectant mothers who are at risk for suboptimal bonding.

In Vivo Myelin Water Quantification Using Diffusion-Relaxation Correlation MRI: A Comparison of 1D and 2D Methods.

Multidimensional Magnetic Resonance Imaging (MRI) is a versatile tool for microstructure mapping. We use a diffusion weighted inversion recovery spin echo (DW-IR-SE) sequence with spiral readouts at ultra-strong gradients to acquire a rich diffusion-relaxation data set with sensitivity to myelin water. We reconstruct 1D and 2D spectra with a two-step convex optimization approach and investigate a variety of multidimensional MRI methods, including 1D multi-component relaxometry, 1D multi-component diffusometry, 2D relaxation correlation imaging, and 2D diffusion-relaxation correlation spectroscopic imaging (DR-CSI), in terms of their potential to quantify tissue microstructure, including the myelin water fraction (MWF). We observe a distinct spectral peak that we attribute to myelin water in multi-component T1 relaxometry, T1-T2 correlation, T1-D correlation, and T2-D correlation imaging. Due to lower achievable echo times compared to diffusometry, MWF maps from relaxometry have higher quality. Whilst 1D multi-component T1 data allows much faster myelin mapping, 2D approaches could offer unique insights into tissue microstructure and especially myelin diffusion.

Paternal bonding in pregnancy and early parenthood: a qualitative study in first-time fathers.

The birth of an infant marks a period of profound change in first-time parents. Parental love and warmth, however, already begin to develop during pregnancy. Also for fathers, the development of bonding to the infant may be a unique process. The current qualitative study aimed to explore views and experiences of first-time fathers on the origins and development of paternal bonding during pregnancy and early childhood. In total, 30 in-depth semi-structured interviews were conducted with expectant fathers (second or third trimester of pregnancy; n = 10) and fathers of infants (0-6 months postpartum; n = 11) and toddlers (2-3 years of age; n = 9). Two major themes were uncovered from the data: feelings of bonding and facilitators of bonding. The first theme was supported with three subthemes: 1) from abstract to concrete, 2) positive emotions, and 3) uncertainties and worries. The second theme, facilitators of bonding, was supported with four subthemes: 1) experiencing the foetus, 2) meeting the child, 3) interaction, and 4) communication. Similar to previous studies, our results suggested that, in most fathers, paternal bonding originates in pregnancy and that it evolves over time. Seeing or feeling the child, both during pregnancy and postpartum, as well as interacting or communicating with the child, appears to facilitate fathers' feelings of bonding. Involving fathers in pregnancy, childbirth, and parenting may be essential for their bonding process.

Parents of young infants report poor mental health and more insensitive parenting during the first Covid-19 lockdown.

BACKGROUND: The Covid-19 pandemic has put an unprecedented pressure on families with children. How parents were affected by the first Covid-19 lockdown during the early postpartum period, an already challenging period for many, is unknown. AIM: To investigate the associations between Covid-19 related stress, mental health, and insensitive parenting practices in mothers and fathers with young infants during the first Dutch Covid-19 lockdown. METHODS: The Dutch Covid-19 and Perinatal Experiences (COPE-NL) study included 681 parents of infants between 0 and 6 months (572 mothers and 109 fathers). Parents filled out online questionnaires about Covid-19 related stress, mental health (i.e. anxiety and depressive symptoms), and insensitive parenting. Hierarchical regression models were used to analyze the data. RESULTS: Parents of a young infant reported high rates of Covid-19 related stress, with higher reported stress in mothers compared to fathers. Additionally, the percentages of mothers and fathers experiencing clinically meaningful mental health symptoms during the pandemic were relatively high (mothers: 39.7% anxiety, 14.5% depression; fathers: 37.6% anxiety, 6.4% depression). More Covid-19 related stress was associated with more mental health symptoms in parents and increased insensitive parenting practices in mothers. CONCLUSIONS: The results emphasize the strain of the pandemic on young fathers' and mothers' mental health and its potential negative consequences for parenting. As poor parental mental health and insensitive parenting practices carry risk for worse child outcomes across the lifespan, the mental health burden of the Covid-19 pandemic might not only have affected the parents, but also the next generation.

The association of unplanned pregnancy with perinatal depression: a longitudinal cohort study.

Perinatal depression is common, affecting approximately 7-13% of women. Studies have shown an association between unplanned pregnancy and perinatal depressive symptoms, but many used a cross-sectional design and limited postnatal follow-up. The current study investigated the association of unplanned pregnancy with perinatal depressive symptoms using a longitudinal cohort study that followed women from the first trimester until 12 months postpartum. Pregnant women (N = 1928) provided demographic and clinical data and information about pregnancy intention at the first trimester. Depressive symptoms were assessed during each trimester of pregnancy and five times postpartum using the Edinburgh Postnatal Depression Scale (EPDS) until 12 months postpartum. Mixed model analyses were used to investigate the association between an unplanned pregnancy and the level of depressive symptoms. Women with an unplanned pregnancy (N = 111, 5.8%) reported persistently higher levels of depressive symptoms during the entire perinatal period compared to women with a planned pregnancy, after adjustment for confounders (p < 0.001). However, the course of depressive symptom scores over time in women with an unplanned pregnancy was similar to that of women with a planned pregnancy. Lower age (p = 0.006), unemployment (p = 0.004), and history of depression (p < 0.001) were significantly associated with higher levels of perinatal depressive symptoms. An unplanned pregnancy may have a long-lasting negative impact on a woman's perinatal mental health. Therefore, women with an unplanned pregnancy may benefit from systematic follow-up during the perinatal period with contingent mental health support.

In sync with your child: The potential of parent-child electroencephalography in developmental research.

Healthy interaction between parent and child is foundational for the child's socioemotional development. Recently, an innovative paradigm shift in electroencephalography (EEG) research has enabled the simultaneous measurement of neural activity in caregiver and child. This dual-EEG or hyperscanning approach, termed parent-child dual-EEG, combines the strength of both behavioral observations and EEG methods. In this review, we aim to inform on the potential of dual-EEG in parents and children (0-6 years) for developmental researchers. We first provide a general overview of the dual-EEG technique and continue by reviewing the first empirical work on the emerging field of parent-child dual-EEG, discussing the limited but fascinating findings on parent-child brain-to-behavior and brain-to-brain synchrony. We then continue by providing an overview of dual-EEG analysis techniques, including the technical challenges and solutions one may encounter. We finish by discussing the potential of parent-child dual-EEG for the future of developmental research. The analysis of multiple EEG data is technical and challenging, but when performed well, parent-child EEG may transform the way we understand how caregiver and child connect on a neurobiological level. Importantly, studying objective physiological measures of parent-child interactions could lead to the identification of novel brain-to-brain synchrony markers of interaction quality.

Improving the generalizability of infant psychological research: The ManyBabies model.

Yarkoni's analysis clearly articulates a number of concerns limiting the generalizability and explanatory power of psychological findings, many of which are compounded in infancy research. ManyBabies addresses these concerns via a radically collaborative, large-scale and open approach to research that is grounded in theory-building, committed to diversification, and focused on understanding sources of variation.

Data harmonisation for information fusion in digital healthcare: A state-of-the-art systematic review, meta-analysis and future research directions.

Removing the bias and variance of multicentre data has always been a challenge in large scale digital healthcare studies, which requires the ability to integrate clinical features extracted from data acquired by different scanners and protocols to improve stability and robustness. Previous studies have described various computational approaches to fuse single modality multicentre datasets. However, these surveys rarely focused on evaluation metrics and lacked a checklist for computational data harmonisation studies. In this systematic review, we summarise the computational data harmonisation approaches for multi-modality data in the digital healthcare field, including harmonisation strategies and evaluation metrics based on different theories. In addition, a comprehensive checklist that summarises common practices for data harmonisation studies is proposed to guide researchers to report their research findings more effectively. Last but not least, flowcharts presenting possible ways for methodology and metric selection are proposed and the limitations of different methods have been surveyed for future research.

Accelerated 3D whole-brain T1, T2, and proton density mapping: feasibility for clinical glioma MR imaging.

PURPOSE: Advanced MRI-based biomarkers offer comprehensive and quantitative information for the evaluation and characterization of brain tumors. In this study, we report initial clinical experience in routine glioma imaging with a novel, fully 3D multiparametric quantitative transient-state imaging (QTI) method for tissue characterization based on T1 and T2 values. METHODS: To demonstrate the viability of the proposed 3D QTI technique, nine glioma patients (grade II-IV), with a variety of disease states and treatment histories, were included in this study. First, we investigated the feasibility of 3D QTI (6:25 min scan time) for its use in clinical routine imaging, focusing on image reconstruction, parameter estimation, and contrast-weighted image synthesis. Second, for an initial assessment of 3D QTI-based quantitative MR biomarkers, we performed a ROI-based analysis to characterize T1 and T2 components in tumor and peritumoral tissue. RESULTS: The 3D acquisition combined with a compressed sensing reconstruction and neural network-based parameter inference produced parametric maps with high isotropic resolution (1.125 × 1.125 × 1.125 mm3 voxel size) and whole-brain coverage (22.5 × 22.5 × 22.5 cm3 FOV), enabling the synthesis of clinically relevant T1-weighted, T2-weighted, and FLAIR contrasts without any extra scan time. Our study revealed increased T1 and T2 values in tumor and peritumoral regions compared to contralateral white matter, good agreement with healthy volunteer data, and high inter-subject consistency. CONCLUSION: 3D QTI demonstrated comprehensive tissue assessment of tumor substructures captured in T1 and T2 parameters. Aiming for fast acquisition of quantitative MR biomarkers, 3D QTI has potential to improve disease characterization in brain tumor patients under tight clinical time-constraints.

The COVID-19 outbreak increases maternal stress during pregnancy, but not the risk for postpartum depression.

The COVID-19 pandemic affects society and may especially have an impact on mental health of vulnerable groups, such as perinatal women. This prospective cohort study of 669 participating women in the Netherlands compared perinatal symptoms of depression and stress during and before the pandemic. After a pilot in 2018, recruitment started on 7 January 2019. Up until 1 March 2020 (before the pandemic), 401 women completed questionnaires during pregnancy, of whom 250 also completed postpartum assessment. During the pandemic, 268 women filled out at least one questionnaire during pregnancy and 59 postpartum (1 March-14 May 2020). Pregnancy-specific stress increased significantly in women during the pandemic. We found no increase in depressive symptoms during pregnancy nor an increase in incidence of high levels of postpartum depressive symptoms during the pandemic. Clinicians should be aware of the potential for increased stress in pregnant women during the pandemic.

Functional Connectome of the Fetal Brain.

Large-scale functional connectome formation and reorganization is apparent in the second trimester of pregnancy, making it a crucial and vulnerable time window in connectome development. Here we identified which architectural principles of functional connectome organization are initiated before birth, and contrast those with topological characteristics observed in the mature adult brain. A sample of 105 pregnant women participated in human fetal resting-state fMRI studies (fetal gestational age between 20 and 40 weeks). Connectome analysis was used to analyze weighted network characteristics of fetal macroscale brain wiring. We identified efficient network attributes, common functional modules, and high overlap between the fetal and adult brain network. Our results indicate that key features of the functional connectome are present in the second and third trimesters of pregnancy. Understanding the organizational principles of fetal connectome organization may bring opportunities to develop markers for early detection of alterations of brain function.SIGNIFICANCE STATEMENT The fetal to neonatal period is well known as a critical stage in brain development. Rapid neurodevelopmental processes establish key functional neural circuits of the human brain. Prenatal risk factors may interfere with early trajectories of connectome formation and thereby shape future health outcomes. Recent advances in MRI have made it possible to examine fetal brain functional connectivity. In this study, we evaluate the network topography of normative functional network development during connectome genesis in utero Understanding the developmental trajectory of brain connectivity provides a basis for understanding how the prenatal period shapes future brain function and disease dysfunction.

Mesothelial cell CSF1 sustains peritoneal macrophage proliferation.

Macrophages play a central role during infection, inflammation and tissue homeostasis maintenance. Macrophages have been identified in all organs and their core transcriptomic signature and functions differ from one tissue to another. Interestingly, macrophages have also been identified in the peritoneal cavity and these cells have been extensively used as a model for phagocytosis, efferocytosis and polarization. Peritoneal macrophages are involved in B-cell IgA production, control of inflammation and wound healing following thermal-induced liver surface injury. These cells presumably require and interact with the omentum, where milky spot stromal cells have been proposed to secrete CSF1 (colony stimulating factor 1). Peritoneal macrophages depend on CSF1 for their generation and survival, but the identity of CSF1 producing cells inside the large peritoneal cavity remains unknown. Here we investigated peritoneal macrophage localization and their interaction with mesothelial cells, the major cell type predicted to secrete CSF1. Our data revealed that mesothelial cells produce membrane bound and secreted CSF1 that both sustain peritoneal macrophage growth.

Correction of motion-induced susceptibility artifacts and B0 drift during proton resonance frequency shift-based MR thermometry in the pelvis with background field removal methods.

PURPOSE: The linear change of the water proton resonance frequency shift (PRFS) with temperature is used to monitor temperature change based on the temporal difference of image phase. Here, the effect of motion-induced susceptibility artifacts on the phase difference was studied in the context of mild radio frequency hyperthermia in the pelvis. METHODS: First, the respiratory-induced field variations were disentangled from digestive gas motion in the pelvis. The projection onto dipole fields (PDF) as well as the Laplacian boundary value (LBV) algorithm were applied on the phase difference data to eliminate motion-induced susceptibility artifacts. Both background field removal (BFR) algorithms were studied using simulations of susceptibility artifacts, a phantom heating experiment, and volunteer and patient heating data. RESULTS: Respiratory-induced field variations were negligible in the presence of the filled water bolus. Even though LBV and PDF showed comparable results for most data, LBV seemed more robust in our data sets. Some data sets suggested that PDF tends to overestimate the background field, thus removing phase attributed to temperature. The BFR methods even corrected for susceptibility variations induced by a subvoxel displacement of the phantom. The method yielded successful artifact correction in 2 out of 4 patient treatment data sets during the entire treatment duration of mild RF heating of cervical cancer. The heating pattern corresponded well with temperature probe data. CONCLUSION: The application of background field removal methods in PRFS-based MR thermometry has great potential in various heating applications and body regions to reduce motion-induced susceptibility artifacts that originate outside the region of interest, while conserving temperature-induced PRFS. In addition, BFR automatically removes up to a first-order spatial B0 drift.

Impact of maternal childhood trauma on child behavioral problems: The role of child frontal alpha asymmetry.

Childhood trauma is associated with many long-term negative outcomes, and is not limited to the individual experiencing the trauma, but extends to subsequent generations. However, mechanisms underlying the association between maternal childhood trauma and child psychopathology are not well understood. Here, we targeted frontal alpha asymmetry (FAA) as a potential underlying factor of the relationship between maternal childhood trauma and child behavioral problems. Electroencephalography (EEG) was recorded from (N = 45) children (Mean age = 57.9 months, SD = 3.13) during an eyes-closed paradigm in order to evaluate FAA. Mothers reported on their childhood trauma experiences using the Childhood Trauma Questionnaire (CTQ), and on their child's behavior using the child behavior checklist (CBCL). We found that maternal childhood trauma significantly predicted child total, internalizing, and externalizing behavior at age 5 years. We also observed a role for FAA such that it acted as a moderator, but not mediator, for behavioral problems. We found that children with relative more right/less left frontal activity were more at risk to develop behavioral problems when their mother had been exposed to trauma in her childhood. These results indicate that child frontal asymmetry may serve as a susceptibility marker for child behavioral problems.

A two-hit story: Seizures and genetic mutation interaction sets phenotype severity in SCN1A epilepsies.

SCN1A (NaV1.1 sodium channel) mutations cause Dravet syndrome (DS) and GEFS+ (which is in general milder), and are risk factors in other epilepsies. Phenotypic variability limits precision medicine in epilepsy, and it is important to identify factors that set phenotype severity and their mechanisms. It is not yet clear whether SCN1A mutations are necessary for the development of severe phenotypes or just for promoting seizures. A relevant example is the pleiotropic R1648H mutation that can cause either mild GEFS+ or severe DS. We used a R1648H knock-in mouse model (Scn1aRH/+) with mild/asymptomatic phenotype to dissociate the effects of seizures and of the mutation per se. The induction of short repeated seizures, at the age of disease onset for Scn1a mouse models (P21), had no effect in WT mice, but transformed the mild/asymptomatic phenotype of Scn1aRH/+ mice into a severe DS-like phenotype, including frequent spontaneous seizures and cognitive/behavioral deficits. In these mice, we found no major modifications in cytoarchitecture or neuronal death, but increased excitability of hippocampal granule cells, consistent with a pathological remodeling. Therefore, we demonstrate for our model that an SCN1A mutation is a prerequisite for a long term deleterious effect of seizures on the brain, indicating a clear interaction between seizures and the mutation for the development of a severe phenotype generated by pathological remodeling. Applied to humans, this result suggests that genetic alterations, even if mild per se, may increase the risk of second hits to develop severe phenotypes.

A phase-cycled temperature-sensitive fast spin echo sequence with conductivity bias correction for monitoring of mild RF hyperthermia with PRFS.

OBJECTIVE: Mild hyperthermia (HT) treatments are generally monitored by phase-referenced proton resonance frequency shift calculations. A novel phase and thus temperature-sensitive fast spin echo (TFSE) sequence is introduced and compared to the double echo gradient echo (DEGRE) sequence. THEORY AND METHODS: For a proton resonance frequency shift (PRFS)-sensitive TFSE sequence, a phase cycling method is applied to separate even from odd echoes. This method compensates for conductivity change-induced bias in temperature mapping as does the DEGRE sequence. Both sequences were alternately applied during a phantom heating experiment using the clinical setup for deep radio frequency HT (RF-HT). The B0 drift-corrected temperature values in a region of interest around temperature probes are compared to the temperature probe data and further evaluated in Bland-Altman plots. The stability of both methods was also tested within the thighs of three volunteers at a constant temperature using the subcutaneous fat layer for B0-drift correction. RESULTS: During the phantom heating experiment, on average TFSE temperature maps achieved double temperature-to-noise ratio (TNR) efficiency in comparison with DEGRE temperature maps. In-vivo images of the thighs exhibit stable temperature readings of ± 1 °C over 25 min of scanning in three volunteers for both methods. On average, the TNR efficiency improved by around 25% for in vivo data. CONCLUSION: A novel TFSE method has been adapted to monitor temperature during mild HT.

A diffusion model-free framework with echo time dependence for free-water elimination and brain tissue microstructure characterization.

PURPOSE: The compartmental nature of brain tissue microstructure is typically studied by diffusion MRI, MR relaxometry or their correlation. Diffusion MRI relies on signal representations or biophysical models, while MR relaxometry and correlation studies are based on regularized inverse Laplace transforms (ILTs). Here we introduce a general framework for characterizing microstructure that does not depend on diffusion modeling and replaces ill-posed ILTs with blind source separation (BSS). This framework yields proton density, relaxation times, volume fractions, and signal disentanglement, allowing for separation of the free-water component. THEORY AND METHODS: Diffusion experiments repeated for several different echo times, contain entangled diffusion and relaxation compartmental information. These can be disentangled by BSS using a physically constrained nonnegative matrix factorization. RESULTS: Computer simulations, phantom studies, together with repeatability and reproducibility experiments demonstrated that BSS is capable of estimating proton density, compartmental volume fractions and transversal relaxations. In vivo results proved its potential to correct for free-water contamination and to estimate tissue parameters. CONCLUSION: Formulation of the diffusion-relaxation dependence as a BSS problem introduces a new framework for studying microstructure compartmentalization, and a novel tool for free-water elimination.

Children prenatally exposed to maternal anxiety devote more attentional resources to neutral pictures.

Maternal anxiety during pregnancy can negatively affect fetal neurodevelopment, predisposing the offspring to a higher risk of behavioral and emotional problems later in life. The current study investigates the association between maternal anxiety during pregnancy and child affective picture processing using event-related brain potentials (ERPs). Mothers reported anxiety during the second trimester using the anxiety subscale of the Symptom Checklist (SCL-90). At age 4 years, child affective picture processing (N = 86) was measured by recording ERPs during viewing of neutral, pleasant, and unpleasant pictures selected from the International Affective Pictures System. The late positive potential (LPP)-an ERP component reflecting individual differences in affective processing-was used as child outcome. The expected positive association between maternal anxiety and LPP amplitude for unpleasant pictures was not found. Nevertheless, we found a positive association between maternal anxiety during pregnancy and LPP amplitudes for neutral pictures in the middle and late time window at anterior locations (all p < .05). These associations remained significant after adjusting for maternal postnatal anxiety and gestational age at birth and after FDR correction for multiple comparisons. Our study provides neurophysiological evidence that children prenatally exposed to higher maternal anxiety devote more attentional resources to neutral pictures, but not to unpleasant pictures. Possibly, these children show enhanced vigilance for threat when viewing neutral pictures. Although useful in dangerous environments, this enhanced vigilance may predispose children prenatally exposed to higher maternal anxiety to developing behavioral and/or emotional problems later in life. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=kEzYi6IS2HA.

Prenatal neural origins of infant motor development: Associations between fetal brain and infant motor development.

Functional circuits of the human brain emerge and change dramatically over the second half of gestation. It is possible that variation in neural functional system connectivity in utero predicts individual differences in infant behavioral development, but this possibility has yet to be examined. The current study examines the association between fetal sensorimotor brain system functional connectivity and infant postnatal motor ability. Resting-state functional connectivity data was obtained in 96 healthy human fetuses during the second and third trimesters of pregnancy. Infant motor ability was measured 7 months after birth using the Bayley Scales of Infant Development. Increased connectivity between the emerging motor network and regions of the prefrontal cortex, temporal lobes, posterior cingulate, and supplementary motor regions was observed in infants that showed more mature motor functions. In addition, females demonstrated stronger fetal-brain to infant-behavior associations. These observations extend prior longitudinal research back into prenatal brain development and raise exciting new ideas about the advent of risk and the ontogeny of early sex differences.

Metabolism Plays a Key Role during Macrophage Activation.

Monocyte and macrophage diversity is evidenced by the modulation of cell surface markers and differential production of soluble mediators. These immune cells play key roles in controlling tissue homeostasis, infections, and excessive inflammation. Macrophages remove dead cells in a process named efferocytosis, contributing to the healthy tissue maintenance. Recently, it became clear that the main macrophage functions are under metabolic control. Modulation of glucose, fatty acid, and amino acid metabolism is associated with various macrophage activations in response to external stimuli. Deciphering these metabolic pathways provided critical information about macrophage functions.